Feature Articles

Pertussis: Severe clinical presentation in pediatric intensive care

and its relation to outcome*
Poongundran Namachivayam, MRCPCH; Kazuyoshi Shimizu, MD; Warwick Butt, FRACP, FJFICM

Objective: To describe our institutional experience in the man-
agement of infants and children with pertussis admitted during a
20-yr period (January 1985 through December 2004) and also to
study the relation between method of presentation and outcome.
Setting: Pediatric intensive care unit in a university-affiliated
tertiary pediatric hospital in Melbourne, Australia.
Design/Methods: Retrospective review of medical records and
radiology reports of patients with a diagnosis of pertussis iden-
tified from the pediatric intensive care unit database.
Results: A total of 49 patients (median age, 6 wks; interquartile
range, 4 – 8 wks) required 55 admission episodes to the pediatric
intensive care unit. Main reasons for admission were apnea with
or without cough paroxysms (63%), pneumonia (18%), and sei-
zures (10%). None of the infants had completed the primary
course of immunization, and 94% had not received a single dose
of pertussis vaccine. Infants presenting with pneumonia pre-
sented earlier (p ⴝ .001), had longer intensive care stay (p ⴝ
.007), higher white cell count (p < .001), lower PaO2 at admission
(p ⴝ .020), and higher mortality. Six infants out of seven needing
circulatory support died (including all four treated with extracor-
poreal membrane oxygenation), and all deaths (n ⴝ 7) occurred in
infants who had pneumonia at presentation.
Conclusion: Patients with pertussis, presenting as apnea (with
or without cough paroxysms), treated in the pediatric intensive
care unit had 100% survival. However, pneumonia as the main
reason for admission and the need for circulatory support is
associated with a very poor outcome. A deeper understanding of
the molecular basis of Bordetella pertussis and its relation to the
human host might offer means for future therapies. (Pediatr Crit
Care Med 2007; 8:207–211)
KEY WORDS: pertussis; intensive care; children; outcome; pre-
sentation; ventilation

P ertussis continues to be a sig-
nificant cause of childhood
morbidity and mortality, giv-
ing rise to 200,000 – 400,000
deaths every year, mostly in developing
countries (1). The recent increase in the
rate of pertussis is related to short-lived
infection and vaccine-induced immunity,
rendering adolescents and adults suscep-
tible to reinfection (2). This reservoir of
infection maintained in the adolescent
population subsequently causes infection
in susceptible infants, who are too young
to be fully vaccinated. More than half of
the severe cases requiring intensive care
manifests in infants too young to be vac-
*See also p. 288.
From the Intensive Care Unit, The Royal Children’s
Hospital, Melbourne, Australia (PN, KS, WB); and the
Department of Pediatrics, University of Melbourne,
Australia (WB).
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
siva.namachivayam@rch.org.au
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000265499.50592.37
cinated (3, 4). Most of the serious com-
plications and deaths related to pertussis
are seen in this age group (5). There is
general agreement that the disease is
toxin mediated, and antibiotics limit the
severity of illness only when started early
in the disease process (6). Pertussis toxin
damages the respiratory epithelium and
can also produce profound systemic and
neurotoxicity.
Infants needing intensive care pre-
dominantly present with apneas with or
without cough paroxysms, pneumonia,
and seizures, and a small proportion
progress to severe respiratory failure,
complicated by pulmonary hypertension
(7). Younger infants may also present
with a rapid progression of disease that is
so compressed and severe that the classic
stages may not be evident. Intensive care
management of pertussis is mainly sup-
portive (suction, oxygen, nasal continu-
ous positive airway pressure, intermittent
positive pressure ventilation). A recent
nationwide survey in Australia (8) showed
that intensive care was provided for 18%
of infants diagnosed with pertussis, and
56% of these infants needed intubation
and ventilation. Two previous reviews re-
port mechanical ventilation rates at 54%
and 42%, respectively (4, 9), and recent
articles highlight poor outcome for pa-
tients with severe pertussis needing ex-
tracorporeal membrane oxygenation
(ECMO) (10, 11). Understanding the
mode of presentation could be crucial in
the subsequent management and even-
tual outcome of these children. In this
article, we offer a single intensive care
unit’s experience of the management and
outcome of severe pertussis based on a
review of children during a 20-yr period.
METHODS AND PATIENTS
Infants and children admitted with a diag-
nosis of pertussis to the pediatric intensive
care unit (PICU) in Royal Children’s Hospital,
Melbourne, during a 20-yr period (January
1985 through December 2004) were included
in the study. Royal Children’s Hospital is a
specialized pediatric hospital serving a popu-
lation of 5 million in the states of Victoria,
Tasmania, and southern New South Wales. All
patients with PICU admission or discharge di-
agnosis of pertussis were identified from the
PICU database using the Australian and New
Zealand pediatric intensive care diagnostic
codes. Case histories were studied in detail by

Pediatr Crit Care Med 2007 Vol. 8, No. 3 207

the authors (PN, KS). Additional information
was also obtained from the PICU database and
from radiology reports. Cases with either con-
firmed pertussis or clinical pertussis (typical
presentation plus a family member positive for
pertussis) were included. Patient demograph-
ics, neonatal history and any preexisting ill-
ness, immunization status, method of presen-
tation, laboratory data, duration and type of
respiratory or circulatory support, complica-
tions, and outcome were recorded. Of note,
there were no major changes in mechanical
ventilation, sedation, and muscle paralysis
guidelines during the study period. ECMO
therapy was introduced in our unit in 1987–
1988 and inhaled nitric oxide therapy in 1993.
This retrospective review was approved as an
audit with our institutional review board.
Based on the method of presentation sub-
jects were divided into three groups. Group 1
(31 of 49 patients, 63%) consisted of patients
who mainly presented with apnea (with or
without cough paroxysms). Group 2 (9 of 49
patients, 18%) patients presented with respi-
ratory insufficiency or respiratory failure due
to pneumonia. The diagnosis of pneumonia was
made based on the clinical presentation and
chest radiography. All patients in this group had
evidence of either focal (3) or diffuse multilo-
bar (6) consolidation on chest radiographs at
admission. Group 3 patients (5 of 49 patients,
10%) presented with seizures. Four children
with pertussis were not included in the groups
either because of different methods of presen-
tation or due to presence of other underlying
illnesses: two with complete lung collapse due
to secretions, one with congenital diaphrag-
matic hernia, and one infant with bilateral
diffuse bronchomalacia.
Statistics. Data are expressed as absolute
values (percentage) or as median (interquar-
tile range); significance testing was made us-
ing one-way analysis of variance with Bonfer-
roni t-test for all pair-wise comparisons after
log transformation of original data, and Fisher
exact test was used in computing relation be-
tween mortality and presentation.
RESULTS
A total of 49 infants and children (24
male patients) with pertussis were admit-
ted to intensive care 55 times. The me-
dian age at admission was 6 wks (inter-
quartile range, 4 – 8 wks), and 46 patients
(94%) were ⬍6 months of age. A total of
45 infants (92%) were of white, and there
were no aboriginal children in our pa-
tient population. There was no significant
difference in age between the three
groups (Table 1). Of the patients, 26% (13
of 49) had been premature infants. Al-
most all children (46 of 49, 94%) were
unimmunized at the time of admission,
and the remaining (6%) had received one
dose of pertussis vaccine. Three children
who presented at an older age (7, 71⁄2, 21
months) had an underlying, unrecog-
nized respiratory condition at admission.
The first had diffuse bilateral bronchoma-
lacia, the second patient had co-existent
adenovirus pneumonia, and the third pa-
tient was diagnosed with congenital dia-
phragmatic hernia. Two thirds of the pa-
tients (34 of 49) were directly admitted to
PICU from the emergency department or
from another referring hospital, and the
remaining patients were admitted from
the hospital ward. Diagnosis was made by
a combination of immunofluorescence
and culture on nasopharyngeal aspirate
in 90% of the subjects (44 of 49). In
three, a diagnosis of clinical pertussis was
made, and one patient each tested posi-
tive for immunoglobulin A antibody and
polymerase chain reaction from nasopha-
ryngeal aspirate.
Table 1 displays patient characteristics
within groups. The median duration of
illness preadmission was 7 days (inter-
quartile range, 5–14 days), but on com-
parison, pneumonia subjects had signifi-
cantly shorter preadmission illness (p ⫽
.001). The PICU length of stay in the
apnea group was considerably shorter
in comparison with the pneumonia
group (p ⫽ .007). Children in group 1
(apnea) and group 3 (seizure) had longer
duration of hospital stay after discharge
from the PICU, and this was related to a
protracted illness due to coughing and
associated feeding difficulties. The PICU
and hospital length of stay for the pneu-
monia group tended to be similar. This
reflects the severity of illness among
these patients, as most of them (seven of
nine patients) subsequently died in the
PICU. Infants presenting with pneumonia
had raised white cell counts (p ⱕ .001)
and lower PaO2 (p ⫽ .020) in comparison
with the apnea group. Eighteen patients
(40%) needed tracheal intubation for re-
spiratory support (Table 2), and the indi-
cations were: severe hypoxic respiratory
failure (n ⫽ 7), progressive hypercapnia
(n ⫽ 2), respiratory arrest after pro-
longed apneas (n ⫽ 5), and seizures (n ⫽
4). The median duration of ventilation
was 84 hrs (interquartile range, 33.5–120
hrs). All patients who did not require
mechanical ventilation survived, and
38% of children (7 of 18) needing intu-
bation died.
Seven infants in the pneumonia group
(15.5%) needed vasoactive support for
progressive circulatory failure (manifest-
ing as worsening perfusion, tachycardia,
and hypotension), and four among them
were eventually placed on ECMO. Echo-
cardiographic data were available for six
of these infants and showed one or
more of the following findings: severe
pulmonary hypertension (all six pa-
tients), dilated and poorly contracting
right ventricle (three patients), and
global myocardial dysfunction (one pa-
tient). Durations of support for the four
infants placed on ECMO were 80, 133,
345, and 408 hrs. Six out of the seven
needing circulatory assistance died,

Table 1. Patient characteristics compared within groups

Apnea Pneumonia Seizure

Variable, Median (IQR) (Group 1) n ⫽ 31, 63% (Group 2) n ⫽ 9, 18% (Group 3) n ⫽ 5, 10% p Valuea

Age, wks 5.5 (4–8) 6 (3.7–10) 5 (3.7–11.5) .837

Illness duration before PICU, days 10 (7–4) 4 (3.7–6.2) 7 (4.7–8.5) .001
ICU length of stay, hrs 39 (26.2–68.5) 186 (57–244.2) 110 (92–129) .007
Hospital length of stay, hrs 294 (208–443) 186 (76.5–382) 454 (282–577.5) .081
White cell count, ⫻109/L 25.2 (16.5–34.5) 76.5 (62.1–108.5) 64 (19.7–74.1) ⬍.001
PaO2 at admission, mm Hg 97 (71–130) 61.5 (54–75) 106 (86.5–121) .020
PaCO2 at admission, mm Hg 48 (42–59.5) 69 (56.5–91) 46.5 (44–72.5) .044
Mortality, n 0 7 0 ⬍.001b

IQR, interquartile range; PICU, pediatric intensive care unit; ICU, intensive care unit.
a
Comparison between groups 1 and 2; bFisher exact test.

208 Pediatr Crit Care Med 2007 Vol. 8, No. 3

which included all patients on ECMO. A hyponatremia in two children, and re- indication for PICU admission is pertussis
detailed description of these patients is lated to hypoxic episodes in two children. pneumonia. The majority of children
given in Table 3. Three infants received One child with severe developmental de- (seven of nine) in the pneumonia group
continuous venovenous hemofiltration lay (due to pertussis encephalopathy) died, and no deaths were seen in other
for renal support, and one patient was died at the age of 14 yrs due to worsening groups.
given both exchange transfusion and cardiac failure secondary to palliated The reported rate of pertussis pneu-
plasmapheresis for toxin clearance. All heart disease. Seven (15.5%) had feeding monia varies around 25% (12, 13). In our
seven children who died had pneumonia difficulties related to coughing episodes study, 18 patients (36%) developed pneu-
as the dominant presentation (Table 3). and needed parenteral nutrition and long monia, and in half of them, it was the
Complications occurred in 30 children hospital stay. All children after discharge presenting illness. Pneumonia evolving
(61%), and most had more than one from PICU were under the care of a re- later in the illness is associated with less
problem. Viral studies (nasopharyngeal spiratory physician. severe disease progression and often re-
aspirate for immunofluorescence and lated to secondary viral infections. Per-
culture) were available in all subjects. DISCUSSION haps the most important feature of our
The frequency and type of viral infections study is the classification of our patients
are shown in Table 4. Pneumonia was This review represents the largest into groups based on the main presenting
identified in 18 patients (36%), and half group of infants and children with per- illness, which enabled us to compare and
of these had pneumonia as initial presen- tussis treated in intensive care. The most
correlate different aspects of treatment
tation. Seizures (9) were thought to be important finding is the poor outcome
and outcome. For example, most patients
toxin induced in five children, caused by associated with this condition if the main
in the apnea group were managed with
supplemental oxygen or nasopharyngeal
Table 2. Respiratory support for different patient groups continuous positive airway pressure as
apposed to infants in the pneumonia
Apnea Pneumonia Seizure Total
(Group 1) n ⫽ 31 (Group 2) n ⫽ 9 (Group 3) n ⫽ 5 n ⫽ 45 group, who needed intubation. This is in
marked contrast to previous literature
IPPV 5 9a 4 18 (4), which report apnea as the main indi-
NCPAP 8 0 1 9 cation for mechanical ventilation. Previ-
Oxygen 18 0 0 18 ous reports (5, 14) identified prematurity
IPPV, intermittent positive pressure ventilation; NCPAP, nasopharyngeal continuous positive as a risk factor for mortality in infantile
airway pressure. pertussis. A total of 13 patients (26%) in
a
Three children initially receiving NCPAP were subsequently intubated for worsening hypoxic our study were born at ⬍37 wks of ges-
respiratory failure. tation, but only one presented with se-

Table 3. Characteristics of children who died of pertussis infection

Duration of ICU
Age, Illness, Length of Highest
Pt Wks Days Stay, Hrs Main Presentation P(A-a)O2/OI Vasoactive Infusionsa Support Cause of Death

1 3 4 21 Pneumonia 554/42 None IPPV Severe pertussis pneumonia,

PHT, severe cardiovascular
compromise; treatment
withdrawn for poor
prognosis
2 6 4 235 Pneumonia 213/17 AD 0.5, NA 0.5, IPPV, HFO, iNO, Severe pertussis pneumonia,
VASO VA-ECMO PHT
3 5 5 96 Pneumonia 454/31 DOB 10, NA 0.5, AD IPPV, HFO, iNO, Treatment withdrawn for poor
bolus, VASO, CA VA-ECMO neurological prognosis;
infusion severe pertussis
encephalopathy
4 7 3 19 Pneumonia 539/30 DOP 15, AD 3, and IPPV Severe pertussis pneumonia,
bolus circulatory failure
5 13 7 369 Pneumonia, shock 626/59 DOB 20, AD 0.4, and IPPV, VA-ECMO Multiorgan failure
bolus
6 4 14 69 Pneumonia 627/31 DOP 20, AD 2, and IPPV Multiorgan failure
bolus
7 10 4 186 Pneumonia 578/63 AD10 and bolus, IPPV, VA-ECMO Severe pertussis pneumonia,
NA1, DOP15, CA PHT, multiorgan failure
infusion

Pt, patient; ICU, intensive care unit; P(A-a)O2/OI, alveolar-arterial oxygen gradient and oxygenation index; IPPV, intermittent positive pressure
ventilation; PHT, pulmonary hypertension; AD, adrenaline; NA, noradrenaline; VASO, vasopressin; HFO, high-frequency oscillation; iNO, inhaled nitric
oxide; VA-ECMO, venoarterial extracorporeal membrane oxygenation; DOB, dobutamine; CA, calcium; DOP, dopamine.
a
Numbers indicate highest dose in micrograms per kilogram per minute.

Pediatr Crit Care Med 2007 Vol. 8, No. 3 209

Table 4. Complications seen in study patients
Complications n (%)
Pneumonia 18 (36)
Seizures 9 (18)
Encephalopathy 5 (10)
Hyponatremia 10 (20)
Acute renal failure
Lung collapse
Pleural effusion
Pneumothorax
Pulmonary hemorrhage
Pneumomediastinum
Pneumoperitoneum
Feeding difficulties 7 (14.2)
Developmental delay
Disseminated intravascular
coagulation
Associated/secondary
infections
Adenovirus
Rhino virus
Respiratory syncytial virus
Parainfluenza
Influenza A
Pseudomonas sepsis
Coagulase-negative sepsis
Candida sepsis
vere disease (pneumonia at presentation)
and eventually died. A previous study
conducted in Australia (8) also did not
identify prematurity as a risk factor for
mortality.
Pertussis is a toxin-mediated disease
associated with several virulence factors,
including pertussis toxin (most widely
studied of all), accounting for the wide-
spread variation in disease severity (15).
Pertussis toxin has multiple proven bi-
ological activities, some of which may
account for the systemic manifestations
of the disease. Severe and fatal pertussis
has been correlated with the degree of
lymphocytosis, a clear manifestation of
pertussis toxin. ECMO has benefited
children with refractory septic shock
(16, 17), and the role of plasmapheresis
in sepsis is currently under evaluation
(18, 19). Both these therapies, with
ECMO in particular, have shown disap-
pointing results in pertussis in our ex-
perience and in published literature
(10, 11, 20). We identified several risk
factors for mortality, such as shorter
preadmission illness, pneumonia at
presentation, leucocytosis, and the
need for circulatory support. Most of
these factors have been reported in pre-
vious literature (5), and moreover,
identifying risk factors does not neces-
sarily offer a solution to the problem.
Severe and refractory pulmonary hyper-
tension often evolves very rapidly and,
210
despite various rescue measures, can be
very difficult to treat. The mechanism
of pulmonary hypertension in pertussis
remains undetermined; however, the
demonstration of leukocyte thrombi in
the pulmonary vein of a fatal case (11)
and the correlation between leukocyto-
2 3. Ranganathan S, Tasker R, Booy R, et al: Per-
sis and mortality (7) lead one to believe
2
2 that therapies aimed at reducing the
2 degree of leukocytosis could be benefi-
1 cial. Exchange transfusion (21) and leu-
1 kopheresis therapy (22) by producing
1
cytoreduction have led to patient sur-
vival, and we suggest these therapies
1
1 should be considered in this high-risk
group.
Disease among adolescents and
adults represent an important reservoir
4
4 of pertussis, and administering booster
2 doses of vaccine to this population
2 might prevent transmission and disease
1 burden in younger infants (23). The
2
1
clinical course of pertussis in immu-
nized children tends to be milder (24),
1
and speeding up the current immuni-
zation schedule to deliver the first dose
earlier (⬍2 months of age) could be
beneficial; moreover, a deeper under-
standing of the molecular basis of Bor-
detella pertussis infection might offer
means for further therapies. Valuable
information obtained from the more re-
cently completed Bordetella genome
project (25, 26) might help in a better
understanding of this organism and its
relation with the human host.
The retrospective nature of our study
is clearly the most important limiting
factor, but dividing our subjects into
groups based on their presentation has
enabled us to more clearly outline the
management and outcome. Infants in our
study represent severe cases with serious
consequences, such as pneumonia, sei-
zures, encephalopathy, multiorgan dys-
function, and death. Most pertussis is a
relatively benign but persistent illness,
and the full effect of the disease on the
community cannot be assessed based on
our results.
In conclusion, pertussis pneumonia as
the main reason for PICU admission is
associated with a very poor outcome. The
need for circulatory support implies a
very poor prognosis. Well-established in-
tensive care therapies like ECMO have
been associated with poor outcome in the
management of pertussis in our experi-
ence. A deeper understanding of the mo-
lecular mechanisms underlying pertussis
infection could be vital for the develop-
ment of future therapies.
REFERENCES
1. Pertussis vaccines. Wkly Epidemiol Rec
1999; 74:137–143
2. von Konig CH, Halperin S, Riffelmann M, et
al: Pertussis of adults and infants. Lancet
Infect Dis 2002; 2:744 –750
tussis is increasing in unimmunized infants:
Is a change in policy needed? Arch Dis Child
1999; 80:297–299
4. Gillis J, Grattan-Smith T, Kilham H: Artifi-
cial ventilation in severe pertussis. Arch Dis
Child 1988; 63:364 –367
5. Vitek CR, Pascual FB, Baughman AL, et al:
Increase in deaths from pertussis among
young infants in the United States in the
1990s. Pediatr Infect Dis J 2003; 22:
628 – 634
6. Tozzi AE, Celentano LP, Ciofi degli Atti ML,
et al: Diagnosis and management of pertus-
sis. CMAJ 2005; 172:509 –515
7. Pierce C, Klein N, Peters M: Is leukocytosis a
predictor of mortality in severe pertussis in-
fection? Intensive Care Med 2000; 26:
1512–1514
8. Elliott E, McIntyre P, Ridley G, et al: National
study of infants hospitalized with pertussis in
the acellular vaccine era. Pediatr Infect Dis J
2004; 23:246 –252
9. Lewis M, Bush GH: Ventilatory support for
children with whooping cough: Experience
with children admitted to a paediatric in-
tensive care unit. Anaesthesia 1980; 35:
979 –983
10. Halasa NB, Barr FE, Johnson JE, et al: Fatal
pulmonary hypertension associated with per-
tussis in infants: Does extracorporeal mem-
brane oxygenation have a role? Pediatrics
2003; 112:1274 –1278
11. Williams GD, Numa A, Sokol J, et al: ECLS in
pertussis: Does it have a role? Intensive Care
Med 1998; 24:1089 –1092
12. Farizo KM, Cochi SL, Zell ER, et al: Epide-
miological features of pertussis in the United
States, 1980 –1989. Clin Infect Dis 1992; 14:
708 –719
13. Heininger U, Klich K, Stehr K, et al: Clinical
findings in Bordetella pertussis infections:
Results of a prospective multicenter surveil-
lance study. Pediatrics 1997; 100:E10
14. Wortis N, Strebel PM, Wharton M, et al:
Pertussis deaths: Report of 23 cases in the
United States, 1992 and 1993. Pediatrics
1996; 97:607– 612
15. Kerr JR, Matthews RC: Bordetella pertussis
infection: Pathogenesis, diagnosis, manage-
ment, and the role of protective immunity. Eur
J Clin Microbiol Infect Dis 2000; 19:77– 88
16. Beca J, Butt W: Extracorporeal membrane
oxygenation for refractory septic shock in
children. Pediatrics 1994; 93:726 –729
17. Goldman AP, Kerr SJ, Butt W, et al: Extra-
corporeal support for intractable cardiorespi-
ratory failure due to meningococcal disease.
Lancet 1997; 349:466 – 469
18. McMaster P, Shann F: The use of extracor-
poreal techniques to remove humoral fac-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
 tors in sepsis. Pediatr Crit Care Med 2003;
4:2–7
19. Reeves JH, Butt WW, Shann F, et al: Contin-
uous plasmafiltration in sepsis syndrome:
Plasmafiltration in Sepsis Study Group. Crit
Care Med 1999; 27:2096 –2104
20. Pooboni S, Roberts N, Westrope C, et al:
Extracorporeal life support in pertussis. Pe-
diatr Pulmonol 2003; 36:310 –315
21. Romano MJ, Weber MD, Weisse ME, et al:
Pertussis pneumonia, hypoxemia, hyperleu-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
kocytosis, and pulmonary hypertension: Im-
provement in oxygenation after a double vol-
ume exchange transfusion. Pediatrics 2004;
114:e264 –E266
22. Grzeszczak MJ, Churchwell KB, Edwards KM,
et al: Leukopheresis therapy for severe infantile
pertussis with myocardial and pulmonary fail-
ure. Pediatr Crit Care Med 2006; 7:580 –582
23. Forsyth K, Tan T, von Konig CH, et al: Poten-
tial strategies to reduce the burden of pertussis.
Pediatr Infect Dis J 2005; 24:S69 –S74
24. Bortolussi R, Miller B, Ledwith M, et al: Clin-
ical course of pertussis in immunized chil-
dren. Pediatr Infect Dis J 1995; 14:870 – 874
25. Preston A: Bordetella pertussis: The intersec-
tion of genomics and pathobiology. CMAJ
2005; 173:55– 62
26. Parkhill J, Sebaihia M, Preston A, et al: Com-
parative analysis of the genome sequences of
Bordetella pertussis, Bordetella parapertus-
sis, and Bordetella bronchiseptica. Nat Genet
2003; 35:32– 40
211
Pediatric staff perspectives on organ donation after cardiac
death in children*
Martha A. Q. Curley, RN, PhD, FAAN; Charlotte H. Harrison, JD, MPH, MTS; Nancy Craig, RRT;
Craig W. Lillehei, MD, FAAP, FACS; Anne Micheli, RN, MS; Peter C. Laussen, MBBS

Objectives: The aims of this project were to describe whether
pediatric clinical staff members believe that a donation after
cardiac death (DCD) program could be consistent with the mission
and core values of a children’s hospital and to identify what staff
consider essential to the acceptability of such a program.
Design: Qualitative study.
Setting: Children’s hospital.
Subjects: Pediatric clinical staff.
Interventions: Data were gathered from pediatric clinical staff
during eight focus groups conducted in a children’s hospital in
March and April 2005.
Measurements and Main Results: Eighty-eight staff members
participated. Six major themes emerged from qualitative analysis
of the data: a) identifying children who could be candidates for
DCD; b) considering the best interests of the dying child; c)
approaching parents about DCD; d) preparing parents for their
child’s DCD; e) doing DCD well; and f) maintaining program
integrity. Themes were used to construct a conceptual framework
describing a model pediatric DCD program. Pediatric staff voiced
numerous concerns. However, they identified “making it happen
for families” who voice a desire to participate in organ donation
as the primary reason for program adoption.
Conclusions: This study provides a framework for understand-
ing pediatric staff perspectives on DCD programs in children.
Results suggest several possible elements that may be helpful in
framing interdisciplinary dialogue and informing institutional
practices in the design of a pediatric DCD program. (Pediatr Crit
Care Med 2007; 8:212–219)
KEY WORDS: non-heart-beating organ donor; organ donation;
transplantation; withdrawal of life support; child; parent; focus
group; qualitative analysis

T he disparity between the num-
ber of patients awaiting organ
donation and the actual num-
ber of organs transplanted
continues to be a significant health care
issue (1–3). One strategy to increase the
number of organs available for donation
is the procurement of select organs from
nonheartbeating donors, also known as
donation after cardiac death (DCD) (4, 5).
The interest in DCD not only is related to
the potential increase in organs for trans-
plantation (2) but derives from the re-
*See also p. 290.
From the Critical Care and Cardiovascular Program
(MAQC), Office of Ethics (CH), Department of Respira-
tory Care (NC), Department of Surgery (CL), Perioper-
ative Nursing (AM), and the Cardiovascular Intensive
Care Unit (PL), Children’s Hospital Boston, Boston, MA.
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
curley@nursing.upenn.edu
Dr. Curley’s current address is University of Penn-
sylvania, School of Nursing, 350 Claire M. Fagin Hall,
420 Guardian Drive, Philadelphia, PA 19104-6096.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262932.42091.09
quests expressed by families of patients
dying from irreversible neurologic inju-
ries when brain death criteria cannot be
met (6).
Few pediatric DCD programs exist,
and the orchestration of a child’s death
with DCD is quite different from what
occurs without DCD (7, 8). First, unlike
competent adult patients, who may have
an opportunity to express an opinion on
organ donation, parents or legal guard-
ians are always asked to provide consent
for DCD for their child. Then, depending
on the DCD protocol, there may be pre-
morbid procedures and drugs administered
that offer no benefit to the child, and may
even cause harm or hasten death, and yet
are deemed useful for organ protection.
Withdrawal of life support usually occurs in
the operating room, often with the child
prepared for immediate laparotomy and
organ procurement once death has been
declared. When the child dies, the sur-
geon cannulates the femoral vessels to
allow the rapid infusion of cold preserva-
tive solution. The immediacy and impor-
tance of postmortem procedures severely
limit the time families can spend with the
child, and in most circumstances, family
members are escorted from the operating
room soon after the declaration of the
child’s death. This is an emotionally dif-
ficult time for families and staff. There is
conflict between wanting to preserve the
integrity and dignity of the child during
the withdrawal of care process and the
need to preserve the function of organs
that are about to be donated.
Although our local organ procure-
ment organization had established active
DCD protocols with several area adult
hospitals, Children’s Hospital Boston had
not developed a DCD program. Senior
leadership viewed developing a DCD pro-
tocol as an institutional concern because
of the unique clinical, ethical, societal,
and legal considerations in pediatric pa-
tients. As such, a multidisciplinary task
force was appointed to first determine
whether a DCD program was consistent
with the hospital mission and, if that de-
termination was affirmative, to develop a
DCD protocol and recommend an imple-
mentation process. The hospital’s mis-
sion, similar to that of other major uni-
versity-affiliated pediatric teaching
institutions, includes excellence in clini-
cal practice, research, education, and

212 Pediatr Crit Care Med 2007 Vol. 8, No. 3

community service. Core values include
the primacy of patients and family-
centered care including sensitivity to and
support for the needs of families from
diverse backgrounds. Organ donation af-
ter brain death is considered a standard of
care, and the institution has an active
transplant program. Co-chaired by an in-
tensive care physician and member of the
hospital office of ethics, the task force
included broad representation of mem-
bers across the hospital community: spe-
cifically, parents, nurses, physicians, so-
cial workers, pastoral care workers, ethics
advisors, and legal counsel.
We designed a qualitative study to pro-
vide the task force with an internal per-
spective on DCD in children. Our primary
objectives were to gather the views of
pediatric staff on whether a DCD program
could be consistent with the mission and
core values of our institution and to
describe what staff members believe are
essential elements of a model pediatric
DCD program. Because of the signifi-
cance of potential concerns regarding
the process of DCD, the opinions of staff
members who would be directly af-
fected by a DCD program are important
to understand.
METHODS
Study Design and Sample. We conducted a
qualitative study, collecting data during eight
1-hr focus group meetings conducted at Chil-
dren’s Hospital Boston in March and April
2005. The qualitative approach was selected
for two reasons. First, there was a paucity of
data on the topic, and qualitative methods are
particularly well-suited for exploratory studies
for which previous literature is limited (9, 10).
Second, inductive methodologies are useful
when the research goal is to understand the
issues that are most important from an insider’s
perspective (10, 11). The multidisciplinary re-
search team held no preconceived assump-
tions of what was or was not important to staff.
Focus groups allowed the investigative team
to capitalize on group dynamics to explore
shared experiences that would be unavailable
through individual interviews (12, 13).
Typical in qualitative research (11, 12),
groups were purposely sampled to represent
key members of the hospital community who
would be directly involved in a DCD program:
specifically, attending intensivists, anesthesi-
ologists, general and transplant surgeons,
medical-surgical intensive care nurses, car-
diac intensive care nurses, operating room
nurses, respiratory therapists, and hospital
clergy. Focus groups were conducted by clin-
ical discipline to allow cross-group compari-
son. Invitations to participate were electroni-
cally mailed to all staff members within each
Pediatr Crit Care Med 2007 Vol. 8, No. 3
constituent group using departmental distri-
bution lists. Physicians in training and tem-
porary staff were excluded. Open invitations
were supplemented by letters of support from
department chiefs or managers. To decrease
participant burden, the focus groups sub-
sumed or supplemented existing staff meet-
ings. Consistent with the recommendation of
the Clinical Investigation Committee regard-
ing the publication of quality improvement
initiatives, at the start of each focus group
members gave their permission for the publi-
cation of de-identified results if the findings
were thought to be of interest outside the
institution.
Data Collection. Each group was moder-
ated by the principal investigator (MC), audio-
taped, and observed by a second member of
the research team and a research assistant.
The principal investigator, trained in both
qualitative methods and group facilitation,
maintained a neutral stance. A research assis-
tant completed field notes that chronicled the
mood and nonverbal interaction of each focus
group.
The focus groups were semistructured.
Ground rules included participant attention to
each person’s comments and acknowledgment
that group consensus was not required.
The moderator began each group with a
review of the purpose of convening the group:
to ask group members their opinion on
whether the hospital should adopt a DCD pro-
tocol. The second member of the research
team defined DCD and general DCD processes
and provided an overview of DCD practices
and organ survival in the United States (5, 7).
Next, participants were asked to verify that
they were representative of their constituent
group. The DCD exemplar case, congruent
with our local Organ Procurement Organiza-
tion protocol, was then read aloud. In the case
scenario, 8-yr-old Michael has suffered a cat-
astrophic head injury with preservation of ap-
neustic breathing. During a team meeting,
Michael’s parents are given the option of with-
drawal of life support. Michael’s parents decide
to withdraw life support and are then given an
opportunity to participate in DCD. His parents
agree to DCD and the scenario unfolds
through premorbid procedures (femoral arte-
rial and venous catheter insertion, heparin
and systemic vasodilator administration),
withdrawal of life support, declaration of
death, and saying last goodbyes in the operat-
ing room. The scenario included a list of
scripted probes to allow discipline-specific dis-
cussion. These included, “Michael’s heart
doesn’t stop within 1 hr of withdrawal of life
support.” “Michael’s parents find it difficult to
leave the operating room when his death is
declared.” “Michael’s electrocardiogram shows
slow wide-complex electrical activity with a
vacillating palpable pulse, so time of death is
unclear.” Each member was then asked to
consecutively respond to an opening question,
specifically, “In light of Children’s Hospital
Boston values and mission, should we adopt a
DCD protocol? If in support, delineate essen-
tial elements of the protocol; if not in support,
delineate major barriers to a DCD protocol.”
Open dialogue then followed providing an op-
portunity for all participants to seek clarifica-
tion of issues presented during the opening
statement.
At the conclusion of each focus group, staff
members were asked to provide a closing com-
ment and complete a brief work profile noting
the year they obtained their professional li-
cense. Demographic questions were avoided to
eliminate individual concerns regarding ano-
nymity. These data were analyzed using de-
scriptive statistics and a statistical software
program (SPSS 11.5). Each participant was
also given a return comment card to offer
additional statements or share comments that
they felt uncomfortable discussing within the
group. None were received.
Data Analysis. The audiotapes were tran-
scribed verbatim and checked for transcrip-
tion accuracy, and all personal identifiers were
removed. The transcripts were uploaded into
NVivo qualitative software (version 2.0.161;
QRS International). Transcribed data were an-
alyzed using common coding techniques for
qualitative data (14). The principal investiga-
tor read all transcripts to search for broad
concepts and themes representing participant
views on DCD. The themes were entered into
a coding dictionary and operationally defined
by the principal investigator. The transcripts
were then read and coded separately by a sec-
ond member of the multidisciplinary research
team (CH, NC, PL). Second readings by team
members representing different disciplines
guarded against disciplinary bias (9). The the-
matic analyses of each transcript were com-
pared for overlap, consensus regarding the
phenomena represented, and the coding ap-
plied. Existing codes were refined, and new
concepts and themes were identified through-
out the iterative process. The research team
reconvened to reach consensus on the opera-
tional definitions of all codes and to review
and comment on a draft conceptual frame-
work posed by the principal investigator. The
research team then reread and recoded each
transcript using the final codes and opera-
tional definitions. Ultimately, agreement was
reached on a working draft of the conceptual
framework that outlined a model pediatric
DCD program. The methodology and final
framework were presented to the task force
charged with making a formal recommen-
dation regarding DCD to senior hospital
leadership. The multidisciplinary task force
concurred that the study findings were repre-
sentative of the data (15).
RESULTS
A total of 88 staff members practicing
an average of 17 ⫾ 10 yrs in pediatrics
participated (Table 1). When considering
the institution’s mission and core values,
213
Table 1. Focus group participants

Years in
Discipline No. Practicea

Nurses
Medical-surgical ICU 12 17 (13)
Cardiac intensive care 10 11 (16)
Operating room 11 26 (10)
Physicians
Intensivists 11 16 (17)
Anesthesiologists 17 12 (17)
Surgeons 9 12 (11)
Respiratory therapists 11 15 (20)
Clergy (Protestant, Jewish, 7 24 (13)
and Catholic faith
traditions)

ICU, intensive care unit.

a
Median (interquartile range).

no group solidly supported or was vehe-

mently opposed to instituting a DCD pro-
gram. Focus group data were used to
build a conceptual framework describing
what pediatric staff members believe are
essential elements of a model pediatric
DCD program (Figure 1). The framework
consists of six major themes: a) identify-
ing children who could be candidates for
DCD; b) considering the best interests
of the dying child; c) approaching par-
ents about DCD; d) preparing parents
for DCD; e) doing DCD well; and f)
maintaining program integrity. Each
theme is presented next with unedited
supporting quotations from focus
group participants (16).
Identifying DCD Candidates. Staff
agreed with the case scenario that the
decision to withdraw life support should
be distinctly separate from any consider-
ation of DCD. Once the clinical team and
family transitioned to a withdrawal-of-
life-support stance, the next step would
include an evaluation of whether the
child would be a DCD candidate. This
would include whether the team expected
the child to experience a cardiac arrest
within the requisite hour after the
withdrawal of life support (7). Staff
noted that the dying process did not
always match initial expectations, ob-
scuring who would actually qualify as a
DCD candidate.
And as smart as we are in terms of
predicting . . . ah . . . who will die in pe-
diatrics, we’re not as smart as we always
think—intensive care unit [ICU] nurse.
Considering the Best Interests of the
Dying Child. Although parents ordinarily
have the right to consent to medical pro-
cedures on behalf of their child, several
focus groups questioned whether parents
Figure 1. Donation after cardiac death (DCD) conceptual framework. Clinician approach to parents
about DCD varies according to the individuality of the parent. The DCD question could “make it
happen for the parent” or burden the parent. When clinicians are obtaining informed consent for DCD,
parents should receive information about how their child’s death would evolve with and without DCD.
Orchestration of death without DCD includes providing family time with the patient after death. If
DCD is chosen, then doing DCD well includes letting the parent know that the DCD process could stop
at any time. Time pressures include separating the parents from the child after death is declared,
instituting organ preservation procedures, and paying attention to the time interval between decla-
ration of death and organ retrieval.
could legitimately give consent for DCD if a conflict of interest built into this that
it was not in the dying child’s own best it’s hard to resolve even with the knowl-
interests and if the child would be un- edge that you know, potentially we’re
likely to choose it for himself or herself. saving a life with this harvesting proce-
I really do not think actually that dure. I have a hard time with solving the
parents can presume altruism on the conflict—ICU physician.
part of a child— clergy. Those of us who have taken care of
Staff voiced concern about the pre- brain death patients in that period of
morbid procedures that clearly were not time before they go to the OR [operating
in the child’s best interest but served to room], which is sometimes, you know,
augment the potential for successful could be two or three shifts worth, um,
transplant organ survival. Staff members you get the sense that, you know, you
also wished to keep their patient interac- keep, you’re doing things that are not in
tions and decisions “pure” and felt that this patient’s best interests and you were
DCD would offer potential conflicts when able to rationalize it by saying this pa-
considering the patient as donor. tient’s already dead. It’s okay because
But on the one extreme I feel like he’s gone, he’s gone. And uh, I mean, I
we’re being asked to set up an organ think you can say that in your head like
bank business and on the other side we’re once an hour sometimes. And you will
in the business of hospital and protecting not have that to fall back on. This patient
life and saving life. And I feel like there’s is not dead—ICU nurse.

214 Pediatr Crit Care Med 2007 Vol. 8, No. 3

 Approaching Parents About DCD.
Staff voiced differences in opinion on
whether DCD should be offered to all
parents and, if offered, how to approach
parents and who, specifically, should be
present during the meeting.
I do not think it’s something neces-
sarily that I would feel comfortable in-
troducing to every single family as part
of the protocol. I think there’s very
select families that it’s right for. Um
and whether or not that’s always 100%
parent-initiated or if you take certain
cues, I think it needs to be considered
somewhat on a case to case basis—ICU
physician.
I think there may be families who
were not approached and then they find
out retrospectively that this was an op-
tion and weren’t given that option be-
cause the physicians thought that this
wasn’t the ‘right family’ um for this—
ICU physician.
Clinicians noted that their current ex-
perience in approaching families to ob-
tain consent for organ donation in the
brain-dead patient varied depending on
the family. Although some parents ask for
an opportunity to donate, other parents
may be burdened by the question.
But again, um, unless there was some
tremendous motivation of the family to,
to make this giving act, maybe it almost
has to be initiated by the family and you
cannot ask for it. And even if the answer
is no, to have been assaulted with the
question is huge— clergy.
Um but I think ultimately our priority
is for that family, what they want, at the
end of life, it’s their child and so if we can
offer something like that it may be a
great thing—ICU physician.
Clinicians also debated who would be
responsible for informing parents of the
possibility for DCD; specifically, is it a
physician’s responsibility at end of life or
the responsibility of organ procurement
agencies throughout life?
It’s not the ICU’s physician’s job to
talk them into donating their organs . . .
it’s a public ethics issue that should be
addressed as a public education—ICU
physician.
This really cannot be done uh if it’s
not initiated by the family. I would be
unwilling to initiate a conversation to
actually uh or to educate them to go
about DCD because that’s, that’s not my
obligation to that family. My obligation
to the family is to care for and to take
them to death in a manner that I and the
family can live with—ICU physician.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
I think the idea of having a team
that’s dedicated to doing this is, is a nice
idea because in some extent that takes a
little bit of the onus off of the, the recip-
ients of the organs and the donors of the
organs meaning the physicians in this
case—ICU physician.
“Making it happen for families” who
voice a desire to participate in organ do-
nation was discussed in every focus group
as the principal reason in support of a
pediatric DCD program. Secondary fac-
tors included increasing organ availabil-
ity and being on the cutting edge of new
programs.
I have participated in one of these in
another institution and this family ap-
proached us. The child had had a lifelong
illness and the mother wanted to give
something back. And you know what, it
did not go that well. They had a really
hard time getting lines in and we’re like
five minutes away from saying we cannot
do this. And it’s so much what the
mother wanted that despite the prob-
lems, it was good—ICU nurse
And so I think there is benefit for, to
the donor families that want to donate.
And if we do not offer that then I think
it’s our, our um, uh, you know, our ob-
ligation to send them across town—ICU
physician.
Preparing Parents for DCD. Staff felt
that parents would require full disclosure
about how their child’s death would
evolve with DCD and without DCD. The
process of withdrawal of life support may
be somewhat different, and what happens
after the declaration of death is very dif-
ferent. Consistent with informed consent,
staff thought that parents should be in-
formed that they could change their
mind at any time if DCD became unbear-
able.
They need a direction, they’re not, I
mean it’s something that they’ve never
done before and hopefully will never have
to do again so I do not think they have a
set idea of, ‘I want to be there when this
happens and this happens.’ They kind of
want some direction as how does this
normally happens. What’s the way to do
this?—ICU nurse.
I think, think it, it can be successful if
people recognize that there will be times
where the harvest is not possible even
when people are in the OR that they may
at that point decide they cannot, they
cannot go through with it, that the OR’s
maybe set up and that the team may be
literally standing out there and the fam-
ily won’t leave—ICU physician
Doing DCD Well. Given the high
stakes and lack of opportunity to redo the
experience for the family, there was a
compelling need to develop a comprehen-
sive protocol so that if DCD was done, it
was done well. Specifically, doing DCD
well includes putting hospital processes
and systems in place that would accom-
modate all possible derivations and re-
spond to all possible problems. DCD
should occur as smoothly as possible
without “hiccups.”
One thing I think we do very well on
[unit] is death. As far as helping parents
and families get to the point um where
they can accept it and grieve it—ICU
nurse.
Hope we would err on the part of
families. I think it’s important that they
[parents] leave here without regrets.
They’re gonna have to live with that—
respiratory therapist.
What if it’s happening at 11:00 am in
the morning and forty people want to
come in. That is extremely disruptive to
twenty-two operating rooms and, you
know, and I think, I think our mission is
to figure out a way for that to work. If it’s
forty members they deserve to be with
that child if that’s what they want—OR
nurse.
Because few centers have pediatric
DCD experience and because the science
of organ preservation is still evolving, it
was difficult for staff to portray an opti-
mal DCD process. They did, however, em-
phasize that they would want to create a
DCD process in which the family out-
comes would be comparable to the cur-
rent process of withdrawal of life support.
It [DCD] doesn’t have to be so differ-
ent, in terms of pain control, in terms of,
you know, family holding, all that, it
seems like, maybe it wouldn’t have to be
so different—ICU nurse.
So that is a problem for me. Uh the
amount of dignity we could give to this
dying— clergy.
Each group noted the pervasive sense
of pressure related to the passage of time,
specifically, time for the declaration of
death, for parents to leave their child’s
bedside, for postmortem procedures, and
for organ procurement.
I’m concerned about the time factor
. . . even after they [parents] make the
decision, they still wait quite a while be-
fore actually, you know, withdrawal of
support, then I’m afraid they might not
give that, it might feel a little over-
whelmed as far as time and being
rushed—respiratory therapist.
215
 I’m thinking from the bereavement
perspective, and that our priority is for
families at the time of death and what-
ever it takes for them and so what if at
that time they can’t say good bye? . . .
that they can’t leave the OR?—ICU
nurse.
Also questioned was when death could
be declared; specifically, when is dead—
dead? Is a patient really dead after 5 mins
of no cardiac output, and is 5 mins
enough to wait before organ procure-
ment?
The EEG [electroencephalogram], the
echocardiogram never stops at three min-
utes. It, it persists long, into this EMD it
persists long after the heart, the heart stops
and perfusion stops—surgeon.
Staff particularly voiced their aversion
to having to ask parents to leave their
child’s bedside after death.
And then they see when there’s no
pulse and the color’s already starting to
look different that they’re gonna have
difficulty leaving that they did not antic-
ipate. If it happens in the unit and you’re
not harvesting, they do have many, you
know, stay as long as they need—
respiratory therapist.
Staff identified several system barriers
to “doing DCD well.” These included in-
consistent attending physician coverage,
operating room availability, and the need
to create a milieu in the operating room
for the withdrawal of life support— one
that would welcome all family members
who are commonly present for a child’s
death in an intensive or palliative care
unit.
Maintaining the Integrity of a DCD
Program. Each group acknowledged that
instituting and sustaining a DCD pro-
gram would be very difficult for families,
staff, and the system. Many recom-
mended program oversight to ensure that
the intended outcomes of DCD were
achieved. Staff were concerned about a
“slippery slope.” There was concern that a
DCD program would be designed at one
level but would evolve into something
else.
We withdraw support all the time and
as long as we do not change how we
withdraw support and the line at which
we withdraw support I have no issue with
that. But obviously that’s an ethical issue
that has to be vetted because we can’t be
withdrawing support more expeditiously
than we do now uh because that becomes
a slippery slope—surgeon.
Although some staff members were
aware of positive DCD testimonials from
216
previous work experiences, some groups
wanted more long-term follow-up data
from parents who denied consent. For
example, is there a difference in the
memories expressed by parents who did
and did not participate in a DCD process,
did the DCD question overburden parents
or affect their relationship with the care
team, and what impact did extended fam-
ily members have on the parents’ DCD
decision?
How do we measure whether that
[DCD] was better or not for the families?
And you cannot do that if the families
have no standard for comparison. And
hopefully they’ll have never had any-
thing to compare this to. So they’ll never
know whether there was a better way.
And I gotta know that it wouldn’t been a
whole lot nicer to pull the curtains, have
a dark room, and sit and just rock your
baby for half an hour after he dies—ICU
physician.
Individual clinician response to DCD
spanned a continuum from a negative
visceral reaction to reasoned objection to
full support of DCD.
It sounds hideous to me—anesthesiol-
ogist.
I would be very uncomfortable getting
involved uh because uh you know it’s a, a
living patient and uh, and uh I will not
know much about this patient because
it’s, it’s different from a brain-dead pa-
tient. Brain-dead patients are not a pa-
tient, it’s a cadaver. No problems taking
that but with this I, it is very problematic—
anesthesiologist.
I’m strongly more in favor of the pro-
tocol because I do think, I think both the
values and mission of the hospital are
served by it— clergy.
Staff members recommended that
their education be supplemented with
ongoing staff support and debriefing.
Staff also supported a culture in which no
staff member who was morally opposed to
DCD would be required to participate.
I think that the inherent difficulty is
being a practicing anesthesiologist as op-
posed to an intensivist or an anesthesi-
ologist intensivist is that the roles are to
some degree radically different and even
if the training is the same, the role that
you play is very, very different. Your job
in the operating room is basically an
ongoing resuscitation and it’s been an
anomaly to bring the patient into the
operating room and not resuscitate
them. That to me is a terrible, terrible
conflict that I think will, we would all
have to help each other with in handling
this kind of issue in the operating
room—anesthesiologist.
Several groups were concerned about
trustworthy image of institution if the
goals of the program were misinterpreted
by the public at large.
And I just think you know you’re just
whacking a beehive like it’s a piñata. I
just cannot imagine it for five organs.
You would take a stick and whack a bee-
hive like this because there’s a whole
bunch of people out there that are just
looking for something to sting—surgeon.
You realize the real concern here is
that the impression that we’re going to
be killing kids for their organs—surgeon.
This is a place where the mission, kind
of begins to conflict. And I do not know
that I would agree that that this en-
deavor is completely contradictory to
care for the family because, in the bigger
picture, it doesn’t necessarily meet all
the needs of this particular family, but it
could mean that, that the hospital as a
caring community can offer something
to another family in need that they could
not have otherwise offered— clergy.
Discipline-Specific Perspectives. Anal-
ysis of discipline-specific focus group data
allowed the identification of primary
themes within each constituent group.
These are outlined in Table 2. Although
there are similarities, primary themes re-
flect the group’s role function and areas
of responsibility. For example, primary
themes in the physician focus groups
centered on approaching parents for con-
sent, potential conflict when considering
the patient as donor, and deciding on
the time interval from pronouncing
death to organ procurement. Primary
themes in the nurse and therapist focus
groups centered on orchestrating a
skilled DCD process.
DISCUSSION
An organization’s decision to offer a
pediatric DCD program is debatable on
numerous levels. Our focus groups raised
important questions that each organiza-
tion will need to address before imple-
menting such a program. Understanding
the perceptions of staff members who
may be directly affected by a DCD proto-
col is important because they are the
individuals responsible for enacting the
program. We constructed a conceptual
framework describing what experienced
clinical staff believe are essential ele-
ments of a model pediatric DCD program.
We identified six major themes. These
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Table 2. Top four issues in each focus group
Nurses
Medical-Surgical ICU Cardiovascular ICU Operating Room
Assurance that the current Creating a legacy Orchestrating death
process could be recreated
Approaching parents Making it happen for parents System barriers
who voice a desire to
participate in organ donation
Visceral response Assurance that the current Separation after the declaration
process could be recreated of death
Individuality of parents Approaching parents Doing DCD well
Physicians
Intensivist Anesthesia Surgeons
Approaching parents When is dead dead? Societal issues
Best interests of this child Best interests of this child Doing DCD well
Orchestrating death Doing DCD well When is dead dead?
Individuality of parents Assurance that the current Approaching parents
process could be recreated
Respiratory Therapist Clergy
Assurance that the current process Best interests of this child
could be recreated
Orchestrating death Approaching parents
Best interests of this child Organ preservation procedures
Time pressure Individuality of parents
ICU, intensive care unit; DCD, donation after cardiac death.
include a) identifying children who could Clinicians were concerned about the
be candidates for DCD; b) considering the lack of data to guide practice concerning
best interests of the dying child; c) ap- the time interval from the declaration of
proaching parents about DCD; d) prepar- death to organ retrieval. They are not
ing parents for DCD; e) doing DCD well; alone. Boissy and colleagues (18) sur-
and f) maintaining program integrity. veyed the opinion of neurointensivists on
Once constructed, the framework was the most appropriate time interval to wait
used successfully to structure interdisci- to initiate organ recovery after the cessa-
plinary dialogue, address staff concerns, tion of cardiac function in DCD. There
and inform institutional practices in the was not a clear consensus among the
design of a model pediatric DCD pro- respondents; 38% favored basing the de-
gram. termination of death on the absence of
DCD brings to the surface several fun- brainstem activity, whereas 60% required
damental personal and professional be- an average of 5 mins and range of 2–10
liefs. For example, when is the patient mins. Responding to staff concerns, the
dead from a biological perspective and task force formed a subgroup to review
from a metaphysical perspective? When the literature and make recommenda-
after acirculation does a patient’s cogni- tions on when it might be logical to set
tion and the capacity to feel pain cease? the time of cardiac death; after what pe-
In pediatric DCD, do parents have the riod of no cerebral perfusion the physio-
moral right to provide consent for their logic events supporting cognition cease
child’s DCD? Seldom in pediatrics have without likelihood of recovery; and after
we ever questioned a parent’s right to what period of no cerebral perfusion the
provide consent for his or her child. Al- experience of pain ceases.
though several of these issues were ad- Deaths occur infrequently in pediatric
dressed in a position paper by the Ethics intensive care and are usually orches-
Committee of the Society of Critical Care trated to provide solace to the patient,
Medicine in 2001 (17), our data show that family, and providers (6, 19). Experienced
these issues are still disconcerting to pe- staff members derive a great deal of pro-
diatric staff. fessional satisfaction from helping family
Pediatr Crit Care Med 2007 Vol. 8, No. 3
members endure their loved one’s death.
Clinicians offer several options to parents
about their presence when withdrawing
their child’s life support (20, 21). Consis-
tent with information sharing in clinical
research, staff members felt that in-
formed consent for DCD should include
providing full disclosure of what death
would be like with and without DCD and
honoring the parents’ option to withdraw
their consent at any step in the DCD
process including after the child has been
declared dead in the operating room.
Staff voiced concern about whether the
current process of death in an ICU could
be recreated in an operating room. Staff
felt that it was important that life support
be withdrawn in the same compassionate
and sensitive manner that is used in the
ICU, showing respect for the patient’s and
family’s dignity. Although it may involve
breaking down traditional physical barri-
ers, ICU staff known to the family should
ideally continue to care for the family in
any area of the hospital where support is
withdrawn.
The routine use of DCD carries the
potential of increasing organ donation,
but little is known about the attitudes of
healthcare professionals (2). We found
that individual opinion varied widely
within each group and that the disci-
plines differed in their primary concerns
about DCD. For example, one of the pri-
mary concerns of the physician group
was how best to approach parents with
DCD while also treating families equita-
bly. Should organ donation be offered to
all parents or just those informed enough
to ask for it? Another concern is address-
ing the needs of the patients while also
supporting the viability of the transplant
organs. From the ICU clinician’s perspec-
tive, role conflicts may exist; specifically,
the interventions to comfort the dying
patient may not be the same for a dying
patient who is also an organ donor.
Nurses and respiratory therapists are
concerned about the process of orches-
trating the child’s death while also pro-
viding parents the solace of donation. Al-
though the venue of end-of-life care is
different, can the team feel confident that
parents received excellent care and com-
passion normally associated with the
withdrawal of life support? In our work,
operating room nurses were particularly
concerned about “doing DCD well” so
that families would have a positive DCD
memory.
Hospital systems are complex, and
maintaining the integrity of a DCD pro-
217
gram, as initially designed, may be diffi-
cult. If a program is adopted, resources
should be made available to ensure inde-
pendent program oversight with author-
ity to intervene and avert potential con-
flict of interests, manage conflicts that
cannot be avoided, and prevent unneces-
sary protocol deviations. The societal is-
sues are also of concern. What is the
possible impact of offering DCD on public
trust in the institution? Although there is
agreement on the need for public educa-
tion on DCD, there is disagreement on
who is in the best position to take the
lead in the community.
There is a paucity of clinical research
associated with DCD. Although the cur-
rent study focused on the clinician per-
spective, little is known about the family
perspective. For example, do we harm or
do we help parents when asking them it
they want to donate their child’s organs?
There are no data that inform us as to
whether we violate a family’s trust by
simply posing the DCD question. Does
the DCD process improve the family’s so-
lace? Although knowledge of organ sur-
vival will help staff members answer
some the difficult questions posed by par-
ents (22–24), multisite prospective co-
hort studies are needed to describe the
long-term impact of the questions we
pose to parents.
Staff cited numerous examples in
which DCD was different from organ do-
nation after brain death. As illustrated in
our conceptual framework, identifying a
DCD candidate includes an opinion of
whether the child would suffer a cardiac
arrest within the requisite hour after the
withdrawal of life support and not a con-
firmatory brain death exam. Considering
the best interest of a dying child is very
different from considering the best inter-
ests of a brain-dead child. Parent-child
separation in the operating room is very
different from that in the ICU. Our con-
ceptual framework can be used to provide
structure to anticipate and respond to the
potential and real problems associated
with DCD and guide multidisciplinary
training programs in DCD.
We chose a qualitative methodology to
collect and analyze our data. Our method
was strategic, allowing us to obtain data
on an extremely sensitive topic from the
constituent base of concern. This ap-
proach allowed the research team to
share what was currently known about
pediatric DCD, explore clinicians’ per-
spectives, and limit misconceptions asso-
ciated with DCD. This strategy also en-
218
abled active participation of some key
individuals considered to be opinion lead-
ers within clinical areas that could poten-
tially be involved with DCD. Although
qualitative methods are useful in devel-
oping theoretical models that describe
and explain individual perspectives
(16), study results may be difficult to
precisely replicate. Our conceptual
framework can be used to design a sur-
vey instrument that reflects the views of
clinical staff who would be directly in-
volved in the DCD process. Once tested,
the instrument could provide a vehicle
to obtain data from a wide population of
staff members across multiple pediatric
centers that could be subjected to quan-
titative analyses.
Our findings should be considered in
light of study limitations. First, although
clinician sampling was purposeful, par-
ticipation was voluntary and the opinions
of those choosing to participate may be
different from those choosing not to par-
ticipate. Second, this study took place in
a children’s hospital in the northeast
United States with predominately white
non-Hispanic staff. There may be impor-
tant geographical and cultural differences
in clinician views on DCD. Third, almost
all participants had never experienced
DCD, and their perspectives may shift
after experiencing a child’s DCD. Finally,
this study focused on clinician perspec-
tives, and additional studies are required
to describe patient and family perspec-
tives.
CONCLUSIONS
Many pediatric centers struggle with
whether to adopt a DCD program. This
article addresses the issue from the staff’s
perspective and provides new information
on what pediatric staff members believe
are essential elements of a model pediat-
ric DCD program. Numerous barriers ex-
ist, but the desired outcome in “making it
happen for families” who voice a desire to
participate in organ donation was identi-
fied as the primary reason to adopt a DCD
protocol. The conceptual framework pre-
sented in this article suggests several pos-
sible elements that may be helpful in
framing interdisciplinary dialogue and
informing institutional practices in the
design of a pediatric DCD program.
ACKNOWLEDGMENTS
We are indebted to the focus group
participants and Amy Durall, MD, and
Heather Healy, RN, for volunteering their
time to observe the focus groups and
complete field notes.
REFERENCES
1. Delmonico FL, Sheehy E, Marks WH, et al:
Organ donation and utilization in the United
States, 2004. Am J Transplant 2005;
5:862– 873
2. Koogler T, Costarino AT Jr: The potential
benefits of the pediatric nonheartbeating or-
gan donor. Pediatrics 1998; 101:1049 –1052
3. Harmon WE, McDonald RA, Reyes JD, et al:
Pediatric transplantation, 1994 –2003. Am J
Transplant 2005; 5:887–903
4. Howard RJ, Schold JD, Cornell DL: A 10-year
analysis of organ donation after cardiac death
in the United States. Transplantation 2005;
80:564 –568
5. Bernat JL, D’Alessandro AM, Port FK, et al:
Report of a National Conference on Donation
after cardiac death. Am J Transplant 2006;
6:281–291
6. Meert KL, Thurston CS, Sarnaik AP: End-of-
life decision-making and satisfaction with
care: parental perspectives. Pediatr Crit Care
Med 2000; 1:179 –185
7. Critical Pathway of Donation after Cardiac
Death. Available at: http://www.unos.org/
SharedContentDocuments/Critical_Pathway_
DCD_Donor.pdf. Accessed March 1, 2005
8. Truog RD, Cist AF, Brackett SE, et al: Rec-
ommendations for end-of-life care in the in-
tensive care unit: The Ethics Committee of
the Society of Critical Care Medicine. Crit
Care Med 2001; 29:2332–2348
9. Giacomini MK, Cook DJ, for the Evidence-
Based Medicine Working Group: Users’
guides to the medical literature: XXIII. Qual-
itative research in health care A: Are the
results of the study valid? JAMA 2000; 284:
357–362
10. Pope C, Mays N: Qualitative research: Reach-
ing the parts other methods cannot reach:
An introduction to qualitative methods in
health and health services research. BMJ
1995; 311:42– 45
11. Morse J: Qualitative Health Research. New-
bury Park, CA, Sage, 1992
12. Morgan D: Focus Groups as Qualitative Re-
search. Qualitative Research Methods, Series
16. London, Sage, 1988
13. Kitzinger J: Qualitative research: Introduc-
ing focus groups. BMJ 1995; 311:299 –302
14. Miles MB, Huberman AM: Qualitative Data
Analysis: An Expanded Source Book. Thou-
sand Oaks, CA, Sage, 1994
15. Mays N, Pope C: Qualitative research: Rigour
and qualitative research. BMJ 1995; 311:
109 –112
16. Giacomini MK, Cook DJ, for the Evidence-
Based Medicine Working Group: Users’
guides to the medical literature: XXIII. Qual-
itative research in health care B: What are
the results and how do they help me care for
my patients? JAMA 2000; 284:478 – 482
Pediatr Crit Care Med 2007 Vol. 8, No. 3
17. Recommendations for nonheartbeating or-
gan donation. A position paper by the Eth-
ics Committee, American College of Criti-
cal Care Medicine, Society of Critical Care
Medicine. Crit Care Med 2001; 29:
1826 –1831
18. Boissy A, Provencio J, Smith C, et al: Neuroin-
tensivists’ opinions about death by neurologi-
cal criteria and organ donation. Neurocrit Care
2005; 3:115–121
19. Burns JP, Mitchell C, Outwater KM, et al:
End-of-life care in the pediatric intensive
Pediatr Crit Care Med 2007 Vol. 8, No. 3
care unit after the forgoing of life-sustaining
treatment. Crit Care Med 2000; 28:
3060 –3066
20. Solomon MZ, Sellers DE, Heller KS, et al: New
and lingering controversies in pediatric end-of-
life care. Pediatrics 2005; 116:872– 883
21. Meyer EC, Ritholz MD, Burns JP, et al: Im-
proving the quality of end-of-life care in the
pediatric intensive care unit: Parents’ prior-
ities and recommendations. Pediatrics 2006;
117:649 – 657
22. Cooper JT, Chin LT, Krieger NR, et al:
Donation after cardiac death: The Univer-
sity of Wisconsin experience with renal
transplantation. Am J Transplant 2004;
4:1490 –1494
23. Foley DP, Fernandez LA, Leverson G, et al:
Donation after cardiac death: The University
of Wisconsin experience with liver transplan-
tation. Ann Surg 2005; 242:724 –731
24. Brook NR, Waller JR, Nicholson ML: Non-
heart-beating kidney donation: Current prac-
tice and future developments. Kidney Int
2003; 63:1516 –1529
219
Assessment of parental presence during bedside pediatric intensive
care unit rounds: Effect on duration, teaching, and privacy*
Lorri M. Phipps, MSN, CPNP; Cheryl N. Bartke, MSN, CPNP; Debra A. Spear, RN, CCRN;
Linda F. Jones, RN, CCRN; Carolyn P. Foerster, RN, BSN, CCRN; Marie E. Killian, RN, BSN;
Jennifer R. Hughes, RN, BSN; Joseph C. Hess, RN, BSN; David R. Johnson, PhD;
Neal J. Thomas, MD, MSc

Objective: There is a paucity of literature evaluating the effects
of family member presence during bedside medical rounds in the
pediatric intensive care unit. We hypothesized that, when com-
pared with rounds without family members, parental presence
during morning medical rounds would increase time spent on
rounds, decrease medical team teaching/education, increase staff
dissatisfaction, create more stress in family members, and violate
patient privacy in our open unit.
Design: Prospective, blinded, observational study.
Setting: Academic pediatric intensive care unit with 12 beds.
Participants: A total of 105 admissions were studied, 81 family
members completed a survey, and 187 medical team staff surveys
were completed.
Interventions: Investigators documented parental presence
and time allocated for presentation, teaching, and answering
questions. Surveys related to perception of goals, teaching, and
privacy of rounds were distributed to participants.
Measurements: Time spent on rounds, time spent teaching on
rounds, and medical staff and family perception of the effects of
parental presence on rounds.
Results: There was no significant difference between time
spent on rounds in the presence or absence of family members
(p ⴝ NS). There is no significant difference between the time
spent teaching by the attending physician in the presence or
absence of family members (p ⴝ NS). Overall, parents reported
that the medical team spent an appropriate amount of time
discussing their child and were not upset by this discussion.
Parents did not perceive that their own or their child’s privacy
was violated during rounds. The majority of medical team
members reported that the presence of family on rounds was
beneficial.
Conclusions: Parental presence on rounds does not seem to
interfere with the educational and communication process. Par-
ents report satisfaction with participation in rounds, and privacy
violations do not seem to be a concern from their perspective.
(Pediatr Crit Care Med 2007; 8:220 –224)
KEY WORDS: pediatrics; medical rounds; bedside rounds; pedi-
atric intensive care unit; parental presence

D espite being an issue con-
fronted daily by in-hospital
medical care providers, there
are few published data regard-
ing the effect of including family members
in bedside medical rounds. In pediatrics,
and specifically in pediatric critical care, it
is unclear as to the best way to succeed in
processing the daily medical information,
*See also p. 291.
From the Divisions of Nursing (LMP, CNB, DAS,
LFJ, CPF, MEK, JRH) and Pediatric Critical Care Med-
icine (JCH, NJT), Department of Pediatrics, and the
Department of Health Evaluation Sciences (NJT), Penn
State Children’s Hospital, Pennsylvania State University
College of Medicine, Hershey, PA; and the Depart-
ments of Sociology, Human Development and Family
Studies, and Demography, Pennsylvania State Univer-
sity, University Park, PA (DRJ).
The authors have not disclosed any potential con-
flicts of interest.
Presented, in part, at the Society of Critical Care
formulating care plans, and educating res-
ident staff and students, all while allowing
sufficient time to complete necessary inter-
ventions and care for new patients.
Should we round at the bedside and ex-
clude the family? Should we allow fami-
lies unlimited access and round away
from the bedside? Can we efficiently in-
volve the family in our bedside rounds
Medicine’s 35th Critical Care Congress, San Francisco,
January 7–11, 2006.
Supported, in part, by a research grant from the
Children, Youth, and Families Consortium, Pennsylva-
nia State University.
For information regarding this article, E-mail:
nthomas@psu.edu
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262798.84416.C5
without timely repercussions and con-
cern for infringement of privacy?
No one can dispute the benefits of
bedside teaching, which have been elo-
quently conveyed through the principles
of Dr. William Osler (1). Rounding at the
bedside provides a unique and essential
teaching opportunity for the training of
physicians and medical staff that has been
tested for decades. However, the practice
of medicine has changed dramatically
since the time of Osler, and now legal,
financial, and patient privacy concerns
have moved to the forefront. Moreover,
advances in technology have not only
changed the practice of medicine but also
the way information is stored and shared.
Thus, it is not surprising that published
surveys of teaching practices in American
medical schools indicate that relatively
little time is spent at the bedside, with
rounds moving into conference rooms

220 Pediatr Crit Care Med 2007 Vol. 8, No. 3

and hallways (2– 4). In fact, recent esti-
mates of bedside rounds have demon-
strated a decline from a rate of 75% fifty
years ago to a rate of ⬍25% today (5).
Rounds away from the bedside may be
viewed as more efficient by some physi-
cians, as they allow the medical team to
discuss the patient, review radiographs
and laboratory results, and formulate a
plan without interruption.
Data suggest that performance pres-
sure, discomfort with impromptu teach-
ing, and a decline in teaching skills or an
erosion in the teaching ethic are also
reasons for the decline in bedside rounds
on adult wards. Patient and family pres-
ence has been viewed as an impediment
to bedside teaching, despite the fact that
the majority of patients viewed bedside
case presentations as positive (6). It has
been suggested that rounds at the bedside
may increase physiologic stress for the
patient or the patient’s family. Moreover,
bedside rounds may foster confusion in
the patient because vast differential diag-
noses are discussed and multiple poten-
tial treatment plans are offered. The pres-
ence of the patient or patient’s family
may also inhibit open communication be-
tween staff members because rounds par-
ticipants may be uncomfortable offering
opposing opinions, asking difficult ques-
tions, or raising ethically challenging is-
sues in front of the patient or family.
Clearly, this may detract from the educa-
tional opportunities for the staff. Further,
there is growing concern about the inva-
sion of patients’ privacy when discussing
details of their medical information in a
public area (4, 5). This is increasingly
important in the era of the Health Insur-
ance Portability and Accountability Act of
1996 (HIPAA), which has greatly affected
the healthcare industry (7).
Data related to these issues in pediat-
rics are limited. Nevertheless, many pedi-
atric intensivists have extrapolated the
adult data to justify the relocation of
rounds away from the bedside, often due
to similar motives. The objective of this
study was to objectively and subjectively
evaluate parental presence during bed-
side medical rounds in a pediatric inten-
sive care unit (PICU) specifically as it
affects the duration of rounds, opportu-
nities for medical student and resident
teaching, staff satisfaction, and the paren-
tal perceptions of privacy. We hypothe-
sized that parental presence during bed-
side medical rounds would increase time
spent on rounds, decrease medical team
teaching and educational opportunities,
Pediatr Crit Care Med 2007 Vol. 8, No. 3
and increase staff dissatisfaction when
compared with rounds without family
members present. We also hypothesized
that families would perceive open rounds
as a violation of patient privacy in our
open unit.
METHODS
This prospective, blinded, observational
study was approved by the Institutional Re-
view Board of Penn State Children’s Hospital,
The Pennsylvania State University College of
Medicine, and the Milton S. Hershey Medical
Center. The requirement for written informed
consent was waived with informed consent
implied by the voluntary completion of the
study survey administered after morning PICU
rounds.
The study was conducted in a 12-bed PICU
at Penn State Children’s Hospital, which is a
combined medical–surgical unit staffed with-
out fellows, averaging ⬎700 admissions each
year. The patient population comprises 36%
medical patients, 30% cardiothoracic surgery
patients, 15% trauma patients, and 8% neu-
rosurgery patients. The pediatric critical care
medicine team rounds twice daily, with our
standard operating procedure consisting of
rounds that are routinely conducted at the
bedside for both morning rounds and evening
sign-out. The pediatric critical care team is
active in the management of all patients in the
PICU, assuming overall care of all medical
admissions and actively co-managing all sur-
gical admissions. The PICU consists of six
open beds separated only by closable curtains,
two private rooms, and two semiprivate
rooms. It is the policy of our PICU that parents
have access to the unit 24 hrs each day, with
the exception of sterile procedures, for which
they are asked to leave the bedside. Families
are never asked to exit the unit during rounds.
The faculty physicians and nursing staff were
blinded to the hypothesis and objectives of the
study.
All PICU admissions during the study pe-
riod were screened for study eligibility. Inclu-
sion criteria mandated that the child be as-
signed to the critical care service or classified
as a critical care patient by the primary ser-
vice. Patients and their families were not eli-
gible if they were deemed floor status and
placed in the PICU for lack of bed availability
on the general pediatric floor or intermediate
care unit. As the unit of measure for this study
was the patient/medical team encounter dur-
ing morning bedside rounds, PICU patients
were eligible to be observed up to two times,
one time with family members present and
one time with family members absent. How-
ever, family members were not asked to leave
the unit at any time during the study to obtain
data without their presence.
The investigators would screen the unit
each morning, Monday through Friday, and
initiate an observation form on every eligible
subject, regardless of whether parents were
present, as long as the patient or family mem-
ber did not meet exclusion criteria. The study
populations were composed of adult family
members of infants and children admitted to
the PICU and members of the critical care
team (principally residents, medical students,
and bedside nurses) assigned to care for eligi-
ble PICU patients. The major exclusion crite-
rion was admission on a weekend and transfer
out of the PICU before a weekday (Monday
through Friday) rounding session. This deci-
sion was made to maintain study consistency
due to the obligatory alteration of the medical
team and rounding practices on the weekend.
Other exclusion criteria included non–
English-speaking family members, patients
who were physically away from the PICU dur-
ing rounds (such as in the operating room or
radiology suite), and patients who were read-
mitted to the PICU during the hospitalization
or had chronic ventilatory dependence. The
decision to exclude the patients with chronic
ventilatory dependence was made based on the
investigators’ supposition that because these
patients were very familiar with our hospital,
unit, and staff, the responses of the family and
the staff were likely to be biased.
Three different methods of data collection
were performed. The initial phase was comple-
tion of a standardized observation form. Inves-
tigators discreetly observed and documented
parental presence, medical team composition,
and amount of time allocated for patient pre-
sentation, teaching, and answering questions.
This form was completed by investigators not
involved in the care of the patient, at a dis-
tance from the bedside, for each selected pa-
tient/team rounding encounter during morn-
ing rounds.
The medical team survey was completed by
the medical team members after completion
of morning rounds and gathered information
pertaining to their perception of the clarity of
goals for the patient, time allocated toward
education, and the effect of family member
presence on morning rounds. The survey was
given to each participating medical team
member for each patient who was observed
that morning after they left the patient’s bed-
side and was then collected by the same inves-
tigator after morning rounds.
The parent survey was completed at the
conclusion of the patient/medical team rounds
by family members who were present during
rounds. This form gathered objective data re-
garding the length of stay, the age of the child,
and the medical team interactions. It also so-
licited subjective data, including their under-
standing of the medical information, the plan
221
of care, and the specific medical goals and of
their perceptions of the privacy of rounds.
The surveys were formatted for optical
scanning of all objective data. Completed sur-
veys were scanned using TELEForm software
(Cardiff, Vista, CA) at the Survey Research
Center of Pennsylvania State University. Data
were exported into SPSS files (SPSS, Chicago,
IL) and examined for errors using descriptive
and frequency runs. Inconsistencies were
identified and corrected. A sample of surveys
was checked manually to ensure the scanning
process was accurate. The objective data were
analyzed using Mann-Whitney rank-sum tests
and bivariate correlation/Pearson correlation.
Data are reported as median values, and a p
value of ⱕ.05 was considered statistically
significant.
RESULTS
A total of 153 consecutive PICU admis-
sions were screened for eligibility, and 64
admissions were excluded from the study
for the following reasons: weekend ad-
mission (n ⫽ 40), patients not physically
present during morning rounds (n ⫽ 7),
non–English-speaking family members
(n ⫽ 2), and patients who were readmit-
ted to the PICU during the hospitaliza-
tion or had chronic ventilatory depen-
dence (n ⫽ 15).
Observation Form. A total of 105 ob-
servations were recorded on 89 PICU pa-
tients. Family members were present
during rounds 60% of the time (Table 1).
The median number of family members
present was two (interquartile range
[IQR], 1–2). The median number of med-
ical team members was seven (IQR, 5–9).
Table 1. Demographics of the three data
collection tools utilized
n %
Observation form (n ⫽ 105)
Family members present on 63 60
rounds
Family members absent from 42 40
rounds
Medical team survey (n ⫽ 187)
Pediatric resident 47 25
Anesthesia resident 19 10
Nurse practitioner 10 5
Charge nurse 1 1
Bedside nurse 60 32
Medical student 43 23
Other (paramedic, respiratory 7 4
therapist)
Parent survey (n ⫽ 81)
Mother 48 59
Father 29 36
Grandparent 3 4
Other 1 1
222
The median time spent on rounds in the
presence of family members was 13 mins
(IQR, 7–20), which was not statistically
different (p ⫽ NS) from the median time
of 11 mins (IQR, 6 –19) spent on rounds
in the absence of family members (Fig.
1). In addition, there was no significant
correlation between time spent on
rounds in the presence or absence of fam-
ily members (r ⫽ .056; p ⫽ NS). The
family members asked the medical team
questions 28% of the time, and the med-
ical team asked family members ques-
tions during bedside rounds on 32% of
the encounters.
The attending provided education at
76% of bedsides when families were
present and 63% of bedsides when fami-
lies were not present. When specifically
analyzing the time spent teaching, there
was no significant difference between the
time spent teaching by the attending phy-
sician in the presence (median, 4 mins;
IQR, 2–10) or absence (median, 5 mins;
IQR, 2–10) of family members (Fig. 2).
Medical Team Survey. A total of 187
medical team member surveys were com-
pleted with a wide variety of respondents
(Table 1). At the completion of rounds,
95% of team members believed that the
plan of care for the day was clear. More-
over, 95% of medical team members did
not believe that the presence of family
members interfered with the discussion
during rounds. The majority of team
members reported that there was ade-
quate time allotted for teaching, and only
eight team members believed that the
presence of family members interfered
with rounds. Table 2 provides examples of
the responses to the open-ended ques-
Figure 1. Time spent on rounds was not different when comparing rounds with family members
present and rounds with family members absent. Solid line, median; shaded box, interquartile range;
whiskers, 10% and 90%.
tions on the medical team survey aimed
at gathering information related to the
medical team perception of parental pres-
ence on PICU rounds.
Parent Survey. A total of 81 family
members submitted a survey, with par-
ents accounting for the majority of re-
spondents (Table 1). The length of hospi-
talization at the time of survey ranged
from 1 to 16 days, with 51% of the chil-
dren having had previous hospital stays.
Of family respondents, 67% indicated
that they were able to ask the team ques-
tions during rounds, and nearly half
(49%) indicated that the team asked
them questions. This is in striking con-
trast to the findings gathered by the di-
rect observations (reported above). At the
conclusion of bedside rounds, 95% of
family members believed they understood
the plan of care for their child. Of those
few family members who indicated that
they did not understand the plan, their
inability to understand medical terminol-
ogy was the most cited reason. Nearly all
family members reported that the medi-
cal team spent an appropriate amount of
time discussing their child (99%). More-
over, 94% of family respondents did not
find the discussion of their child upset-
ting. Nearly all respondents (98%, 79 of
81) indicated that they had no concerns
regarding privacy.
DISCUSSION
The study of physician rounding prac-
tices in America dates back to ⬎60 yrs
ago when Romano (8) subjectively studied
the reactions and behaviors of 100 patients
at the Peter Bent Brigham Hospital during
Pediatr Crit Care Med 2007 Vol. 8, No. 3
bedside teaching rounds. He reported
that rounds at the bedside were a means
of educating and reassuring patients,
concluding that rounding at the bedside
“is not a traumatic emotional experience”
(8). Since then, others have reported sim-
ilar findings in studying inpatient adults
(2, 9). Simons et al. (10) examined phys-
iologic markers of stress to more objec-
tively assess this question. They studied
the effects of bedside case presentations
on heart rate, blood pressure, and serum
catecholamine levels in 20 adult intensive
care unit patients with suspected acute
myocardial infarction. There was a
small but clinically insignificant
change in systolic and diastolic blood
pressures but no change in heart rate or
serum norepinephrine concentrations.
They concluded that bedside rounds did
not produce physiologic stress for these
patients (10).
Unfortunately, the literature related to
this issue in pediatrics is sparse and the
extrapolation of adult findings would
seem suspect. The pediatric medical com-
munity has changed considerably in the
past several decades, with much more at-
tention paid to the philosophy of family-
centered care. Family-centered care in
pediatrics is based on the understanding
Figure 2. Time spent teaching on rounds was not different when comparing rounds with family
members present and rounds with family members absent. Solid line, median; shaded box, interquar-
tile range; whiskers, 10% and 90%.
that the family is the child’s primary
source of strength and support and that
the child’s and the family’s perspectives
and information are important in clinical
decision making (11). Whether we can
apply these principles to medical rounds,
specifically when caring for critically ill
or injured children, is unknown.
The issue of pediatric bedside rounds
outside of the PICU has previously been
studied. Lewis et al. (12) compared
rounds at and away from the bedside in a
pediatric oncology unit. These investiga-
tors found that rounding at the bedside
positively affected the parental attitude
toward physicians and improved resident
education of the physician–patient rela-
tionship. Conversely, they also found that
the medical staff favored rounds away
from the bedside for their educational
opportunities (12). More recently, Jarvis
et al. (13) assessed the effect of family
presence during rounds on patient care
decision making, student and resident
teaching, nursing practice, and parental
satisfaction. The investigators reported a
favorable response by both nursing staff
and parents. However, although the res-
ident and student staff were positive
about increased communication, they
were concerned about a decrease in
teaching opportunities and less efficient
work time.
Results of the present study, the larg-
est to date that attempts to address this
issue among PICU patients, suggest that
the presence of family members on
rounds was beneficial to families and
caregivers alike. The families reported
that the discussion on rounds was not
upsetting, that they had adequate time to
ask questions, and that adequate time
was allotted to the care of their child.
Family members reported that their in-
clusion in rounds enhanced their under-
standing of the plan of care for their
child, thus validating this rounding
model as consistent with the principals of
family-centered care (11). Importantly,
family members also reported very few
concerns regarding violation of their pri-
vacy. The medical team members were
equally positive, and the vast majority of
house staff reported no concerns regard-
ing the time allotted to education. This
conclusion was borne out in direct obser-
vation, as there was no difference in time
allotted to teaching, regardless of
whether families were present at the bed-
side. In addition, we found that the pres-
ence of family members on rounds did
not significantly increase the amount of
time spent on rounds. In fact, in striking
contrast to our hypotheses, the presence
of family members at the bedside during
medical team rounds had no demonstra-
ble negative effect from any perspective.
Any conclusions of this study, how-
ever, must be balanced by several limita-
tions. First, there was no true compari-
son group. This limitation was well
understood and scrutinized a priori, and
the decision was made not to change the
rounding practices of our PICU so that we
could gain the most unbiased knowledge
of the effect of parental presence. The
only comparisons that could be per-
formed were in the examination of differ-
ences in time allotted to overall round-
ing, and specifically to resident teaching,
among patients whose families were or
were not present at the time of rounds. It
may have been more insightful to com-
pare bedside rounds with rounds at a

Table 2. Sample of the answers to open-ended question from the medical staff survey regarding parental presence on medical rounds

● “Family presence for this patient was overall a positive experience; it allowed the parents to actively participate in the plan. After rounds, the father
stated how much he appreciates the ‘team’ approach to his child’s care, and that all members seem to communicate well.”
● “Family able to listen to physician’s plans and physician able to speak with family after rounds to clarify plans for day.”
● “Team was able to discuss prognosis and serious complications of patient’s injury without interference from the family.”
● “It was helpful to have mom here—she provided otherwise unknown information.”

Pediatr Crit Care Med 2007 Vol. 8, No. 3 223

remote site, such as a conference room,
and complete the same observations and
survey the same groups. This comparison
may offer more insight as to which type
of rounds staff and parents prefer. Al-
though this study supports the inclusion
of the parents on rounds from both the
parent and medical staff perspective, the
addition of a control group may be more
perspicacious at determining the most
efficient and educationally productive
rounding style. However, the fact that
rounds were conducted in a routine man-
ner, with no modifications made for the
study, suggests that the results are appli-
cable to our daily practice. In effect, we
took no measures to alter the way our
PICU conducted rounds. Parents were
not notified of the study, nor were they
asked to leave or participate. In addition,
the fact that the investigators were all
well established members of the PICU
team whose presence in the unit would
seem quite routine further minimizes the
potential for skewed data.
This study was conducted in a medium-
sized PICU, with a well-established and
cohesive medical, nursing, and ancillary
staff. Certainly, these factors must be
considered when extrapolating these data
and inferring reproducibility of the re-
sults and conclusions to larger units with
diverse staffing patterns.
Another limitation of the present
study is the exclusion of specialty ser-
vices. The interactions of a surgical or
medical subspecialty consulting service
with staff and family members may not be
comparable with those of the critical care
team. Therefore, the results of this study
should not be generalized to other med-
ical or surgical teams that care for chil-
dren in the PICU but, rather, serve as an
impetus for further study among these
specialties. The potential for selection
bias is another possible weakness of this
study design. The only family members
who were surveyed were those who at-
tended morning rounds. Whether these
family members were similar to those
family members who did not attend
morning rounds is unknown and was not
assessed. In addition, medical team mem-
bers were asked, but not required, to
224
complete the surveys. It is possible, but
unlikely, that only those with a favorable
experience chose to complete the form.
Moreover, family presence is an accepted
norm of our practice, and it is plausible
that medical team members chose to
complete the survey in a positive manner
so as not to seem negative or opposi-
tional. Family members may have also
chosen to complete the form in a positive
manner, fearing repercussions from a neg-
ative response. To minimize these con-
cerns, all surveys were completed anony-
mously, and this fact was made clear to all
participants before enrollment.
Finally, it should be noted that there
were a few outlying negative responses
from both staff and parents surveyed. It
was perceived, but disproved with data,
that the time to complete rounds was
indeed extended when families were
present. It could be assumed that even
small, nonsignificant increases in time
could affect efficiency in a larger unit.
Furthermore, there were a small number
of parent comments about the “perfor-
mance” and accuracy of information be-
ing presented by inexperienced residents
and medical students. Understandably,
this could affect the trust and comfort
level parents assigned to the staff caring
for their child.
In conclusion, bedside teaching is a
vital method of clinical teaching. Al-
though family presence has been impli-
cated as a potential barrier to bedside
teaching, the present study demonstrates
that both families and medical staff mem-
bers view the process favorably. Further-
more, we have found that inclusion of
families in the rounding process does not
significantly extend the time needed to
complete rounds or detract from the ed-
ucational opportunities of the resident
staff. Finally, we found that parents did
not perceive rounding at the bedside as
an encroachment on their or their child’s
privacy. We recommend that medical
teams strongly consider allowing parents
to be present during routine medical
rounds in the PICU. A prospective, con-
trolled, multicenter study is needed to
validate these results and enhance their
generalizability.
ACKNOWLEDGMENT
We thank Dr. Robert Tamburro for his
insightful critique of this article. We also
thank the entire staff of the Pediatric
Intensive Care Unit at Penn State Chil-
dren’s Hospital for assistance in obtain-
ing the information presented in this
manuscript.
REFERENCES
1. Burns CR: In search of wisdom: William Os-
ler and the humanities. Med Educ 2003; 37:
165–167
2. Lehmann LS, Brancati FL, Chen MC, et al:
The effect of bedside case presentations on
patients’ perceptions of their medical care.
N Engl J Med 1997; 336:1150 –1155
3. Tremonti LP, Biddle WB: Teaching behaviors
of residents and faculty members. J Med
Educ 1982; 57:854 – 859
4. LaCombe MA: On bedside teaching. Ann In-
tern Med 1997; 126:217–220
5. Janicik RW, Fletcher KE: Teaching at the
bedside: A new model. Med Teach 2003; 25:
127–130
6. Wang-Cheng RM, Barnas GP, Sigmann P, et
al: Bedside case presentations: Why patients
like them but learners don’t. J Gen Intern
Med 1989; 4:284 –287
7. Angelos P: Compliance with HIPAA regula-
tions: Ethics and excesses. Thorac Surg Clin
2005; 15:513–518
8. Romano J: Patients’ attitudes and behavior in
ward round teaching. JAMA 1941; 117:
664 – 667
9. Ramani S, Orlander JD, Strunin L, et al:
Whither bedside teaching? A focus-group
study of clinical teachers. Acad Med 2003;
78:384 –390
10. Simons RJ, Baily RG, Zelis R, et al: The
physiologic and psychological effects of the
bedside presentation. N Engl J Med 1989;
321:1273–1275
11. Schor EL: Family Pediatrics: Report of the
Task Force on the Family. American Acad-
emy of Pediatrics Task Force on the Family.
Pediatrics 2003; 111:1541–1571
12. Lewis C, Knopf D, Chastain-Lorber K, et al:
Patient, parent, and physician perspectives
on pediatric oncology rounds. J Pediatr 1988;
112:378 –384
13. Jarvis JD, Woo M, Moynihan A, et al: Parents
on rounds: Joint decision making in rounds
in the PICU result in positive outcomes and
increased satisfaction. Abstr. Pediatr Crit
Care Med 2005; 6:626
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Institutional policies on determination of medically inappropriate
interventions: Use in five pediatric patients*
Regina Okhuysen-Cawley, MD; Mona L. McPherson, MD, MPH; Larry S. Jefferson, MD, FCCM

Objective: To describe recent experience using the Texas Ad-
vance Directives Act to facilitate care of terminally ill children
managed in the two tertiary pediatric hospitals of the Texas
Medical Center, Houston, TX.
Design: Retrospective chart review.
Setting: Two multidisciplinary pediatric intensive care units in
Houston, TX.
Patients: Five terminally ill children whose parents were un-
able to acquiesce to comfort or palliative care.
Interventions: Implementation of the Texas Advanced Direc-
tives Act of 1999.
Results: Suspension of interventions thought to be medically
inappropriate by the physicians of record in four of the five cases,
with transfer of care in one instance.
Conclusions: Use of institutional policies in accordance with
the Texas Advance Directives Act may assist in the care of
terminally ill children and their families. (Pediatr Crit Care Med
2007; 8:225–230)
KEY WORDS: pediatrics; advance directive; terminally ill; inter-
ventions

T he medical advances that
characterized the latter half of
the 20th century, particularly
in the areas of prevention and
critical care, ushered in an era of dra-
matic changes in the trajectories of com-
mon illnesses and injuries, allowing
cures previously deemed impossible. Al-
though medical progress continues, with
decreasing mortality and improvement in
other outcome indicators in individuals
of all ages, some disease processes remain
intractable.
In some cases, life-sustaining inter-
ventions such as mechanical ventilation
or renal replacement therapy must be
continued at patient or surrogate insis-
tence for prolonged periods of time, de-
spite a certain poor outcome, to the pos-
*See also p. 293.
From Critical Care Medicine and Medical Ethics
Committee, Department of Pediatrics, College of Med-
icine, University of Arkansas for Medical Sciences,
Arkansas Children’s Hospital, Little Rock, AR (ROC);
and Section of Critical Care Medicine, Department of
Pediatrics, and Center for Medical Ethics and Health
Policy, Baylor College of Medicine, Texas Children’s
Hospital, Houston, TX (MM, LJ).
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
okhuysencawleyregina@uams.edu
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000264317.83788.ED
sible detriment of patient comfort, a
phenomenon observed in intensive care
units of all types. Failure to assent to redi-
rection of care to goals that emphasize
comfort when cure is no longer possible,
with limitation or withdrawal of interven-
tions that are perceived to be dispropor-
tionately burdensome or nonbeneficial by
the healthcare team, may prolong suffer-
ing, needlessly complicate the dying pro-
cess, and create significant conflict with
surrogates for patients with limited deci-
sional capacity, including children.
In some instances (1), courts have en-
dorsed patient or surrogate insistence on
continued intervention, possibly foster-
ing the reluctance of medical profession-
als to limit nonbeneficial interventions.
This occurs despite the wide variability in
surrogates’ capacity to comprehend med-
ical facts and make sound decisions. It is
not uncommon to observe patients, for
whom no reasonable hope of resolution
of organ dysfunction is likely, remain for
weeks—with obvious discomfort during
routine medical or nursing care— on in-
terventions such as mechanical ventila-
tion solely because the patient or surro-
gate, empowered by the high value placed
by society on patient autonomy and sur-
rogate authority, wants “everything
done.”
The last few decades have brought in-
creased interest in this difficult problem
and improved understanding of optimal
end-of-life care in patients of all ages,
from neonates to the elderly. Several ap-
proaches have been proposed over the
years to help mediate disagreements, no-
tably the concept of medical futility,
which was fraught with the pitfalls atten-
dant to its subjective and imprecise na-
ture. Statements by internationally rec-
ognized entities such as the American
Medical Association (2) and the Society of
Critical Care Medicine have instead em-
phasized the importance of a shared, bal-
anced, and patient-centered decision-
making process and have thus effectively
promoted the creation of guidelines and
policy statements regarding the care of
terminally ill patients (3).
Position statements by the American
Academy of Pediatrics (4 –7) have pro-
vided some guidance in the care of criti-
cally ill infants and children, emphasiz-
ing the “best interest” standard, which
can be difficult to define. The Royal Col-
lege of Paediatrics and Child Health of
the UK, in its 2004 Withholding or With-
drawing Life Sustaining Treatment in
Children: A Framework for Practice (8),
eloquently stated:
All members of the child health team,
in partnership with parents, have a
duty to act in the best interests of the
child. This includes sustaining life and
restoring health to an acceptable stan-
dard. However, there are circumstances
in which treatments that merely sus-

Pediatr Crit Care Med 2007 Vol. 8, No. 3 225

 tain “life” neither restore health nor
confer other benefit and hence are no
longer in the child’s best interests.
Although the majority of families fac-
ing a child’s approaching death are even-
tually able to agree to comfort measures,
particularly when palliative care consul-
tation and interventions have been wisely
integrated into the child’s treatment plan
at the time of diagnosis, some families
are simply unable to agree with redirec-
tion of care in the terminal stages of
disease. In this article, we describe our
experience with the application of insti-
tutional policies to mediate conflict re-
garding perceived medically inappropri-
ate interventions in five ventilator-
dependent, irreversibly ill children for
whom no additional therapeutic options,
including experimental protocols, were
available, and who were cared for in the
Texas Medical Center. The institutional
policies were in accordance with legisla-
tion unique to the State of Texas.
The term “medically inappropriate
care,” for the purposes of this discussion,
describes life-sustaining interventions
provided to children with immediately
life-threatening, terminal, and irrevers-
ible conditions not amenable to correc-
tion with state-of-the-art pediatric care,
especially if discomfort is evident. The
interventions thought to be medically in-
appropriate are thus judged to be dispro-
portionately burdensome by the team
caring for the patient.
Texas Advance Directives Act
of 1999
Texas legislation regarding end-of-life
care originated in 1977, with the creation
of the Texas Natural Death Act, the equiv-
alent of a “living will,” which allows a
terminally ill patient to order the physi-
cian to withhold or withdraw life-support
treatment and measures. In 1988, repre-
sentatives from hospitals and universi-
ties, primarily from institutions based in
the Texas Medical Center in Houston,
convened the Houston Bioethics Network
to address the various issues surrounding
medical care.
By 1993, the volume of end-of-life is-
sues presented to the Network, primarily
concerning perceived medically inappro-
priate care, had escalated. This coincided
with an era of increasing debate sur-
rounding the concept of medical futility,
which had become a focal discussion and
division point. In August 1993, the Hous-
ton Citywide Task Force on Medical Fu-
226
tility was formed, and after much schol-
arly debate, published its guidelines (9),
which represented a concerted effort to
mediate and attempt to resolve conflicts
that complicate end-of-life care.
Special Bill 414, introduced into the
Texas legislature in 1997, encompassed
the directive to physicians, the durable
power of attorney for healthcare deci-
sions, and the out-of-hospital do-not-
attempt resuscitation legislation. In June
1997, Governor George W. Bush vetoed
the bill. Further negotiations ensued
with the participation of the Texas Hos-
pital Association, the New Mexico Hospi-
tals and Health Systems Association, the
American Association of Retired Persons,
the Texas Conference of Catholic Health
Facilities, and the Texas National Right to
Life committees. Without further opposi-
tion, the bill, re-titled Special Bill 1260,
was signed into law by Governor Bush on
June 18, 1999.
Determination of Medically
Inappropriate Interventions
Special Bill 1260 created the current
Texas Advance Directives Act, which out-
lines a procedure whereby interventions
judged to be medically inappropriate by
an attending physician caring for a pa-
tient, qualified for this Act by the irre-
versible or terminal nature of his or her
disease, can be legally withheld or discon-
tinued, despite the objections of the pa-
tient or surrogate medical decision
maker.
For the purposes of this Act, “irrevers-
ible” is defined as “a condition, injury, or
illness that may be treated but is never
cured or eliminated, that leaves a person
unable to care for or make decisions for
the person’s own self; and that without
life-sustaining treatment provided in ac-
cordance with the prevailing standard of
medical care is fatal.” The concept “ter-
minal condition” is defined in this Act,
which does not distinguish children from
adults regarding time constraints, as “an
incurable condition caused by injury, dis-
ease, or illness that according to reason-
able medical judgment will produce
death within six months, even with avail-
able life-sustaining treatment provided in
accordance with the prevailing standard
of medical care. . .” (10).
Legally sanctioned discontinuation of
life-sustaining interventions can occur
after review by an ethics or medical com-
mittee and grants immunity from civil,
criminal, and professional disciplinary
actions. Although this law allows for flex-
ibility in the appointment and constitu-
tion of a given hospital’s institutional re-
view committee, it clearly defines
timelines for family notification and case
review and requires a 10-day mandatory
waiting period during which institution-
facilitated physician or hospital transfer
may occur before the discontinuation of
interventions determined to be medically
inappropriate (9). The instructions for re-
solving conflict in cases involving medi-
cally inappropriate care under the Texas
Advance Directives Act of 1999, when
structured, documented discussion has
failed may, be summarized as follows:
● The physician’s refusal to comply with
the patient’s or surrogate’s request for
continued medically inappropriate care
should be reviewed by a hospital-
appointed medical or ethics committee
in which the attending physician does
not participate. The patient or his sur-
rogate must receive written informa-
tion regarding the ethics consultation
process.
● The patient or surrogate must be given
notice of 48 hrs and an invitation to
participate in the consultation process.
A June 2003 revision to the law re-
quires that additional information re-
garding the right to transfer the patient
from the institution planning a review
must be provided to the patient or sur-
rogate before the meeting can take place.
This 48-hr waiting period can only be
waived through mutual agreement. A
written summary regarding the deci-
sions reached during the consultation
must be provided to the patient or sur-
rogate.
● The written summary, as detailed
above, must be included in the pa-
tient’s medical record.
● If the conflict remains unresolved, the
physician and the facility must make a
reasonable effort to transfer the pa-
tient’s care to another physician will-
ing to comply with the requested treat-
ment within the same institution, an
alternative care setting within the
same facility, or another facility.
● Available life-sustaining measures, in-
cluding nutrition, hydration, mechan-
ical ventilation, vasoactive infusions,
and renal replacement therapy, must
be continued pending the transfer op-
erations outlined above. Such therapy
need not be continued beyond the 10-
day period after the written decision is
provided to the patient or surrogate,
Pediatr Crit Care Med 2007 Vol. 8, No. 3
 unless a court order is received to con-
tinue life-sustaining therapy. Life-
sustaining treatments may not be en-
tered into the chart as medically
unnecessary until the prescribed time
period has expired.
● The patient or surrogate may request a
court-ordered time extension, which
should only be granted if there is a
reasonable likelihood of securing a pro-
vider or hospital able and willing to
continue the disputed treatment.
● Treatments, including life-sustaining
ones, may be discontinued by the treat-
ment team if no extension is granted.
In addition, every effort should be
made to ensure patient comfort when
mechanical ventilation and renal replace-
ment therapies are discontinued. Al-
though nutrition and hydration are not
obligatory when death is imminent,
they may be made available in amounts
carefully adapted to the patient’s hemo-
dynamic and respiratory status to avoid
potentially distressing respiratory or
gastrointestinal symptoms. Many fami-
lies find the continued provision of dis-
crete amounts of nutrition comforting.
Although practical experience with
resolution of perceived futility by the due
process procedures outlined above is lim-
Figure 1. Patient outcomes after discussion of the Texas Advance Directives Act.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
ited, a recent publication by Fine and
Mayo (11) suggests that implementation
of these policies in an adult hospital in-
creased not only the numbers of referrals
for evaluation of medically inappropriate
care, but also the number of instances in
which families agreed to the withdrawal
of perceived futile treatment and de-
creased the time to resolution of conflict
from weeks to days and from days to
hours.
After obtaining consent from the au-
thorizing institutional review board at
both tertiary pediatric institutions where
these children were cared for, Baylor Col-
lege of Medicine (for Texas Children’s
Hospital) and the University of Texas
Health Science Center–Houston (for Me-
morial Hermann Children’s Hospital), we
performed a retrospective review of the
five patients’ charts. A summary of each
case follows (Fig. 1).
Description of Patients
Patient 1 was a 4-month-old African-
American boy with complex congenital
heart disease who developed severe car-
diopulmonary failure. The child could
not be successfully weaned from mechan-
ical ventilation, despite several attempts.
Multidisciplinary evaluation revealed
complete tracheal rings with a very long,
severely stenotic tracheal segment fur-
ther compromised by a vascular ring. The
constellation of malformations was not
deemed to be amenable to surgical recon-
struction or long-term mechanical venti-
lation. Increasing doses of opioids and
benzodiazepines were necessary to en-
sure patient comfort.
Patient 2 was a severely cachectic
2-yr-old African-American boy with early
onset Cockayne syndrome, displaying the
severe encephalopathy, renal insuffi-
ciency, wasting, and contractures charac-
teristic of the syndrome. The child had
been lost to follow-up for many months.
He presented with end-stage renal failure
and severe acute respiratory distress syn-
drome. The child remained anuric after 8
wks of peritoneal dialysis and dependent
on high levels of ventilatory support, in-
cluding high inspired oxygen tensions
and positive-end expiratory pressure.
High doses of opioids and benzodiaz-
epines were required for adequate anal-
gesia and sedation.
Patient 3 was an 8-yr-old Turkish boy
who had developed T-cell leukemia re-
fractory to chemotherapy administered in
several European countries. He had de-
veloped central nervous system and tes-
227
ticular relapse after bone marrow trans-
plantation in the United States. His
course was further complicated by severe
respiratory failure due to herpes virus
pneumonia, an intracranial hemorrhage,
and marked encephalopathy. Distress
manifested during nursing and medical
procedures during periods of neuromus-
cular blockade was managed with titra-
tion of opioids and benzodiazepines. The
child’s gas exchange was marginal, de-
spite an inspired oxygen fraction of
⬎70% and a positive end-expiratory pres-
sure of 12 cm H2O for ⬎4 wks. No further
therapy was deemed feasible by the
child’s oncologists.
Patient 4 was a 5-month-old Latin-
American boy who had required bilateral
nephrectomy within a few weeks of birth
for severe polycystic kidney disease, with
rapid expansion of the renal masses caus-
ing significant respiratory embarrass-
ment. He had been managed with perito-
neal dialysis but had subsequently
experienced bilateral hemispheric in-
farcts involving the vast majority of his
cerebral cortex, leading to coma and in-
ability to maintain a patent airway. Dis-
tress noted during any medical or nurs-
ing intervention was addressed with
adjustments in his regimen of analgesia
and sedation.
Patient 5 was a 3-month-old African-
American boy with Trisomy 18 requiring
full ventilatory support for chronic lung
disease complicated by severe congestive
heart failure. The child had congenital
heart malformations, including atrial and
ventricular septal defects and a widely
patent ductus arteriosus. The child was
also thought to have cardiomyopathy. He
had renal insufficiency after an episode of
acute renal failure and residua of severe
necrotizing enterocolitis, with repeated
episodes of small bowel obstruction and
severe hepatic dysfunction due to depen-
dence on total parenteral nutrition. In
addition, he had severe craniofacial and
limb abnormalities, including micro-
cephaly, cleft lip and palate, severely mal-
formed upper extremities, and clubfeet.
Other than manifesting discomfort with
procedures, for which he received in-
creasing amounts of opioids and benzo-
diazepines, the infant did not interact
with his environment.
Given the extent and severity of his
medical problems, the child was
thought to be a poor candidate for re-
pair of his cardiac defects, and with-
drawal of life-sustaining interventions
had been recommended in view of per-
228
ceived suffering in the face of a poor
expected functional and developmental
outcome.
Discussions with Families and
Eventual Outcomes
Each family participated in structured,
multidisciplinary discussions regarding
the limited benefits and significant bur-
dens of continued intervention during
the children’s prolonged intensive care
unit admissions, which exceeded 4 wks
in all cases. The discussions included a
full verbal description of the policy and
provision of written copies of the insti-
tutional policy for patients managed at
Texas Children’s Hospital, a prescribed
procedural step in the policy at that
institution.
The physicians participating in each
child’s care presented likely outcomes for
each patient, based on their personal and
collective experience. The pediatric in-
tensivists, cardiologists, and surgeons
caring for the child with the complex
congenital heart and airway malforma-
tions, patient 1, thought that he would
probably die during or after an attempt at
airway reconstruction and that he was
not a suitable candidate for chronic me-
chanical ventilation. His family opted for
comfort care shortly after receiving and
reviewing the document. This infant died
without apparent distress shortly after ex-
tubation.
The uniformly lethal nature of early
onset Cockayne disease was reiterated to
the family members of the affected child,
patient 2, by the intensive care and pedi-
atric nephrology teams. It was antici-
pated that this child would succumb to
worsening respiratory failure because ac-
cess for prolonged renal replacement
therapy had been lost with the onset of
fungal peritonitis. The family agreed to
removal of ventilatory support after re-
viewing the institutional policy, and the
boy died without apparent distress within
a few hours of extubation.
The other three families refused limi-
tation or withdrawal of mechanical ven-
tilation, despite several additional struc-
tured discussions in the presence of
subspecialists, other members of the
healthcare team, including social work-
ers and chaplains, and, in the case of the
Turkish child, Turkish Embassy repre-
sentatives, all of whom had long-term
relationships with the families. All three
families cited religious beliefs as the rea-
son for wanting to continue the disputed
interventions. The three cases were
therefore referred to the institutional re-
view committees for evaluation. Consul-
tation with other tertiary care facilities
for possible transfer was sought for pa-
tients 3 and 4 after the review commit-
tees concurred with the attending physi-
cians that life-sustaining medical
treatments could be considered medically
inappropriate. The consulted subspecial-
ists, one of whom personally evaluated
the child and met with his parents,
agreed with the managing team and de-
clined transfer.
The child with leukemia, patient 3,
was placed on pressure support ventila-
tion with room air and a positive-end-
expiratory pressure of 4 cm H2O after the
10-day waiting period prescribed by the
Texas Advance Directives Act of 1999.
The decision not to extubate the boy was
made to accommodate the father’s fear
that the child would be uncomfortable if
extubated. The child died due to progres-
sive hypoxemia but without apparent dis-
comfort, with the aid of supplemental
sedation, with his family, a Muslim chap-
lain, and representatives of the Turkish
Embassy at the bedside approximately 35
mins after his ventilatory settings were
modified.
The infant with severe sequelae of
polycystic kidney disease, patient 4, was
extubated at the conclusion of the 10-day
waiting period after the institutional re-
view committee unanimously agreed that
continued invasive therapy was inap-
propriate, and died peacefully approxi-
mately 2.5 hrs later, with his family at
the bedside.
The attending physicians held fre-
quent meetings with the families of the
two children from whom life-support was
eventually withdrawn utilizing the Texas
Advance Directives Act process. Both
families were reassured on a daily basis
during the 10-day waiting period that
they had done everything in their power
to ensure their child’s survival. Both fam-
ilies repeatedly reiterated their apprecia-
tion of the physicians’ efforts on behalf of
their children during the waiting period
and accepted their child’s death calmly
when it occurred.
The children who were ultimately
withdrawn from support following the
process outlined by the Texas Advance
Directives Act would have most likely
succumbed to complications of their un-
derlying diseases or their treatment,
namely, acute respiratory distress syn-
drome in the case of the child with leu-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
kemia and of complications of renal fail-
ure if the child with complications of
polycystic kidney disease had undergone
tracheostomy for chronic ventilation. It
was thought by the managing physicians
that continuing the interventions in
question would have merely delayed
death.
Although prolonged survival has been
described in children with Trisomy 18,
the family of patient 5 had been asked to
allow withdrawal of mechanical ventila-
tion given the child’s perceived suffering
and dismal functional prognosis. The in-
fant had been the subject of a bioethics
committee consultation before referral
for institutional review, and the mother
had received a copy of the institutional
policy on medically inappropriate care.
The attending neonatologist transferred
the infant from the intensive care nursery
to the pediatric intensive care unit in the
same hospital to a pediatric surgeon who
offered to assume care of the patient dur-
ing the institutional review meeting.
The infant received six additional
months of support in the pediatric inten-
sive care unit before discharge home on
full mechanical ventilation after trache-
ostomy, complete correction of his ana-
tomical cardiac defects, resection of sev-
eral intestinal strictures, and creation of
a gastrostomy with fundoplication for re-
fractory gastroesophageal reflux. The
child was eventually weaned to predomi-
nantly nocturnal ventilation but had a
sudden, massive upper and lower gastro-
intestinal hemorrhage at home 2 yrs after
discharge. This event was quickly fol-
lowed by cardiopulmonary arrest, from
which he could not be resuscitated.
Conclusion
Families faced with the approaching
death of a child can most often be guided
toward comfort-centered care, which
may include withholding or withdrawing
life-sustaining measures, using kindness,
sensitivity, and carefully structured dis-
cussions. Creating a palliative care plan
as soon as possible after the diagnosis of a
life-limiting condition is made may help
prevent distress at all levels. Social work-
ers, family members, and friends can be
extremely helpful in assisting with the
communication of difficult concepts, the
provision of emotional support, and in
ensuring that basic needs such as proper
sleep and nutrition are met. Most families
appreciate and derive benefit from the
spiritual support provided by their own
Pediatr Crit Care Med 2007 Vol. 8, No. 3
clergy or hospital chaplains for this most
difficult journey.
Frequent and clear communication
with families, with the aid of professional
interpreters and other members of the
healthcare team as indicated, is of ex-
treme importance in setting the stage for
a smooth transition to terminal care so
that the child is able to die in a manner
that is consistent with the Institute of
Medicine’s definition of a good death: “A
decent or good death is one that is: free
from avoidable distress and suffering for
patients, families, and caregivers; in gen-
eral accord with the patients’ and fami-
lies’ wishes; and reasonably consistent
with clinical, cultural and ethical stan-
dards. A bad death, in turn, is character-
ized by needless suffering, dishonoring
of patient or family wishes or values,
and a sense among participants or ob-
servers that norms of decency have
been offended” (12).
The advisability of interventions of
questionable benefit must be carefully
considered before their implementation,
once again making a clear distinction be-
tween interventions that are available but
not obligatory from those that are neces-
sary for the child’s well-being. As elo-
quently stated by Truog et al. (13), inten-
sivists should be “as skilled and
knowledgeable at forgoing life-sustaining
treatments as they are at delivering care
aimed at survival and cure.”
Physicians caring for dying patients
must assume a directive role, recalling
that the word “doctor” derives from the
Latin docere, or teacher, and as such,
should be kind and assertive when con-
veying their views. The shared nature of
responsibility should be reiterated when
coordinating treatment plans for dying
patients. Recommending a clear and con-
sistent path is preferable to enumerating
several possible options, which grieving
families may find bewildering.
Parents of children dying of a pro-
tracted illness in the United States fre-
quently voice that having to decide when
interventions are to be withdrawn gener-
ates feelings of guilt, a sense of having
given up on their child, and a great fear of
events for which they have no experience.
They frequently describe this situation as
the most difficult matter they have faced.
A careful, caring discussion away from
the bedside that affirms life, distinguish-
ing natural death from inappropriate acts
that hasten it, and reviews the events
likely to take place when life-prolonging
interventions are withheld or withdrawn,
coupled with a promise that the child will
be kept comfortable, may be extremely
useful during end-of-life discussions. The
family may visibly relax with the inten-
sivist’s reassurance, and a plan for com-
fort care may be crafted with input from
the family and other team members.
Cultural differences likely played a sig-
nificant role in parental reluctance to
agree to limitation or withdrawal of care
in the unfortunate cases presented in this
article. Studies in neonatal and adult pa-
tients have shown that families of Afri-
can-American patients tend to be more
distrustful of medical professionals (14,
15). It is possible that this is also a prob-
lem with other minority populations.
Other families possibly at increased risk
for dissent and conflict when limitation
or withdrawal of life-sustaining interven-
tions is recommended are those with sin-
gle parents or those insured by Medicaid
(16). Early involvement of social workers
in settings where prolonged admissions
or a poor outcome are anticipated is cru-
cial (16, 17). Mediation using healthcare
professionals or pastoral care support
from backgrounds similar to those of
family members at odds with physician
recommendations often results in agree-
ment regarding disputed interventions.
There are no simple solutions to per-
sistent conflicts complicating end-of-life
care. An important step was made by the
American Medical Association when rec-
ommending the use of due process to
help mediate disputes. Reticence to the
implementation of policies such as the
one described in this article is under-
standable. Medical science is imperfect,
and as noted by Truog et al. (13), the
situations in which physiologic futility
can be accurately invoked are extremely
rare. Other futility judgments are even
more problematic.
However, such reticence does not ad-
dress the tragic problem of preventable
suffering that dying children, who may be
distressed by the simplest of medical pro-
cedures, may experience. Similarly, ter-
minally ill patients of any age receiving
high doses of sedative agents or neuro-
muscular blockade may not be able to
manifest physical pain or discomfort and
are thus possibly harmed by undue pro-
longation of life-sustaining interventions.
We believe that the implementation of
established institutional policies, in pa-
tients for whom no other therapies are
available, in accordance with the recom-
mendation of the American Medical As-
sociation, utilizing an empathetic, disin-
229
terested, dispassionate, and consistent
review panel with access to all the rele-
vant information in a manner that ap-
proximates the “ideal observer” de-
scribed by Firth (18), in situations in
which families insist on the continua-
tion of interventions deemed to be med-
ically inappropriate allows for thought-
ful discernment, patient advocacy, and
the preservation of physicians’ profes-
sional integrity while providing an ave-
nue for continuation of interventions
acceptable to other physician providers
and institutions willing to accept qual-
ified patients in transfer, as illustrated
by the management of patient 5.
Institutional policies allow, utilizing
due process, the discontinuation of med-
ically inappropriate interventions that
may prolong suffering. Although this
may be regarded as harsh, coercive, and
intrusive, particularly in a country that
gives utmost importance to patient au-
tonomy and to surrogate authority in the
case of patients with limited decisional
capacity, parental or surrogate authority
is not absolute, nor should their interests
preempt those of the dying, possibly suf-
fering patient.
In addition, the steps involved in pol-
icy implementation—when no other es-
tablished treatment or appropriate re-
search protocol is available—may provide
reassurance to all involved that the case
has been carefully reviewed by other spe-
cialists and, in some instances, by other
institutions. It may provide, albeit amidst
the grief at the child’s death and anger
regarding policy implementation, a sense
of relief that the decision to suspend the
disputed treatments has been taken out
of the surrogates’ hands, as evidenced by
the relief manifested by the families of
the two children who were withdrawn
from support after institutional review in
Houston and in the impressions of Fine
230
et al. (11, 19), witnessing similar reac-
tions in the families of a young infant and
in adult patients in Dallas.
Most importantly, it may ultimately
ensure that the best possible medical care
is provided to the most vulnerable indi-
viduals by abbreviating the duration of
disproportionately burdensome interven-
tions while facilitating the continuation
of all indicated comfort measures.
ACKNOWLEDGMENTS
We thank Virginia Gremillion, MPH,
Memorial Hermann Hospital Systems,
Houston, TX, for her invaluable help in
the creation of this article; Dr. Paul K.
Minifee, Baylor College of Medicine; and
Micah Hester, PhD, and Suzanne
Speaker, University of Arkansas for Med-
ical Sciences College of Medicine.
REFERENCES
1. In re the Conservatorship of Helga M. Wan-
glie, PX-91-283, District Probate Division,
4th Judicial District of the County of Henne-
pin, State of Minnesota
2. Medical futility in end-of-life care: Report of
the Council on Ethical and Judicial Affairs.
JAMA 1999; 281:937–941
3. Truog RD, Cist AF, Brackett SE, et al: Rec-
ommendations for end-of-life care in the in-
tensive care unit: The Ethics Committee of
the Society of Critical Care Medicine. Crit
Care Med 2001; 29:2332–2348
4. American Academy of Pediatrics Committee
on Bioethics: Guidelines on foregoing life-
sustaining medical therapy. Pediatrics 1994;
93:532–536
5. American Academy of Pediatrics Committee
on Bioethics: Ethics and the care of critically
ill infants and children. Pediatrics 1996; 98:
149 –152
6. American Academy of Pediatrics Committee
on Child Abuse and Neglect and Committee
on Bioethics: Foregoing life-sustaining med-
ical treatment in abused children. Pediatrics
2000; 106:1151–1153
7. American Academy of Pediatrics Committee
on Bioethics and Committee on Hospital
Care: Palliative care for children. Pediatrics
2000; 166:351–357
8. Withholding or Withdrawing Life Sustaining
Treatment in Children: A Framework for
Practice. Second Edition. London, Royal Col-
lege of Paediatrics and Child Health, 2004
9. Halevy A, Brody BA: The Houston process-
based approach to medical futility. Bioethics
Forum 1998; 14:10 –17
10. Texas Advance Directives Act 76(R). In. 76(R)
ed; 1999. Available at: http://www.capitol.state.
tx.us/statutes/docs/HS/content/htm/HS.002.
00.000166.00.htm. Accessed May 24, 2005
11. Fine R, Mayo TW: Resolution of futility by
due process: Early experience with the Texas
Advance Directives Act. Ann Intern Med
2003; 138:743–746
12. Field MJ, Behrman RE (Eds): When Children
Die: Improving Palliative and End-of-Life
Care for Children and Their Families. Wash-
ington, DC, National Academies Press, 2003,
p 40
13. Truog RD, Brett AS, Frader J: The problem
with futility. N Engl J Med 1992; 326:
1560 –1563
14. Moseley KL, Church A, Hempel B, et al: End-
of-life choices for African-American and
white infants in a neonatal intensive-care
unit: A pilot study. J Natl Med Assoc 2004;
96:933–937
15. Boulware LE, Cooper LA, Ratner LE, et al:
Race and trust in the health care system.
Public Health Rep 2003; 118:358 –365
16. Studdert DM, Burns JP, Mello MM, et al:
Nature of conflict in the care of pediatric
intensive care patients with prolonged stay.
Pediatrics 2003; 29:1489 –1497
17. Studdert DM, Mello MM, Burns JP, et al:
Conflict in the care of patients with pro-
longed stay in the ICU: Types, sources, and
predictors. Crit Care Med 2003; 31:
2107–2117
18. Firth R: Ethical absolutism and the ethical
observer. Philos Phenomenol Res 1952; 12:
317
19. Fine RL, Whitfield JM, Carr BL, et al: Medical
futility in the neonatal Intensive care unit:
Hope for a resolution. Pediatrics 2005; 116:
1219 –1222
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Continuing Medical Education Article

Increasing use of extracorporeal life support in

methicillin-resistant Staphylococcus aureus sepsis in children
C. Buddy Creech, MD, MPH; B. Gayle Johnson, RN; Randall E. Bartilson, BSN, RN;
Edmund Yang, MD, PhD; Frederick E. Barr, MD, MSCI

LEARNING OBJECTIVES
On completion of this article, the reader should be able to:
1. Identify factors associated with survival in infants and children with severe methicillin-resistant Staphylococcus aureus
(MRSA) who are treated with extracorporeal life support.
2. Describe the relationship between age and outcome in infants and children with severe S. aureus infections treated with
extracorporeal life support.
3. Define the strengths and limitations of the Extracorporeal Life Support Organization (ELSO) database for research on
extracorporeal support in critically ill infants and children.
All authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining
to this educational activity.
Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity.
Visit the Pediatric Critical Care Medicine Web site (www.pccmjournal.org) for information on obtaining continuing medical
education credit.

Background: Pediatric cases of fulminant community-associ-
ated methicillin-resistant Staphylococcus aureus (MRSA) infec-
tions requiring extracorporeal life support (ECLS) have been re-
ported, but the frequency of ECLS use for severe presentations of
staphylococcal disease is unknown.
Objective: To describe the frequency and characteristics of
children with MRSA infections requiring ECLS using local and
international databases.
Methods: The reasons for use of ECLS in children 0 –18 yrs of
age were determined in both the Vanderbilt Children’s Hospital
medical record system and the Extracorporeal Life Support Orga-
nization database during the years 1994 –2005. Demographic
characteristics, ventilatory management, and measurements of
cardiopulmonary status in subjects undergoing ECLS with a pre-
ECLS diagnosis of infection with Staphylococcus aureus and
MRSA were included.
Results: Three subjects with MRSA sepsis requiring ECLS were
identified at Vanderbilt since 2000. Before that time, no cases due
to MRSA were reported. The three subjects were previously
healthy adolescents with severe necrotizing pneumonia associ-
ated with skin/soft-tissue infection and two died. A total of 45
patients requiring ECLS for MRSA infection were identified in the
International Extracorporeal Life Support Organization database,
with nearly half reported in the past 2 yrs (20 of 45 patients). The
median age was 2.4 yrs (interquartile range, 0.36 –14 yrs), with
peaks noted in infancy and adolescence. In Extracorporeal Life
Support Organization subjects with MRSA, survival to discharge
was highest in infants and young children aged 1– 4 yrs (65% and
71%, respectively) and lowest in the age ranges of 5–9 yrs and
13–18 yrs (0% and 31%, respectively). There were no statistically
significant differences in pre-ECLS ventilatory settings, cardiopul-
monary status, or frequency of complications between survivors
and nonsurvivors.
Conclusions: The use of ECLS for MRSA infection seems to be
increasing both locally and internationally. High mortality rates,
particularly in older patients, are concerning and highlight the
increasing problem with this pathogen. (Pediatr Crit Care Med
2007; 8:231–235)
KEY WORDS: Staphylococcus aureus; sepsis; extracorporeal
membrane oxygenation; methicillin-resistant Staphylococcus au-
reus; adolescent; extracorporeal life support

*See also p. 294.
Assistant Professor, Pediatric Infectious Diseases
and Pediatric Clinical Research Office (CBC); Research
Nurse Specialist II, Pediatric Clinical Research Office
(BGJ); Manager, ECMO Services (REB); Assistant Pro-
fessor of Surgery, Department of Pediatric Surgery
(EY); Associate Professor, Pediatric Critical Care (FEB);
Vanderbilt University Medical center and Children’s
Hospital, Nashville, TN.
The authors have not disclosed any potential con-
flicts of interest.
Supported, in part, by the Vanderbilt Clinical Research
Scholars Program, National Institutes of Health Public
Health Service award K12 RR017697 (to Dr. Creech).
For information regarding this article, E-mail:
buddy.creech@vanderbilt.edu
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262801.81331.C7

Pediatr Crit Care Med 2007 Vol. 8, No. 3 231

I nfections in children and adoles-
cents due to community-associ-
ated methicillin-resistant Staphy-
lococcus aureus (CA-MRSA) have
increased during recent years, with the
pathogen accounting for 70% of all com-
munity-associated staphylococcal infec-
tions in some regions (1). The majority of
CA-MRSA infections present as uncom-
plicated skin and soft-tissue infections,
but multifocal abscesses, necrotizing
pneumonia, and fulminant staphylococ-
cal sepsis have been described (1– 4).
Gonzalez et al. (1) recently described a
severe staphylococcal sepsis syndrome in
adolescents in Houston, TX, that was as-
sociated with substantial morbidity and
mortality and high rates of necrotizing
pneumonia and osteoarticular infections.
Similarly, Adem et al. (5) reported two
children with MRSA-associated Water-
house-Friderichsen syndrome— both re-
quired extracorporeal life support
(ECLS). These reports prompted us to
review the medical records of subjects
requiring ECLS at Vanderbilt Children’s
Hospital and to query the Extracorporeal
Life Support Organization (ELSO) data-
base to determine the frequency and
characteristics of children 0 –18 yrs of age
with MRSA infections requiring ECLS.
METHODS
Local Database. As a participant in the
ELSO surveillance program, Vanderbilt Uni-
versity Medical Center maintains a local data-
base of all patients in whom ECLS is utilized.
After approval of the study by the Vanderbilt
University Medical Center Institutional Review
Board, charts of all pediatric patients with a
pre-ECLS diagnosis of MRSA infection were
reviewed. A pre-ECLS diagnosis of MRSA in-
fection was defined as having cardiorespira-
tory failure and the pre-ECLS organism code
corresponding to MRSA. Charts were reviewed
for demographic information (age, sex, ethnic-
ity), pre-ECLS ventilatory settings, ventilatory
settings at 24 hrs of ECLS, measurements of
cardiopulmonary status (systolic blood pres-
sure, diastolic blood pressure, oxygen index),
type of extracorporeal membrane oxygenation
(ECMO) support (venoarterial, venovenous),
post-ECLS complications, and clinical out-
come. ELSO database definitions were used
for each of these characteristics.
International ELSO Database. The ELSO
database is an international voluntary registry
maintained in Ann Arbor, MI. It has been in
existence since 1986, receives passive reports
of adult and pediatric patients requiring
ECLS, and has been used previously by mem-
bers of our group to describe other clinical
syndromes (6). The database was queried for
all patients 0 –18 yrs of age, between 1994 and
232
2005, who required ECLS and had a pre-ECLS
or on-ECLS infection due to S. aureus. Only
those with a pre-ECLS diagnosis of staphylo-
coccal infection were included in the study.
From these subjects, those with a pre-ECLS
diagnosis of MRSA were identified by the
unique identification number corresponding
to MRSA. Subjects were excluded from anal-
ysis for the following reasons: age of ⬍7
days (neonates) or concomitant diagnoses of
meconium aspiration, burn injuries, con-
genital diaphragmatic hernia, congenital
heart disease, or malignancy. Mortality was
defined as failure to survive to discharge.
Statistical analysis was performed using
Stata 8.0 (Stata, College Station, TX) for Win-
dows (Microsoft, Redmond, WA). Comparison
of categorical outcomes and exposures was con-
ducted using Pearson chi-square. Nonparamet-
ric tests for comparison of median values be-
tween groups were used when appropriate.
RESULTS
Local Database
Three patients were identified at
Vanderbilt Children’s Hospital since 2000
who presented with CA-MRSA sepsis and
whose adjunctive treatment included
ECLS.
Case 1. A 15-yr-old white girl with no
medical history was admitted to Vander-
bilt Children’s Hospital in March 2005
with 5 days of left shoulder pain. On the
day before admission, she developed my-
algia, pharyngitis, and persistent emesis,
which progressed in severity. At presen-
tation to Vanderbilt Children’s Hospital,
she was severely ill, with respiratory dis-
tress, hypoxia, and hypotension. Chest ra-
diography revealed small bilateral infil-
trates, and she was begun on ceftriaxone
and azithromycin for presumed commu-
nity-acquired pneumonia. Her cardiopul-
monary status continued to decline, re-
quiring mechanical ventilation and
vasopressive support. Laboratory studies
performed at that time demonstrated a
white blood cell count of 3200 cells/␮L
with 80% neutrophils, hematocrit of
31%, and platelet count of 127,000 cells/
␮L. During the next 48 hrs, severe hyp-
oxia and hypotension persisted, and she
was begun on vancomycin and clindamy-
cin. After failure of inhaled nitric oxide
and high-frequency oscillatory ventila-
tion, venovenous ECLS was begun. Blood
cultures obtained at admission and for 5
days afterward revealed MRSA. Based on
this finding and shoulder pain, arthro-
centesis of the left shoulder joint was
performed, which demonstrated no evi-
dence of acute infection. However, mul-
tiple abscesses were noted within the cen-
tral nervous system, chest, abdomen,
pelvis, and extremities by computed to-
mography; each peripheral abscess was
drained percutaneously, and fluid culture
confirmed the presence of MRSA. Echo-
cardiography revealed no evidence of in-
fective endocarditis, but ultrasonography
showed thrombophlebitis of the left bra-
chiocephalic vein that was subsequently
resected. After 4 wks of therapy with van-
comycin and gentamicin, mechanical
ventilation was discontinued. At dis-
charge from the hospital 2 wks later, she
had no significant neurologic sequelae
and was treated with trimethoprim/
sulfamethoxazole and rifampin to com-
plete a total of 8 wks of therapy.
Case 2. A 14-yr-old white boy with no
medical history was admitted to Vander-
bilt Children’s Hospital in June 2005 after
3 days of right knee and hip pain. On the
day of admission, he developed nausea,
vomiting, and fever. He visited his pedi-
atrician 5 hrs after onset of symptoms but
collapsed in the parking lot of the physi-
cian’s office. Due to hypotension and
poor perfusion, aggressive fluid resusci-
tation and mechanical ventilation were
initiated, and he was emergently trans-
ferred to the Vanderbilt Children’s Hos-
pital Critical Care Unit. At admission, the
patient was hypotensive and had poor pe-
ripheral perfusion with absent peripheral
pulses. Chest radiograph was significant
for bilateral interstitial infiltrates. Physi-
cal examination revealed a healing tick
bite on the distal right lower extremity
and multiple petechiae on the extremities
and trunk. The musculoskeletal examina-
tion was normal, with no evidence of
joint effusion in the knee. Despite aggres-
sive fluid resuscitation, vasopressive
agents, and mechanical ventilation, hy-
poxemia and lactic acidosis persisted;
therefore, venovenous ECLS was initiated
(venovenous ECMO). Although veno-
venous ECMO is often successful at re-
versing hemodynamic instability in pa-
tients with respiratory failure and septic
shock and is associated with lower risk of
central nervous system infarction, lactic
acidosis, systemic hypotension, and poor
oxygen delivery persisted in this patient,
necessitating a conversion to venoarterial
ECMO. Complications included mechan-
ical failure of the oxygenator, pulmonary
hemorrhage, and need for hemofiltration
due to acute renal failure. Despite maxi-
mum therapeutic measures, brain death
was confirmed by transcranial Doppler on
the sixth hospital day. Multiple blood cul-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
tures were positive for MRSA. Postmor-
tem analysis revealed severe necrotizing
pneumonia and 5 mL of purulent exudate
in the right hip joint. Culture of the joint
fluid grew one colony of MRSA.
Case 3. A 14-yr-old white boy with 5
days of fatigue and right knee pain was
admitted to the Vanderbilt Children’s
Hospital Critical Care Unit in November
2004 due to hypotension and respiratory
collapse. His medical history was unre-
markable and social history was signifi-
cant for participation on his high school
football team. Physical examination re-
vealed tachycardia and decreased breath
sounds throughout the chest. Chest ra-
diograph confirmed the presence of dif-
fuse, bilateral interstitial infiltrates and
right-sided pneumothorax. After failure
of high-frequency oscillatory ventilation,
aggressive fluid resuscitation, and vaso-
pressive support, venovenous ECLS was
begun. After the identification of MRSA
from the blood and tracheal secretions,
broad spectrum antibiotic therapy was
narrowed to vancomycin, gentamicin, Figure 1. Patient flowchart from identification in the International Extracorporeal Life Support
and rifampin. The patient remained on Organization (ELSO) Database to inclusion in study analysis. ECLS, extracorporeal life support; S.
ECLS for nearly 5 wks, requiring contin- aureus, Staphylococcus aureus; MRSA, methicillin-resistant S. aureus.
uous venovenous hemofiltration for renal
failure and aggressive inotropic support.
Multisystem organ failure ensued and life
support measures were discontinued due
to the ineffectiveness of maximum ther-
apeutic support.

International ELSO Database

Summary. In the years 1994 –2005,
319 subjects were identified with a pre-
ECLS or on-ECLS diagnosis of infection
due to S. aureus (Fig. 1). Of these, 134
were excluded because documentation of
S. aureus infection was not made before
initiation of ECLS. Seventeen patients
were excluded due to age of ⬍7 days, and
40 patients were excluded due to the
presence of exclusionary comorbid con-
ditions. Of the remaining 123 subjects, 45
(37%) had pre-ECLS infection with
MRSA. In the first decade of surveillance
(1994 –2003), 25 cases of pre-ECLS infec-
tion due to MRSA were identified; in the
years 2004 –2005 alone, 20 cases were
identified, a substantial increase from
previous years (Fig. 2). The annual over-
all use of ECLS did not change signifi-
cantly during the study period (median
annual pediatric respiratory runs, 207;
range, 190 –235). In total, S. aureus–
related sepsis represented 2% of all pedi-
atric, nonneonatal ECLS cases from 1986
to 2005.
Figure 2. Frequency of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) sepsis
requiring extracorporeal life support. ELSO, Extracorporeal Life Support Organization; MSSA, me-
thicillin-susceptible S. aureus.
Demographics of ELSO Database. The rates in the ELSO database demonstrated
median age of all patients with a pre- decreased survival in the staphylococcal
ECLS diagnosis of infection with S. au- group (57.3% vs. 47%, p ⫽ .027). Sur-
reus was 2.7 yrs (interquartile range, vival rates for MRSA-related ECLS were
0.33–12.8 yrs). The median age of pa- highest in infants and children of ⬍4 yrs
tients with a pre-ECLS diagnosis of MRSA of age and were lowest in adolescents and
was 2.4 yrs (interquartile range, 0.36 – children of ⬎5 yrs of age (Fig. 3). In
14.1 yrs), with disease peaks in infancy survivors, end-organ complications were
and adolescence (Fig. 3). Overall survival common, with renal failure observed
to discharge was 47% in those with pre- most frequently (60%). Neurologic com-
ECLS S. aureus infections. Survival to plications were the least commonly ob-
discharge was equally poor in those pa- served (22%).
tients with MRSA (49%, p ⫽ .770). Com- Diagnoses, Support Type, and Cardio-
paring overall staphylococcal survival pulmonary Status for MRSA-related
rates with pediatric respiratory survival ECLS. Diagnosis data were available for

Pediatr Crit Care Med 2007 Vol. 8, No. 3 233


Figure 3. Biphasic age distribution of extracorporeal life support for pre– extracorporeal life support
methicillin-resistant Staphylococcus aureus (MRSA) infection. ELSO, Extracorporeal Life Support
Organization.
Table 1. Pre-extracorporeal life support ventilatory data of patients with methicillin-resistant Staph-
ylococcus aureus-related extracorporeal life support (International Extracorporeal Life Support Or-
ganization database, 1994 –2005)
Ventilatory rate, breaths/min
Peak inspiratory pressure (cm H2O)
Positive end-expiratory pressure, cm H2O
Airway pressure, cm H2O
Oxygen index
Data are provided as median (interquartile range) or mean ⫾
32 of 45 patients (71%). The most fre-
quent diagnosis provided was staphylo-
coccal septicemia (11 of 32 patients) fol-
lowed by staphylococcal pneumonia (6 of
32 patients). Overall, 16 subjects had the
diagnosis of either pneumonia, pleurisy,
lung abscess, or empyema. The majority
of patients (53%) received venoarterial
ECMO therapy. No difference in mortality
was observed based on the use of venoar-
terial forms of ECMO vs. those that were
solely venovenous. There were no signif-
icant differences in either pre-ECLS ven-
tilatory settings or cardiopulmonary sta-
tus between survivors and nonsurvivors
in those requiring ECLS for MRSA sepsis
(Table 1). Similarly, assessment of venti-
latory settings and cardiopulmonary sta-
tus at 24 hrs of ECLS revealed no signif-
icant differences between survivors and
nonsurvivors, although mean airway
pressure at 24 hrs showed a trend toward
statistical significance (17.9 vs. 13.3 mm
Hg, p ⫽ .06).
DISCUSSION
In this retrospective review of the
Vanderbilt Children’s Hospital ECMO da-
tabase and the International ELSO data-
234
Overall Survivors Nonsurvivors p Value
20 (6–30) 12 (6–30) 24 (10–30)
44.5 ⫾ 16.0 49 ⫾ 17.6 40.9 ⫾ 14.0
10.3 ⫾ 5.5 10.7 ⫾ 5.6 10 ⫾ 5.6
23.9 ⫾ 9.3 24.2 ⫾ 10.4 23.6 ⫾ 8
43.8 ⫾ 31 54.3 ⫾ 33.7 36.1 ⫾ 27.3
SD.
base, we sought to describe the epidemi-
ology of pediatric patients with presumed
MRSA sepsis requiring ECLS. At the out-
set, based on local experience, we hypoth-
esized that the use of ECLS for MRSA
infection had sharply increased and that a
substantial proportion of disease was
found in the adolescent population.
These hypotheses were proven correct—
nearly half of all cases of MRSA-related
ECLS have occurred since 2004, and the
age distribution of cases follows a bipha-
sic distribution, reaching a second peak
during adolescent years. In addition, the
age-related mortality rates, although high-
est in the age group of 5–9 yrs, remain
higher than the mean pediatric respiratory
ECLS mortality throughout adolescence.
We also hypothesized that differences in
ventilatory settings, pre-ECLS blood gas
measurements, or mode of ECMO between
survivors and nonsurvivors of ECLS could
be useful in predicting what group of pa-
tients may have more favorable outcomes;
however, no clinically significant differ-
ences were found between survivors and
nonsurvivors.
S. aureus is a ubiquitous microbe
that, in approximately 30% of humans,
serves a commensal role in its primary
colonization niche, the anterior nares (7).
However, under the appropriate circum-
stances, in the permissive host, S. aureus
readily converts from commensal to
pathogen and produces a wide array of
disease—from uncomplicated furuncles
to staphylococcal sepsis and death. Com-
plicating things further is the rapid emer-
gence of methicillin resistance in com-
munity-based S. aureus strains—strains
capable of effective colonization, sus-
tained transmission, and virulent disease
phenotypes (8).
The three patients described from our
institution were considered to have CA-
MRSA infections based on epidemiologic
risk factors and antibiotic susceptibility
patterns. This is an important distinction
because CA-MRSA strains are genotypi-
cally and phenotypically distinct from
their healthcare-associated MRSA prede-
cessors. Naimi et al. (9), in comparing
CA-MRSA with healthcare-associated
.58 MRSA infections, showed that the median
.14 age in CA-MRSA is significantly lower
.73
.84 than with healthcare-associated MRSA
.1 infection (23 vs. 68 yrs, p ⬍ .001) and
that the vast majority (75%) of CA-MRSA
infections involve the skin/soft tissue.
Similarly, Fridkin et al. (10), from data
collected in three specific communities
(Baltimore, Atlanta, and 12 hospitals in
Minnesota), reported that CA-MRSA par-
ticularly affects young children with pre-
dominantly skin and soft-tissue infec-
tions (77%). This, then, raises a
fundamental question: what series of
events or risk factors lead to the develop-
ment of cardiopulmonary failure in
young, otherwise healthy individuals in a
situation in which the predominant phe-
notype is a relatively uncomplicated skin
and soft-tissue infection?
Gonzalez et al. (11), using the experi-
ence of Texas Children’s Hospital, make
the case for microbial factors, such as the
Panton–Valentine leukocidin and colla-
gen adhesin, which may be associated
with more severe presentations such as
necrotizing pneumonia. In their series of
nearly 92 patients with invasive CA-MRSA
disease, 51% had evidence of pulmonary
disease, with a disproportionate number
of these (when compared with methicil-
lin-susceptible S. aureus) encoding genes
for Panton–Valentine leukocidin. This is
consistent with their previous report of
severe staphylococcal sepsis in adoles-
cents in which all of the clinical isolates
from the cohort carried genes for Pan-
ton–Valentine leukocidin (1). However,
Pediatr Crit Care Med 2007 Vol. 8, No. 3
microbial factors are clearly only one side
of the story, as the epidemiology of or-
ganisms leading to skin and soft-tissue
infections are typically the same clones
that lead to overwhelming sepsis and the
need for intensive care support.
There are limitations when using this
retrospective study design. First, ELSO is
a passive surveillance system. As a result,
it is possible that some patients were ei-
ther incorrectly entered into the database
or missed entirely due to a lack of report-
ing. It is also possible that at the time of
ECLS initiation, susceptibility data were
unknown and organisms were coded as S.
aureus rather than more specifically as
MRSA. Second, detailed information re-
garding all facets of patient care are un-
available in the current surveillance sys-
tem. Therefore, co-existing morbidities,
adjunctive therapies, and other poten-
tially confounding factors cannot be con-
sidered in the analysis. Third, epidemio-
logic data about pathogens isolated from
ECLS patients are not available, nor are
the isolates archived for further analysis.
Thus, differences that might exist at the
microorganism level (CA-MRSA vs. hos-
pital-associated MRSA, presence of spe-
cific toxins) cannot be ascertained.
Fourth, there are only a small number of
pediatric patients who have required
ECLS for MRSA sepsis, making it possible
to conclude mistakenly that there are no
significant differences between survivors
and nonsurvivors of ECLS when, in fact,
differences exist (type II error). Finally,
the database does not provide sufficient
Pediatr Crit Care Med 2007 Vol. 8, No. 3
information for us to make larger epide-
miologic observation, such as the propor-
tion of all MRSA cases that require ECLS
and whether this varies significantly by
age. Future prospective studies of pediat-
ric MRSA sepsis are needed to help elim-
inate some of these limitations.
CONCLUSIONS
The use of ECLS for pediatric MRSA
infections has increased dramatically in
the last 2 yrs and is associated with sig-
nificantly higher mortality rates when
compared with overall pediatric respira-
tory ECLS mortality rates. Based on car-
diopulmonary assessments pre-ECLS and
at 24 hrs post-ECLS, it is unclear which
patients are at higher risk of mortality;
however, pediatric patients of ⬎5 yrs of age
seem to have the lowest survival rates.
ACKNOWLEDGMENTS
We acknowledge the work of Peter Ry-
cus and the ECMO Registry of the Extra-
corporeal Life Support Organization
(ELSO), Ann Arbor, MI, and thank Dr.
Kathryn Edwards for manuscript review.
REFERENCES
1. Gonzalez BE, Martinez-Aguilar G, Hulten
KG, et al: Severe Staphylococcal sepsis in
adolescents in the era of community-
acquired methicillin-resistant Staphylococ-
cus aureus. Pediatrics 2005; 115:642– 648
2. Kaplan SL, Hulten KG, Gonzalez BE, et al:
Three-year surveillance of community-
acquired Staphylococcus aureus infections
in children. Clin Infect Dis 2005; 40:
1785–1791
3. Kravitz GR, Dries DJ, Peterson ML, et al:
Purpura fulminans due to Staphylococcus
aureus. Clin Infect Dis 2005; 40:941–950
4. Lina G, Piemont Y, Godail-Gamot F, et al:
Involvement of Panton-Valentine leukocidin-
producing Staphylococcus aureus in pri-
mary skin infections and pneumonia. Clin
Infect Dis 1999; 29:1128 –1132
5. Adem PV, Montgomery CP, Husain AN, et al:
Staphylococcus aureus sepsis and the Water-
house-Friderichsen syndrome in children.
N Engl J Med 2005; 353:1245–1251
6. Halasa NB, Barr FE, Johnson JE, et al: Fatal
pulmonary hypertension associated with per-
tussis in infants: Does extracorporeal mem-
brane oxygenation have a role? Pediatrics
2003; 112(6 Pt 1):1274 –1278
7. Casewell MW, Hill RL: The carrier state: Me-
thicillin-resistant Staphylococcus aureus.
J Antimicrob Chemother 1986; 18(Suppl A):
1–12
8. Pan ES, Diep BA, Charlebois ED, et al: Pop-
ulation dynamics of nasal strains of methi-
cillin-resistant Staphylococcus aureus–and
their relation to community-associated dis-
ease activity. J Infect Dis 2005; 192:811– 818
9. Naimi TS, LeDell KH, Como-Sabetti K, et al:
Comparison of community- and health care-
associated methicillin-resistant Staphylococ-
cus aureus infection. JAMA 2003; 290:
2976 –2984
10. Fridkin SK, Hageman JC, Morrison M, et al:
Methicillin-resistant Staphylococcus aureus
disease in three communities. N Engl J Med
2005; 352:1436 –1444
11. Gonzalez BE, Hulten KG, Dishop MK, et al:
Pulmonary manifestations in children with
invasive community-acquired Staphylococ-
cus aureus infection. Clin Infect Dis 2005;
41:583–590
235
Continuing Medical Education Article

Implementation of a medical emergency team in a large pediatric

teaching hospital prevents respiratory and cardiopulmonary arrests
outside the intensive care unit
Richard J. Brilli, MD, FCCM, FAAP; Rosemary Gibson, RN, MSN; Joseph W. Luria, MD, FAAP;
T. Arthur Wheeler, MS, MBA; Julie Shaw, MSN, MBA, RN; Matt Linam, MD; John Kheir, MD;
Patricia McLain, RN; Tammy Lingsch, RN, BSN; Amy Hall-Haering, RN, MSN; Mary McBride, MD

LEARNING OBJECTIVES
On completion of this article, the reader should be able to:
1. Define the potential barriers to the implementation of a medical emergency team (MET) in pediatric teaching hospitals.
2. Describe the criteria that are appropriate for the activation of MET in a pediatric teaching hospital.
3. Identify the situations in which MET can and cannot be effective in preventing codes.
All authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining
to this educational activity.
Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity.
Visit the Pediatric Critical Care Medicine Web site (www.pccmjournal.org) for information on obtaining continuing medical
education credit.

Objective: We implemented a medical emergency team (MET)
in our free-standing children’s hospital. The specific aim was to
reduce the rate of codes (respiratory and cardiopulmonary ar-
rests) outside the intensive care units by 50% for >6 months
following MET implementation.
Design: Retrospective chart review and program implementation.
Setting: A children’s hospital.
Patients: None.
Interventions: The records of patients who required cardiore-
spiratory resuscitation outside the critical care areas were re-
viewed before MET implementation to determine activation crite-
ria for the MET. Codes were prospectively defined as respiratory
arrests or cardiopulmonary arrests. MET-preventable codes were
prospectively defined. The incidence of codes before and after
MET implementation was recorded.
Measurements and Main Results: Twenty-five codes occurred
during the pre-MET baseline compared with six following MET im-
plementation. The code rate (respiratory arrests ⴙ cardiopulmonary
arrests) post-MET was 0.11 per 1,000 patient days compared with
baseline of 0.27 (risk ratio, 0.42; 95% confidence interval, 0 – 0.89;
p ⴝ .03). The code rate per 1,000 admissions decreased from 1.54
(baseline) to 0.62 (post-MET) (risk ratio, 0.41; 95% confidence inter-
val, 0 – 0.86; p ⴝ .02). For MET-preventable codes, the code rate
post-MET was 0.04 per 1,000 patient days compared with a baseline
of 0.14 (risk ratio, 0.27; 95% confidence interval, 0 – 0.94; p ⴝ .04).
There was no difference in the incidence of cardiopulmonary arrests
before and after MET. For codes outside the intensive care unit, the
pre-MET mortality rate was 0.12 per 1,000 days compared with 0.06
post-MET (risk ratio, 0.48; 95% confidence interval, 0 –1.4, p ⴝ .13).
The overall mortality rate for outside the intensive care unit codes
was 42% (15 of 36 patients).
Conclusions: Implementation of a MET is associated with a
reduction in the risk of respiratory and cardiopulmonary arrest
outside of critical care areas in a large tertiary children’s hospital.
(Pediatr Crit Care Med 2007; 8:236 –246)
KEY WORDS: cardiopulmonary arrest; respiratory arrest; pediat-
rics; children; rapid response system; medical emergency team

*See also p. 297.
Associate Chief of Staff, Medical Director, Pediatric
Intensive Care Unit, Professor, Pediatrics, Division of
Critical Care Medicine, Cincinnati College of Medicine,
Cincinnati, OH (RJB); Clinical Nurse Specialist (RG),
Associate Professor of Clinical Pediatrics (JWL), Senior
Decision Support Analyst (TAW), Senior Clinical Direc-
tor (JS), Pediatric Infectious Disease Fellow (ML), Reg-
istered Nurse II (PM), Care Manager, Heart Center (TL),
Clinical Director Manager of Patient Services (AH),
Cincinnati Childrens’ Hospital Medical Center, Cincin-
nati, OH; Clinical Fellow in Critical Care Medicine,
Department of Anesthesia, Perioperative and Pain
Medicine, Childrens’ Hospital of Boston, Boston, MA
(JK); Pediatric Cardiology Fellow, Washington Univer-
sity, St. Louis, MO (MM).
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
rich.brilli@cchmc.org
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262947.72442.EA

236 Pediatr Crit Care Med 2007 Vol. 8, No. 3

I n response to the United States
Congress’ mandate that U.S. hos-
pitals develop a culture of safety,
the Agency for Healthcare Re-
search and Quality developed national pa-
tient safety indicators (1). Failure to res-
cue, defined as a death resulting from a
complication rather than the primary di-
agnosis, is one of these indicators (2).
In-hospital cardiopulmonary arrests that
occur outside the intensive care unit
(ICU) represent failure-to-rescue events.
The Institute for Healthcare Improve-
ment’s Saving 100,000 Lives Campaign
has advocated the deployment of in-
hospital medical emergency teams
(METs) as a means to rescue patients and
reduce hospital mortality rates (3). Re-
cent reports in adult hospitals have
shown that METs decrease the number of
cardiopulmonary arrests that occur out-
side the ICU and can decrease postoper-
ative mortality, mean duration of hospital
length of stay, and overall hospital mor-
tality (4 –9).
Recently, more information has be-
come available about in-hospital cardio-
pulmonary arrests in children. The inci-
dence of in-hospital cardiopulmonary
arrests in pediatric patients (including
those occurring in the ICU) varies be-
tween 0.7% and 3% of all hospital admis-
sions (10, 11). The survival-to-discharge
rate for such patients is poor and varies
between 15% and 27% (11, 12). Cardio-
pulmonary arrests that occur outside the
critical care units in pediatric hospitals
are uncommon but also have a poor sur-
vival rate. Suominen et al. (10) reported
12 cardiopulmonary arrests outside the
ICU from among 32,400 hospital admis-
sions (0.03%). Outside the ICU, cardio-
pulmonary arrests accounted for 10.1%
of in-hospital cardiopulmonary arrests,
and the discharge survival rate for these
patients was 33%. Others report that
8.5% to 14% of all in-hospital cardiopul-
monary arrests in children occur outside
the ICU, and the mortality rate for these
patients is 50% to 67% (10 –13). This
high mortality rate in children makes
prevention of in-hospital, out-of-ICU
cardiopulmonary arrest particularly
important.
Currently there are limited data avail-
able in pediatrics regarding METs and
their impact on in-hospital, out-of-ICU
cardiopulmonary arrests. In the only pe-
diatric report to date, Tibballs et al. (14)
described a trend toward reduction in
risk for out-of-ICU cardiopulmonary ar-
rest after MET implementation, al-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
though the risk reduction did not reach
statistical significance. In response to
the Institute for Healthcare Improve-
ment imperative and the desire to elim-
inate failure-to-rescue events, we imple-
mented a MET. The specific aim of the
initiative, based on published adult hos-
pital experience, was to reduce the rate of
codes (respiratory arrest and cardiopul-
monary arrest) outside the ICUs by 50%
for ⬎6 months following MET implemen-
tation. This report describes the imple-
mentation strategies and results of this
performance improvement initiative.
METHODS
This performance improvement project re-
ceived expedited review and approval by the
hospital Institutional Review Board. Informed
consent was waived.
Pre-Arrest Variable Analysis. Medical
records of the 44 non-ICU patients hospital-
ized between 2001 and 2004 who suffered ap-
nea (respiratory arrest) or cardiopulmonary
arrest were retrospectively examined. The crit-
ical care unit areas of the hospital were the
pediatric ICU (PICU), cardiac ICU, neonatal
ICU, operating room, emergency department,
and cardiac catheterization laboratory. This
performance improvement initiative was in-
tended to reduce or eliminate all out-of-ICU
respiratory or cardiopulmonary arrests. To
succinctly name these events, we used the
term “code,” which was defined as a respira-
tory arrest alone (apnea) or a cardiopulmonary
arrest (apnea ⫹ asystole or apnea ⫹ nonper-
fusing heart rhythm) wherein the interven-
tions provided by the hospital code alert team
included airway resuscitation (bag-valve mask
ventilation and/or tracheal intubation) and/or
cardiac resuscitation (chest compressions
and/or cardioversion/defibrillation). Demo-
graphic and clinical data from the 4 hrs before
the code were recorded. This data consisted of
70 precode variables including vital signs; se-
lect lab values; documented physical exam
findings by the bedside nurse, respiratory
therapist, or physician; and clinical narrative
descriptions of the patient.
After initial chart review, the ten most fre-
quent variables that exceeded critical thresh-
olds were subjected to analysis to determine
which variables or combination of variables
were most likely to predict a code. The result
of this analysis was candidate sets of MET
trigger criteria, consisting of “either/or” and
“and” combinations. Each set of trigger crite-
ria was ranked according to the percentage of
the 44 cases with which it was associated. A
90% confidence interval was calculated to in-
dicate the percentage of future codes that the
trigger set could be associated with. The final
set of activation (trigger) criteria was chosen
based on the clinical judgment of experts, bal-
ancing each trigger set’s calculated rank
against the ease of measure and detection,
anticipated false alarm rate, and practical con-
siderations regarding their effective use by
hospital staff.
Development and Implementation of the
MET. A multidisciplinary group was convened
that consisted of bedside nurses, respiratory
therapists, physicians (residents, fellows, fac-
ulty), and nursing managers from the general
care floors and PICU. The group was charged
with a) identifying clinical triggers to activate
the MET; b) identifying MET membership; c)
implementing the MET throughout the hospi-
tal; and d) establishing outcome measures,
including team performance. The MET was
introduced on pilot units over a 4-month time
period using small tests of change, with the
“model for improvement” serving as the orga-
nizing framework for the group (15).
The MET was defined as experienced clini-
cians dispatched to evaluate and triage pa-
tients who were perceived as having a declin-
ing clinical status. A prospective decision to
create a two-tiered hospital system response to
clinical patient deterioration was made. The
first-tier response would continue as the code
alert team, which responds immediately to all
in-hospital respiratory or cardiopulmonary ar-
rests and provides immediate resuscitation,
stabilization, and triage to the appropriate
care unit. A new second-tier response, the
MET, would be an added in-hospital response
to assess clinically deteriorating patients. This
team would arrive within 15 mins after acti-
vation. MET functions included assessment,
stabilization if necessary, and triage of general
care floor patients to the most appropriate
unit in the hospital. MET members included a
PICU fellow, PICU nurse, senior pediatric res-
ident, respiratory therapist, and the manager
of patient services (in-hospital nursing super-
visor in charge of general floor patient place-
ment). The MET would be joined at the bed-
side by the general care unit staff including
but not limited to the nurse and physicians
caring for the patient and the family. The MET
was activated via pagers after calling a single
phone number. Education about the new team
took place over a 4-month implementation
and education period and included presenta-
tions at nursing shift changes, nursing lead-
ership and shared governance meetings, phy-
sician divisional and faculty meetings, and
resident conferences. Education was supple-
mented with posters, phone stickers, and re-
source handouts for all involved units. The
posters and handouts included the team pur-
pose, goals, function, and team membership;
information about when to call (triggers);
number to call; and instructions about how to
give feedback. A simple survey tool, developed
to assess team performance and staff satisfac-
tion, was distributed to the 215 staff involved
in the 27 MET consults (Appendix 1). The
surveys were available on the hospital intra-
net. All MET activations were official medical
consults, and the completed consult form
served as both medical record documentation
237
of MET activity and data collection tool (Ap-
pendix 2). Communication from the general
care unit, emergency department, and operat-
ing room physician staff directly to the PICU
physician staff to discuss patients requiring
urgent ICU admission was not prohibited or
eliminated by the MET system. These commu-
nications were not categorized as MET con-
sults.
Post-MET Outcome Data Analysis. Code
rates were analyzed during three different
time periods. Rates were defined using two
different denominators (1,000 hospital non-
ICU patient days and 1,000 non-ICU hospital
admissions). The pre-MET period (baseline)
was 15 months, from October 2003 through
January 2005, and included codes before any
planning or development of the MET (Fig. 1).
The implementation and education period
(implementation) was from February through
May 2005 and included codes that occurred
during the MET-related tests of change. The
post-MET period was from June 2005 through
January 2006 and reflects data after full hos-
pital implementation of the MET. The imple-
mentation plus post-MET periods total 12
months.
At study outset and before retrospective
chart review or data analysis, the MET plan-
ning group recognized that some in-hospital
codes might not be prevented by MET imple-
Figure 1. All codes outside the intensive care unit (ICU) before and after medical emergency team
(MET) implementation. *Data presented are one-tailed; two tailed analysis is presented under the
Results section. CI, confidence interval; O-D, October through December; J–M, January through
March; A–J, April through June; J–S, July through September; MRT, medical response team.
238
mentation. Clinical conditions that occurred
suddenly or without clinical warning or events
that happened in an environment not accessi-
ble to a MET, such as during the administra-
tion of general anesthesia outside the operat-
ing room, were clinical events that the
planning group prospectively identified as
“codes not preventable by MET.” These in-
cluded a) pulmonary embolus; b) new sei-
zures; c) sudden plugged or occluded trache-
otomy tube; d) code by an adult visitor; e) code
occurring during general anesthesia adminis-
tered outside the operating room (i.e., radiol-
ogy suite); f) code resulting from an acute
drug overdose; and g) code in our ambulatory
clinics. Furthermore, it was recognized that
some codes might not be prevented by a MET
but might be prevented by other hospital-wide
system interventions, as described by Braith-
waite et al (16). All code event records were
reviewed. Each event was examined using the
clinical conditions noted previously or, for the
presence of unrecognized MET triggers, other
vital sign changes that might have alerted the
clinician to the code event that occurred. Each
code event was categorized as MET prevent-
able, MET not preventable, or MET not pre-
ventable but preventable by other means.
Final patient disposition (death or hospital
discharge) was recorded for all outside the ICU
codes for each study time period. For all MET
consults, triage disposition (remain on gen-
eral care unit or transfer to ICU) and final
disposition (death or discharge) were re-
corded. Vital signs recorded on the MET con-
sult forms were used to analyze the physio-
logic status of the patient at the time of MET
consult. Mortality rates were adjusted to 1,000
non-ICU patient days and 1,000 non-ICU ad-
missions.
Statistical Analysis. Comparison of code
rates and mortality for the baseline vs. the
MET implementation and post-MET time pe-
riods was done with an analysis of relative risk
using SAS 9.1.3 (Proc FREQ, TABLES State-
ment, RELRISK Option). Statistical p values
and associated 95% confidence intervals (CIs)
are reported as both one-sided and two-sided.
We believe that reporting one-sided tests is
justified by the demonstrated uniform success
in cardiac arrest rate reduction by METs in the
adult medical literature. That justification is
augmented by clinical consensus that imple-
mentation of a MET could not realistically
make code rates worse. Because traditional
statistical methods suggest the use of two-
tailed analysis of outcomes associated with a
clinical intervention, we present our results
using both methods. Statistical significance
was defined as p ⬍ .05.
RESULTS
Table 1 shows the analysis of prearrest
data from codes before MET implemen-
tation. After examination of 1,024 combi-
nations of prearrest variables from prior
codes, no set of variables was sensitive or
specific enough for use as MET activation
triggers. The planning group combined
expert consensus and the retrospective
chart analysis to determine the MET ac-
tivation criteria (Table 2).
Outside the ICU, code rates are de-
picted in Figure 1. The post-MET code
rate was significantly lower compared
with baseline (one-tailed analysis). Using
two-tailed analysis to compare pre- and
post-MET code rates per 1,000 patient
days revealed a risk ratio of 0.42 (95% CI
0.173–1.03; p ⫽ .057). The post-MET
code rate per 1,000 non-ICU admissions
was 0.62 compared with baseline of 1.54:
Risk ratio (two-tailed) was 0.41 (95% CI
0.167– 0.99; p ⫽ .047).
Table 3 describes the clinical grouping
for all 19 code events that were not pre-
ventable by MET. One code event, occur-
ring during the baseline period (an acute
drug overdose), was not preventable by
MET but was deemed preventable by
other hospital system interventions.
MET-preventable code rates are de-
picted in Figure 2. For MET-preventable
codes, the post-MET rate was signifi-
cantly lower compared with baseline
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Table 1. Identifying potential medical emergency team trigger variables from retrospective chart Code rates in the ICUs and mean hos-
review: Six representative “either/or” criterion measures pital length of stay (LOS) did not change
during the periods of this study. During
90% Confidence
the pre-MET period, the ICU code rate
Interval, %a
was 5.1 codes per 1,000 ICU days (61
Minimum Maximum Clinical Variable codes per 12,098 days) compared with 6.6
codes per 1,000 ICU days (63 codes per
57.2 81.6 Increase respiratory rate and work of breathing or low oxygen 9,526 days) during the post-MET period
saturations (p ⫽ .13). Mean hospital LOS was 5.8
54.8 79.6 Low oxygen saturations or neurological agitation days during the baseline period and 5.9
52.5 77.7 Increased work of breathing or decreased consciousness
47.9 73.7 Increased work of breathing or neurological agitation days during the post-MET period (p ⫽
47.9 73.7 Low oxygen saturations or increased respiratory rate not significant).
47.9 73.7 Increased oxygen requirement or decreased consciousness The MET was activated 27 times dur-
a
ing the 12 months of the study. The num-
These results indicate that a two-measure set chosen from this list identifies code situations with ber of MET consults was nearly equal
the indicated success rate, when the occurrence of either one of the measures in the set is used as the
across all general care units. The most
criterion for identifying a potential code.
frequent trigger to activate the MET was
staff concern about the patient (Fig. 3).
The most frequent physiologic distur-
(one-tailed analysis). Using two-tailed one-tailed analysis (Table 4). Similarly,
bance cited for activating the MET was
analysis to compare pre- and post-MET the rates were not different using two-
increased work of breathing. Vital signs
preventable code rates per 1,000 patient tailed analysis (data not shown).
for all patients at the time of MET consult
days revealed a risk ratio of 0.27 (95% CI During the baseline period, there were
were recorded on the MET consult form.
0.061–1.20; p ⫽ .085). Post-MET prevent- 25 codes (respiratory arrest plus cardio-
For patients ⱖ10 yrs of age, the median
able code rates per 1,000 non-ICU admis- pulmonary arrest): nine cardiopulmonary
heart rate was 123 beats/min (25%, 109
sions were 0.21 compared with baseline arrests (seven died) and 16 respiratory
beats/min; 75%, 132 beats/min), median
of 0.8: Risk ratio (two-tailed) was 0.26 arrests (four died). Post-MET there were
respiratory rate was 32 breaths/min
(95% CI 0.059 –1.15; p ⫽ .076). six codes: two cardiopulmonary arrests
(25%, 18 breaths/min, 75%, 56 breaths/
Cardiopulmonary arrest rates, which (both died) and four respiratory arrests
min), and median systolic blood pressure
exclude patients with only a respiratory (one died). During the implementation
was 111 torr (25%, 106 torr; 75%, 120
arrest (per 1,000 patient days and per period there were five codes: four cardio-
torr). For patients ⬎2 and ⬍10 yrs of age,
1,000 admissions), were reduced by pulmonary arrests (one died) and one re-
the median heart rate was 150 beats/min
⬎60% following MET implementation spiratory arrest (none died). The mortal-
(25%, 130 beats/min; 75%, 180 beats/
compared with baseline; however, these ity rate for all codes that occurred outside
min), median respiratory rate was 29
rates were not statistically different using the ICU was 42% (15 of 36 patients). The
breaths/min (25%, 25 breaths/min; 75%,
mortality rates per 1,000 patient days and
35 breaths/min), and median systolic
per 1,000 non-ICU admissions were not
Table 2. Medical emergency team activation cri- blood pressure was 88 torr (25%, 83 torr;
different between the baseline period and
teria 75%, 111 torr). For patients ⱕ2 yrs of
post-MET period (Table 5).
age, the median heart rate was 156 beats/
During the entire study period, there
● Increased work of breathing and any of the min (25%, 140 beats/min; 75%, 167
were 15 cardiopulmonary arrests outside
following beats/min), median respiratory rate was
y Worsening retractions the ICU. The mortality rate was 67% (10 of
45 breaths/min (25%, 36 breaths/min;
y Saturations ⬍90% despite supplemental 15 patients). For patients with respiratory
75%, 52 breaths/min), and median sys-
oxygen arrest alone, the mortality rate was 24%
y Cyanosis tolic blood pressure was 97 torr (25%, 88
(5 of 21 patients). Table 4 outlines mortality
● Agitation or decreased level of consciousness torr; 75%, 107 torr). The hospital LOS for
● Staff concern or worry about the patient
data for only cardiopulmonary arrest pa-
patients before MET consult ranged from
● Parental concern about the child tients—mortality rates were not different
4 to 26 days, and all patients had been
before and after MET implementation.
appropriately triaged to the general care
unit at the time of original hospital ad-
Table 3. Number of code events not preventable by medical emergency team (MET; n ⫽ 19) mission. After MET consult, 13 patients
remained on the general care floor and 13
Baseline I & E Period Post-MET were transferred to the ICU. One patient
developed increased respiratory depres-
Seizures 7⫺(A) 2⫺(A) 2⫺(A)
Pulmonary embolus 0 1⫺(A) 0 sion several hours after the MET consult
Plugged tracheotomy 2⫺(A) 0 0 decision was to keep the child on the
Code by adult visitor 0 0 0 general care unit. The child was trans-
Code during general anesthesia outside 2⫺(A) 0 2⫺(A) ferred to the PICU without further inci-
OR (i.e., radiology) dent. All but two patients for whom a
Code in ambulatory clinic 0 0 0
Drug overdose 1⫺(B) 0 0 MET consult was obtained were dis-
charged home. One patient with urosep-
I & E, implementation and education; A, MET not preventable; OR, operating room; B, MET not sis was transferred to the PICU after MET
preventable but preventable by other means. consult and died 3 wks later in the PICU.

Pediatr Crit Care Med 2007 Vol. 8, No. 3 239

 diatric report to describe the impact of a
MET on the incidence of out-of-ICU re-
spiratory arrests without cardiac arrest as
well as cardiopulmonary arrests. Prior
adult and pediatric studies have focused
on cardiac arrest rates before and after
MET implementation. The implementa-
tion of a MET in our free-standing ter-
tiary children’s hospital significantly de-
creased the incidence of all codes
(respiratory arrests plus cardiopulmonary
arrests) that occurred outside the ICU
(Figs. 1 and 2) relative to pre-MET risk
(relative risk ratio). The incidence of car-
diopulmonary arrest alone decreased by
60% after MET implementation com-
pared with baseline; however, these dif-
ferences did not reach statistical signifi-
cance (Table 4). The specific aim of this
project, to decrease the rate of all codes
outside the ICU by 50% for ⬎6 months
following MET implementation, was
achieved. For all non-ICU codes, post-
MET mortality rates decreased compared
with baseline (Table 5), although these
differences did not reach statistical sig-
nificance.
Few data are available regarding MET
implementation in children’s hospitals.
In the only pediatric study we identified,
Figure 2. Medical emergency team (MET) preventable codes before and after MET implementation.
*Data presented are one-tailed; two tailed analysis is presented under the Results section. ICU,
Tibballs et al. (14) described the conver-
intensive care unit; CI, confidence interval; O–D, October through December; J–M, January through sion of a code blue team to a medical
March; A–J, April through June; J–S, July through September; MRT, medical response team. emergency team in a tertiary pediatric
hospital in Australia. They demonstrated
Table 4. Comparative data for cardiopulmonary arrests occurring outside the intensive care unit
a decrease in the rate of out-of-ICU car-
(ICU)a: Before and after the medical emergency team (MET) diac arrests from 0.19 of 1,000 admis-
sions before MET implementation to 0.11
Risk Ratio (95% CI) of 1,000 admissions after MET implemen-
Baseline Post-MET One-Tailed Analysis tation (risk ratio 1.71; 95% CI 0.59 –5.01;
p ⫽ .32). They also demonstrated a trend
Patient days 92,188 52,494 toward a reduction in the risk of death
Non-ICU hospital admits 16,255 8,419
No. of non-ICU cardiopulmonary arrestsa 9 2 from 0.12 of 1,000 admissions to 0.06 of
Rate per 1,000 hospital days 0.10 0.04 0.39 (0–1.4); p ⫽ .11 1,000 admissions (p ⫽ NS). Tibballs et al.
Rate per 1,000 admissions 0.56 0.24 0.43 (0–1.6); p ⫽ .14 concluded that this lack of statistical
Deaths 7 2 mortality difference was in part due to
Mortality per 1,000 hospital days 0.08 0.04 0.50 (0–1.9); p ⫽ .19
the low incidence of in-hospital cardiac
Mortality per 1,000 non-ICU admits 0.43 0.24 0.55 (0–2.1); p ⫽ .23
arrest in the pediatric population. Like
CI, confidence interval. Tibballs et al., we found a decrease in
a
Cardiopulmonary arrest refers to (apnea ⫹ asystole) or (apnea ⫹ nonperfusing heart rhythm). cardiopulmonary arrest rates before and
after MET implementation (Table
4 — 60% decrease); however, these differ-
The other patient transferred to the PICU cent of staff respondents thought the ences did not reach statistical signifi-
for hemodynamic instability (probable MET consult was helpful (Appendix 1, cance. In contrast to Tibballs et al., be-
sepsis) died 5 months later in the PICU. question 9). cause our study examined out-of-ICU
Eighty-eight of 215 performance as- respiratory arrests and cardiopulmonary
sessment surveys were completed (re- DISCUSSION arrests (codes), we found a significant
sponse rate 41%). More than 85% of gen- decrease in the incidence of all out-of-
eral care unit staff respondents reported To our knowledge, this is the first re- ICU codes after MET implementation
satisfaction with MET consult team inter- port describing the implementation of a (Figs. 1 and 2). Because children often
action—they felt included in the deci- pediatric MET in the United States and have respiratory arrest without cardiac
sion-making process and their concerns only the second report in pediatric pa- arrest and these isolated respiratory
were respected (Fig. 4). Eighty-one per- tients. Furthermore, this is the first pe- events can be a source of morbidity and

240 Pediatr Crit Care Med 2007 Vol. 8, No. 3

Table 5. Comparative mortality data for non-intensive care unit (ICU) codesa: Before and after the mortality, our study sought to look at
medical emergency team (MET) how a MET would affect both respiratory
and cardiopulmonary arrests that occur
Baseline Post-MET Risk Ratio (95% CI)
outside the ICU. Examining all codes, in-
Patient days 92,188 52,494 cluding respiratory arrests without car-
Non-ICU hospital admits 16,255 8,419 diac arrest, is important in children be-
No. of non-ICU codesa 25 6 cause in our study and in those of others,
Deaths 11 3 these patients can have significant mor-
Mortality per 1,000 hospital patient days 0.12 0.06 0.48 (0–1.4); p ⫽ .13
Mortality per 1,000 non-ICU admits 0.67 0.36 0.53 (0–1.5); p ⫽ .16
tality—24% (5 of 21) (13). To examine
the possibility that our out-of-ICU code
CI, confidence interval. rates decreased because either hospital
a
Code means respiratory arrest alone or cardiopulmonary arrest. LOS increased (larger denominator) or
ICU codes increased (patients arrested in
the ICU instead of on the general care
unit), we compared these variables dur-
ing baseline and post-MET periods and
found no differences. Like Tibballs et al.,
our study showed that mortality rates per
1,000 non-ICU admissions for patients
who had only cardiopulmonary arrest
outside the ICU were lower—pre-MET
(0.43) compared with post-MET (0.24);
however, these values were not statisti-
cally different (risk ratio 0.55; p ⫽ .23).
Our improvement initiative was not pow-
ered to determine a mortality difference;
however, one reason for the lack of sta-
tistical mortality difference may be that
21 of the 36 code patients had only a
respiratory arrest. Patients with respira-
tory arrest but without cardiac arrest are
more likely to survive to hospital dis-
charge, thus potentially diminishing our
ability to discern a difference in mortality
rates before and after MET implementa-
tion (13, 17). In our patients, the mortal-
Figure 3. Reasons for medical emergency team activation. An individual patient could have ity rate for patients with respiratory ar-
multiple reasons. BP, blood pressure; RR, respiratory rate; MD, physician; RT, respiratory rest alone was 24% (5 of 21) compared
therapist; RN, nurse; LOC, level of consciousness; Sats, saturations; WOB, work of breathing;
with 67% (10 of 15) for cardiopulmonary
MRT, medical response team.
arrest patients. We speculate that given
the aforementioned mortality rates, even
the elimination of one code outside the
ICU has potential impact to save lives,
although that may not be evident when
examining aggregate hospital mortality
rates.
Our findings and those of Tibballs et
al. (14), which suggest a reduction in
cardiopulmonary arrest rates alone, are
similar to previous reports in adult hos-
pitals. Goldhill et al. (18) reported a 26%
reduction in out-of-ICU cardiac arrests
over a 6-month period after the imple-
mentation of a “patient at-risk team.”
Bellomo et al. (4) reported a 66% relative
risk reduction in cardiac arrests outside
the ICU among medical patients, a 63%
relative risk reduction in cardiac arrests
among surgical patients, and an overall
relative risk reduction in cardiac arrests
Figure 4. Inpatient care unit staff after medical emergency team survey results. MRT, medical response of 65% following implementation of a
team. MET. These adult reports are consistent

Pediatr Crit Care Med 2007 Vol. 8, No. 3 241

with the 60% reduction in cardiac arrests
that we observed after MET implementa-
tion. More recently, DeVita et al. (8), in a
retrospective analysis of 3,269 MET acti-
vations over 6.8 yrs, reported a 17% re-
duction in out-of-ICU cardiac arrest after
implementation of a MET, but the pro-
portion of fatal cardiac arrests was not
different when pre- and post-MET time
periods were compared. In contrast, in-
vestigators from the Medical Emergency
Response Improvement Team (MERIT)
study in Australia randomized 23 hospi-
tals to either introduce the MET system
or continue functioning in their usual
manner (19). These investigators did not
find a difference in out-of-ICU cardiac
arrest rates or hospital mortality between
control hospitals and MET hospitals.
Most recently, Winters et al. (20) summa-
rized MET adult outcome data and ques-
tioned the rush to implement METs.
They suggested that more study is needed
and that other interventions to prevent
out-of-ICU cardiac arrests might be just
as effective as the MET.
Reliable and consistent use of a MET,
which includes prompt recognition when
MET trigger criteria occur, may not be
sufficient to completely eliminate codes
(respiratory arrests or cardiopulmonary
arrests) outside the ICU. Recognizable
changes in clinical status of patients, be-
fore code events, are important determi-
nants of the efficacy of a MET. These
signs and symptoms of clinical deteriora-
tion must occur slowly enough (minutes
to hours) for clinical staff to recognize
them and call for advice or help. Patients
who suffer abrupt deterioration, as a re-
sult of sudden events that are not pre-
ceded by clinically recognizable signs or
symptoms, are not likely to benefit from a
MET. Examples of such events include
but are not limited to new-onset seizures
and sudden dysrhythmias. Similarly, code
events that occur in areas of the hospital
not easily accessible to MET (e.g., general
anesthesia delivered outside the operat-
ing room such as in radiology) will likely
not be prevented by a MET. Among all 36
codes, 19 were deemed not preventable
by MET (Table 3). Four such events oc-
curred during the post-MET period. One
code occurred as a result of an acute drug
overdose, and although not preventable
by MET, this event likely was potentially
preventable by other hospital safety sys-
tems. In our study (Fig. 2), two MET-
preventable codes occurred during the
post-MET period. Retrospective review of
these cases indicated that both patients
242
had vital sign changes before cardiopul-
monary arrest, which if recognized by
clinical staff should have activated the
MET. These cases represent failures of
the MET system and opportunities to ex-
amine more effective MET implementa-
tion strategies. Tibballs et al. (14) de-
scribed four cases of sudden cardiac
arrest wherein the patients did not meet
MET trigger criteria because the clinical
events were sudden. These cases were
sudden dysrhythmia, vagal stimulation
during nasogastric tube placement, and
intracerebral hemorrhage. These exam-
ples suggest that although a MET can
reduce codes outside the ICU, challenges
remain to refine pediatric-specific MET
activation criteria and, more important,
to implement hospital systems to help
clinical staff reliably recognize triggers in
a timely fashion. Education of staff about
MET trigger criteria is not sufficient.
Braithwaite et al. (16) found that MET
consults could be used as markers for
medical errors. Those authors found that
31% of MET consults were generated be-
cause a medical error had occurred and,
more important, that other hospital sys-
tems, other than a MET team, required
revision to prevent future events. Elec-
tronic alarm systems generating auto-
matic warning alerts could offer superior
results compared with the system we
have described, because such a system
bypasses the need for staff to remember
the trigger criteria; however, the addi-
tional cost in personnel to monitor the
warning system and to keep the false
alarm rate to a minimum could be pro-
hibitive.
The clinical criteria that best suggest
when to activate a MET have been con-
troversial and include changes in respi-
ratory rate, changes in blood pressure,
deteriorating level of consciousness,
and clinician worry or concern (21–23).
Foraida et al. (24) suggested that a fo-
cused organized response (MET activa-
tion) to predefined abnormal physiologic
criteria can be developed and might im-
prove outcome. Adult-oriented MET acti-
vation criteria usually include five to
eight physiologic variables (7, 25). In
contrast, MET activation triggers in pedi-
atrics offer unique challenges because vi-
tal sign-related triggers must be adjusted
to age-specific norms, and therefore the
number of variables for staff to remember
increases substantially compared with
the adult population. The activation cri-
teria provided by Tibballs et al. (14) in-
cluded five respiratory rate criteria, ten
heart rate criteria, five blood pressure
criteria, plus any change in neurologic
status. Similarly, the pediatric early
warning score (PEWS), which combines
vital sign variables, perfusion, and neuro-
logic assessments, has ⬎20 signs that are
combined into an aggregate warning
score (26). Duncan et al. (27) suggested
that using a PEWS score of 5 could iden-
tify ⬎75% of code blue calls with ⱖ1 hr
warning. We chose a MET trigger system
with five clinical and two intuitive crite-
ria (Table 2). We chose these in part be-
cause our retrospective code analysis did
not reveal discriminatory vital sign or
laboratory variables that could consis-
tently identify children at risk. In addi-
tion, we tried to keep things simple. After
MET rollout, we reviewed all MET con-
sult forms and found a large range of vital
signs abnormalities for each age group,
but specific cutoffs that might increase
the sensitivity or specificity of our cur-
rent MET triggers were lacking. The most
common reason for MET activation in
pediatric hospitals was concern by a
nurse or respiratory therapist (Fig. 3)
(14). This suggests that a clinician’s in-
tuitive assessment of the patient may be
of greater importance than any specific
vital sign threshold. Despite this, we be-
lieve that more work is needed to identify
a simple and effective early warning trig-
ger system for children at risk for respi-
ratory or cardiopulmonary arrest outside
the ICU.
There are many barriers to MET im-
plementation (28). Like DeVita et al. (8),
we found that a key barrier to successful
MET implementation involved changing
institutional cultural perceptions about
traditional professional role norms. It be-
came apparent during MET implementa-
tion that for physicians, the concept of a
MET was equated with loss of control.
For other caregivers, the MET repre-
sented an opportunity and a challenge to
change the communication patterns be-
tween general floor staff and the ICU.
Comments from the caregiver survey re-
flect these significant cultural barriers: a)
“The ICU is taking over the care of pa-
tients on the inpatient unit”; b) “this will
take away educational and decision mak-
ing opportunities for the residents”; and
c) “physicians display a lack of respon-
siveness for the concerns of the nurses.”
Others have reported similar concerns
about turf and control. Hodgetts et al.
(29) reviewed 139 cases of avoidable adult
in-hospital cardiac arrests to determine
individual and system factors that influ-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
enced the rate of occurrence of cardiac
arrests. They described multiple factors
that contributed to in-hospital cardiac ar-
rests including failure by staff to recog-
nize abnormal lab values, failure by
nurses to notify physicians about abnor-
mal laboratory values, and reluctance by
junior doctors to seek assistance from
senior doctors. As the MET concept was
introduced, issues of turf and control
were acknowledged and reassurance was
provided that the MET was an additional
resource for clinical decision making.
Caregivers were encouraged to use the
MET as a supplementary resource when a
clear plan about patient disposition was
in doubt and not as a mechanism to sup-
plant the traditional role of the resident,
fellow, or attending. Furthermore, it was
made clear that the MET was not an ad-
versarial recourse to settle disputes be-
tween physicians and nurses. General
care unit clinical staff were encouraged to
contact the physician most familiar with
the patient before calling the MET. Direct
communication between general care
unit physicians and ICU physicians about
rapidly deteriorating patients continued
and in some instances replaced MET ac-
tivation.
Local unit managers and hospital
leaders were important for the success of
the project. Senior hospital leaders were
needed to provide clear authority that the
MET initiative was an important hospital
priority. Similarly, local unit leaders were
key—they determined the most appropri-
ate methods to introduce the MET in
their respective areas (slides, posters, pre-
sentations) and provided sustainability
through feedback to staff about each MET
consult. Spread and sustainability of the
MET system were enhanced by spontane-
ous communication among clinical staff
describing nonconfrontational collabora-
tion between the MET and the caregivers
who activated the team. Galhotra et al.
(30) reported that nurses caring for adult
patients who had activated a MET consult
valued the experience, and the confidence
they gained made them likely to use the
system a second time. Figure 4 quantifies
general floor staff satisfaction with the
implemented system. Providing clinical
staff with a mechanism for feedback and
comment about the MET process was an-
other important aspect of implementa-
tion. Debriefings and discussions after
MET consult helped to build enthusiasm
for the project and emphasized the role of
team in improving patient mortality. Ap-
pendix 1 describes the performance as-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
sessment feedback survey, and Figure 4 is
a sample of the survey data. This real-
time feedback allowed MET implementa-
tion to occur without the process being
perfect before rollout. Feedback could be
analyzed quickly and the MET system
rapidly adjusted in response.
This report has several limitations and
presents some controversial issues. First,
the MET activation criteria used in our
hospital were effective and may serve as a
framework for others, but these criteria
have not been validated across multiple
centers. The success using these criteria
in our hospital may relate as much to
implementation strategies as to specific
activation criteria. Second, some will not
agree with our definitions of “MET-
preventable” codes. The definitions were
prospectively determined, and the chart
of each patient was reviewed to determine
whether MET triggers were present be-
fore the code. We believe that by present-
ing all code rates and preventable code
rates, the reader can fully evaluate the
potential impact of a MET. Third, this is
the first pediatric report to include both
respiratory arrest and cardiopulmonary
arrest data, whereas prior studies have
focused only on cardiopulmonary arrests.
This makes comparison with other stud-
ies more difficult. Because respiratory ar-
rest alone was common in our study and
some of these patients died, we would be
remiss to exclude these patients from re-
view. To facilitate comparison, we have
included data about only cardiopulmo-
nary arrests in Table 4. Fourth, previous
reports and a recent consensus confer-
ence normalized cardiac arrest data or
code data to 1,000 admissions (28). We
chose to adjust our data to 1,000 patient
days, because we believe that the risk for
a code is much more dependent on the
days of exposure to the risk (i.e., total
hospital days) than on total admissions,
which does not take into account varying
length of stay. Using the 1,000 admission
denominator, our results and conclu-
sions did not change; however, so the
reader can compare our data with prior
reports, we present both denominators in
the text, figures, and tables. Fifth, as
mentioned in the methods, our analysis
uses both one-tailed and two-tailed statis-
tical tests. Most clinical studies that ana-
lyze outcome differences before and after
an intervention (drug treatment, diag-
nostic intervention) use two-tailed anal-
ysis because the outcome after the inter-
vention could be either worse or better.
Because there is no reasonable concern
that implementing a MET will worsen
outcome, we believe that one-tailed anal-
ysis is most appropriate. For complete-
ness we have presented data using both
analytic approaches.
This improvement initiative has pro-
vided a template for how to implement a
MET team in a large tertiary teaching
children’s facility. More important, this
study demonstrates that implementation
of a MET can reduce the incidence of
respiratory and cardiopulmonary arrests
outside the critical care areas in a single
children’s hospital. More long-range data
are needed to fully examine the effect of
METs on pediatric hospital mortality.
REFERENCES
1. University of California, San Francisco, Stan-
ford University Evidence-Based Practice Cen-
ter: Evidence Research Measures of Patient
Safety Based on Hospital Administrative
Data: The Patient Safety Indicators. Rock-
ville, MD, Agency for Healthcare Research
and Quality, 2002
2. Sedman A, Harris M, Schulz K, et al: Rele-
vance of the Agency for Healthcare Research
and Quality Patient Safety Indicators for Chil-
dren’s Hospitals. Pediatrics 2005; 115:135–145
3. 100K Lives Campaign—Getting Started Kit:
Rapid Response Teams. Available at: http://www.
ihi.org/IHI/Programs/Campaign/Campaign.
htm?TabId⫽1.Accessed February 6, 2006
4. Bellomo R, Goldsmith D, Uchino S, et al: A
prospective before-and-after trial of a medi-
cal emergency team. Med J Aust 2003; 179:
283–287
5. Bristow PJ, Hillman KM, Chey T, et al: Rates
of in-hospital arrests, deaths and intensive
care admission: The effect of a medical emer-
gency team. Med J Aust 2000; 173:236 –240
6. Buist M, Moore G, Bernard S, et al: Effects of
a medical emergency team on reduction of
incidence of and mortality from unexpected
cardiac arrests in hospital: Preliminary
study. BMJ 2002; 324:387–389
7. Bellomo R, Goldsmith D, Uchino S, et al:
Prospective controlled trial of effect of med-
ical emergency team on postoperative mor-
bidity and mortality rates. Crit Care Med
2004; 32:916 –921
8. DeVita M, Braithwaite R, Mahidhara R, et al:
Use of medical emergency team responses to
reduce hospital cardiopulmonary arrests.
Qual Saf Health Care 2004; 13:251–254
9. Kenward G, Castle N, Hodgetts T, et al: Eval-
uation of a Medical Emergency Team one
year after implementation. Resuscitation
2004; 61:257–263
10. Suominen P, Olkkola K, Voipio V, et al: Ut-
stein style reporting of in-hospital paediatric
cardiopulmonary resuscitation. Resuscita-
tion 2000; 45:17–25
11. Reis A, Nadkarni V, Perondi M, et al: A pro-
spective investigation into the epidemiology
243
 of in-hospital pediatric cardiopulmonary re-
suscitation using the international Utstein
reporting style. Pediatrics 2002; 109:
200 –209
12. Nadkarni V, Larkin G, Peberdy M, et al: First
documented rhythm and clinical outcome
from in-hospital cardiac arrest among chil-
dren and adults. JAMA 2006; 295:50 –57
13. Lopez-Herce J, Garcia C, Dominquez P, et al:
Characteristics and outcome of cardiorespi-
ratory arrest in children. Resuscitation 2004;
63:311–320
14. Tibballs J, Kinney S, Duke T, et al: Reduction
of paediatric in-patient cardiac arrest and
death with a medical emergency team: Pre-
liminary results. Arch Dis Child 2005; 90:
1148 –1152
15. Langley G, Nolan K, Nolan T, et al: The
Improvement Guide: A Practical Approach
to Enhancing Organizational Performance.
1st ed. San Francisco, CA, Jossey-Bass,
1996
16. Braithwaite R, DeVita M, Mahidhara R, et al:
Use of medical emergency team (MET) re-
sponses to detect medical errors. Qual Saf
Health Care 2004; 13:255–259
17. López-Herce J, García C, Rodriquez-Nunez
A, et al: Long-term outcome of paediatric
244
cardiorespiratory arrest in Spain. Resuscita-
tion 2005; 64:79 – 85
18. Goldhill DR, Worthington L, Mulcahy A, et
al: The patient-at-risk team: Identifying and
managing seriously ill ward patients. Anaes-
thesia 1999; 54:853– 860
19. MERIT study investigators: Introduction of
the medical emergency team (MET) system:
A cluster-randomized controlled trial. Lan-
cet 2005; 365:2091–2097
20. Winters B, Pham J, Pronovost P: Rapid re-
sponse teams—Walk, don’t run. JAMA 2006;
296:1645–1647
21. Hodgetts T, Kenward G, Vlachonikolis I, et
al: The identification of risk factors for car-
diac arrest and formulation of activation cri-
teria to alert a medical emergency team. Re-
suscitation 2002; 54:125–131
22. Buist M, Bernard S, Nguyen TV, et al: Asso-
ciation between clinically abnormal observa-
tions and subsequent in-hospital mortality: A
prospective study. Resuscitation 2004; 62:
137–141
23. Oggioni R, Bandini F, Fradella G, et al: Bed-
side clinical severity score to assess patients
at risk and to prevent in-hospital cardiac
arrest. Crit Care Med 2004; 32:A65
24. Foraida M, DeVita M, Braithwaite S, et al:
Improving the utilization of medical crisis
teams (condition C) at an urban tertiary care
hospital. J Crit Care 2003; 18:87–94
25. Subbe C, Williams E, Gemmell L, et al: Are
medical emergency teams picking up enough
patients with increased respiratory rate? Crit
Care Med 2004; 32:1983–1984
26. Monaghan A: Detecting and managing dete-
rioration in children. Paediatr Nurs 2005;
17:32–35
27. Duncan H, Hutchison J, Parshuram C: The
pediatric early warning system score: A se-
verity of illness score to predict urgent med-
ical need in hospitalized children. J Crit Care
2006; 21:271–279
28. DeVita M, Bellomo R, Hillman K, et al: Find-
ings of the First Consensus Conference on
Medical Emergency Teams. Crit Care Med
2006; 34:2463–2478
29. Hodgetts T, Kenward G, Vlachonikolis I, et
al: Incidence, location, and reasons for avoid-
able in-hospital cardiac arrest in a district
general hospital. Resuscitation 2002; 54:
115–123
30. Galhotra S, Scholle C, Dew M, et al: Medical
emergency teams: A strategy for improving
patient care and nursing work environments.
J Adv Nurs 2006; 55:180 –187
Pediatr Crit Care Med 2007 Vol. 8, No. 3
 Appendix 1. Medical Emergency Team (MET) Responder Evaluation Form

Pediatr Crit Care Med 2007 Vol. 8, No. 3 245

 Appendix 2. Medical Emergency Team (MET) Consultation Form

246 Pediatr Crit Care Med 2007 Vol. 8, No. 3

Cardiac Intensive Care

Transhepatic Broviac catheter placement for long-term central

venous access in critically ill children with complex congenital
heart disease*
Athar M. Qureshi, MD; John F. Rhodes, MD; Elumulai Appachi, MD;
Muhammad A. Mumtaz; Brian W. Duncan, MD; Jeremy Asnes, MD; Penny Radavansky, RN;
Larry A. Latson, MD

Objective: Critically ill children with cardiac disease often
require prolonged central venous access. Thrombosis of systemic
veins or the need to preserve vessels for future cardiac proce-
dures limits sites for placement of central venous catheters in
these patients. This study evaluates the use of Broviac placement
via the transhepatic approach for this patient population.
Design: A retrospective review.
Setting: A tertiary care center.
Patients: All children with complex congenital heart disease
who underwent transhepatic Broviac placement between May
2000 and April 2004.
Interventions: Transhepatic Broviac placement.
Measurements and Main Results: Thirty-two children with a
median age of 5 months (20 days–5.3 yrs) and a median weight
of 4.2 kg (2.2–24.9 kg) underwent 40 transhepatic Broviac place-
ments. There were three (8.8%) procedural-related complications.
One patient suffered an intra-abdominal bleed requiring an urgent
laparotomy and removal of the Broviac, one patient required
transfusion because of a mild self-contained intra-abdominal
bleed, and one patient developed temporary complete heart block.
There was one catheter infection. Thrombus was noted by echo-
cardiography on the tip of two Broviacs; however, no intracardiac
vegetations or embolic events occurred. There was no mortality
related to the procedure. Broviacs remained in place for a median
of 36 days (1 day– 6 months). Five Broviacs were dislodged
inadvertently (two during cardiac massage and three resulting
from patient manipulation). The remaining Broviacs were elec-
tively removed safely without coil embolization. At a median
follow-up of 3.5 months (10 days–3 yrs), there have been no
long-term complications related to the Broviacs.
Conclusions: Transhepatic Broviac catheters can be used
safely in critically ill children with cardiac disease and remain
indwelling for adequate periods of time. This modality of pro-
longed vascular access should be considered for children whose
veins are occluded or need to be preserved for future procedures.
(Pediatr Crit Care Med 2007; 8:248 –253)
KEY WORDS: cardiac catheterization; cardiovascular disease;
critically ill children; transhepatic; Broviac

C
hildren with complex con-
genital heart disease often
have prolonged intensive
care stays involving long-
term administration of intravenous
medications and nutrition. Because of
their prolonged hospitalizations and
multiple procedures, many of these pa-
*See also p. 298.
From the Departments of Pediatric and Congenital
Heart Disease (AMQ, JFR, MAM, BWD, JA, PR, LAL)
and Pediatric Critical Care (EA), The Children’s Hospital
at The Cleveland Clinic, Cleveland, OH.
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
quresha@ccf.org
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000265327.93745.89
tients require long-term central venous
access and may develop occluded sys-
temic veins as a consequence (1–3).
Preservation of neck and groin vessels
in these patients also is necessary for
future cardiac surgeries and catheter-
izations (1). Peripherally inserted cen-
tral catheters (PICC) are generally the
preferred method of establishing long-
term central venous access. However,
in the setting of difficult peripheral ve-
nous access, or when preservation of
vessels is important (e.g., in patients
with single ventricle physiology), alter-
natives to PICC and traditional tun-
neled catheters may be advantageous.
Unconventional venous access proce-
dures involving the intercostal veins
(4), the azygous vein (5), and direct
right atrial access (6) previously have
been reported in the setting of occluded
veins. In children, inferior vena caval ac-
cess via the translumbar approach (7–9)
has been used in such circumstances, and
the transhepatic approach (2, 7, 8, 10)
also has been reported in small case se-
ries. The purpose of this study was to
evaluate the use and safety of transhe-
patic Broviac placement in children.
MATERIALS AND METHODS
A retrospective review was performed on
all patients entering the cardiac catheteriza-
tion laboratory from June 2000 to May 2004 at
The Children’s Hospital at The Cleveland
Clinic, Cleveland, OH. Approval for the review
was obtained in accordance with our institu-
tional review board guidelines and policy. To
assess the indications and outcomes of the
procedure charts, laboratory investigations,
echocardiograms, and catheterization reports
were reviewed. Before patients underwent

248 Pediatr Crit Care Med 2007 Vol. 8, No. 3

transhepatic Broviac placement, significant
liver pathology was ruled out clinically. Ele-
vated liver enzymes were not considered con-
traindications. Hepatomegaly or situs abnor-
malities did not preclude patients from the
procedure.
The indication for transhepatic Broviac in-
sertion, e.g., single ventricle physiology, ve-
nous occlusion, or vessel preservation, was
determined from the review. Catheters were
evaluated until removal, dislodgement, or the
patient died. Complications were specifically
reviewed. Bleeding was considered a compli-
cation if the patient required a blood transfu-
sion. Similarly, any adverse event during the
procedure that required an intervention (e.g.,
temporary pacing) was noted. Thrombus for-
mation was defined as a clot seen by echocar-
diography in the heart or inferior vena cava
(IVC) or on catheter tips. Embolic events also
were sought as an indirect marker of possible
thrombus formation. Infection was considered
in the setting of new positive blood cultures,
drainage from the wound sites, or if there was
a clinical scenario of sepsis. Malfunction was
considered if a catheter was adjusted or re-
moved because of inadequate blood draws or
delivery of medications. Dislodgement was
categorized as early (⬍2 wks after the proce-
dure) or late (⬎2 wks after the procedure). In
the intermediate-term follow-up, we looked
for possible sequelae to catheter placement;
e.g., hepatomegaly out of proportion to coex-
isting heart disease, neurologic events, or ev-
idence of intracardiac clots or venous throm-
boses on follow-up echocardiograms. Results
are expressed as percentages, mean ⫾ SD, and
medians with ranges.
Procedure. All procedures were performed
under general anesthesia. Coagulation studies
were performed on the patients before the
procedure, as most of the patients were re-
ceiving anticoagulants. Aspirin therapy was
not discontinued; however, anticoagulation
was discontinued 2 hrs before the procedure
for patients receiving heparin and 72 hrs
before the procedure for patients receiving
warfarin (to achieve an international nor-
malized ratio of ⬍2). Perioperative antibiot-
ics were administered if patients were not
already receiving antibiotics or were not re-
ceiving adequate staphylococcal coverage.
The right chest and abdomen were prepared
and draped in a sterile fashion (left in the
case of some heterotaxy syndromes with si-
tus abnormalities). Local anesthesia (1% li-
docaine) was administered to the lowest in-
tercostal space in the midaxillary line. A
22-gauge Chiba needle (Inrad, Kentwood,
MI) was inserted just above the lowest rib (to
avoid injury to the neurovascular bundle)
along the midaxillary line or even more in-
ferior when the liver was displaced. The nee-
dle was directed cranially toward the xiphoid
process and angled slightly posterior (Fig.
1). The position was confirmed by fluoros-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Figure 1. Position of the Chiba needle just before
access as seen on anterior-posterior (top) and
lateral (bottom) projections. The needle is di-
rected toward the xiphoid process and posterior.
In this case, the entry site was well below the
lowest rib, because of the inferior displacement of
the liver.
copy in the anterior-posterior and lateral
projections, before the actual puncture was
performed. Using biplane cineangiography
and small contrast injections, an adequate-
sized hepatic vein was identified by contrast
entering a vessel draining to the right
atrium via the IVC. A 0.014- to 0.018-inch
guidewire was advanced to the right atrium
or superior vena cava. The tract was dilated,
and the small guidewire was then exchanged
for a 0.035-inch guidewire, which was ad-
vanced to an intracardiac position.
The equipment used for catheter place-
ment was from a Hickman-Broviac kit (CR
Bard, Salt Lake City, UT). An 8-Fr peel-away
sheath (for a 7-Fr double-lumen catheter) or a
5-Fr peel-away sheath (for a 4.2-Fr single-
lumen catheter) was advanced to the right
atrium over the guidewire.
A tunneled Broviac tract was made along
the anterior chest wall. Lidocaine injections
(1%) were administered along the entire
length of the site chosen for the tract. A
small horizontal incision was made at the
superior end of the tract (exit site), and the
entry site (site of the initial access with
the Chiba needle) also was enlarged with a
small horizontal incision. The catheter
length was determined by measuring the
length from the puncture site to the xiphoid
process (IVC–right atrium junction on fluo-
roscopy). The vertical height (from the entry
site to the top of the chest) was subtracted,
and the Broviac catheter was cut at a beveled
angle. The Broviac was advanced through
the tunneled tract. Subsequently, the cath-
eter was inserted through the peel-away
sheath and positioned in the IVC–right
atrium junction, while the sheath was
peeled away simultaneously. Position was
confirmed with a small hand contrast injec-
tion and both ports were confirmed to draw
and flush easily. Both the entry and exit sites
were sutured securely with a 5-0 Prolene
and dressed in sterile fashion (Fig. 2). For
patients receiving anticoagulation, heparin
was resumed 2 hrs after the procedure or
warfarin was restarted the same day. A chest/
abdominal radiograph was obtained to con-
firm position once the patients were in the
pediatric intensive care unit, along with a
hematocrit level if indicated (Fig. 3). A rou-
tine heparin flush protocol was used to keep
the lumens patent.
RESULTS
Thirty-two patients underwent place-
ment of 40 transhepatic Broviac catheters
during the study period. The indication
for the procedure in all cases was the
long-term administration of total paren-
teral nutrition, inotropes, and/or antibi-
otics. The study patients were a heterog-
enous population of children with
complex congenital or acquired heart dis-
ease who were critically ill (Table 1) in
the pediatric intensive care unit. In all
patients, PICC placement and traditional
methods of Broviac placement were con-
sidered. Fifteen (46.9 %) patients with
single-ventricle physiology underwent
transhepatic Broviac placement because
of concerns about potential thrombosis
in the superior vena cava (which could
preclude an eventual Fontan operation)
from more conventional forms of catheter
placement. Five (15.6%) patients under-
went transhepatic Broviac placement be-
cause of bilateral femoral venous occlusion.
Twelve (37.5%) patients underwent place-
ment in an attempt to preserve their fem-
oral veins for future catheterizations.
The median age was 5 months (20
days–5.3 yrs), and the median weight of
the patients was 4.2 kg (2.2–24.9 kg).
There were 14 males and 18 females.
Four patients had transverse orientation
of the liver (none true situs inversus to-
talis), and we obtained access where the
249
 Table 1. Patients and cardiac lesions

Lesion No.

PA/VSD/MAPCAs 10
Hypoplastic left heart syndrome 6
Shone’s complex 4
Heterotaxy 3
Double-outlet right ventricle 3
Hypoplastic right-heart variants 2
Cardiomyopathy 2
Ebstein’s anomaly 1
Truncus arteriosus 1
Total 32

PA/VSD/MAPCAs, pulmonary atresia, ventric-

ular septal defect with multiple aortopulmonary
collateral arteries.

one patient suffered an intra-abdominal

bleed that required an urgent laparot-
omy, with subsequent full recovery. This
patient was a 1.5-month-old baby with
Figure 2. Lateral view (bottom) showing the entry and exit sites of a transhepatic Broviac catheter. hypoplastic left-heart syndrome who had
Note that the entry site is above the lowest rib, in the midaxillary line. The top panel shows the tip of undergone a stage 1 Norwood operation.
the catheter in the right atrium. In the periprocedure period, he was noted
to have had elevated coagulation param-
eters. He became hemodynamically un-
stable because of bleeding around the
liver and required resuscitation. During
this process, the Broviac catheter became
dislodged; this was not immediately no-
ticed. The combination of ongoing blood
loss from the puncture site and infusion
of blood products through the Broviac
into the intraperitoneal space led to he-
modynamic instability requiring an ur-
gent operation. Eventually, rapid internal
jugular venous access had to be obtained
for the resuscitation event because of the
displaced Broviac catheter. A 1-month-
old with hypoplastic left-heart syndrome
(also following a stage I Norwood opera-
tion) required a blood transfusion be-
Figure 3. An abdominal chest radiograph obtained in the intensive care unit. This particular patient
cause of a drop in hematocrit, which was
had heterotaxy syndrome, and the transhepatic Broviac catheter was placed from the left (L). The thought to be related to an intracapsular
catheter is in a good position, with the tip just at the diaphragm (arrow). liver bleed. This patient underwent cath-
eterization at the same time as Broviac
placement and the anticoagulation dur-
more dominant portion of the liver was placed in reaction to separate episodes of ing the procedure may have contributed
present. This was from the right side in illnesses). Two patients were transferred to the intracapsular accumulation of
two patients and from the left side in two to local hospitals with their Broviac cath- blood. A 3-wk-old boy with pulmonary
patients. A 7-Fr double-lumen catheter eters indwelling. One patient was sent atresia/ventricular septal defect and mul-
was placed in 36 procedures and a 4.2-Fr home with the transhepatic Broviac cath- tiple aortopulmonary collateral arteries
single-lumen catheter was placed in four eter indwelling while he received special- developed complete heart block, which
cases. All of the 4.2-Fr catheters were ized home nursing care. This catheter required temporary dual chamber pacing
placed in children ⬍3 kg. However, four was later removed electively at our facil- in the pediatric intensive care unit. This
children who were ⬍3 kg underwent ity. The rest of the patients were cared for patient also underwent a complete hemo-
placement of a 7-Fr double-lumen cath- as inpatients while their catheters re- dynamic catheterization at the same time
eter when there was a need for two ports. mained indwelling because of their co- as Broviac placement, and catheter ma-
One patient underwent placement of a morbid conditions. nipulation via transhepatic access likely
transhepatic Broviac catheter on four dif- Procedural Adverse Events. There resulted in transient complete heart
ferent occasions (one catheter became were three (8.8%) procedural-related block. There were no procedural-related
dislodged and the others were electively complications. In our initial experience, deaths.

250 Pediatr Crit Care Med 2007 Vol. 8, No. 3

 Indwelling Catheter-Related Compli-
cations. Catheters remained indwelling
for a median of 36 days (1 day– 6
months), with a total of 1,742 catheter
days. There were four complications re-
lated to the indwelling catheter. Throm-
bus formation was seen on the ends of
two catheters (1.1/1,000 catheter days).
Both of these catheters were removed
slowly without incident. One patient de-
veloped sepsis with positive blood cul-
tures, and as a result, the transhepatic
Broviac catheter was removed (infection
rate of 0.57/1,000 catheter days). There
were no embolic events. Adjustment of a
Broviac catheter was required in one pa-
tient in the intensive care unit resulting
from malfunction of the catheter (0.57/
1,000 catheter days).
Five Broviac catheters were dislodged
inadvertently. Four of these dislodge-
ments occurred in patients from the first
15 procedures. Two dislodgements were
during episodes of cardiopulmonary re-
suscitation; one was early (the same day,
described above) and one was late (1
month later during a prolonged episode
of resuscitation). During the latter pa-
tient’s episode, two peripheral intrave-
nous catheters were inserted for access,
and the child underwent repeat transhe-
patic Broviac placement 1 day later (sin-
gle-ventricle physiology). Three dis-
lodgements (7.5% or 1.7/1,000 catheter
days) occurred as a result of patient
manipulation; all were late. None of the
late dislodgements resulted in hemody-
namic instability.
Removal and Follow-Up. Elective re-
moval of the catheters was performed at
the bedside, at least 1 day before antici-
pated discharge from the hospital (with
the exception of transferred patients or
the patient that was sent home, in whom
catheters were removed at our facility as
an outpatient). Patients received midazo-
lam and morphine, and 1% lidocaine was
administered in the skin around the cuff.
Blunt dissection was performed to ex-
trude the cuff, and the Broviac catheters
were withdrawn during the course of
30 – 45 mins. The exit wound was sutured
with 5-0 Prolene or dressed with Steri-
Strips (3M, St. Paul, MN) if the wound
was small. Hemostasis was achieved with
manual pressure. None of the Broviac
tracts were coiled. During elective re-
moval of the Broviac catheters, there
were no complications. Specifically, there
were no problems related to bleeding (no
increase in abdominal girth) or retained
fragments during the removal process.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
At a median follow-up of 3.5 months
(10 days–3 yrs) after catheter removal,
there have been no intermediate-term se-
quelae related to the procedure. Nine of
the 12 patients (75%) in whom the pro-
cedure was performed in an attempt to
preserve the groin vessels have under-
gone catheterizations, and femoral ve-
nous access was successfully obtained in
all nine. However, seven (21.8%) patients
eventually died as a result of their com-
plex cardiac disease.
DISCUSSION
In 1995, three separate reports were
published on the transhepatic approach
for cardiac catheterization in children
lacking conventional central venous ac-
cess sites (2, 3, 11). Since then, this mo-
dality has become an important tool for
pediatric interventional cardiologists in
the setting of occluded neck and groin
vessels or when preservation of these ves-
sels is necessary. The transhepatic ap-
proach for access has been found to be a
safe alternative for diagnostic (11–13)
and interventional (14, 15) catheteriza-
tion in children. Crummy and colleagues
(16) first described the placement of a
central venous catheter in the IVC via the
transhepatic route in an adult patient.
Subsequently, a number of other small
reports have been published on transhe-
patic placement of indwelling catheters
in children (2, 7, 8, 10).
Technical Considerations and Fol-
low-Up Care. Our current report provides
a large single-center experience on trans-
hepatic Broviac catheter placement in
children. The technique we used involved
transhepatic access by fluoroscopic guid-
ance only (15). Others have advocated the
use of ultrasound to obtain transhepatic
access (7, 8, 12, 17) and hypothesized
that the use of ultrasound minimizes po-
tential complications associated with flu-
oroscopic guidance alone, particularly
bleeding complications related to multi-
ple attempts to access hepatic vessels
(17). In our experience, transhepatic ac-
cess was obtained quickly in all patients
who proceeded to the catheterization lab-
oratory for placement of transhepatic
Broviac catheters. Fluoroscopy was vital
in identifying our landmarks in both
anterior-posterior and lateral projections
before the actual puncture was per-
formed. Ventilation was held while posi-
tioning the Chiba needle and while per-
forming the actual puncture to make
sure that the needle was not in the prox-
imity of the diaphragm or lungs. In pa-
tients who had hyperinflation of the
lungs and consequently ran the risk of
injury to the lungs, we chose to make our
entry site lower, down in the right upper
quadrant (midaxillary line) rather than in
the lowest intercostal space. Finally, if a
hepatic vein was not identified, the Chiba
needle was withdrawn completely rather
than manipulating the needle within the
liver, which can be difficult and poses a
risk to vascular and biliary structures in
the liver.
Despite the above measures, there
were three (8.8%) procedural-related
complications in our series, predomi-
nately in our initial experience. As with
any new procedure, a learning curve may
be involved. Operators should be cogni-
zant of the fact that concomitant cardiac-
catheterization procedures may entail ad-
ditional risks. Because of heparin
administration during cardiac catheter-
ization, bleeding may be encountered
with transhepatic Broviac placement. In
addition, patients might be receiving an-
ticoagulants before the procedure. Ade-
quate hemostasis should be achieved
after each unsuccessful attempt to can-
nulate a hepatic vein and after the proce-
dure is complete. We have not been ad-
ministering protamine to avoid bleeding
problems, because many of these patients
do require some degree of anticoagula-
tion (shunts, single ventricles). Instead,
we prefer achieving hemostasis via man-
ual pressure, although this may require
holding pressure for longer periods of
time. It is important that pressure be
applied to both the entry and exit sites
but particularly the entry site, which is
the site of entry into the liver paren-
chyma. Manipulation of sheaths and
wires should be minimized via the trans-
hepatic approach if a cardiac catheteriza-
tion is to be performed at the same time.
The transhepatic approach places wires
and sheaths in the vicinity of the atrio-
ventricular node and could result in heart
block, especially in small infants, as was
seen in our series. This usually is tran-
sient; however, the catheterization labo-
ratory where this procedure is being per-
formed should be equipped with pacing
catheters in addition to essential resusci-
tation medications and equipment. Real-
izing the potential complications that can
be encountered because of the anatomy
of the liver, this procedure should be per-
formed only by personnel experienced in
transhepatic access. Keeping these pre-
cautionary measures in mind, the proce-
251
dure can be performed safely with mini-
mal morbidity.
Periodic monitoring of transhepatic
Broviac catheters while they remain in-
dwelling is important. We did not rou-
tinely check liver enzymes or hematocrits
or perform abdominal ultrasounds after
the catheterization as others have shown
that this is not necessary after uncompli-
cated transhepatic access (11). However,
we did perform radiographs and/or trans-
thoracic echocardiography to evaluate
catheter tips if there was a question about
the functionality or position of the
Broviac catheter. Radiographs did iden-
tify an acute bend in the catheter at the
junction of the tunneled tract and entry
point in one Broviac catheter, which re-
quired adjustment at the bedside. Al-
though we were able to adjust the cath-
eter in this case (by opening the entry
site), it is generally difficult to adjust the
length of the catheter once it is in posi-
tion. Since then, we have tunneled our
tract in a way to make this angle in the
catheter course less acute. Alternatively,
the tract can be tunneled perpendicular
in the abdomen for a less acute curve.
Similarly, we propose that patients be
monitored for at least 24 hrs after re-
moval of the catheters for signs of hemo-
dynamic instability. Although it has been
suggested that sheath tracts should be
coiled in the liver parenchyma after per-
forming transhepatic access for proce-
dures in children (11, 14, 15), this may
not be applicable to catheters placed via
the transhepatic route that have been in-
dwelling for a substantial period of time.
Sommer and colleagues (2) reported
transhepatic Broviac catheter removal at
the bedside without coiling of the tract
and hypothesized that chronic catheter
placement results in the formation of a
fibrosed tract. Using this protocol, we saw
no bleeding complications during or after
the removal process. Although retained
catheters have been reported in the liter-
ature (18), no catheter fragments were
retained as a result of the removal pro-
cess in our series.
Transhepatic Broviac catheter place-
ment was efficacious in terms of provid-
ing adequate access for desirable periods
of time in our patient population. Inter-
estingly, we were able to place a catheter
in the same patient on four different oc-
casions during the course of his pro-
tracted illness. Thus, multiple separate
procedures involving transhepatic access
can be safely performed (3, 10, 19), and
this can be an important consideration
252
for patients requiring central venous ac-
cess for lengthy periods of time or on a
repetitive basis. If needed, adequate cath-
eter care can be provided at local facilities
and even at home in certain situations.
Comparison with Other Modalities.
When long-term access is required in
critically ill children, PICC are the pre-
ferred method, if feasible. PICC have sev-
eral advantages. The method of insertion
is less invasive, sometimes they can be
placed at the bedside, and they generally
provide central venous access for ade-
quate periods of time. However, when
peripheral intravenous access cannot be
obtained because of multiple previous
blood draws or intravenous catheters, al-
ternative modalities may have to be con-
sidered. In addition, in patients who have
single-ventricle physiology, there is a
need to preserve femoral and jugular
veins for future procedures. Placement of
PICC cannot result in only peripheral ve-
nous thromboses, but central venous
thromboses as well (20). Thrombosis of
veins in these patients may make future
surgeries or catheterizations difficult or
even impossible. Transhepatic Broviac
catheters may, therefore, be preferred
more so than conventional forms of
Broviac placement (in the upper or lower
limbs) and PICC in patients who might
need a future Glenn/Fontan operation.
Some of our patients were not single-
ventricle patients, yet they underwent
transhepatic Broviac placement. The ra-
tionale in this group of patients was to
preserve their femoral venous vessels for
future interventional catheterizations.
From our report, it is difficult to deter-
mine whether femoral vessels would have
become occluded had they been used for
more traditional Broviac placement. Nev-
ertheless, in the group of patients who
underwent transhepatic Broviac place-
ment to preserve their vessels, successful
cannulation of the femoral vessels oc-
curred in all patients who underwent re-
peat catheterization.
In addition to the above indications,
some patients required two ports because
of drug incompatibilities, the need for
continuous inotropic support, or the
need for frequent venous blood sampling.
In our experience, this is advantageous as
well, because a relatively large catheter
(in some instances, 7-Fr) can be placed in
hepatic vessels, making two ports avail-
able. This may not be possible if the sub-
clavian or femoral venous routes are used
for Broviac placement.
Infection and thrombus formation with
Broviac catheters is a complication, regard-
less of the route chosen for insertion. By
using the transhepatic route, the rates of
infections and thrombosis in our report are
similar to what was found in a prospective
study comparing femoral and jugular
Broviac catheters in neonates (2.48 vs.
2.32/1,000 catheter days and 0.83 vs. 0.77/
1,000 catheter days, respectively) (21). Dis-
lodgement, although infrequent, remains a
potential risk with any type of Broviac cath-
eter, as well. This is supported by a wide
range of dislodgement rates in the litera-
ture (2.8% to 24%) (22) and in our report
(7.5%). However, as was seen in our patient
that required an urgent operation, with
transhepatic Broviac catheters, an immedi-
ate radiograph to confirm intravascular po-
sition should be performed after episodes of
cardiopulmonary resuscitation. We have
subsequently found that dislodgement also
can be minimized with proper suturing/
fixation and education of care providers.
CONCLUSIONS
In summary, children with complex
congenital heart disease often are at risk
for occlusion of the neck and groin ves-
sels as a result of chronic indwelling vas-
cular catheters inserted in these sites.
Preservation of these vessels is very im-
portant in some patients for future sur-
geries (such as the Glenn/Fontan pro-
cedures) and catheterizations. The
transhepatic approach is an alternative
for the placement of central venous
Broviac catheters, even in small children.
Transhepatic Broviac catheters should be
placed only by personnel experienced
with transhepatic access. This approach
especially can be considered for chil-
dren with complex congenital heart dis-
ease, but also in any child in whom
conventional central venous access is
problematic.
REFERENCES
1. Ing F, Fagan TE, Grifka RG, et al: Recon-
struction of stenotic or occluded iliofemo-
ral veins and inferior vena cava using in-
travascular stents: Re-establishing access
for future cardiac catheterization and car-
diac surgery. J Am Coll Cardiol 2001; 37:
251–257
2. Sommer RJ, Golinko RJ, Mitty HA: Initial
experience with percutaneous transhepatic
cardiac catheterization in infants and chil-
dren. Am J Cardiol 1995; 75:1289 –1291
3. Johnson JL, Fellows KE, Murphy JD:
Transhepatic central venous access for car-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
 diac catheterization and radiologic inter-
vention. Cathet Cardiovasc Diagn 1995;
35:168 –171
4. Solomon BA, Solomon J, Shlansky-Goldberg
R: Percutaneous placement of an intercostal
central venous catheter for chronic hyperali-
mentation guided by transhepatic venogra-
phy. J Parenter Enteral Nutr 2001; 25:42– 44
5. Meranze SG, McLean GK, Stein EJ, et al:
Catheter placement in the azygos system: An
unusual approach to venous access. AJR
Am J Roentgenol 1985; 144:1075–1076
6. Oram-Smith JC, Mullen JL, Harken AH, et al:
Direct right atrial catheterization for total
parenteral nutrition. Surgery 1978; 83:
274 –276
7. Azizkhan RG, Taylor LA, Jaques PF, et al:
Percutaneous translumbar and transhepatic
inferior vena caval catheters for prolonged
vascular access in children. J Pediatr Surg
1992; 27:165–169
8. Robertson LJ, Jaques PF, Mauro MA, et al:
Percutaneous inferior vena cava placement
of tunneled silastic catheters for prolonged
vascular access in infants. J Pediatr Surg
1990; 25:596 –598
9. Cheatham JP, McCowan TC, Fletcher SE:
Percutaneous translumbar cardiac catheter-
ization and central venous line insertion: An
Pediatr Crit Care Med 2007 Vol. 8, No. 3
alternative approach in children with con-
genital heart disease. Catheter Cardiovasc
Interv 1999; 46:187–192
10. De Csepel J, Stanley P, Padua EM, et al:
Maintaining long-term central venous access
by repetitive hepatic vein cannulation. J Pe-
diatr Surg 1994; 29:56 –57
11. Shim D, Lloyd TR, Cho KJ, et al: Transhe-
patic cardiac catheterization in children:
Evaluation of efficacy and safety. Circulation
1995; 92:1526 –1530
12. McLeod KA, Houston AB, Richens T, et al:
Transhepatic approach for cardiac catheteri-
sation in children: Initial experience. Heart
1999; 82:694 – 696
13. Wallace MJ, Hovsepian DM, Balzer DT:
Transhepatic venous access for diagnostic
and interventional cardiovascular proce-
dures. J Vasc Interv Radiol 1996; 7:579 –582
14. Shim D, Lloyd TR, Beekman RH III: Trans-
hepatic therapeutic cardiac catheterization:
A new option for the pediatric intervention-
alist. Catheter Cardiovasc Interv 1999; 47:
41– 45
15. Shim D: Transhepatic catheterization: Its
role in pediatric cardiac practice. J Invasive
Cardiol 2001; 13:310 –313
16. Crummy AB, Carlson P, McDermott JC, et al:
Percutaneous transhepatic placement of a
Hickman catheter. AJR Am J Roentgenol
1989; 153:1317–1318
17. Johnston TA, Donnelly LF, Frush DP, et al:
Transhepatic catheterization using ultra-
sound-guided access. Pediatr Cardiol 2003;
24:393–396
18. Jones SA, Giacomantonio M: A complication
associated with central line removal in the
pediatric population: Retained fixed catheter
fragments. J Pediatr Surg 2003; 38:594 –596
19. Book WM, Raviele AA, Vincent RN: Repetitive
percutaneous transhepatic access for myo-
cardial biopsy in pediatric cardiac transplant
recipients. Cathet Cardiovasc Diagn 1998;
45:167–169
20. Allen AW, Megargell JL, Brown DB, et al:
Venous thrombosis associated with the
placement of peripherally inserted central
catheters. JVIR 2000; 11:1309 –1314
21. Murai DT: Are femoral Broviac catheters ef-
fective and safe? A prospective comparison of
femoral and jugular venous Broviac cathe-
ters in newborn infants. Chest 2002; 121:
1527–1530
22. Weiner ES, McGuire P, Stolar CJ, et al: The
CCSG prospective study of venous access de-
vices: An analysis of insertions and causes for
removal. J Pediatr Surg 1992; 27:155–163
253
Increased calcium supplementation is associated with morbidity
and mortality in the infant postoperative cardiac patient*
Peter C. Dyke II, MD; Andrew R. Yates, MD; Clifford L. Cua, MD; Timothy M. Hoffman, MD;
John Hayes, PhD; Timothy F. Feltes, MD; Michelle A. Springer, MS, CGC; Roozbeh Taeed, MD

Objective: The purpose of this study was to assess the asso-
ciation of calcium replacement therapy with morbidity and mor-
tality in infants after cardiac surgery involving cardiopulmonary
bypass.
Design: Retrospective chart review.
Setting: The cardiac intensive care unit at a tertiary care
children’s hospital.
Patients: Infants undergoing cardiac surgery involving cardio-
pulmonary bypass between October 2002 and August 2004.
Interventions: None.
Measurements and Main Results: Total calcium replacement
(mg/kg calcium chloride given) for the first 72 postoperative
hours was measured. Morbidity and mortality data were collected.
The total volume of blood products given during the first 72 hrs
was recorded. Infants with confirmed chromosomal deletions at
the 22q11 locus were noted. Correlation and logistic regression
analyses were used to generate odds ratios and 95% confidence
intervals, with p < .05 being significant. One hundred seventy-
one infants met inclusion criteria. Age was 4 ⴞ 3 months and
weight was 4.9 ⴞ 1.7 kg at surgery. Six infants had deletions of
chromosome 22q11. Infants who weighed less required more
calcium replacement (r ⴝ ⴚ.28, p < .001). Greater calcium
replacement correlated with a longer intensive care unit length of
stay (r ⴝ .27, p < .001) and a longer total hospital length of stay
(r ⴝ .23, p ⴝ .002). Greater calcium replacement was significantly
associated with morbidity (liver dysfunction [odds ratio, 3.9; con-
fidence interval, 2.1–7.3; p < .001], central nervous system com-
plication [odds ratio, 1.8; confidence interval, 1.1–3.0; p ⴝ .02],
infection [odds ratio, 1.5; confidence interval, 1.0 –2.2; p < .04],
extracorporeal membrane oxygenation [odds ratio, 5.0; confi-
dence interval, 2.3–10.6; p < .001]) and mortality (odds ratio, 5.8;
confidence interval, 5.8 –5.9; p < .001). Greater calcium replace-
ment was not associated with renal insufficiency (odds ratio, 1.5;
confidence interval, 0.9 –2.3; p ⴝ .07). Infants with >1 SD above
the mean of total calcium replacement received on average fewer
blood products than the total study population.
Conclusions: Greater calcium replacement is associated with
increasing morbidity and mortality. Further investigation of the
etiology and therapy of hypocalcemia in this population is war-
ranted. (Pediatr Crit Care Med 2007; 8:254 –257)
KEY WORDS: heart defects; congenital; calcium; hypocalcemia;
critical care; infant; intensive care units; pediatric

S erum calcium is a function of
calcium intake, absorption,
and mobilization of skeletal
stores mediated by parathyroid
hormone and vitamin D. Calcium exists
*See also p. 300.
From the Department of Pediatrics, The Ohio State
University, and Columbus Children’s Hospital, The
Heart Center, Columbus, OH.
The authors have not disclosed any potential con-
flicts of interest.
Address requests for reprints to: Peter C. Dyke II,
MD, Department of Pediatrics, The Ohio State Univer-
sity, and Columbus Children’s Hospital, The Heart Cen-
ter, Columbus, OH 43205-2696. E-mail: lpdyke@
gmail.com
Dr. Taeed’s current address is Division of Critical
Care Medicine, The University of Texas Health Sci-
ences Center at San Antonio, San Antonio, TX. Ms.
Springer’s current address is Kimball Genetics, Den-
ver, CO.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000260784.30919.9E
in the body in a protein-bound form (usu-
ally albumin), an ionized or unbound
form (Ca2⫹), and a chelated form. Many
disease states can lead to alterations in
calcium homeostasis including parathy-
roid dysfunction, alterations in vitamin D
metabolism, neoplasia, and some bone
disorders.
Serum ionized calcium was first dem-
onstrated to correlate with measures of
cardiac contractility by McLean and Hast-
ings in 1934 (1–3). Hypocalcemia is a
known complication of critical illness (4 –
7). Hypocalcemia is a commonly recog-
nized metabolic derangement in the pe-
diatric cardiac intensive care unit
(PCICU) after cardiopulmonary bypass
(8 –10). Low serum ionized calcium con-
centration is associated with myocardial
dysfunction and hypotension (11, 12).
Hypocalcemia is associated with in-
creased length of stay, morbidity, and
mortality in critically ill patients (13, 14).
For these reasons, ionized calcium levels
are closely monitored in the PCICU, and
calcium replacement therapy is given to
maintain serum Ca2⫹ levels. Many car-
diac centers use calcium replacement to
maintain ionized calcium levels of 1–1.2
mmol/L in the immediate postoperative
period.
The purpose of this study was to assess
the association of calcium replacement
therapy with morbidity and mortality in
infants after cardiopulmonary bypass car-
diac surgery.
MATERIALS AND METHODS
This study was approved by the Institu-
tional Review Board at Columbus Children’s
Hospital. A retrospective chart review of in-
fants undergoing cardiopulmonary bypass was
performed. All infants ⬍1 yr of age who un-
derwent cardiac surgery involving cardiopul-
monary bypass from October 2002 to August
2004 were reviewed. Exclusion criteria were
weight ⬍2 kg, preoperative extracorporeal
membrane oxygenation (ECMO) support, and

254 Pediatr Crit Care Med 2007 Vol. 8, No. 3

preoperative renal insufficiency (serum creat- Table 1. Comparison of survivors and nonsurvivors
inine ⬎1.5 mg/dL) or liver insufficiency (as-
partate aminotransferase or alanine amino- Nonsurvivors, Survivors,
transferase ⬎250 units/dL). If infants All, No. (%) or No. (%) or No. (%) or
underwent more than one procedure that oth- Mean ⫾ SD Mean ⫾ SD Mean ⫾ SD p Value
erwise met inclusion criteria during the study
No. 171 19 (11) 152 (89)
period, only the first procedure performed was Age, mos 4⫾3 3⫾3 4⫾3 .20
included for analysis. The practice of all inten- Weight, kg 4.9 ⫾ 1.7 4.2 ⫾ 1.5 5.9 ⫾ 1.7 .07
sivists caring for these infants was to use sup- Male 95 (55) 15 (16) 80 (84) .03
plemental calcium chloride to maintain serum Female 76 (45) 4 (5) 72 (95)
ionized calcium levels ⬎1.2 mmol/L in the ECMO 11 (6) 8 (73) 3 (27) ⬍.001
immediate postoperative period or until the No ECMO 160 (94) 11 (7) 149 (93)
patient was hemodynamically stable. Serum
ECMO, extracorporeal membrane oxygenation.
phosphorus and magnesium were measured
regularly and supplemented as needed.
Demographic information including age,
weight, gender, diagnosis, and type of surgery Table 2. Primary cardiac diagnosis for 171 pa- imaging study. Nineteen infants (11%)
tients died before hospital discharge.
was obtained. Data were collected for the first
10 days after surgery for all outcomes except The mean total amount of calcium
No. of Patients
calcium supplementation and blood product administered during the first 3 postoper-
Primary Cardiac Diagnosis with Diagnosis
administration. Calcium supplementation and ative days was 170 mg/kg, and the median
blood product administration were recorded Ventricular septal defect 37 was 80 mg/kg. The SD was 241 mg/kg
for the first three postoperative days. Outcome Atrioventricular septal 37 (Table 3). No patients in the study re-
measurements noted were PCICU length of defect ceived a continuous calcium infusion
stay, overall hospital length of stay, liver in- Tetralogy of Fallot 17 during the study period. No infants in the
sufficiency, renal insufficiency, dialysis use, D-transposition of the great 16
study had preexisting kidney disease. Cal-
documented bacterial infection, central ner- arteries
Hypoplastic left heart 13 cium replacement was higher in smaller
vous system event (seizure or abnormal radio- infants (r ⫽ ⫺.28, p ⬍ .001). A high
syndrome
logic imaging), ECMO support, and mortality. Truncus arteriosus 6 calcium replacement correlated with
The result of chromosomal analysis by fluo- Double outlet right 5 longer PCICU length of stay (r ⫽ .27, p ⬍
rescent in situ hybridization for microdeletion ventricle .001) and longer total hospital length of
at the 22q11 locus was noted. Total blood Tetralogy of Fallot with 5
stay (r ⫽ .23, p ⫽ .002). A high calcium
product administration (whole blood, packed pulmonary atresia
Coarctation of the aorta 5 replacement was significantly associated
red blood cells, fresh frozen plasma, cryopre-
cipitate, platelets, and albumin) during the Double inlet left ventricle 4 with morbidity (liver dysfunction [odds
first 72 postoperative hours was recorded. The
Tricuspid atresia 4 ratio, 3.9; confidence interval, 2.1–7.3;
total calcium replacement (mg/kg CaCl2) for
Pulmonary atresia 4 p ⬍ .001], central nervous system com-
Total anomalous 3
the first 72 postoperative hours was measured. plication [odds ratio, 1.8; confidence in-
pulmonary venous
Statistical Analysis. Correlation, Wilcox- connection
terval, 1.1–3.0; p ⫽ .02], infection [odds
on’s rank-sums, and logistic regression analy- Interrupted aortic arch or 3 ratio, 1.5; confidence interval, 1.0 –2.2;
ses were used for data analysis, with p ⬍ .05 as aortic arch hypoplasia p ⫽ .04], ECMO [odds ratio, 5.0; confi-
significant. Odds ratios and age-adjusted odds Tricuspid regurgitation 2 dence interval, 2.3–10.6; p ⬍ .01]) and
ratios were derived by exponentiating the co- and/or stenosis mortality (odds ratio, 5.8; confidence in-
efficients from the logistic regression. For Pulmonary artery stenosis 2 terval, 5.8 –5.9; p ⬍ .01) (Table 4). The
continuous independent variables in the logis- Aortic stenosis 2
Partial anomalous 1 association between renal dysfunction
tic models, odds ratios are based on a 1 SD
pulmonary venous and calcium replacement did not reach
change.
connection statistical significance. The probability of
Pulmonary valve stenosis 1 mortality as a function of total calcium
Mitral regurgitation 1 chloride per kilogram administered dur-
RESULTS Mitral stenosis 1
Atrial septal defect 1
ing the first three postoperative days is
One hundred seventy-one infants met Heterotaxy/asplenia 1 demonstrated in Figure 1.
inclusion criteria. At the time of surgery, syndrome with single Table 5 compares the infants based on
the average age (⫾SD) was 4 (⫾3) months ventricle standard deviations of total CaCl2 supple-
and the weight (⫾SD) was 4.9 (⫾1.7) kg. mentation. One hundred fifty-three re-
There were no significant differences be- ceived ⬍1 SD above the mean of CaCl2/kg.
tween survivors and nonsurvivors based Eighteen received ⬎1 SD above the mean
on age or weight. Females (95%) survived once during the 10-day observation pe- of CaCl2/kg. Those who received ⬎1 SD
more often than males (84%) (chi-square riod. Twelve infants (7%) had at least one above the mean were significantly more
p ⫽ .03; Table 1). The cardiac diagnoses measured serum creatinine level ⬎1.5. likely to experience liver dysfunction,
are listed in Table 2. Many infants had Four infants (2%) required dialysis ther- central nervous system complication, in-
complex heart disease with more than apy for renal failure. Nineteen infants fection, ECMO, and renal dysfunction.
one lesion. Nineteen infants (11%) had (11%) had a culture-documented infec- Those who received ⬎1 SD above the
elevated alanine aminotransferase or as- tion. Ten infants (6%) had either a clin- mean were also younger, weighed less,
partate aminotransferase levels at least ical seizure or a newly abnormal neuro- and were more likely to experience longer

Pediatr Crit Care Med 2007 Vol. 8, No. 3 255

hospital stays and longer PCICU stays. Seventy-seven were tested for deletion at gram had a greater risk of liver dysfunc-
Infants who received ⬎1 SD above the the chromosome 22q11 locus. Six had a tion, central nervous system event, infec-
mean of CaCl2/kg received fewer blood deletion at the 22q11 locus. Infants with tion, need for ECMO support, and death.
products on average than those who re- a 22q11 deletion received on average 294 A significant association between calcium
ceived 1 SD below the mean of CaCl2/kg. mg/kg CaCl2. Two of six received no sup- administration and renal dysfunction was
plemental calcium. Of the remaining four not demonstrated.
with the 22q11 chromosomal deletion There is a well-known association be-
Table 3. Total calcium chloride (CaCl2) given per
who required calcium supplementation, tween transfusion with citrated blood
patient during the first three postoperative days
the range of calcium administration was products and serum albumin and hy-
CaCl2, mg CaCl2, mg/kg 69 –997 mg/kg. Three of six with a 22q11 pocalcemia. However, those in our study
deletion died. These three patients required who received more calcium chloride re-
Mean (SD) 735 (949) 170 (241) the least amount of supplemental calcium ceived fewer blood products, on average,
Median (range) 412 (0–6868) 80 (0–2215) of all patients with a 22q11 deletion. than those who received less calcium
supplementation. It appears that the hy-
DISCUSSION pocalcemia in these infants was not due
Table 4. An increased risk in calcium chloride to blood product administration. Chro-
supplementation is associated with an increased Hypocalcemia is common in the mosomal deletion at the 22q11 locus is
risk of morbidity and mortality PCICU (4, 8). Calcium replacement also a well-known cause of hypocalcemia
therapy is commonly used to avoid the in general but does not explain the asso-
Odds Ratio deleterious effects of hypocalcemia on ciation seen in this study population.
Outcome (95% CI) Significance myocardial performance. We have dem- Seventy-seven infants in the study had
onstrated that morbidity and mortality 22q11 deletion analysis. The infants with
Death 5.8 (5.8–5.9) ⬍.01
Renal insufficiency 1.5 (0.9–2.3) .07 are associated with more calcium re- a 22q11 chromosomal deletion who died
Hepatic 3.9 (2.1–7.3) ⬍.01 placement. There was a significant asso- required the least amount of calcium sup-
dysfunction ciation between higher calcium chloride plementation. More than half of the study
CNS event 1.8 (1.1–3.0) .02 supplementation and lower weight at the population was not tested for a deletion of
Infection 1.5 (1.0–2.2) .04 time of surgery. However, weight alone chromosome 22q11 because there was no
ECMO 5.0 (2.3–10.6) ⬍.01
Any morbidity 7.6 (3.8–15.1) ⬍.01 did not account for the association be- clinical suspicion based on cardiac lesion
tween calcium administration and mor- and phenotype. Blood product administra-
CI, confidence interval; CNS, central nervous bidity and mortality. After correction for tion and chromosomal deletion at the
system; ECMO, extracorporeal membrane oxy- weight, infants who required ⬎1 SD above 22q11 locus do not account for the associ-
genation. the mean of calcium chloride per kilo- ation between calcium administration and
morbidity and mortality.
Hypocalcemia can be corrected with
the administration of supplemental cal-
cium chloride. It is common practice in
the PCICU to maintain serum ionized cal-
cium levels within a predetermined nor-
mal range by supplementing with cal-
cium chloride. The clinical effect of
maintaining serum ionized calcium lev-
els above a defined threshold by admin-
istering serial intravenous bolus doses of
calcium chloride is unknown. The effi-
cacy of frequent calcium chloride boluses
in maintaining normocalcemia has not
been formally evaluated. This retrospec-
tive analysis finds a significant associa-
tion between calcium supplementation
and morbidity and mortality.
The reason for the association be-
tween calcium administration and mor-
bidity and mortality is not known. We
hypothesize that calcium supplementa-
tion does not prevent the morbidity and
mortality associated with hypocalcemia.
It is possible that hypocalcemia is the
Figure 1. Probability of death vs. total calcium chloride per kilogram given in the first 72 postoperative
hours. Data points represent percentage mortality for patients grouped per 50 mg of CaCl2/kg given secondary effect of an unidentified pri-
during the observation period. The first data point represents the probability of mortality of patients mary process in these patients. It is also
receiving no calcium chloride. Subsequent data points represent the probability of mortality of possible that calcium metabolism is al-
patients grouped in 50-mg dosing intervals. The vertical line is 1 SD above the mean and is included tered in a fashion that affects the out-
only for reference. come of infants after cardiac surgery. The

256 Pediatr Crit Care Med 2007 Vol. 8, No. 3

Table 5. Patient characteristics by total calcium chloride per kilogram administered in first 72 REFERENCES
postoperative hours
1. Hastings AB: Franklin Chambers McLean
Patients Below Patients Above 1888 –1968. Trans Assoc Am Physicians
All Patients, Mean ⫹ 1 SD, Mean ⫹ 1 SD, 1969; 82:40 –22
% or % or % or Significance, 2. Franklin C. McLean, 1888 –1968. J Bone
Mean (SD) Mean (SD) Mean (SD) p Joint Surg Am 1969; 51:413– 415
3. Urist MR: Phoenix of physiology and medi-
Total no. 171 153 18 cine: Franklin Chambers McLean. Perspect
CaCl2 administered, 170 (241) 112 660 Biol Med 1975; 19:23–58
mg/kg 4. Fuhrman BP: Hypocalcemia and critical illness
Death 11 6 50 ⬍.001 in children. J Pediatr 1989; 114:990 –991
Average length of 11 (18) 10 (14) 26 (36) ⬍.001 5. Desai TK, Carlson RW, Geheb MA: Hypocal-
stay, days cemia and hypophosphatemia in acutely ill
Average ICU LOS, 7 (10) 6 (6) 17 (25) ⬍.001
patients. Crit Care Clin 1987; 3:927–941
days
6. Zaloga GP, Chernow B: Hypocalcemia in crit-
Average age, mos 4 (3) 4 (3) 3 (3) .013
Average weight, kg 4.9 (1.7) 5 (2) 3.6 (1.2) ⬍.001 ical illness. JAMA 1986; 256:1924 –1929
Any morbidity 33 27 83 ⬍.001 7. Lynch RE: Ionized calcium: Pediatric perspec-
ECMO 6 3 33 ⬍.001 tive. Pediatr Clin North Am 1990; 37:373–389
Renal dysfunction 7 4 33 ⬍.001 8. Cuneo BF, Langman CB, Ilbawi MN, et al:
Liver dysfunction 11 7 44 ⬍.001 Latent hypoparathyroidism in children with
Infection 11 10 22 ⬍.001 conotruncal cardiac defects. Circulation
CNS events 6 4 22 .002 1996; 93:1702–1708
Dialysis 2 2 6 NS 9. Kost GJ: The significance of ionized calcium
Average blood 154 165 120 NS
in cardiac and critical care. Availability and
products, mL
critical limits at US medical centers and chil-
DiGeorge syndrome 6 3 3 NS
dren’s hospitals. Arch Pathol Lab Med 1993;
CaCl2, calcium chloride; ICU, intensive care unit; LOS, length of stay; ECMO, extracorporeal 117:890 – 896
membrane oxygenation; CNS, central nervous system; NS, not significant. 10. Robertie PG, Butterworth JF, Prielipp RC, et
Patients listed in column 3 received ⬍1 SD above the mean of total calcium chloride per kilogram. al: Parathyroid hormone responses to
Patients listed in column 4 received ⬎1 SD above the mean of total calcium chloride per kilogram. marked hypocalcemia in infants and young
children undergoing repair of congenital
heart disease. J Am Coll Cardiol 1992; 20:
672– 677
cardiac myocyte is known to be less sen- at different intervals based on the clinical 11. Desai TK, Carlson RW, Thill-Baharozian M,
sitive to calcium during acidosis (15). indications of each patient, and therefore et al: A direct relationship between ionized
Calcium as a second messenger is a key there is not a standard frequency of serum calcium and arterial pressure among patients
component in the excitation-contraction calcium measurements among our patient in an intensive care unit. Crit Care Med
coupling process. It is known that the population. Finally, serum hypocalcemia 1988; 16:578 –582
calcium flux in the cardiac myocyte is may simply be a secondary marker of a 12. Lang RM, Fellner SK, Neumann A, et al: Left
altered during heart failure and the sar- primary process that causes increased mor- ventricular contractility varies directly with
coplasmic reticulum calcium concentra- bidity and mortality. blood ionized calcium. Ann Intern Med 1988;
108:524 –529
tion is lower in heart failure (16). It is
13. Desai TK, Carlson TW, Geheb MA: Prevalence
possible that the increased morbidity and CONCLUSIONS and clinical implications of hypocalcemia in
mortality demonstrated in this study are acutely ill patients in a medical intensive
due to a decrease in myocardial calcium Critically ill infants after cardiopulmo- care setting. Am J Med 1988; 84:209 –214
sensitivity. It is possible that the method nary bypass frequently require calcium 14. Broner CW, Stidham GL, Westenkirchner
of calcium supplementation via serial in- supplementation to maintain serum ion- DF, et al: Hypermagnesemia and hypocalce-
travenous bolus therapy is less effective ized calcium levels ⱖ1.2 mmol/L. This is mia as predictors of high mortality in criti-
than previously thought. the first analysis of the association of cally ill pediatric patients. Crit Care Med
The limitations of this study include calcium supplementation and morbidity 1990; 18:921–928
those inherent in a retrospective chart and mortality in infants after cardiac sur- 15. Than N, Shah N, White J, et al: Effects of
acidosis and hypoxia on the response of iso-
review. In addition, we have defined hy- gery. Greater calcium replacement is as-
lated ferret cardiac muscle to inotropic
pocalcemia as a serum ionized calcium sociated with increasing morbidity and
agents. Cardiovasc Res 1994; 28:1209 –1217
⬍1.2 mmol/L. There is not a consensus mortality. The nature of this association 16. Vatta M, Chang AC: Molecular and cellular
definition of hypocalcemia among pediat- is not known. Further investigation of mechanisms in myocardial dysfunction. In:
ric heart centers, and different centers hypocalcemia and pharmacologic meth- Heart Failure in Children and Young Adults.
use different thresholds to treat hypocal- ods of altering calcium homeostasis and First Edition. Chang AC, Towbin JA (Eds).
cemia. Serum ionized calcium is measured calcium supplementation is warranted. Philadelphia, Saunders, 2006, pp 1–12

Pediatr Crit Care Med 2007 Vol. 8, No. 3 257

Neonatal Intensive Care

A preliminary report—Heparin counteracts indomethacin effect on

ductus arteriosus in very low birthweight infants*
Tiina H. Ojala, MD, PhD; Liisa Lehtonen, MD, PhD

Objective: We report a clinical observation showing that con-
tinuous exposure to heparin via a central venous catheter is
associated with patent ductus arteriosus treatment failure with
indomethacin in very low birthweight infants.
Study Selection: A clinical observational case report in infants
weighting <1501 g.
Data Extraction: This study compares the rates of patent
ductus arteriosus treatment failure during a) the index period
from June 2, 2003, to August 22, 2003, when all very low birth-
weight infants with a peripherally inserted central venous cath-
eter received continuous infusion of heparinized parenteral nutri-
tion; b) the baseline period of 1 yr before the index period; and c)
the postindex period of 1 yr after the index period.
Data Synthesis: The rate of patent ductus arteriosus treatment
failure with indomethacin increased significantly during the index
period compared with the baseline (odds ratio, 7.0; 95% confi-
dence interval, 1.41–34.7; p ⴝ .017) and postindex periods (odds
ratio, 33.8; 95% confidence interval, 4.72–243; p ⴝ .0005). The
result was confirmed in logistic multivariable regression analysis.
Conclusion: This observation, based on a case series and their
controls, serves as a basis for a new hypothesis suggesting that
continuous exposure to heparin through heparinized central ve-
nous infusion significantly increases patent ductus arteriosus
treatment failure with indomethacin. This hypothesis needs to be
tested in a randomized controlled trial. (Pediatr Crit Care Med
2007; 8:258 –260)
KEY WORDS: heparin; indomethacin; patent ductus arteriosus;
peripherally inserted central venous catheter; very low birth-
weight infant

A patent ductus arteriosus
(PDA) continues to be a chal-
lenging problem in preterm in-
fants. In the Vermont-Oxford
Network, 37% (quartile25 26%, quartile75
45%) of very low birthweight (VLBW) in-
fants had a symptomatic PDA, 34% (quar-
tile25 21%, quartile75 43%) received indo-
methacin treatment, and 8% (quartile25
2%, quartile75 11%) underwent a ductal
ligation (1). Failure of the initial pharma-
cologic treatment leads to major surgery
in the most critically ill preterm infants,
leading to risk of complications (2). In
addition, major surgery requires a large,
*See also p. 302.
From the Department of Pediatrics, Turku Univer-
sity Central Hospital (THO, LL) and the Department of
Pediatrics, Hospital for Children and Adolescents
(THO), Helsinki, Finland.
Supported, in part, by a grant from Turku Univer-
sity Central Hospital (EVO).
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
tiina.h.ojala@hus.fi
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262793.08216.C6
highly specialized medical team, thus in-
creasing the costs of treatment of VLBW
infants. Therefore, there is a need for new
information about the factors enhancing
both the spontaneous closure and the ef-
fects of pharmacologic treatment of PDA
in preterm infants. We report a clinical
observation derived from a case series
suggesting that continuous exposure to
heparin via a central venous catheter is
associated with PDA treatment failure
with indomethacin in VLBW infants.
MATERIALS AND METHODS
This study compares the rates of PDA treat-
ment failure during a) the index period from
June 2, 2003, to August 22, 2003, when all
VLBW infants with a peripherally inserted cen-
tral venous catheter (PICC) received continu-
ous infusion of heparinized parenteral nutri-
tion and when we recognized a clinical
problem with PDA treatment failure; b) the
baseline period of 1 yr before the index period;
and c) the postindex period of 1 yr after the
index period. All infants born in Turku Uni-
versity Central Hospital weighting ⬍1501 g
were included. The diagnosis of PDA was made
at the age of 3 days (median 3, range 3–7) on
the basis of on cardiac ultrasound performed
by the attending neonatologist. All infants
with any ductal shunt at this age received
indomethacin treatment according to the hos-
pital policy of early medical closure of the
duct. The treatment included three doses of
indomethacin, starting with a loading dose of
0.2 mg/kg, followed by 0.1 mg/kg every 24 hrs.
During indomethacin treatment, daily fluid
intake was restricted to 80 –100 mL/kg.
If long-term parenteral nutrition was ex-
pected, the infant received a PICC (Medex-
medical, 27CV), which was inserted by a clini-
cian at the bedside. The central location of the
catheter was confirmed by a chest radiograph.
During the baseline period, the PICC was
flushed every 12 hrs using 1 mL of a heparin
sodium solution (5 IU/mL). During the index
period, heparin was added to the continuous
parenteral nutrition solution in a concentra-
tion of 0.6 IU/mL. This change in the practice
was implemented to decrease the risk of cath-
eter colonizations by decreasing the number
of PICC manipulations. Based on the findings
of an increased need for ductal ligations, the
practice of adding heparin to the nutrition
infusion was changed back to the original hep-
arin flushes twice a day. No other changes in
treatment or handling procedures were pre-
sented over the reported 2-yr period.
To compare the rates of PDA treatment
failure during the three periods, the data were
tested using a repeated-measures analysis of

258 Pediatr Crit Care Med 2007 Vol. 8, No. 3

Table 1. Clinical data in very low birthweight infants with a peripherally inserted central venous fections were detected at the median age
catheter, born during the baseline, index, and postindex periods of 16 days (range 7– 65).
In the logistic multivariable regres-
Baseline Index Postindex
sion analysis of the whole study popula-
(n ⫽ 30) (n ⫽ 10) (n ⫽ 37) p Value
tion, the PDA treatment failure was asso-
Antenatal steroids, n (%) 29 (97) 9 (90) 34 (92) .545 ciated with the index period, when all
PROM, n (%) 8 (27) 4 (40) 9 (24) .636 VLBW infants with a peripherally inserted
Birth weight, g a 900 (485–1415) 818 (690–1310) 935 (390–1500) .809 central venous catheter (PICC) received
Gestational age, wksa 27.4 (24.0–33.0) 25.6 (24.3–30.0) 28.3 (23.3–30.3) .632 continuous infusion of heparinized par-
RDS, n (%) 28 (93) 10 (100) 33 (89) .429
Neonatal death, n (%) 2 (6.7) 0 (0) 6 (16) .330 enteral nutrition (p ⫽ .004).
PDA, n (%)b 17 (61%) 8 (80) 17 (55) .443
PDA surgery, n (%)b DISCUSSION
Primary 0 (0%) 1 (10) 1 (3.2) .271
Treatment failure 7 (25) 7 (70)c 2 (6.4) .0002
Infections, n (%)
We describe an observation, based on a
Early onset (⬍3 days) 1 (3.3) 0 (0) 1 (2.7) 1.000 case series and their controls, concerning
Late onsetb 7 (25) 2 (20) 5 (16) .780 an association between continuous expo-
NEC, n (%)b 1 (3.6) 1 (10) 3 (9.7) .557 sure to heparin via a central venous cath-
ROP, n (%)b 0 (0) 0 (0) 2 (6.5) .797 eter and failure of PDA treatment with
PIVH grade 3–4, n (%) 3 (11) 4 (40) 4 (13) .101
PVL, n (%)b 0 (0) 1 (10) 0 (0) .145 indomethacin in VLBW infants. After re-
viewing MEDLINE and Cochrane data-
PROM, premature rupture of membranes; RDS, respiratory distress syndrome; PDA, patent bases, we found no previous reports of
ductus arteriosus; NEC, necrotizing enterocolitis; ROP, retinopathy of prematurity; PIVH, peri- such an association.
intraventricular hemorrhage; PVL, periventricular leucomalasia. In our study, no differences were de-
a
Median (range); bnumber of studied infants is reduced due to neonatal deaths; cp ⬍ .02 compared tected in potential confounding factors,
with baseline and postindex period (Fisher’s exact test, two-tailed). p values are presented for such as the incidence of respiratory dis-
intergroup differences by repeated-measures analysis of variance or Fisher’s exact test.
tress syndrome or exposure to antenatal
steroids, between the index, baseline, and
variance and Fisher’s exact test. Data are given during the index period when compared postindex period. Furthermore, no
as number (%), median (range), or odds ratio with the baseline (OR 7.0; 95% CI 1.41– changes in the practice of PICC insertion
(OR) and 95% confidence interval (CI). The 34.7; p ⫽ .017) and postindex periods (OR were detected between the periods. The
effects of heparin via arterial catheters (radial 33.8; 95% CI 4.72–243; p ⫽ .0005). If increased incidence of late-onset blood-
or umbilical) were assessed within the group baseline and postindex periods were com- culture-positive infections in infants with
of infants treated with indomethacin during a heparinized arterial catheter can prob-
bined and compared with the index pe-
either the baseline or the postindex period. ably be explained as a complication of
riod, PDA treatment failure risk increased
Multivariate logistic regression analysis was
by up to 13-fold during the index period PDA ligation.
further used to investigate the relationship
(OR 13.0; 95% CI 2.81–59.7; p ⫽ .0016). A PICC is often needed to administer
between PDA treatment failure and perinatal/
Within the group of the surviving in- medications and parenteral nutrition for
postnatal clinical factors listed in Table 1, in-
cluding study period, presence of PICC, and fants born during the baseline and a prolonged period in VLBW infants.
presence of arterial catheter. This study was postindex periods, the continuous infu- However, these catheters can become dis-
approved by the Ethics Committee of the Uni- sion of heparin to the arterial catheter lodged, infected, or blocked. Heparin is
versity Central Hospital of Turku, Finland. (n ⫽ 19) during indomethacin treatment commonly used to reduce these compli-
tended to increase the risk of treatment cations, although there is not enough
evidence of its benefits in neonates. Fur-
RESULTS failure (OR 4.75; 95% CI 0.92–24.6; p ⫽
thermore, it can cause bleeding and al-
.063) when compared with the infants
No difference in clinical characteris- lergic reactions (3). Recently, it has been
with no arterial catheter (n ⫽ 40). There
tics of the infants was detected during the reported in adults that heparin exhibits
were no differences in the median birth
index, baseline, and postindex periods potent vasodilatory properties in both
weight (818 g [690 –1310] vs. 900 g [485–
(Table 1). Similarly, there were no veins and arteries. The concentration-
changes in the proportion of the infants 1415], p ⫽ .632, respectively) or gesta- dependent vasodilatory action of heparin
receiving a PICC between the baseline (30 tional age (25.6 wks [24 –30] vs. 26.7 wks has been linked to an endothelial release
of 35, 86%), index (10 of 13, 77%) and [24 –33], p ⫽ .809, respectively) between of nitric oxide and histamine (4, 5). This
postindex periods (37 of 44, 84%, p ⫽ the infants with or without an arterial vasodilatory effect has been shown to be
.744). The PICC was inserted on the first catheter during indomethacin treatment. indomethacin-resistant. From a clinical
or second day of life in 61 infants. A total The clinical characteristics of the infants point of view, heparin is used in prevent-
of 16 infants received the PICC on day of (given in Table 1) were similar between ing vascular spasms in cardiac surgery
life 2– 4 (three infants during the baseline these two groups (p ⬎ .211) except that (6). The vasodilatation may also contrib-
period, three during the index period, late-onset blood-culture-positive infec- ute to the hypotension associated with
and ten during the postindex period) tions were more frequent in infants with high boluses of heparin (7).
after initially having an umbilical ve- a heparinized arterial catheter compared Our observation suggests that the va-
nous catheter. with those without an arterial catheter sodilatory effect of heparin counteracts
The rate of PDA treatment failure with during the indomethacin treatment (50% the effect of indomethacin when used to
indomethacin increased significantly vs. 9%, p ⫽ .016, respectively). The in- induce ductal closure. Biochemical fac-

Pediatr Crit Care Med 2007 Vol. 8, No. 3 259

tors, mainly prostaglandin and nitric ox-
ide, in combination with anatomical fac-
tors regulate ductal closure in preterm
infants (8). It may be that the immature
ductal tissue is highly sensitive to the
vasodilatory effect of heparin mediated
through the increased endothelial nitric
oxide release. The ductal tissue of a pre-
term infant with PICC will be exposed to
heparin via the left-to-right PDA shunt.
After passing the pulmonary circulation,
heparin returns to the left side of the
heart and flows through the PDA back to
the lungs. As a result, ductal tissue will be
in continuous contact with heparin. It
still remains to be studied whether the
heparin could also disturb the spontane-
ous closure of the ductus arteriosus.
The heparin infused into the arterial
circulation may be less potent in prevent-
ing ductal closure during indomethacin
treatment. This may be explained by the
fact that the systemic venous return is
diminished in preterm infants with a
large left-to-right ductal shunt. Further-
more, the heparin may also bind to tissue
components during capillary perfusion.
Heparinized arterial infusion may predis-
pose preterm infants to hypotension, in-
creasing the hemodynamic effects of PDA
during the critical first days of life.
Due to the retrospective design and
relatively small number of observations,
there remains a possibility of an influence
of other factors related to prematurity,
although we found no differences in clin-
ical characteristics of the study groups
(Table 1). Furthermore, two control
groups were chosen— both pre- and post-
index period—to exclude the potential in-
fluences of unidentified trends in care
practices occurring by time. No other
260
changes in treatment or handling proce-
dures were introduced in the unit except
including heparin in the parenteral nu-
trition over the reported 2-yr period. This
report is, however, a preliminary obser-
vation and serves as a basis for a new
hypothesis to be studied in formal trials.
To test the hypothesis whether hepa-
rinized PICC infusion increases PDA in-
cidence and PDA treatment failure inci-
dence, we would need a randomized
controlled trial including a group with
heparinized PICC infusion and another
group with nonheparinized PICC infu-
sion. To detect a group difference of 25%
in PDA incidence, 62 VLBW infants would
be needed in each group (␣ ⫽ .05,
␤ ⫽ .2). To detect a 45% increase in the
incidence of PDA treatment failure, 23
VLBW infants would be needed in each
group (␣ ⫽ .05, ␤ ⫽ .2). Similarly, 34
VLBW infants with PDA would be needed
in each group to show whether heparin
in an arterial catheter would increase
PDA treatment failure by 30% (␣ ⫽ .05,
␤ ⫽ .2). Experimental models should be
used to study the hemodynamic effects
and the mechanisms of action of heparin
on ductal tissue.
CONCLUSIONS
Our findings suggest that continuous
exposure to heparin through heparinized
central venous infusion may increase
PDA treatment failure with indometha-
cin. With the increasingly challenging
patients who require neonatal intensive
care, the need for central venous cathe-
ters, together with arterial catheters, is
growing. Therefore, there is a need to
evaluate heparin against alternative ways
to prolong the patency of the catheters,
as our observation suggests that contin-
uous infusion of heparin ⱖ0.6 IU/mL in
central venous catheters may impair the
effectiveness of indomethacin.
ACKNOWLEDGMENT
We are grateful to Satu Ekblad, re-
search nurse in the Department of Pedi-
atrics, University of Turku, Finland, for
the data processing.
REFERENCES
1. Vermont Oxford Network 2004 database sum-
mary. Burlington, VT, Vermont Oxford Net-
work, September 2005
2. Van Overmeire B, Chemtob S: The pharmaco-
logic closure of the patent ductus arteriosus.
Semin Fetal Neonatal Med 2005; 10:177–184
3. Shah P, Shah V: Continuous heparin infusion
to prevent thrombosis and catheter occlusion
in neonates with peripherally placed percuta-
neous central venous catheters. Cochrane Da-
tabase Syst Rev 2005; 20(3):CD002772
4. Tasatargil A, Golbasi I, Sadan G, Karasu E:
Unfractioned heparin produces vasodilatory
action on human internal mammary artery by
endothelium-dependent mechanisms. J Car-
diovasc Pharmacol 2005; 45:114 –119
5. Tangphao O, Chalon S, Moreno HJ, et al: He-
parin-induced vasodilation in human hand
veins. Clin Pharmacol Ther 1999; 66:232–238
6. Seltzer J, Gerson J: Decrease in arterial pres-
sure following heparin injection prior to car-
diopulmonary bypass. Acta Anaesthesiol
Scand 1979; 23:575–578
7. Mandal A, Lyden T, Saklayen M: Heparin low-
ers blood pressure: Biological and clinical per-
spectives. Kidney Int 1995; 47:1017–1022
8. Hammerman C: Patent ductus arteriosus:
Clinical relevance of prostaglandins and pros-
taglandin inhibitors in PDA pathophysiology
and treatment. Clin Perinatol 1995; 22:
457– 479
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Clinical Investigations

Abnormalities of coagulation related to the use of inhaled nitric

oxide before extracorporeal membrane oxygenation
Amerik C. de Mol, MD; Arno F. J. van Heijst, PhD; Marc Brouwers, MD; Ton F. J. de Haan, MSc;
Frans H. J. M. van der Staak, PhD; Kian D. Liem, PhD

Objective: Evaluation of the influence of previous inhaled nitric
oxide (iNO) treatment on the occurrence of clotting complications
and disseminated intravascular coagulation during extracorporeal
membrane oxygenation (ECMO).
Design: Retrospective study in newborns treated with venoar-
terial ECMO during a 5-yr period.
Setting: Neonatal intensive care unit of a university medical
center.
Patients: A total of 59 newborns with severe respiratory insuf-
ficiency treated with venoarterial ECMO.
Interventions: Patients received iNO before ECMO (iNO group)
or not (control group).
Measurements and Main Results: There were no differences
between the groups for patient characteristics and medication
use before ECMO, except for norepinephrine. After correction for
diagnosis and duration of ECMO, significantly more clotting com-
plications and disseminated intravascular coagulation as individ-
ual variables were seen in the iNO group. For the combination of
clotting complications and disseminated intravascular coagula-
tion, there was a significantly higher prevalence in the iNO group.
Conclusions: In our population, we found a remarkable rela-
tionship between clotting complications or disseminated intra-
vascular coagulation and iNO use before ECMO treatment, which
needs further prospective research before conclusions can be
drawn. (Pediatr Crit Care Med 2007; 8:261–263)
KEY WORDS: pediatrics; inhaled nitric oxide; extracorporeal
membrane oxygenation; clotting

V enoarterial extracorporeal
membrane oxygenation (ECMO)
is a rescue therapy for neo-
nates with severe respiratory
failure (1). One of the major causes for
complications of ECMO is the distur-
bance in normal coagulation, resulting in
an increased risk of disseminated intra-
vascular coagulation (DIC) and clotting
complications in the ECMO system (2, 3).
Because persistent pulmonary hyperten-
sion is one of the most important indica-
tions for ECMO in newborns, inhaled ni-
tric oxide (iNO) is usually part of the
treatment before the start of ECMO (4).
Although used for its specificity as a pul-
monary vasodilator, iNO has systemic ef-
From the Departments of Neonatology (ACM,
AFJH, MB, KDL), Epidemiology and Bio-statistics
(TFJH), and Pediatric Surgery (FHJMS), Radboud Uni-
versity Nijmegen Medical Center, Nijmegen, The Neth-
erlands.
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
a.c.demol@cukz.umcn.nl
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262888.24742.81
fects as well (5). There are suggestions in
literature that iNO might be involved in
the initiation of the coagulation cascade
(6 –13).
The aim of this study is to evaluate the
influence of previous iNO treatment on
the occurrence of clotting complications
and DIC during the ECMO treatment.
MATERIALS AND METHODS
In a retrospective study of a 5-yr period, 85
patients treated with ECMO in our hospital
were analyzed. The project was approved by
the institutional review board. Patients with
congenital diaphragmatic hernia were ex-
cluded (n ⫽ 26) because, in our center, iNO is
not part of the standard treatment protocol in
congenital diaphragmatic hernia (14). In ad-
dition, patients with congenital diaphragmatic
hernia on ECMO receive tranexamic acid, an
antifibrinolytic drug, during the operation. Fi-
nally, 59 patients were included, of which 25
patients received iNO treatment before ECMO
(iNO-group) and 34 patients started with
ECMO without previous iNO treatment (con-
trol group). The control group consists of pa-
tients from the time before the introduction of
iNO at our institution and from the time that
there was limited availability of iNO. No more
patients were included from the time when
iNO was fully available. Through the study
period, selection criteria to start iNO were
based on an oxygenation index of ⱖ25 while
on assisted ventilation. Patients were treated
with 20 ppm NO. The iNO group and the
control group were compared for gestational
age, birth weight, lowest arterial oxygen satu-
ration, lowest Pa O 2 , maximum alveolar–
arterial difference in partial pressure of oxygen
before ECMO, ventilatory settings, postnatal
age at the initiation of ECMO, duration of
ECMO, worst pH before ECMO, and Apgar
scores at 1 and 5 mins using Student’s t-test.
Primary diagnoses were compared using
Fisher exact test. The independence between
sex and iNO in this study was analyzed using a
chi-square test.
All patients received a heparin-loading
dose of 150 units/kg at the initiation of ECMO.
After this, heparinization was checked every
hour by measuring the activated clotting time,
aiming for values between 200 and 220 secs
(Hemochron, ITC Europe, Italy). iNO was
stopped immediately after the initiation of
ECMO. We studied differences in the occur-
rence of clotting complications or DIC be-
tween the iNO group and the control group.
Clotting complications were defined as cere-
bral infarction on ultrasound, computed to-
mographic scan, or magnetic resonance image
or clot formation in the ECMO system by

Pediatr Crit Care Med 2007 Vol. 8, No. 3 261

visual inspection. The diagnosis of DIC was drome and sepsis. There was no signifi- mortality in term infants with hypoxic
based on laboratory results performed on a cant difference in pre-ECMO medication respiratory failure (15). Clotting compli-
daily basis with a D-dimer concentration of between the two groups except for the cations and DIC are major problems for
⬎10,000 units/L in combination with decreas- use of norepinephrine (four patients in patients receiving ECMO. Because of the
ing fibrinogen levels to values of ⬍1500 mg/L. the iNO group vs. no patient in the con- potential effects on the coagulation cas-
We performed a linear logistic-regression trol group [Fisher exact test, p ⫽ .03]). cade, the use of iNO in this population
analysis (Statistical Analysis System, SAS In- Mean oxygenation index at or near the has been of our concern (6 –13).
stitute, Cary, NC) to look for significant rela- time iNO was initiated was 38 ⫾ 9. In this retrospective study, we found a
tions with iNO treatment before ECMO. For
The occurrence of clotting complica- remarkable relationship between the oc-
clotting complications and DIC, iNO treat-
tions or DIC during ECMO is shown in currence of clotting complications or DIC
ment and primary diagnosis were included in
Table 2. A p value just above the defined and the use of iNO before ECMO. After
the regression models. Other factors included
were gestational age, birth weight, postnatal
level of significance was observed for the correction for diagnosis and duration of
age at start of ECMO, and pre-ECMO medica- relationship between previous iNO use ECMO, both clotting complications and
tion. Patient characteristics are presented as and clotting complications and DIC. This DIC were significantly more present in
mean ⫾ SD. Odds ratios for complications are became statistically significant (odds ra- the iNO group than in the control group.
presented with a 95% confidence interval; p tio, 3.4 [95% confidence interval, 2.1– When combined, clotting complications
values of ⬍.05 were considered significant. 22.6] and 4.5 [1.3–19.6]) after correction or DIC occurred significantly more often
for diagnosis and duration of ECMO. For in the iNO group than in the control
RESULTS the combination of clotting complica- group. The fact that the difference in
tions or DIC, a statistically significant clotting complications and DIC between
No significant differences were found relationship with previous iNO was found, the iNO group and control group in-
for pre-ECMO characteristics between which persisted after correction for diagno- creased after correction for diagnosis
groups (Table 1). More than one primary sis and duration of ECMO (odds ratio, 5.6 might be explained by the fact that there
diagnosis was found in several patients. [95% confidence interval, 1.7–20.4]). were more patients with sepsis in the
In the iNO group, two patients were di- control group. Because sepsis, even with-
agnosed with the combination of sepsis DISCUSSION out ECMO, is related to the occurrence of
and pneumonia, one patient with meco- clotting complications and DIC, these
nium aspiration syndrome and sepsis and iNO effectively reduces the number of complications might already be present
one patient with respiratory distress syn- ECMO treatments but does not reduce in these patients. Pretreatment with iNO
of newborns in need of ECMO therapy
seems to have an effect on the coagula-
Table 1. Characteristics of inhaled nitric oxide (iNO) and control groups tion cascade in this study. It is hard to
explain this from the known effects of
iNO Group Control Group iNO. Based on literature, hypothetical ex-
(n ⫽ 25) (n ⫽ 34) planations might be found in vascular
and tissue damage, apoptosis, an increase
Mean SD Mean SD p Values
in free radicals, and increased expression
Pre-ECMO variable of factors initiating the coagulation cas-
Gestational age, wks 39 2 39 3 .69 cade, like tissue factor. In term infants,
Birth weight, g 3422 586 3392 626 .86 prolonged (24 – 48 hrs) exposure to iNO is
Lowest SaO2, % 64 22 63 21 .85 associated with an increase in markers of
Lowest PaO2, mm Hg 42 17 35 11 .11
Maximum P (A-a)O2, mm Hg 636 21 644 14 .12 oxidative injury in serum samples (6).
PIP, cm H2O 36.8 1.8 37.5 2.6 .45 Kobayashi et al. (7) found a relationship
MAP, cm H2O 19.6 2.1 19.5 2.5 .74 between long-term inhalation of NO and
PEEP, cm H2O 5.0 1.2 4.6 1.2 .25 activation of the clotting system by in-
Duration of ECMO, hrs 173 52 155 74 .27
creasing the lung expression of tissue fac-
Postnatal age at start of ECMO, hrs 59 68 53 63 .70
Worst pH 7.31 0.16 7.26 0.16 .29 tor. It is known that free radicals and
Apgar score at 1 min 5.4 3.1 5.8 2.8 .63 apoptosis are likely to play a role in the
Apgar score at 5 mins 6.3 2.4 6.9 2.2 .30 expression of tissue factor and increased
Sex (male/female) 13/12 25/9 .05 thrombin generation on the surface of
Primary diagnosisa No. (%) No. (%) monocytes, macrophages, and endothe-
MAS 19 (76) 19 (56) .17
lial cells (8 –11). Finally NO can influence
Sepsis 4 (16) 8 (24) .53
Pneumonia 2 (8) 7 (21) .28 coagulation variables in vitro via nitrosy-
RDS 2 (8) 2 (6) 1.00 lation of thiol groups (12, 13). The clini-
Primary PPHN 2 (8) 5 (15) .69 cal relevance of these mechanisms re-
Total number of primary diagnoses 29 41 mains unclear. It is speculative whether
there might be a cumulative effect in the
ECMO, extracorporeal membrane oxygenation; SaO2, arterial oxygen saturation; P(A-a)O2, alveolar-
arterial difference in partial pressure of oxygen; PIP, positive inspiratory pressure before ECMO; MAP, initiation of the coagulation cascade by
mean airway pressure before ECMO; PEEP, positive end-expiratory pressure before ECMO; MAS, the combination of iNO and a consecutive
meconium aspiration syndrome; RDS, respiratory distress syndrome; PPHN, persistent pulmonary ECMO treatment.
hypertension of the newborn. We recognize the limitations of a ret-
a
Several patients had more then one primary diagnosis. rospective study design in which patients

262 Pediatr Crit Care Med 2007 Vol. 8, No. 3

Table 2. Occurrence of clotting complications and disseminated intravascular coagulation (DIC)
during extracorporeal membrane oxygenation (ECMO) in the inhaled nitric oxide (iNO) group and
control group
iNO Control
Group Group
(n ⫽ 25) (n ⫽ 34)
Complication n (%) n (%)
Clotting 10 (40) 6 (18)
DIC 10 (40) 6 (18)
Clotting and/ 17 (68) 9 (26)
or DIC
a
Statistically significant (p ⬍ .05) after correction for diagnosis or after correction for diagnosis
and ECMO duration.
Odds ratios (OR) are presented with a 95% confidence interval (CI) for each complication before
and after correction for diagnosis and for diagnosis and duration of ECMO.
are not randomized and findings could be
influenced by many factors. However, we
are not aware of any study focusing on
the possible negative effects of iNO treat-
ment before ECMO. Because iNO has
been accepted as standard therapy for
newborns with severe respiratory insuffi-
ciency with pulmonary hypertension,
prospective studies are hard to perform
because of medical and ethical consider-
ations. Due to the limited capacity of iNO
treatment in our hospital during the
study period, the start of iNO depended
on its availability. If more patients with
an iNO indication were presented at the
same time with limited availability of iNO
the choice to use iNO in which patient
was at the discretion of the treating phy-
sician and bias related to myriad factors
cannot be ruled out. Although the two
groups were not completely homoge-
neous for diagnosis, especially sepsis and
meconium aspiration syndrome, this was
not statistically significant. To correct for
the possible influence of primary diagno-
sis on complications, we did, however,
perform a logistic-regression analysis.
Treatment in both groups was equal, ex-
cept for the use of norepinephrine, which
was used significantly more often in the
iNO group. It is unclear whether this was
related to the use of iNO. Finally, the
control group had a higher percentage of
Pediatr Crit Care Med 2007 Vol. 8, No. 3
ygenation. Semin Perinatol 2000; 24:
406 – 417
2. ELSO Registry Report, July 2006. Ann Arbor,
MI, Extracorporeal Life Support Organiza-
Regression Analysis tion, 2006
3. Zwischenberger JB, Nguyen TT, Upp R, et al:
Corrected Complications of neonatal extracorporeal
membrane oxygenation: Collective experi-
For Diagnosis ence from the Extracorporeal Life Support
Not Corrected and Duration Organization. J Thorac Cardiovasc Surg
For Diagnosis of ECMO 1994; 107:838 – 849
OR (95% CI) p OR (95% CI) OR (95% CI) 4. Kinsella JP, Abman SH: Inhaled nitric oxide:
a a
Current and future uses in neonates. Semin
3.1 (1.0–10.8) .056 3.4 (2.1–22.6) 3.4 (1.0–11.8) Perinatol 2000; 24:387–395
3.1 (1.0–10.8) .056 4.5 (1.3–19.6)a 4.3 (1.2–17.4)a
5. Weinberger B, Laskin DL, Heck DE, et al:
5.9 (2.0–19.3) .001 6.4 (2.1–22.6)a 5.9 (1.7–20.4)a
The toxicology of inhaled nitric oxide. Toxi-
col Sci 2001; 59:6 –16
6. van Meurs KP, Cohen TL, Guang Y, et al:
Inhaled NO and markers of oxidant injury in
infants with respiratory failure. J Perinatol
2005; 25:463– 469
7. Kobayashi T, Gabazza EC, Shimizu S, et al:
Long-term inhalation of high-dose nitric ox-
ide increases intra-alveolar activation of co-
male patients than the iNO group. Al- agulation system in mice. Am J Respir Crit
though this was just above of the level of Care Med 2001; 163:1676 –1682
significance, any influence on the find- 8. Polack B, Pernod G, Barro C, et al: Role of
ings cannot be excluded. oxygen radicals in tissue factor induction by
If our results would be confirmed by endotoxin in blood monocytes. Haemostasis
prospective studies, it is of great interest 1997; 27:193–200
9. Greeno EW, Bach RR, Moldow CF: Apoptosis
to further investigate the possible mech-
is associated with increased cell surface tis-
anisms of iNO on the coagulation system.
sue factor procoagulant activity. Lab Invest
Major clot formation in the circuit can be 1996; 75:281–289
detected by circuit inspection, but small 10. Golino P, Ragni M, Cirillo P, et al: Effects of
clots can escape into the circulation of tissue factor induced by oxygen free radicals
the patient and cause (small) infarctions. on coronary flow during reperfusion. Nat
Disturbance in other organ functions can Med 1996; 2:35– 40
also be involved in DIC. We should be 11. Umansky V, Hehner SP, Dumont A, et al:
aware of this potential risk of using iNO Co-stimulatory effect of nitric oxide on en-
in newborns with respiratory failure qual- dothelial NF-kappaB implies a physiological
self-amplifying mechanism. Eur J Immunol
ifying for ECMO treatment.
1998; 28:2276 –2282
12. Simon Di, Mullins ME, Jia L, et al: Polyni-
CONCLUSIONS trosylated proteins: Characterization, bioac-
tivity, and functional consequences. Proc Nat
In this retrospective study, we found a
Acad Sci U S A 1996; 93:4736 – 4741
remarkable relationship between clotting
13. Catani MV, Bernassola F, Rossi A, et al: In-
complications or DIC and iNO use before hibition of clotting factor XIII activity by
ECMO treatment. A prospective, random- nitric oxide. Biochem Biophys Res Commun
ized study is indicated, which should also 1998; 249:275–278
investigate the mechanisms of possible 14. The Neonatal Inhaled Nitric Oxide Study
adverse effects of iNO on the coagulation Group: Inhaled nitric oxide and hypoxic re-
system before and during ECMO, before spiratory failure in infants with congenital
strong conclusions can be made. diaphragmatic hernia. Pediatrics 1997;
6:838 – 845
15. Finer NN, Barrington KJ: Nitric oxide for
REFERENCES
respiratory failure in infants born at or near
1. Rais-Bahrami K, Short BL: The current sta- term. Cochrane Database Syst Rev 2001;
tus of neonatal extracorporeal membrane ox- CD000399
263
Energy expenditure in critically ill children
Christine M. Hardy Framson, PhD, RD, CNSD; Neal S. LeLeiko, MD, PhD; Gerard E. Dallal, PhD;
Ronenn Roubenoff, MD, MHS; Linda K. Snelling, MD; Johanna T. Dwyer, DSc, RD

Objective: To assess the measured resting energy expenditure
pattern over time in a group of critically ill children who were
admitted to a pediatric intensive care unit and to determine
whether a hypermetabolic response, i.e., >10% above predicted,
occurred in a pattern similar to that observed in adults. A sec-
ondary aim was to compare the accuracy of a newly derived
prediction equation specific to the pediatric intensive care unit
and the measured resting energy expenditure.
Design: A prospective, clinical, observational study.
Setting: A pediatric intensive care unit of a tertiary care
medical center.
Patients: Forty-four children (29 males, 15 females) ages 2
wks to 17 yrs.
Interventions: None.
Measurements and Main Results: During the course of their
stay in the pediatric intensive care unit, 44 patients’ measured
resting energy expenditure was assessed using indirect calorim-
etry 94 times at up to three time points. The first measurement
was at a mean time of 25 ⴞ 10 (ⴞSD) hrs after admission, the
second at 73 ⴞ 16 hrs, and the third immediately before dis-
charge, which occurred at a mean of 193 ⴞ 93 hrs after admis-
sion. Measured energy expenditure varied only slightly (7% to
10%) from the first to second and the second to third measure-
ments. Evidence for hypermetabolism was not apparent. Generally,
the prediction equations performed well. Mean measured resting
energy expenditure for all measurements was 821 ⴞ 653 kcals/24
hrs. The Schofield equation estimate was 798 ⴞ 595 kcals/24 hrs
and the White equation estimate was 815 ⴞ 564 kcals/24 hrs (p ⴝ
not significant). Nineteen (20%) measurements were >110% above
the age-appropriate Schofield-predicted equation, and 30 measure-
ments (32%) were <90% below that predicted by Schofield. Conse-
quently, 45% of measured resting energy expenditure measurements
were within 90% to 110% of that predicted by the Schofield equation.
The White equation was inaccurate (not within 10% of measured
resting energy expenditure) in 66 of 94 measurements (70%). The
discrepancy was greatest (100%) in children with measured rest-
ing energy expenditure <450 kcal/24 hrs.
Conclusion: The hypermetabolic response apparent in adults
was not evident in these critically ill children. Currently avail-
able prediction equations cannot substitute for indirect calo-
rimetry measurement of energy expenditure in guiding nutri-
tional support in pediatric intensive care units. (Pediatr Crit
Care Med 2007; 8:264 –267)
KEY WORDS: pediatrics; energy expenditure; critical illness

C ritically ill children are at a
high nutritional risk because
of their relatively high energy
requirements and limited en-
ergy reserves (1, 2). Frequent monitoring
of their energy expenditure is necessary
From the Divisions of Pediatric Gastroenterology, Nu-
trition, and Liver Diseases (CMHF, NSL) and Pediatric
Critical Care (LKS), Hasbro Children’s Hospital at Rhode
Island Hospital, Providence, RI; Jean Mayer U.S. Depart-
ment of Agriculture Human Nutrition Research Center on
Aging (CMHF, GED) and Friedman School of Nutrition,
School of Medicine (CHF, JD), Tufts University, Boston,
MA; and Frances Stern Nutrition Center, Tufts-New En-
gland Medical Center, Boston, MA (JD).
Supported, in part, by the National Institutes of
Health, National Center for Research Resources, Gen-
eral Clinical Research Center, grant M01 RR-00054 at
Tufts-New England Medical Center.
Dr. Roubenoff is employed by Millennium Pharma-
ceuticals. The remaining authors have not disclosed
any potential conflicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262802.81164.03
to accommodate any variations in energy
expenditure throughout the course of ill-
ness. An accurate assessment of chil-
dren’s acute energy needs is necessary to
avoid the untoward effects of either un-
derfeeding or overfeeding, both of which
impair immune function and wound
healing (3–5).
In clinical practice, energy needs often
are estimated by the use of prediction
equations, although they are not accurate
enough to estimate the energy require-
ments of the critically ill child hospital-
ized in a pediatric intensive care unit
(PICU) (4 – 8). Indirect calorimetry is the
preferred method to determine energy re-
quirements in hospitalized patients, but
it requires expensive equipment and
trained staff. Its use may be limited in the
assessment and monitoring of the sickest
children, who require a great deal of di-
rect care that cannot be interrupted for
such measurements.
Critically ill children are expected to
differ in their energy expenditure from
healthy children. For example, it has
been suggested that growth ceases during
the metabolic response to illness or in-
jury in children (1, 5). Additionally, chil-
dren who require mechanical ventilation
and aggressive sedation will have little or
no spontaneous respiratory effort or
physical activity (6). Among these pa-
tients, total daily energy expenditure
should be equivalent to resting energy
expenditure. Recent studies have shown
that critically ill children exhibited lit-
tle or no elevation in metabolic rate
during different phases of a critical ill-
ness (7–10).
The goal of this study was to describe
the potential variations in energy ex-
penditure among critically ill children
during the course of their admission to
the PICU in an effort to identify poten-
tial periods of hypermetabolism. We
also assessed the use of a prediction
equation developed by White and col-
leagues (11) especially for use on criti-
cally ill children.

264 Pediatr Crit Care Med 2007 Vol. 8, No. 3

MATERIALS AND METHODS
Patient Population. Children admitted to
the PICU at Hasbro Children’s Hospital, Prov-
idence, RI, from June 1999 through October
2001 were eligible for recruitment into the
study if they were without overt signs or
symptoms of chronic disease and either a)
breathing spontaneously without the need for
supplemental oxygen or b) mechanically ven-
tilated with an oxygen requirement of ⬍60%
and the absence of an audible air leak around
the endotracheal tube.
Energy Expenditure. Resting energy ex-
penditure was assessed by indirect calorimetry
using a DeltaTrac Metabolic Monitor (Sensor-
medics, Yorba Linda, CA). The equipment was
calibrated using a reference gas with a known
concentration of 96% oxygen and 4% CO2 be-
fore each measurement and was also cali-
brated using the alcohol-burn technique
monthly. Each measurement occurred at least
30 mins after any type of treatment interven-
tion and lasted 30 mins.
Measurements of energy expenditure were
made on up to three occasions for each en-
rolled patient. The first measurement was at-
tempted within 24 hrs of admission to the
PICU. The second measurement was made ap-
proximately 48 hrs after the first measure-
ment. The third measurement was made
within 24 hrs before discharge from the PICU
on patients who required a longer admission.
This study was approved by the Human
Institutional Review Board at Rhode Island
Hospital. A parent or guardian provided in-
formed consent, and assent also was obtained
whenever possible from children 8 yrs of age
or older.
Clinical Data. Age, weight, and height or
length were recorded at admission. At the time
of each metabolic measurement, weight when
available, temperature, blood pressure, heart
rate, and the Pediatric Risk of Mortality
(PRISM) score were obtained. The PRISM
score is a standardized scoring tool that mea-
sures the severity of illness and the risk of
mortality from a set of 14 variables derived
from physiologic and laboratory data (12). It
was calculated by one of the investigators
(CHF) at the time of each indirect calorimetry
measurement. Also, admission diagnosis, type
and route of nutrition support, and total cal-
ories received for the 24-hr period before met-
abolic measurement were collected.
Respiratory status data also were collected,
including the need for mechanical ventilation
(yes or no) and the FIO2 concentration deliv-
ered by the ventilator, as well as ·VO2, ·VCO2,
and respiratory quotient (rate of oxygen con-
sumed/rate of CO2 produced). These were re-
corded to provide an estimate of macronutri-
ent use at each time point.
Prediction Equations. The Schofield pre-
diction equations that are based on weight
were used to predict resting energy expendi-
ture (13). For the purposes of this study, hy-
permetabolism was defined as measured en-
ergy expenditure (MEE) ⬎110% above that and mean height was 102 ⫾ 48 cm. Mean
predicted by the age-appropriate Schofield length of stay in the PICU was 6.2 ⫾ 4.8
equation, and hypometabolism was defined as days. Thirteen patients were admitted af-
MEE ⬍90% of that predicted in the study
ter an elective procedure; the remaining
population (14).
patients were admitted as a result of an
An equation developed specifically for crit-
ically ill children by White and colleagues (11) acute illness or injury. Thirty-one of the
also was calculated for each patient to assess patients required some type of surgery
its accuracy. It would be considered useful and (general, cardiac, orthopedic, or neuro-
accurate if its prediction of energy expenditure surgery). Nutritional assessment was per-
fell within 10% of MEE in at least half of the formed on each patient at the time of
study population. admission by the nutritionist (CHF). All
Data Analysis. Comparisons between vari- patients were determined to be well nour-
ables at each time point were made using the ished at that time. A total of 94 metabolic
Student’s t-test. Correlation analysis was per-
measurements were performed on 44 pa-
formed to describe the associations of age,
weight, respiratory quotient, PRISM score, heart
tients. In all cases, the patients tolerated
rate, temperature, and FIO2 with MEE. Statistical the study well, and no complications
analysis was performed using SPSS, version 13.0 were noted.
(SPSS, Chicago, IL). The limit of agreement Table 1 describes the characteristics of
analysis according to the method of Bland and the study population. Table 2 describes
Altman (15) was used to examine the accuracy of the various parameters associated with
predictions by the White equation. energy metabolism in these patients. En-
ergy intakes, albeit inadequate, gradually
RESULTS increased during the course of recovery
from the first measurement to the third.
Forty-four patients (29 males, 15 fe-
PRISM scores, heart rate, and tempera-
males) were studied. Mean (⫾SD) age was
ture decreased, and the respiratory quo-
5.16 ⫾ 5.87 yrs (range, 0 –17); mean
tient rose slightly during the same time.
weight at admission was 23 ⫾ 23.2 kg,
Age and weight were the only variables
that significantly correlated with MEE at
all three measurements (p ⬍ .0001).
Table 1. Patient characteristics and reason for
admission
Mean MEEs for all patients at each
time point are summarized in Table 2.
Age (mean ⫾ SD) 5.2 ⫾ 5.9 Few patients demonstrated a hyper-
Sex (M/F) (n) 29/15 metabolic response (i.e., MEE ⬎110%
Reason for admission (n) of prediction) at any of the measure-
Acute illness 17
Trauma 13
ments: eight of 41 (19%) at the first
Elective 14 measurement, five of 36 (14%) at the
Neurosurgery 4 second, and six of 17 (35%) at the third.
Cardiovascular 7 Conversely, many patients exhibited an
General 1 energy expenditure that would be con-
Orthopedic 1
Ear, nose, throat 1 sidered hypometabolic (i.e., MEE ⬍90%
of prediction): nine (22%) at the first
Table 2. Comparison of variables at each time point for all patients available at that time
Time 1 Time 2 Time 3
Mean MEE—All Measures n ⫽ 41 n ⫽ 36 n ⫽ 17
Time of MEE ⫾ SD, hours 25 ⫾ 10.3 73.5 ⫾ 16.3 192.5 ⫾ 93.4
after PICU admission
PRISM score 3.4 ⫾ 2.9 2.5 ⫾ 2.4a,c 1.3 ⫾ 1.5a,b
MEE, kcals/day 842 ⫾ 645 785 ⫾ 636a,c 846 ⫾ 741
Surgical patients (n) 915 ⫾ 677 (30) 855 ⫾ 677 (25) 912 ⫾ 831 (12)
Nonsurgical (n) 641 ⫾ 478 (11) 627 ⫾ 525 (11) 686 ⫾ 501 (5)
p, surgical vs. nonsurgical .10 .24 .31
Respiratory quotient 0.83 ⫾ 0.12 0.83 ⫾ 0.07 0.88 ⫾ 0.16
FIO2 (%) 0.28 ⫾ 0.08 0.25 ⫾ 0.06 0.21 ⫾ 0
Heart rate, beats per minute 132 ⫾ 32 121 ⫾ 30 125 ⫾ 28
Temperature, °C 37.3 ⫾ 0.6 37 ⫾ 0.7 37 ⫾ 0.6
Total energy intake, kcals/day 163 ⫾ 134 289 ⫾ 248 793 ⫾ 567
MEE, measured energy expenditure; PICU, pediatric intensive care unit; PRISM, pediatric risk of
mortality.
a
p ⬍ .05 vs. time 1; bp ⬍ .05 vs. time 2; cp ⬍ .05 vs. time 3. All values are mean ⫾ SD.

Pediatr Crit Care Med 2007 Vol. 8, No. 3 265

measurement, 15 (42%) at the second, changes in resting energy expenditure energy normally used for growth toward
and six (35%) at the third. during the course of admission were rel- meeting the metabolic demands of the
Patients who required surgery did not atively small (i.e., ⫾60 calories/24 hrs) in acute insult (2). However, such a redis-
differ significantly from nonsurgical pa- the majority of children in our study. tribution of energy would be difficult to
tients in their MEE at any time (p ⫽ .10, MEE fluctuated little during the course of quantify for the short term, because en-
.24, or .31 at each of the three measure- admission to the PICU and most energy- ergy expenditure used for growth is very
ments, respectively). Mean MEE did not expenditure measurements were below, small, especially in older children (⬍5%),
differ significantly during the course of rather than above, predicted estimates. and is indistinguishable from the mea-
admission (Table 2). These findings and other studies suggest surement of the resting metabolic rate.
Compared with a mean MEE (⫾SD) of that children do not become hypermeta- Despite the inherent heterogeneity of
841 ⫾ 645 calories/day, the Schofield bolic while they are critically ill (5– 8), patients admitted to the PICU, there was
equations estimated mean energy expen- supporting a conservative approach, in- a remarkable similarity in MEE in our
diture to be 798 ⫾ 595 calories/day, and cluding measurement of energy expendi- patients compared with those in other
the White equation for critically ill chil- ture, when attempting to estimate energy studies. Mean MEE was similar to energy
dren estimated the mean energy expendi- needs in critically ill children. expenditure, as calculated by the
ture to be 815 ⫾ 564 calories/day. Nei- The evident lack of a sharply elevated Schofield equations. In a study by Taylor
ther the Schofield nor White equation metabolic rate in critically ill children and colleagues (9), MEE was measured
mean values differed significantly from may be the result of the re-channeling of daily for 7 days in 57 patients. The num-
the mean MEE.
Figure 1 illustrates a modified Bland-
Altman plot that compares prediction
estimates using the White equation for
critically ill children with indirect cal-
orimetry measurements at each time
point. The prediction estimates within
10% of MEE are considered clinically
useful in individual patients. This plot
shows that those with the lowest MEE
(⬍450 calories/24 hrs), who were the
smallest children, were least likely to
have energy requirements predicted
within 10% of measured by the White
equation. Children with MEE ⬎500 cal-
ories/24 hrs appeared to have their en-
ergy requirements predicted more accu-
rately by the White equation, especially at
the first two measurements.
Figure 2 displays the distribution of all
measurements of MEE by the time of
each measurement. No particular time-
related pattern in these measurements
was apparent.

DISCUSSION
Figure 1. Modified Bland-Altman plot of comparison of measured energy expenditure (MEE) to energy
It is often assumed that children re- requirements calculated using the White prediction equation for critically ill children at each time
semble adults in their metabolic response point. Dashed lines indicate ⫾10% MEE.
to critical illness or injury. In adults, en-
ergy expenditure rises early in the course
of their stay and it remains elevated until
the acute illness begins to resolve (15–
18). Plank and Hill (18) describe this phe-
nomenon of hypermetabolism during
critical illness in a group of 33 adults
with severe sepsis after major blunt
trauma. The ratio of measured vs. pre-
dicted energy expenditure rose during
the first 4 –5 days, peaking at 9 –12 days,
declining gradually, and remaining hy-
permetabolic 11 days thereafter.
We found little evidence to support Figure 2. Distribution of measured energy expenditure values during the course of admission to a
this pattern in our study. Mean observed pediatric intensive care unit.

266 Pediatr Crit Care Med 2007 Vol. 8, No. 3

ber of measurements obtained on day 1
and day 3 was similar to that in the
present study, as was the mean time of
measurement. Energy expenditure at
these times was comparable between the
two studies.
In another study, Vasquez Martinez
and colleagues (7) attempted to charac-
terize energy expenditure in the early
post-injury period in a group of 43 criti-
cally ill children. They also compared
MEE with nine different prediction meth-
ods and found that even with an early
measurement of energy expenditure, the
majority of patients did not demonstrate
a hypermetabolic response to the insult.
Those patients had higher mean PRISM
scores and inspired oxygen concentra-
tions, suggesting that they were sicker
and more stressed than our patients.
However, their findings support our con-
clusion that children do not become hy-
permetabolic when critically ill and that
prediction methods are too imprecise for
use in critically ill children.
Many studies that have examined the
use of prediction methods to determine
energy requirements for critically ill chil-
dren (4 –11) conclude that prediction
methods are not accurate for them and
that indirect calorimetry is the preferred
method to determine energy needs most
accurately. Therefore, it would be inter-
esting to determine in a future study
whether most practitioners working in
PICUs determine their patients’ energy
needs using indirect calorimetry, predic-
tion equations, or rough rules of thumb.
The prediction equation of White and
colleagues (11) was developed from indi-
rect calorimetry measurements in a pop-
ulation of 100 critically ill children who
had been admitted to an intensive care
unit. They measured each child once, at
an average of 48 hrs after admission.
When we calculated predicted mean en-
ergy expenditure with this equation in
the current study, the result was similar
to mean MEE. However, the White pre-
diction equation, specifically developed
for use in critically ill children, was too
inaccurate to use because it exhibited a
wide range of variability, confirming find-
ings from another study (9). For a pre-
diction method to be considered accu-
rate, it must predict within 10% of a
Pediatr Crit Care Med 2007 Vol. 8, No. 3
measured value in at least half of the
patients. The White equation predicted
accurately in only 30% of measurements,
indicating that it was not accurate
enough for use in this population. Figure
1 illustrates the large number of mea-
surements that fell ⬎10% above or below
MEE. The White equation was also the
least precise in predicting requirements
in the smallest patients in our study. This
was not expected, because the equation
was derived from measurements on a
population of younger and smaller pa-
tients than ours.
It is difficult to develop a prediction
equation that accurately estimates energy
requirements in critically ill children, be-
cause patients admitted to a PICU are
usually more heterogeneous than criti-
cally ill adults in their age, weight, mus-
cle mass, level of growth and maturity,
and diagnosis. Also, the criteria for ad-
mission to a PICU often are broad, allow-
ing admission of children with many de-
grees of illness severity.
CONCLUSION
Children may differ from adults in
that when they are critically ill, they do
not exhibit the hypermetabolism that has
been well described in adults. The White
equation is too imprecise for use in crit-
ically ill children, especially infants. Be-
cause a valid prediction equation for use
in critically ill children does not yet exist,
measurement of energy expenditure us-
ing indirect calorimetry remains the best
way to guide nutritional support in PICU
patients.
REFERENCES
1. Chwals WJ: Overfeeding the critically ill
child: Fact or fiction? New Horizons 1994;
2:147–155
2. Klein S, Kinney J, Jeejeebhoy K, et al: Nutri-
tional support in clinical practice: Review of
published data and recommendations for fu-
ture research directions. Am J Clin Nutr
1997; 66:683–706
3. Chwals, WJ: Infant and pediatric nutrition.
In: Nutrition in Critical Care. Zaloga GP
(Ed). St. Louis, MO, Mosby, 1994, pp
727–763
4. Verhoeven JJ, Hazelzet JA, van der Voort E,
et al: Comparison of measured and predicted
energy expenditure in mechanically venti-
lated children. Int Care Med 1998; 24:
464 – 468
5. Jaksic T: Effective and efficient nutritional
support of the injured child. Surg Clin N Am
2002; 82:379 –391
6. Vernon DD, Witte MK: Effect of neuromus-
cular blockade on oxygen consumption and
energy expenditure in sedated, mechanically
ventilated children. Crit Care Med 2000; 28:
1569 –1571
7. Vazquez Martinez JL, Martinez-Romillo PD,
Diez Sebastian J, et al: Predicted versus mea-
sured energy expenditure by continuous on-
line indirect calorimetry in ventilated, criti-
cally ill children during the early postinjury
period. Pediatr Crit Care Med 2004; 5:19 –27
8. Hardy CM, Dwyer J, Snelling LK, et al: Pit-
falls in predicting resting energy require-
ments in critically ill children: A comparison
of predictive methods to indirect calorime-
try. Nutr Clin Pract 2002; 17:182–189
9. Taylor RM, Cheeseman P, Preedy V, et al: Can
energy expenditure be predicted in critically
ill children? Pediatr Crit Care Med 2003;
4:176 –180
10. Briassoulis G, Venkataraman S, Thompson
AE: Energy expenditure in critically ill chil-
dren. Crit Care Med 2000; 28:1166 –1172
11. White MS, Shepard RW, McEniery JA: En-
ergy expenditure in 100 ventilated, critically
ill children: Improving the accuracy of pre-
dictive equations. Crit Care Med 2000; 28:
2307–2312
12. Pollack MM, Patel KM, Ruttiman UE: PRISM
III: An updated pediatric risk of mortality.
Crit Care Med 1996; 24:743–752
13. Schofield WN: Predicting basal metabolic
rate, new standards and review of previous
work. Hum Nutr Clin Nutr 1985; 39(Suppl 1):
5– 41
14. Weissman C, Kemper M, Askanazi J, et al:
Resting metabolic rate of the critically ill
patient: Measured versus predicted. Anesthe-
siology 1986; 64:673– 679
15. Bland JM, Altman DG: Statistical methods
for assessing agreement between two meth-
ods of clinical measurements. Lancet 1986;
1:307–310
16. Chiolero R, Ravelly JP, Tappy L: Energy me-
tabolism in sepsis and injury. Nutrition 1997;
13:45S–51S
17. Moriyama S, Okamoto K, Tabira Y. Evalua-
tion of oxygen consumption and resting en-
ergy expenditure in critically ill patients with
systemic inflammatory response syndrome.
Crit Care Med 1999; 27:2133–2136
18. Plank LD, Hill GL: Sequential metabolic
changes following induction of the systemic
inflammatory response in patients with se-
vere sepsis or major blunt trauma. World
J Surg 2000; 24:630 – 638
267
Mortality before and after initiation of a computerized physician
order entry system in a critically ill pediatric population*
Adam Keene, MD; Lori Ashton; David Shure, MD; Dorrie Napoleone, MT (ASCP); Chhavi Katyal, MD;
Eran Bellin, MD

Objective: A worrisome increase in mortality has been reported
recently following the initiation of a computerized physician order
entry (CPOE) system in a critically ill pediatric transport population.
We tested the hypothesis that such a mortality increase did not occur
after the initiation of CPOE in a pediatric population that was directly
admitted to the neonatal and pediatric intensive care units at Mon-
tefiore Medical Center during two 6-month periods before CPOE and
one 6-month period immediately after CPOE was initiated. Mortality
in the pre- and post-CPOE time periods was compared, and adjust-
ment for potentially confounding covariates was performed.
Setting: The pediatric and neonatal intensive care units at
Montefiore Medical Center.
Patients: All patients admitted from the emergency room or
operating room or as transfers from other institutions directly to
the pediatric and neonatal intensive care units at Montefiore
Medical Center.
Interventions: None.
Measurements and Main Results: Overall, 29 (3.16%) of the
917 patients in the pre-CPOE period and nine (2.41%) of the
374 patients in the post-CPOE period died during their hospital
stay (p ⴝ .466). The power to detect the hypothesized mortality
increase was 81.7%. The variables that remained significant risk
factors for mortality after adjustment were shock (odds ratio,
9.41; 95% confidence interval, 2.90 –30.49), prematurity (odds
ratio, 3.57; 95% confidence interval, 1.74 –7.30), male gender
(odds ratio, 3.31; 95% confidence interval, 1.47–7.69), or a hema-
tologic/oncologic diagnosis (odds ratio, 3.14; 95% confidence
interval, 1.44 – 6.86). Post-CPOE initiation status remained unas-
sociated with mortality after adjusting for all covariates (odds
ratio, 0.71; 95% confidence interval, 0.32–1.57).
Conclusion: Mortality did not increase during CPOE initiation.
(Pediatr Crit Care Med 2007; 8:268 –271)
KEY WORDS: pediatrics; computerized physician order entry;
mortality

I n a recent article in Pediatrics (1),
Han and colleagues demonstrate a
greater than two-fold increase in
mortality during a 5-month pe-
riod after the initiation of a computerized
physician order entry (CPOE) system in a
pediatric interhospital transport popula-
tion at Children’s Hospital of Pittsburgh.
Although it is surprising that this inter-
vention could have had such a profound
*See also p. 304.
From the Divisions of Critical Care Medicine (AK)
and Pediatric Critical Care (CK) and Department of
Medicine (DS), Outcome Analysis Decision Support
(EB), Montefiore Medical Center, Albert Einstein Col-
lege of Medicine, Bronx, NY; and Emerging Health
Information Technology, Yonkers, NY (LA, DN, EB).
The authors have not disclosed any potential con-
flicts of interest.
Supported by the Clinical Investigation Core of the
Center for AIDS Research at the Albert Einstein College
of Medicine and Montefiore Medical Center, funded by
the National Institutes of Health (NIH I-51519).
For information regarding this article, E-mail:
akeene@montefiore.org
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000260781.78277.D9
effect on mortality, the authors do de-
scribe how the disruption of normal pa-
tient care procedures after the initiation
of CPOE may have resulted in lethal de-
lays in care. Although there is substantial
documentation of the ability of CPOE sys-
tems to reduce medication errors in the
inpatient and intensive care unit (ICU)
settings, these benefits must be called
into question if CPOE initiation increases
mortality (2–5). The ways in which CPOE
initiation may adversely effect patient
care may include the disruption of work-
flow, human-machine interface errors, a
loss of feedback, and information errors
(1, 6, 7). If these problems are inherent to
CPOE, they would call into question the
recent recommendations by the Leapfrog
Group (8) and others for widespread im-
plementation of CPOE.
As a quality-assurance project at Mon-
tefiore Medical Center (MMC), we exam-
ined whether a mortality increase com-
parable with that described by Han and
colleagues (1) occurred in a similarly at-
risk population during our CPOE initia-
tion phase. To study a group of patients
with similar baseline demographics, mor-
tality rates, and potential vulnerability to
the effects of CPOE, we reviewed the
mortality experience of patients directly
admitted to the neonatal and pediatric
ICUs during two 6-month periods 1 and 2
yrs before CPOE initiation and one
6-month period immediately after. This
study was approved by the MMC institu-
tional review board.
MATERIALS AND METHODS
CPOE Implementation. MMC purchased
the PHAMIS LastWord Online Medical Record
System in 1995 (now GE Centricity, GE
Healthcare, Slough, UK). At the time, Last-
Word was unique in its ability to handle a
complex integrated medical system, such as
MMC, which has two large campuses consist-
ing of 1,047 hospital beds with ⬎60,000 an-
nual discharges. The system’s initial imple-
mentation occurred from 1995 to 1997. This
consisted of replacing 11 registration systems
and assigning unique medical record numbers
to each patient, bringing results online for all
testing and computerizing all pharmacy func-
tions, as well as all medical records coding and
abstracting. During the next phase, work-
groups consisting of physicians, nurses, phar-
macists, and members of the health informa-

268 Pediatr Crit Care Med 2007 Vol. 8, No. 3

tion management team were formed to Data Collection. Clinical information re- missions in the post-CPOE period. Over-
perform workflow analysis and to ensure that corded in LastWord was retrospectively repli- all, 29 (3.16%) patients admitted during
the CPOE system was tailored to each specific cated to a database that populates MMC’s own the pre-CPOE period and nine (2.41%)
patient care area. This phase required approx- quality-improvement software, Clinical Look- patients admitted in the post-CPOE pe-
imately 1 yr to complete. ing Glass (MMC, Bronx, NY). In addition to
riod died under MMC care (p ⫽ .466). The
Beginning in 1999, MMC units were date of admission, age, race, gender, and mor-
brought into the system one at a time. Func- tality data, admission diagnoses were retro- mortality in the neonatal ICU was re-
tionality included 100% CPOE and online spectively collected and classified into one of duced from 6.49% to 5.93%, and the
charting for medication administration, vital 12 diagnostic categories via a uniform algo- mortality in the pediatric ICU was re-
signs, and additional flow sheet data. The rithm. Key personnel in the pediatric and neo- duced from 1.21% to 0.78%, but neither
CPOE functions included medication and non- natal ICUs during CPOE initiation, as well as of these differences was statistically sig-
medication orders and unit-specific order sets, the personnel responsible for coordinating the nificant.
as well as electronic signing, review, audit, process, were also interviewed. The demographic characteristics of
and renewal of all orders. No paper orders or Statistical Analysis. Based on our hypoth-
patients in the pre- and post-CPOE peri-
charts were permitted once a unit was acti- esis that mortality would not increase from
vated. This ensured that the entire care team 2.80% to 6.57% after CPOE implementation
ods are shown in Table 1. The only sta-
was working from a single source of online as described by Han and colleagues (1), we tistically significant differences between
data for all orders and resulting documenta- calculated that we would require 852 patients the pre- and post-CPOE groups were that
tion. Before implementation, in-service train- in the pre-CPOE group and 426 patients in the the latter had a higher percentage re-
ing was performed in person and online in post-CPOE group to achieve 80% power. corded as “other” race (18.7% vs. 12.2%)
each unit. The curriculum included a 4-hr Differences between patient groups were and a higher percentage of cardiac admis-
training session for all nurses and a 2-hr ses- calculated by the Mann-Whitney U test for sion diagnoses (11.0% vs. 6.5%). The per-
sion for all physicians. For the first 3 wks of continuous data and by the chi-square or Fisher’s centage of patients admitted to the neo-
implementation, information technology spe- exact tests for categorical data. Because of
natal ICU in the post-CPOE period was
cialists and specially trained pharmacists, correlated data, generalized estimating equa-
nurses, and physicians were present at all tions with robust standard errors also were lower (31.6% vs. 37.0%) and their me-
times. Two such specialists were present in the used to determine the significance levels of dian age was greater (23.0 vs. 15.1
ICUs studied at all times for the first week of the differences among all groups. A purposeful months), but these differences were not
implementation and one was present for the selection logistic regression process (initially statistically significant.
final 2 wks. including all variables with p ⬍ .25) was used The demographic characteristics of
Because of the perceived vulnerability of to determine which factors were indepen- survivors and non-survivors are shown in
the patient population and the complex dently associated with mortality (9). Data were Table 2. As compared with survivors,
weight-based nature of pediatric medication analyzed using the STATA software program
non-survivors were younger by a statisti-
administration, CPOE was initiated in the version 9.1 (StataCorp, College Station, TX).
cally significant margin (median months,
neonatal and pediatric ICUs last. MMC person-
nel already had up to 3 yrs of experience with 0.018 vs. 19.8), more likely to be admit-
RESULTS
CPOE before it was brought to these units. ted to the neonatal ICU (76.3% vs.
Patients. The study included all patients There were 917 patient admissions in 34.2%), and more likely to be male
admitted directly from the delivery, emergency, the pre-CPOE period and 374 patient ad- (79.0% vs. 55.4%). They were more
or operating rooms, or as transfers from other
institutions, to the neonatal ICU at MMC from Table 1. Demographic characteristics and admission diagnoses of patientsa
September 2000 through February 2001,
September 2001 through February 2002, All Patients Before CPOE After CPOE
and September 2002 through February (n ⫽ 1,291) (n ⫽ 917) (n ⫽ 374) pb
2003. In addition, all patients directly ad-
mitted from emergency or operating rooms or Age, monthsc 17.3 (0.02–121.7) 15.0 (0.02–121.7) 23.1 (0.03–121.7) .196
as transfers from other institutions to the pe- Prematurity, n (%) 237 (18.4) 169 (18.4) 68 (18.2) .917
diatric ICU at MMC from June through De- Neonatal ICU admission, n (%) 457 (35.4) 339 (37.0) 118 (31.6) .290
cember in 2000, 2001, and 2002 were in- Transfer, n (%) 155 (12.0) 113 (12.3) 42 (11.3) .595
cluded. Patients in the first two time periods Male gender, n (%) 724 (56.1) 510 (55.6) 214 (57.2) .599
Black race, n (%) 454 (35.2) 329 (35.9) 125 (33.4) .402
from each unit were combined to form the
White race, n (%) 141 (10.9) 100 (10.9) 41 (11.0) .976
pre-CPOE group, and patients in the last time Hispanic race, n (%) 514 (39.8) 376 (41.0) 138 (36.9) .172
period from each unit formed the post-CPOE Other race, n (%) 182 (14.1) 112 (12.2) 70 (18.7) .007
group. Patients transferred to these units from Respiratory, n (%) 370 (28.7) 268 (29.2) 102 (27.3) .481
other floors were excluded to ensure that the Infectious/immunologic, n (%) 237 (18.4) 72 (18.8) 65 (17.4) .562
subjects in the pre-CPOE groups had not been Neurologic, n (%) 190 (14.7) 27 (13.9) 63 (16.8) .168
exposed to CPOE on other floors and that the Gastrointestinal/hepatic, n (%) 186 (14.4) 28 (14.0) 58 (15.5) .472
subjects in the post-CPOE groups were being Toxic/metabolic, n (%) 134 (10.4) 90 (9.8) 44 (11.8) .297
exposed to CPOE for the first time. The time Hemotologic/oncologic, n (%) 120 (9.3) 88 (9.6) 32 (8.6) .559
Cardiac, n (%) 101 (7.8) 60 (6.5) 41 (11.0) .007
periods studied differed between units because Trauma, n (%) 66 (5.1) 48 (5.2) 18 (4.8) .755
CPOE initiation took place at different times Shock, n (%) 25 (1.9) 16 (1.7) 9 (2.4) .434
in each unit. The time periods were chosen to Renal, n (%) 14 (1.1) 9 (1.0) 5 (1.3) .575
avoid seasonal differences in the pre- and post- Endocrine, n (%) 12 (0.9) 8 (0.9) 4 (1.1) .738
CPOE study periods. Additionally, the time
periods studied were chosen because there CPOE, computerized physician order entry; ICU, intensive care unit.
a
were no major changes in terms of structure, Multiple admission diagnoses per patient recorded; bp values were determined by Mann-Whitney
administration, or staffing ratios in these U test for nonparametric continuous data (age) or by chi-square or Fisher’s exact test (all other
units during these times. categories); cdata are non-parametric and presented as median (interquartile range).

Pediatr Crit Care Med 2007 Vol. 8, No. 3 269

Table 2. Demographic characteristics and admission diagnoses of survivors and nonsurvivorsa implementation were felt to be difficult
and tedious, and the system was per-
Survivors Nonsurvivors
ceived as cumbersome and non-intuitive.
(n ⫽ 1,253) (n ⫽ 38) pb
Because of the complexity of the CPOE
Age, monthsc 19.8 (0.025–122.1) 0.018 (0.01–0.03) ⬍.001 initiation, the period of on-site assistance
Prematurity, n (%) 218 (17.4) 19 (50.0) ⬍.001 was extended by 1–2 wks in the ICUs
Neonatal ICU admission, n (%) 428 (34.2) 29 (76.3) ⬍.001 studied. Overall, however, it was felt that
Transfer, n (%) 153 (12.2) 2 (5.3) .194 the process occurred without compro-
Male gender, n (%) 694 (55.4) 30 (79.0) .004
Black race, n (%) 439 (35.0) 15 (39.5) .573
mise to patient care, primarily because of
White race, n (%) 138 (11.0) 3 (7.9) .544 the constant availability of live support
Hispanic race, n (%) 497 (39.7) 17 (44.7) .529 from technicians, as well as pharmacists
Other race, n (%) 179 (14.3) 3 (7.9) .265 and other personnel who already were
CPOE 365 (29.1) 9 (23.7) .466 familiar with the system.
Respiratory, n (%) 348 (27.8) 22 (57.9) ⬍.001
Infectious/immunologic, n (%) 223 (17.8) 14 (36.8) .003
Neurologic, n (%) 179 (14.3) 11 (29.0) .012 DISCUSSION
Gastrointestinal/hepatic, n (%) 173 (13.8) 13 (34.2) ⬍.001
Toxic/metabolic, n (%) 129 (10.3) 5 (13.2) .569 Because of the complexity of medical
Hemotologic/oncologic, n (%) 107 (8.5) 13 (34.2) ⬍.001
Cardiac, n (%) 95 (7.6) 6 (15.8) .063
organizations, it is hard to understand
Trauma, n (%) 65 (5.2) 1 (2.6) .481 why an intervention that is beneficial in
Shock, n (%) 20 (1.6) 5 (13.2) ⬍.001 one organization might be detrimental in
Renal, n (%) 13 (1.0) 1 (2.6) .350 another. This becomes particularly diffi-
Endocrine, n (%) 12 (1.0) 0 (0.0) 0.545 cult to assess when the intervention ex-
ICU, intensive care unit; CPOE, computerized physician order entry.
amined is one as complex as the institu-
a
Multiple admission diagnoses per patient recorded; bp values were determined by Mann-Whitney tion of a CPOE system. Factors that have
U test for nonparametric continuous data (age) or by chi-square or Fisher’s exact test (all other been hypothesized to effect the outcomes
categories); cdata nonparametric and presented as median (interquartile range). of CPOE initiation include the organiza-
tional readiness for change, the project
management, and the technical nature of
Table 3. Factors significantly associated with mortality when adjusted for other covariates in a model the system (2, 10 –12). In the ICU setting,
that included pre- or post-CPOE statusa the degree to which a CPOE system is
customized to the needs of the ICU has
Variable Odds of Mortality 95% Confidence Interval p
been shown to be important (3). In the
CPOE 0.71 0.32–1.57 .392
case of the CPOE initiation experience
Shock 9.41 2.90–30.49 ⬍.001 described by Han and colleagues (1), all of
Prematurity 3.57 1.74–7.30 ⬍.001 these factors might have had adverse ef-
Male gender 3.31 1.47–7.69 .004 fects, because the system was implemented
Hematology/oncology diagnosis 3.14 1.44–6.86 .004 hospital-wide with little preparatory train-
CPOE, computerized physician order entry.
ing, live technical support apparently was
a
A purposeful selection logistic-regression analysis was performed that included all variables with only briefly available, and workflow analysis
p values ⬍.25 in univariate analysis. Unit of admission was left out of this analysis because of was not performed to specifically tailor the
collinearity with age. system to each unit (1).
The CPOE implementation experience
at MMC was quite different. The prepara-
likely to have respiratory (57.9% vs. nosis. Post-CPOE initiation status re- tory phase took place during approxi-
27.8%), hematologic/oncologic (34.2% mained unassociated with mortality after mately 2 yrs rather than the 3 months
vs. 8.5%), infectious disease/immuno- adjusting for all covariates (OR, 0.71; described by Han and colleagues (1), the
logic (36.8% vs. 17.8%), or gastrointes- 95% CI, 0.32–1.57). No significant inter- system was specifically tailored to the pe-
tinal/hepatic (34.2% vs. 13.8%) issues actions were detected in this model. diatric critically ill, the initiation phase
at admission diagnosis. They also were There was no appreciable change in any included more extensive support and
more likely to be diagnosed as being in of these analyses when generalized esti- training, and the most vulnerable patient
shock (13.2% vs. 1.6%) or premature mating equations were used. In addition, groups were involved only after extensive
(50.0% vs. 17.4%) at admission. when a logistic-regression model was de- hospital-wide experience with the system.
Because of collinearity with age, unit veloped via purposeful selection that in- After adjusting for potentially confound-
of admission was not included in the cluded unit of admission instead of age, ing variables, our analysis of the MMC
main logistic regression model. The vari- CPOE initiation status remained unasso- experience with CPOE initiation also had
ables that remained significant risk fac- ciated with mortality (OR, 0.72; 95% CI, very different results. The change in per-
tors for mortality after logistic regression 0.32–1.63). admission mortality from 3.16% to
analysis and their associated odds ratios We interviewed key personnel who 2.41% and the adjusted OR of 0.71 essen-
(ORs) are shown in Table 3. These in- were still at MMC in 2006 and were tially rules out the experience reported by
cluded shock (OR, 9.41), prematurity present during the CPOE initiation peri- Han and colleagues (1). This finding con-
(OR, 3.57), male gender (OR, 3.31), or a ods in 2002–2003. Their memories of the curs with that of Del Becarro and col-
hematologic/oncologic (OR, 3.14) diag- experience were mixed. The first days of leagues (13), who recently found no in-

270 Pediatr Crit Care Med 2007 Vol. 8, No. 3

crease in mortality after CPOE initiation
in pediatric ICU patients. That study,
however, looked at mortality for an ex-
tended period after CPOE initiation (13
months) and, thus, may have diluted the
effect of implementation-induced prob-
lems.
Does this mean that for the pediatric
critically ill, CPOE is necessarily safe if
specifically tailored and carefully imple-
mented? Not necessarily. CPOE has been
initiated in many other pediatric ICUs
worldwide in the last decade, but the ef-
fect of these interventions on mortality
remains unreported. The few available
studies of CPOE on pediatric ICU patients
have examined errors in receiving medi-
cation, rather than mortality, and have
shown mixed results (14, 15). Even care-
fully planned CPOE implementations
have gone awry (16). More studies of the
factors that determine successful CPOE
implementation are clearly needed.
The limitations of this study include
its retrospective nature, the fact that it
reports the experience with CPOE initia-
tion at only one site, and the fact that it
was not powered to detect small differ-
ences in relative mortality. This lack in
the degree of certainty of the effect of
CPOE initiation on mortality is repre-
sented by the wide confidence interval
(0.32–1.57) around the OR for CPOE sta-
tus. In addition, because severity-of-
illness scoring was not routinely recorded
prospectively in this group of patients, we
were not able to report such scores. How-
ever, the similar baseline mortality of our
patient group to that reported by Han and
colleagues (1) suggests that our group
was comparably vulnerable to risk from
CPOE initiation. In addition, the similar
characteristics of patients in the pre- and
post-CPOE periods indicate that these
groups were comparable. Unlike the pa-
tient group studied by Han and col-
leagues (1), only about 12% of our pa-
tients were transferred from other
institutions, which may have had an ef-
fect on the difference in outcomes. Given
our previously described patient selec-
tion, we believe our population was
somewhat different from that reported on
Pediatr Crit Care Med 2007 Vol. 8, No. 3
by Han and colleagues (1), but that it
perhaps was more representative of the
typical pediatric ICU admission. There
was a reduction in the percent of patients
admitted to the neonatal ICU during the
post-CPOE period and a corresponding
increase in median (but not mean) age.
Both of these factors were associated with
mortality by univariate analysis. The im-
pression of an administrator for the neo-
natal ICU during these time periods was
that admission numbers dropped because
referring hospitals increased their capac-
ity to care for lower-complexity critically
ill children, thus limiting transfers to
only the sickest children. This explana-
tion is consistent with the combined 18%
drop in admissions to both units from
76.4 per month in the pre-CPOE periods
to 62.3 per month in the post-CPOE pe-
riod.
CONCLUSION
The initiation of CPOE for the pediat-
ric critically ill at MMC took place with-
out the increase in mortality reported
during a similar initiation period by Han
and colleagues (1). Careful preparation,
unit-by-unit tailoring, and extensive
technical support may have improved the
results at MMC. The pediatric critically ill
are particularly vulnerable to major alter-
ations in healthcare delivery; implemen-
tation of CPOE for these patients must be
performed with great foresight and care.
REFERENCES
1. Han YY, Carcillo JA, Venkataraman ST, et al:
Unexpected increased mortality after imple-
mentation of a commercially sold computer-
ized physician order entry system. Pediatrics
2005; 116:1506 –1512
2. Ahmad A, Teater P, Bentley TD, et al: Key
attributes of a successful physician order en-
try system implementation in a multihospi-
tal environment. J Am Med Inform Assoc
2002; 9:16 –24
3. Ali NA, Mekhjian HS, Kuehn PL, et al: Spec-
ificity of computerized physician order entry
has a significant effect on the efficiency of
workflow for critically ill patients. Crit Care
Med 2005; 33:110 –114
4. Mekhjian HS, Kumar RR, Kuehn L, et al:
Immediate benefits realized following imple-
mentation of physician order entry at an ac-
ademic medical center. J Am Med Inform
Assoc 2002; 9:529 –539
5. Oppenheim MI, Vidal C, Velasco FT, et al:
Impact of a computerized alert during phy-
sician order entry on medication dosing in
patients with renal impairment. Proc AMIA
Symp 2002; 577–581
6. Koppel R, Metlay JP, Cohen A, et al: Role of
computerized physician order entry systems
in facilitating medication errors. JAMA 2005;
293:1197–1203
7. Ash JS, Berg M, Coiera E: Some unintended
consequences of information technology in
health care: The nature of patient care infor-
mation system-related errors. J Am Med In-
form Assoc 2004; 11:104 –112
8. The Leapfrog Group for Patient Safety: Re-
warding higher standards. Online at: www.
leapfroggroup.org. Date accessed
9. Hosmer D, Lemeshow S: Applied Logistic
Regression. New York, Wiley-Interscience,
2000
10. Shekelle PG, Morton SCKE: Costs and bene-
fits of health information technology, evi-
dence report/technology assessment 132.
Publication No. 06 –E006. Rockville, MD,
AHRQ, 2006
11. Ash JS, Stavri PZ, Kuperman GJ: A consen-
sus statement on considerations for a suc-
cessful CPOE implementation. J Am Med In-
form Assoc 2003; 10:229 –234
12. Southon FC, Sauer C, Grant CN: Information
technology in complex health services: Orga-
nizational impediments to successful tech-
nology transfer and diffusion. J Am Med In-
form Assoc 1997; 4:112–124
13. Del Beccaro MA, Jeffries HE, Eisenberg MA,
et al: Computerized provider order entry im-
plementation: No association with increased
mortality rates in an intensive care unit. Pe-
diatrics 2006; 118:290 –295
14. Mullett CJ, Evans RS, Christenson JC, et al:
Development and impact of a computerized
pediatric anti-infective decision support pro-
gram. Pediatrics 2001; 108:E75
15. Potts AL, Barr FE, Gregory DF, et al: Com-
puterized physician order entry and medica-
tion errors in a pediatric critical care unit.
Pediatrics 2004;113:59 – 63
16. Aarts J, Doorewaard H, Berg M: Understand-
ing implementation: The case of a comput-
erized physician order entry system in a large
Dutch university medical center. J Am Med
Inform Assoc 2004; 11:207–216
271
Evidence-Based Journal Club

A critical appraisal of “Blind and bronchoscopic sampling methods

in suspected ventilator-associated pneumonia: A multicentre
prospective study” by Mentec et al. (Intensive Care Med 2004; 30:
1319 –1326)
Mark D. Weber, RN, CPNP; Satid Thammasitboon, MD, MHPE

Additional evidence-based journal club reviews are available on “Peds CCM: The Pediatric Critical Care Medicine Web site,”
found at http://pedsccm.org

Objective: To review the findings and discuss the implications
of utilizing tracheal aspirate vs. protected bronchial brush spec-
imens in the diagnosis of ventilator-associated pneumonia.
Design: A critical appraisal of an original article on diagnostic
accuracy of different sampling methods for ventilator-associated
pneumonia, with selected literature review.
Findings: The investigators conducted a multicenter, prospec-
tive experimental study comparing the accuracy of culture sam-
ples from blind tracheal aspirate, blind protected telescoping
catheter (PTC), bronchoscopic PTC, and bronchoscopic bron-
choalveolar lavage for the diagnosis of ventilator-associated
pneumonia. Using the area under receiver operating characteris-
tics curve, bronchoscopic bronchoalveolar lavage had a value of
0.98, bronchoscopic PTC had a value of 0.85, blind PTC had a
value of 0.83, and blind tracheal aspirate had a value of 0.78. With
visible secretions expelled from the catheter, the blind PTC would
be equally accurate as bronchoscopic bronchoalveolar lavage.
Conclusions: The use of blind PTC with visible secretions is a
viable alternative to bronchoscopic bronchoalveolar lavage in
diagnosis of ventilator-associated pneumonia. (Pediatr Crit Care
Med 2007; 8:272–275)
KEY WORDS: intensive care; diagnostic techniques; pneumonia

A n otherwise healthy 2-yr-old
boy is admitted to the pediatric
intensive care unit with trau-
matic brain injury. A right
frontotemporoparietal craniectomy and
evacuation of the subdural hematoma are
performed without complication. The
postoperative course is complicated by
severe intracranial hypertension, treated
with ventriculostomy drainage and os-
motic and pentobarbital therapy. On pe-
diatric intensive care unit day 4, his chest
radiograph reveals a new right lower lobe
From the Department of Pediatrics, West Virginia
University School of Medicine, Morgantown, WV.
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
mweber@hsc.wvu.edu
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262901.82640.4B
infiltrate. The resident reports on rounds
that the patient had a fever of 38.6°C,
with a new leukocytosis. The resident
plans to complete sepsis workup and start
empirical antibiotics for suspected venti-
lator-associated pneumonia (VAP). The
respiratory therapist suggests that a pro-
tected bronchial brush specimen may be
more useful than a conventional blind
tracheal aspirate in confirming or refut-
ing the diagnosis of VAP. Although the
protected bronchial brush theoretically
sounds superior to simple tracheal aspi-
rate, you have no experience with the
technique. You wonder if there is any
evidence supporting the use of this tech-
nique to diagnosis VAP. You decide to
perform a literature search to help an-
swer this question.
THE SEARCH
First, you start by creating a clinical
question in the “PICO” format. You ex-
plained to your resident that an answer-
able clinical question should consist of
four components: P ⫽ patient, popula-
tion, or problem; I ⫽ intervention, prog-
nostic factor, or exposure; C ⫽ compari-
son of intervention; O ⫽ outcome that is
measured. The following clinical ques-
tion was created: in patients with sus-
pected VAP (P), how accurate is protected
specimen sampling (I) compared with
conventional tracheal aspirate in the di-
agnosis of VAP (O)? The well-built clinical
question helps you combine the proper
terms required for literature search in
the query language. You enter “ventila-
tor-associated pneumonia” and “tracheal
aspirate” on the freely accessible PubMed
MEDLINE search engine (http://www.
pubmed.gov). You see a recent prospec-
tive, multicenter study about the tech-
nique (1). You download this article and
prepare to critically appraise it, using the
“Users’ Guides to the Medical Literature”
on diagnostic studies as a guide (2).

272 Pediatr Crit Care Med 2007 Vol. 8, No. 3

Table 1. Likelihood ratios
Method Threshold Sensitivity
Blind TA ⱖ105 82
Blind PTC ⱖ103 62
Blind PTC vse ⱖ103 82
Broncho PTC ⱖ103 71
Broncho PTC vse ⱖ103 81
Broncho BAL ⱖ104 94
LR⫹, likelihood ratio positive (the likelihood of a positive test in those with the disease compared
with the likelihood of a positive test in those without the disease); LR⫺, likelihood ratio negative (the
likelihood of a negative test in those with the disease compared with a negative test in those without
the disease); auROCc, areas under the receiver operating characteristics curve; 95% CI, 95% confi-
dence interval; Blind TA, blind tracheal aspirate; Blind PTC, blind protected telescoping catheter; vse,
visible secretions expelled; Broncho PTC, bronchoscopic protected telescoping catheter; Broncho BAL,
bronchoscopic bronchial alveolar lavage.
Briefly, this study involved 63 adult
patients, 50 –74 yrs of age, from five in-
tensive care units who were receiving
mechanical ventilation for ⬎48 hrs and
had clinically suspected VAP. The criteria
for suspected VAP were: 1) new and per-
sistent alveolar infiltrates on chest radio-
graph and 2) purulent tracheal aspirates
or at least two of the following: fever of
ⱖ38°C or hypothermia of ⬍36.5°C, leu-
kocytosis of ⬎10 ⫻ 1012/L or leukopenia
⬍4 ⫻ 1012/L, decrease in PaO2/FIO2 ratio
of ⬎20 mm Hg.
ARE THE RESULTS OF THE
STUDY VALID?
Primary Questions
Was There an Independent, Blind
Comparison with a Reference Standard?
The study compared four sampling meth-
ods: blind tracheal aspirate (blind TA),
blind protected telescoping catheter
(blind PTC), bronchoscopic PTC, and
bronchoscopic bronchoalveolar lavage
(bronchoscopic BAL) in the diagnosis of
VAP. Without a perfect gold standard, the
physicians in charge of the patients used
the 1992 International Consensus Con-
ference criteria for VAP (3) with a bron-
choscopic BAL as the best available refer-
ence standard to make the final
diagnosis. The only way to diagnose VAP
with certainty is by performing a lung-
tissue biopsy for the actual pathologic
findings of pneumonia. Although the ap-
proach of an open lung biopsy is superior
to bronchoscopic BAL, it is clearly too
invasive and impractical, and is thus not
justified to apply to patients with sus-
pected VAP. Although the physicians
Pediatr Crit Care Med 2007 Vol. 8, No. 3
WHAT ARE THE RESULTS?
Specificity LR⫹ LR⫺ auROCc 95% CI
Does This Valid Evidence
67 2.48 0.27 0.783 0.65–0.91 Demonstrate an Important
94 10.3 0.40 0.829 0.72–0.94 Ability of This Test to
90 8.20 0.20 0.902 0.79–1.01
94 11.83 0.31 0.848 0.74–0.95 Accurately Distinguish Patients
100 ⬁ 0.19 0.913 0.81–1.0 Who Do and Do Not Have a
100 ⬁ 0.06 0.977 0.92–1.02 Specific Disease?
The likelihood ratios for the test re-
sults are calculated based on the sensitiv-
ity and specificity provided by the article
(Table 1).
The authors used areas under the re-
ceiver operating characteristics curve to
determine the best threshold and the op-
erating characteristics of the four sam-
pling techniques. When samples with vis-
were not blinded to the test results, this
ible secretions were considered, the
reference standard includes an objective accuracy of blind PTC with visible secre-
test: bronchoscopic BAL threshold of tions approached that of bronchoscopic
ⱖ104 colony-forming units (cfu)/mL as a BAL, which is the best available reference
positive culture. standard (area under the receiver operat-
Did the Patient Sample Include an ing characteristics curve, 0.902 vs. 0.977;
Appropriate Spectrum of Patients to p ⫽ .22).
Whom the Diagnostic Test Will Be Ap- A critical concern is the high number
plied in Clinical Practice? The investiga- of patients who were receiving antibiotics
tors included an appropriate spectrum of when enrolled in the study. Although the
patients in the study. A total of 63 pa- concurrent use of antibiotics invariably
tients (50 –74 yrs) were studied. The gen- creates confounding effect on the clinical
eral patient types were 83% medical outcomes, it is an accurate representa-
patients, 16% unscheduled surgical pa- tion of patients with suspected VAP in the
tients, and 2% scheduled surgical pa- real practice. The profiles of these pa-
tients. Of these 63 patients, however, 11 tients are critically ill, mechanically ven-
tilated for ⱖ48 hrs, and commonly im-
were labeled as “uncertain pneumonia.”
Providing no gold standard to determine munocompromised; hence, they are
definitive diagnoses, it would be wrong to likely to be on antibiotic therapy when
artificially classify these patients into ei- the VAP is suspected. It would be a great
ther VAP or non-VAP for data analyses. It challenge to conduct a study that ex-
left the investigators no option but to cludes patients who are on antibiotics. It
exclude the “uncertain pneumonia” cate- is important to remember that our actual
gory from the final analyses. The patient clinical dilemma is to get an accurate
diagnosis of VAP that can then help with
exclusion certainly imposes an inevitable
the decision in initiating antibiotic ther-
threat to the validity of the study.
apy or in tailoring the regimens of con-
current antibiotics.
Secondary Questions
WILL THE RESULTS HELP ME
Did the Results of the Test Being Eval- IN CARING FOR MY PATIENT?
uated Influence the Decision to Perform
the Reference Standard? No. Each pa-
Is the Diagnostic Test Available,
tient enrolled in the study underwent all
Affordable, Accurate, and
four types of sampling methods in the
same order. Precise in Your Setting?
Were the Methods for Performing the Within our institution, the protected
Test Described in Sufficient Detail to Per- bronchial brushes are readily available.
mit Replication? Yes. The authors pro- The price for the brush itself is quite
vide electronic supplementary material small, averaging around $25. After the
that includes the sampling protocol used specimen is sent for microbiologic anal-
(available at: http://dx.doi.org/10.1007/ ysis, the reports are listed in an exponen-
s00134-004-2284-7). tial amount of colony-forming units per
273

Figure 1. Likelihood ratio nomogram. TA, tracheal aspirate; PTC, protected telescoping catheter; Vse,
visible secretions expelled. Reproduced with permission from Fagan (7).
milliliter. This method of reporting is
similar to that done in the literature,
therefore allowing a simple application of
the data in this study. The relevant ques-
tion, of course, is whether this study per-
formed in adults can be applied to chil-
dren. Although the microbiology and rate
of VAP may differ between adult and pe-
diatric intensive care unit patients, there
is no reason to believe the diagnostic
accuracy of these methods should differ
based on a patient’s age.
Can We Generate a Clinically
Sensible Estimate of Our
Patient’s Pretest Probability?
Because the pretest probability or
prevalence of VAP in this study was very
high (65%), we have to estimate a more
reasonable pretest probability for our pa-
tient. The prevalence of VAP depends on
the population studied and diagnostic cri-
teria used. Accurate data on epidemiology
of VAP are limited by the lack of a uni-
versally accepted gold standard for diag-
274
nosis. From recent literature, the median
prevalence of 20% (range, 5– 65%) (4, 5)
is the best estimate and seems applicable
to the patient in our scenario.
Extensive literature also exists on the
use of clinical findings to determine
“clinical likelihood” of pneumonia (i.e.,
Clinical Pulmonary Infection Score
[CPIS]) (6). A clinician could further in-
corporate the individual patient’s value
with the baseline prevalence to come up
with a clinically sensible estimate of pre-
test probability for a particular patient.
Will the Resulting Posttest
Probabilities Affect Our
Management and Help
Our Patient?
In deciding whether the evidence
about the diagnostic test is relevant, we
need to determine how the test changes
our estimated probability of VAP before
the test (pretest probability) to that after
the test result (posttest probability). The
diagnostic sampling method that pro-
duces a large shift from pretest to post-
test probabilities for VAP is most likely
to be useful in clinical practice. Using
the likelihood ratio (LR) nomogram (7)
(Fig. 1), a positive culture from blind
PTC (LR⫹ of 10.3) would shift pretest
probability of 20% to posttest probabil-
ity of 72%. On the other hand, a nega-
tive culture from blind PTC (LR⫺ of
0.4) would decrease the probability of
having VAP from 20% down to 9%. The
posttest probability can also be calcu-
lated by converting the pretest proba-
bility to odds (p/[1 ⫺ p]), multiplying
the pretest odds by the LR, and then
converting the posttest odds back to a
probability (odds/[1 ⫹ odds]) (8).
The visualization of secretions ex-
pelled from the telescoping catheter with
a negative culture enhances the test per-
formance in excluding the disease (LR⫺
of 0.2). The areas under the receiver op-
erating characteristics curve of PTC with
visualized secretions is actually almost
equivalent to the gold standard, broncho-
scopic BAL. Again, using the likelihood
ratio nomogram, the negative culture
from the blind PTC with visible secretion
would decrease the probability of having
VAP to only 4.7%, which could be low
enough for a clinician to discontinue an-
tibiotics. The suboptimal sensitivity of a
blind PTC specimen without visible se-
cretions compared with bronchoscopic
BAL has been shown in another study (4).
All false-negative PTC specimens in the
study by Brun–Buisson et al. (4), how-
ever, showed epithelial/bronchial cells
and few polymorphonuclear cells on di-
rect examination, suggesting improper
samplings. The knowledge based on this
evidence could guide an effective sam-
pling method. To avoid exposing patients
to adverse outcomes from de-escalation
or discontinuation of antibiotics in false-
negative cases, blind PTC must be re-
peated when epithelial/bronchial cells
and few polymorphonuclear cells are re-
ported. The blind PTC must also be re-
peated in the absence of visible secretions
from the catheter when the pretest prob-
ability of VAP is high.
The primary sampling technique in
current pediatric practice consists of a
blind, nonquantitative tracheal aspirate.
Applying LR⫹ and LR⫺ for blind TA with
quantitative culture in this study, the
posttest probability of positive and nega-
tive cultures are 38% and 6% respec-
tively. The difference in the posttest prob-
ability of a positive blind PTC compared
with TA is striking (72% vs. 38%). Blind
Pediatr Crit Care Med 2007 Vol. 8, No. 3
PTC therefore is a promising technique
to reduce inappropriate antibiotic usage.
In the patients with low pretest probabil-
ity, however, the tracheal aspirate is a
convenient and effective sampling
method to rule out VAP (posttest proba-
bility of only 6%). Although this finding
is consistent with previous studies, the
best threshold for positivity of quantita-
tive TA has been inconsistent, with the
thresholds ranging from 10 4 to 10 6
cfu/mL (4, 9, 10).
Integrating this combined evidence,
we have concluded that a blind PTC
should be considered before empirical an-
tibiotic therapy in patients with high pre-
test probability or high severity of illness.
The presence of visible secretions is re-
quired. Empirical antimicrobial therapy
can then be initiated, and the culture
results from the blind PTC can direct the
optimization of antibiotic therapy. A
blind TA provides no additional benefit in
this circumstance. In cases of low pretest
probability and low severity of illness, a
blind TA with quantitative culture is the
best screening method. The LR⫺ of 0.27
for TA will lead to a low posttest proba-
bility, which is comparable with the LR⫺
of blind PTC being 0.2. The direct Gram-
negative stain examination of TA allows
withholding antibiotic therapy if no bac-
teria are present. A positive Gram-
negative stain on the blind TA, however,
suggests the need for a blind PTC before
initiation of antibiotic therapy. The cul-
ture findings from the blind PTC will help
confirm the diagnosis and guide antibi-
otic therapy. The actual effectiveness (ap-
propriate treatment of VAP and avoidance
of antibiotics in its absence) of this strat-
egy has yet to be proven.
Brun-Buisson et al. (4) used a similar
approach to diagnose and manage VAP,
integrating severity of presentation, clin-
ical likelihood of pneumonia, and early
microbiological data (Gram stains and
early quantitative cultures of specimens).
Pediatr Crit Care Med 2007 Vol. 8, No. 3
The blind PTC allowed physicians to pro-
vide effective therapy within 2–24 hrs of
diagnosis of VAP in ⬎80% of patients.
The authors also proposed that the use of
semiquantitative cultures with thresh-
olds corresponding to 104 cfu/mL could
enhance specificity of the blind TA. This
technique, however, was not as good as
the blind PTC in the current study (spec-
ificity of 82% vs. 97%). Some studies
have suggested the quantitative culture is
what matters, regardless of the sampling
techniques. The quantitative culture
from blind TA could have a diagnostic
accuracy comparable with that of BAL
(10 –13). The effectiveness of this ap-
proach is a great research question that
has yet to be answered with a well-
designed, prospective study.
SCENARIO RESOLUTION
You decide to send a blind protected
bronchial brush specimen (with secre-
tions visualized), and you start the pa-
tient on broad-spectrum antibiotics. After
2 days, the culture comes back positive as
Streptococcus pneumoniae, 103 cfu/mL.
The patient’s antibiotics are narrowed
down to cefuroxime to complete a 10-day
course. Within 4 days, there is a resolu-
tion of fever, leukocytosis, and the patient
is able to tolerate significant reduction of
ventilatory support.
REFERENCES
1. Mentec H, May-Michelangeli L, Rabbat A, et
al: Blind and bronchoscopic sampling meth-
ods in suspected ventilator-associated pneu-
monia: A multicentre prospective study. In-
tensive Care Med 2004; 30:1319 –1326
2. Jaeschke R, Guyatt GH, Sackett DL: Users’
guides to the medical literature: III. How to
use an article about a diagnostic test. B:
What are the results and will they help me in
caring for my patients? The Evidence-Based
Medicine Working Group. JAMA 1994; 271:
703–707
3. Pingleton SK, Fagon JY, Leeper KV: Patient
selection for clinical investigation of ventila-
tor-associated pneumonia: Criteria for eval-
uating diagnostic techniques. Chest 1992;
102:553S–556S
4. Brun-Buisson C, Fartoukh M, Lechapt E, et
al: Contribution of blinded, protected quan-
titative specimens to the diagnostic and ther-
apeutic management of ventilator-associated
pneumonia. Chest 2005; 128:533–544
5. Richards MJ, Edwards JR, Culver DH, et al:
Nosocomial infections in pediatric intensive
care units in the United States: The National
Nosocomial Infections Surveillance System.
Pediatrics 1999; 103:804. Available at: http://
www.pediatrics.org/cgi/content/full/103/4/
e39
6. Pugin, JR, Auckenthaler N, Mili JP, et al:
Diagnosis of ventilator-associated pneumo-
nia by bacteriologic analysis of broncho-
scopic and nonbronchoscopic “blind” bron-
choalveolar lavage fluid. Am Rev Respir Dis
1991; 143:1121–1129
7. Fagan TJ: Nomogram for Bayes theorem.
N Engl J Med 1975; 293:257
8. Deeks JJ, Alman DG: Statistics notes: Diag-
nostic test 4. Likelihood ratios. BMJ 2004;
329:168 –169
9. Jourdain B, Novara A, Joly-Guillou ML, et al:
Role of quantitative cultures of endotracheal
aspirates in the diagnosis of nosocomial
pneumonia. Am J Respir Crit Care Med 1995;
152:241–246
10. Torres A, El Ebiary M, Padro L, et al: Valida-
tion of different techniques for the diagnosis
of ventilator-associated pneumonia: Compar-
ison with immediate postmortem biopsy.
Am J Respir Crit Care Med 1994; 149:
324 –331
11. Papazian L, Thomas P, Garbe L, et al: Bron-
choscopic or blind sampling techniques for
the diagnosis of ventilator-associated pneu-
monia. Am J Respir Crit Care Med 1995;
152:1982–1991
12. Papazian L, Martin C, Meric B, et al: A reap-
praisal of blind bronchial sampling in the
microbiologic diagnosis of nosocomial bron-
chopneumonia. Chest 1993; 103:236 –242
13. Torres A, Fabregas N, Ewig S, et al: Sampling
methods for ventilator-associated pneumo-
nia: Validation using different histologic and
microbiological references. Crit Care Med
2000; 28:2799 –2804
275
Brief Report

Identification of adrenal insufficiency in pediatric critical illness*

Kusum Menon, MD, MSc, FRCPC; Margaret Lawson, MD, MSc, FRCPC

Objective: To determine physicians’ beliefs and practices re-
garding adrenal dysfunction in pediatric critical illness.
Design: Cross-sectional mail survey.
Setting: Canada.
Participants: All members of the Canadian Pediatric Endocrine
Group and all physicians identified as practicing pediatric inten-
sive care medicine in any of 16 tertiary care teaching centers in
Canada.
Interventions: Three pediatric intensive care physicians and
three pediatric endocrinologists reviewed the questionnaire be-
fore administration to ensure clarity. We asked participants to
report their views on the following: a) the frequency of adrenal
insufficiency in pediatric critical illness; b) diagnosis/definition of
adrenal insufficiency in pediatric critical illness; and c) the use of
empirical glucocorticoids in fluid/vasopressor-resistant hypoten-
sion in pediatric critical illness.
Measurements and Main Results: Forty-six of 57 (80.7%) en-
docrinologists responded, with 43 participating (75.4%). Among
intensivists, 59 of 70 (84.3%) responded with no refusals. Of
intensivists, 81.4% believe that adrenal insufficiency occurs
sometimes or often in critically ill pediatric intensive care unit
patients, whereas 41.8% of endocrinologists believe adrenal in-
sufficiency occurs never or rarely in these patients. Six definitions
of adrenal insufficiency were proposed (varying cortisol level vs.
peak/increment of cortisol in response to corticotropin), with no
consensus on the definition of adrenal insufficiency from the
endocrinologists or intensivists. Half (50.9%) of intensivists said
they would sometimes or often empirically treat hypotensive
pediatric patients with glucocorticoids, whereas 81.0% of endo-
crinologists would occasionally or never recommend glucocorti-
coids on this basis.
Conclusions: There is no consensus among pediatric intensiv-
ists or endocrinologists as to how often adrenal insufficiency
occurs in pediatric critical illness or how to diagnose this condi-
tion. Despite this lack of consensus, however, many pediatric
intensivists would empirically treat hypotensive patients who they
suspect may have adrenal insufficiency. Prospective studies are
required to determine the definition, frequency, and appropriate
treatment of adrenal insufficiency in critically ill pediatric pa-
tients. (Pediatr Crit Care Med 2007; 8:276 –278)
KEY WORDS: adrenal insufficiency; adrenal hypofunction; corti-
costeroids; intensive care; corticotropin; critical care

A drenal insufficiency (AI) is a
clinical condition that in its ex-
treme may be characterized by
tachycardia and hypotension,
which are resistant to fluid and inotrope
therapy. If not promptly treated with
stress doses of replacement glucocorti-
coids and mineralocorticoids, it may be
fatal (1, 2). However, tachycardia and hy-
potension are common presentations of a
wide spectrum of disease processes in
critically ill patients, thus making adre-
nal dysfunction difficult to diagnose in
this patient population.
*See also p. 305.
From the Department of Pediatrics, Children’s Hos-
pital of Eastern Ontario and University of Ottawa, On-
tario, Canada.
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
menon@cheo.on.ca
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262796.38637.15
The incidence of adrenal dysfunction
in critically ill children reported in the
literature varies considerably from 4% to
52% (3– 6). The only six available pediat-
ric studies focused primarily on children
with septic shock (3–5, 7) and after open-
heart surgery (8) and had small numbers.
Furthermore, all six studies (3– 8) used
different definitions for the diagnosis of
AI, making the results hard to compare
and interpret in the broader context of
pediatric critical care. There are cur-
rently no published studies in pediatric
critical care that show improved mortal-
ity following treatment with glucocorti-
coids of critically ill patients with diag-
nosed AI.
With ⬎11,000 children being admit-
ted to 16 pediatric critical care units in
Canada each year, AI has the potential to
affect a significant number of children.
However, as a result of the existing con-
troversy in the literature regarding the
identification, diagnosis, and treatment
of critically ill children with adrenal in-
sufficiency, there are no clear guidelines
for the management of these children.
Therefore, to clearly delineate the issues
for a future comprehensive cohort study,
we undertook a survey study on the cur-
rent beliefs of pediatric intensivists and
endocrinologists around the incidence,
definition, and empirical treatment of AI
in this patient population.
METHODS
Study Population. The survey was sent to
all physicians practicing pediatric critical care
medicine in any of the 16 tertiary-care pediat-
ric intensive care units (PICUs), as well as all
pediatric endocrinologists in Canada. A list of
all practicing pediatric endocrinologists was
obtained with permission from the Canadian
Pediatric Endocrine Group. Fellows, retired
members, and endocrinologists whose prac-
tice did not include consultations within the
PICU were excluded from the survey. The sur-
vey was conducted between May and Septem-
ber of 2004.
Survey Development and Administration.
Two surveys were developed with parallel
themes, one for the pediatric intensivists and
one for the pediatric endocrinologists. Each

276 Pediatr Crit Care Med 2007 Vol. 8, No. 3

survey consisted of two sections. The first sec- pediatric intensive care patients, their re- whereas 80.7% of endocrinologists stated
tion recorded information on physician char- sponses were diffusively spread across the that they would never or only occasion-
acteristics, such as Royal College certification, choices (Fig. 1). The most common diag- ally recommend this.
years in practice, and availability of endocrine nostic criterion used by the pediatric en- There was no association among sur-
consultations in the PICU. The second section
docrinologists was a peak cortisol level vey responses regarding the prevalence,
consisted of three questions that examined the
following: a) the frequency with which each
after standard-dose corticotropin stimu- diagnosis, and treatment of AI in pediat-
physician thought secondary AI occurred in lation testing of ⬍500 nmol/L (18.1 ␮g/ ric critical illness and physician charac-
pediatric critical illness; b) how they would dL), whereas the most common criterion teristics, such as Royal College certifica-
diagnose/define adrenal dysfunction in pediat- for pediatric intensivists was a baseline tion, years in practice, or the involvement
ric critical illness (Table 1); and c) whether cortisol level of ⬍138 nmol/L (5.0 ␮g/ of endocrinology in the PICU.
they would ever treat patients with fluid/ dL). In addition, 30% of pediatric inten-
vasopressor-resistant hypotension without sive care physicians and 23% of pediatric
formal adrenal testing. Potential answers to endocrinologists stated that they would DISCUSSION
questions a) and c) in the second section in- use further unlisted criteria to aid with
cluded never, rarely, sometimes, often, and There has been a long-standing con-
the diagnosis. Of pediatric intensivists,
always. The three questions were developed troversy regarding the existence, diagno-
after an extensive review of the literature on AI
15% stated that they were unsure of the
diagnostic criteria and/or they would ask sis, and significance of adrenal dysfunc-
in pediatric critical illness (3– 8) and in con-
endocrinology to interpret the results. Of tion in pediatric critical illness. During
sultation with three pediatric endocrinologists
and three pediatric intensive care physicians. pediatric intensive care physicians, 12% the last 10 yrs, several small pediatric
Surveys were mailed with a self-addressed, stated that they would use clinical crite- studies have attempted to study this con-
stamped envelope, and physicians were asked ria only and would not perform formal dition, but with varying and inconclusive
to return the survey within 2 wks. Four weeks adrenal testing. Approximately 50% of all results. A survey study conducted in the
after the first mailing, physicians who had not physicians surveyed responded that they United Kingdom in 2005 (9) also found
returned the survey were sent a reminder let- would use more than one of the diagnos- that practices with regard to use of ste-
ter by mail and e-mail. The study was approved roids in children with septicemia vary
tic criteria listed.
by the Research Ethics Board of the Children’s
When asked if they would use glu- considerably among PICUs. The findings
Hospital of Eastern Ontario.
Statistical Analysis. Descriptive statistics cocorticoids empirically to treat hypoten- of our survey indicate that this contro-
were calculated for all demographic data and sive patients without adrenal testing, versy persists both within and among
to calculate the frequencies of responses for 50.9% of pediatric intensivists stated that the specialties providing care to these
each question. Tests of association were used they would do so sometimes or often, children.
to assess relationships between responses and
Royal College certification, years in practice,
or availability of endocrinology consultation Table 1. Definitons/diagnostic criteria used in the survey
to the PICU. In the case of ordinal variables,
Definition
Spearman’s rank-correlation test was used.
Overall numbers were too small to analyze
Baseline cortisol ⬍138 nmol/L (5.0 ␮g/dL)
practice patterns by center.
Baseline cortisol ⬍200 nmol/L (7.2 ␮g/dL)
Increment (after low-dose corticotropin) ⬍200 nmol/L (7.2 ␮g/dL)
RESULTS Increment (after low-dose corticotropin) ⬍250 nmol/L (9.0 ␮g/dL)
Peak (after low-dose corticotropin) ⬍500 nmol/L (18.1 ␮g/dL)
Fifty-seven pediatric endocrinologists Peak (after low-dose corticotropin) ⬍500 nmol/L (18.1 ␮g/dL) and/or increment ⬍200 nmol/L
and 70 pediatric intensive care physicians (7.2 ␮g/dL)
were eligible for the survey. Forty-three Other
(75.4%) of the 57 eligible pediatric endo-
crinologists responded, as did 59 (84.3%)
of the 70 eligible pediatric intensive care
physicians in Canada. A total of 62.8% of
the endocrinologists and 54.3% of the
intensive care physicians had Royal Col-
lege training in their respective special-
ties, and the majority of physicians re-
sponding had been in practice for ⬎5 yrs
(62.8% of endocrinologists and 74.6% of
intensivists).
Most (81.4%) of the pediatric intensiv-
ists believed that adrenal dysfunction oc-
curs sometimes or often in pediatric in-
tensive care patients, whereas 41.8% of
pediatric endocrinologists believed that it
rarely or never occurs in this population.
When physicians were asked which of the
six potential criteria they would use for Figure 1. Laboratory diagnostic criteria used by pediatric endocrinologists and intensive care physi-
the diagnosis of adrenal dysfunction in cians to diagnose adrenal insufficiency.

Pediatr Crit Care Med 2007 Vol. 8, No. 3 277

 There are only six published studies
that have specifically addressed AI in pe-
diatric (not neonatal) critical illness, in-
tensive care, sepsis, or septic shock (3– 8).
Five of the six studies used different def-
initions of AI, and the two studies that
used similar definitions (3, 5) in similar
patient populations (meningococcal dis-
ease) found differing incidences of AI (4%
vs. 17%). Furthermore, only two studies
correlated the presence of AI by their
definition with clinically important out-
comes, such as longer duration of vaso-
pressor therapy (4) and the presence of
catecholamine-resistant shock (7).
The controversy in the literature sur-
rounding adrenal dysfunction in pediatric
critical illness is further deepened by the
debate regarding the existence of relative
vs. absolute AI. Again, there is no consen-
sus on the diagnosis of absolute AI as
manifested by the different definitions
used in the literature (3, 7). In addition,
four of the six pediatric studies (4 – 6, 8)
do not mention or discuss relative vs.
absolute AI but simply refer to AI in pe-
diatric critical illness. A potential limita-
tion of our survey is that respondents
may have been unclear as to whether our
question on the definition referred to ab-
solute or relative AI and, hence, gave us
the broad range of responses noted. How-
ever, the survey question on the diagno-
sis/definition of adrenal dysfunction in
pediatric critical illness included a line
for comments and not one of the 113
respondents mentioned the concept of
relative vs. absolute AI.
Given the varied and limited published
reports concerning children, it is not sur-
prising that practicing pediatric intensiv-
ists and endocrinologists in Canada have
different views on the frequency and di-
agnosis of adrenal dysfunction in pediat-
ric critical illness. Interestingly, despite
the available literature mentioned previ-
ously, 41.8% of pediatric endocrinolo-
gists surveyed still stated that they be-
lieve this condition rarely or never occurs
in critically ill children. It is possible that
this discrepancy exists because they do
not believe that the biochemical AI seen
in these patients correlates with a clini-
278
cally significant outcome or because the
endocrinologists do not agree with the
definitions used in these studies. A fur-
ther possibility and potential limitation of
our study is that endocrinologists may
have interpreted the term adrenal dys-
function as meaning only primary AI,
which they may feel rarely occurs. Given
the diversity of patients in PICUs, it is
more likely that dysfunction may occur at
the level of the hypothalamus, pituitary,
and/or the adrenal gland (10, 11), de-
pending on the patient, which may fur-
ther contribute to the existing difficulty
with diagnosis.
Despite the lack of published studies
on the benefits of short-term glucocorti-
coid use in this patient population with a
confirmed diagnosis of adrenal dysfunc-
tion, 50.9% of intensivists would empiri-
cally treat hypotensive pediatric patients
with gluco-/mineralocorticoids. In addi-
tion, all 15% of pediatric intensivists who
were unsure of how to diagnose adrenal
dysfunction stated that they often treated
hypotensive patients empirically. How-
ever, one must be cautious about the
empirical use of glucocorticoids, as there
is some evidence to suggest that even
short-term glucocorticoid use in the crit-
ically ill pediatric intensive care popula-
tion may be associated with side effects,
such as hyperglycemia (12), leukocytosis
(13), and critical care polyneuropathy
(14).
Overall, our survey showed that there
is no consensus on the incidence, diag-
nosis, or treatment of AI in pediatric crit-
ical illness. This raises the concern that
critically ill children throughout Canada
may be receiving different treatments for
this condition, with potentially different
outcomes, depending on the views and
experience of the pediatric intensivist or
endocrinologist involved in their care.
The results of this survey highlight the
need for a large-scale epidemiologic
study using adrenal-function testing
that correlates various definitions of AI
with clinically important outcomes,
such as hypotension and mortality, to
determine the frequency, appropriate
diagnostic method, and ultimate treat-
ment of this potentially life-threatening
condition.
REFERENCES
1. Bouachour G, Tirot P, Gouello JP, et al: Ad-
renocortical function during septic shock.
Intensive Care Med 1995; 21:57– 62
2. Hinshaw LB, Beller BK, Chang AC, et al:
Corticosteroid/antibiotic treatment of adre-
nalectomized dogs challenged with lethal E.
coli. Circ Shock 1985; 16:265–277
3. Riordan FA, Thomson AP, Ratcliffe JM, et al:
Admission cortisol and adrenocorticotrophic
hormone levels in children with meningo-
coccal disease: Evidence of adrenal insuffi-
ciency? Crit Care Med 1999; 27:2257–2261
4. Hatherill M, Tibby SM, Hilliard T, et al: Ad-
renal insufficiency in septic shock. Arch Dis
Child 1999; 80:51–55
5. Bone M, Diver M, Selby A, et al: Assessment
of adrenal function in the initial phase of
meningococcal disease. Pediatrics 2002; 110:
563–569
6. Menon KCC: Adrenal function in pediatric
critical illness. Pediatr Crit Care Med 2002;
3:112–116
7. Pizarro CF, Troster EJ, Damiani D, et al:
Absolute and relative adrenal insufficiency in
children with septic shock. Crit Care Med
2005; 33:855– 859
8. Ando M, Park IS, Wada N, et al: Steroid
supplementation: A legitimate pharmaco-
therapy after neonatal open heart surgery.
Ann Thorac Surg 2005; 80:1672–1678
9. Hildebrandt T, Mansour M, Al Samsam R:
The use of steroids in children with septice-
mia: Review of the literature and assessment
of current practice in PICUs in the UK. Pae-
diatr Anaesth 2005; 15:358 –365
10. Chiolero R, Berger M: Endocrine response to
brain injury. New Horiz 1994; 2:432– 442
11. Cohan P, Wang C, McArthur DL, et al: Acute
secondary adrenal insufficiency after trau-
matic brain injury: A prospective study. Crit
Care Med 2005; 33:2358 –2366
12. Markovitz BP, Randolph AG: Corticosteroids
for the prevention and treatment of post-
extubation stridor in neonates, children, and
adults. Cochrane Database Syst Rev 2000,
CD001000
13. Cream JJ: Prednisolone-induced granulocy-
tosis. Br J Haematol 1968; 15:259 –267
14. Tabarki B, Coffinieres A, Van Den BP, et al:
Critical illness neuromuscular disease: Clin-
ical, electrophysiological, and prognostic as-
pects. Arch Dis Child 2002; 86:103–107
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Case Reports

Tissue plasminogen activator for a left atrial thrombus after

Senning repair
Cecile Tissot, MD; Peter C. Rimensberger, MD; Yacine Aggoun, MD; Afksendyios Kalangos, MD, PhD;
Hulya Ozsahin, MD; Maurice Beghetti, MD; Eduardo M. da Cruz, MD

Objective: To avoid the surgical removal of an obstructive
thrombus in a Senning baffle by the administration of recombi-
nant tissue-type plasminogen activator.
Setting: A pediatric intensive care unit in a children’s univer-
sity hospital.
Patients: A 3-yr-old male was diagnosed with a large left atrial
thrombus 2 wks after Senning repair for D-transposition of the
great arteries. The child presented with massive chylous pleural,
pericardial effusions, and cardiac tamponade, secondary to par-
tial obstruction of the pulmonary venous channel.
Intervention: Thrombolysis with recombinant tissue-type plas-
minogen activator was instituted.
Results: We observed a resolution of the thrombus in <48 hrs.
Minor local bleeding was the only noted side effect. No signs of
systemic thromboembolization were detected.
Conclusion: Early thrombolysis with recombinant tissue-type
plasminogen activator could be considered a possible alternative
to surgical thrombectomy in selected postoperative pediatric
cases, although there may be a potential risk of serious bleeding.
(Pediatr Crit Care Med 2007; 8:279 –281)
KEY WORDS: thrombosis; atrium; pediatric; chylothorax; congen-
ital heart disease

I ntracardiac thrombi are a rarely
reported complication after car-
diac surgery for congenital heart
disease (1, 2), particularly when
not associated with indwelling catheters
(3). Treatment is often a challenge,
mostly when the thrombus is located in
the left cardiac cavities, because of the
potential risk of systemic embolic com-
plications (4). Available therapeutic op-
tions are surgical thrombectomy, hepa-
rinization, or thrombolysis. Surgical
thrombectomy carries significant risks in
the early postoperative period, related to
inflammatory tissue prone to bleeding
during surgical re-intervention and to
the need for extracorporeal circulation.
From the Pediatric Cardiology Unit (CT, YA, MB,
EDC) and the Pediatric Onco-Hematology Unit (HO),
Department of Pediatrics, and the Service of Pediatric
and Neonatal Intensive Care (PR, EDC), Children’s Uni-
versity Hospital of Geneva; and the Service of Cardio-
vascular Surgery, Department of Surgery, University
Hospital of Geneva (AK), Geneva, Switzerland.
The authors have not disclosed any potential con-
flict of interest.
No financial support was received for this study.
For information regarding this article, E-mail:
eduardo.dacruz@hcuge.ch
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262889.14026.85
These risks have to be weighed against
those of medical therapy with anticoagu-
lation or fibrinolysis that may endanger
patients with serious bleeding complica-
tions. We report a case of a partly ob-
structed left atrial thrombus following
Senning repair for D-transposition of the
great arteries, which was successfully
treated with recombinant tissue-type
plasminogen activator (rt-PA), with only
minor side effects.
DESCRIPTION OF THE CASE
A 3-yr-old male patient was referred to
our institution for D-transposition of the
great arteries, associated with a small
ventricular septal defect and a complex
mild-to-moderate valvular and subvalvu-
lar pulmonary stenosis. Taking into ac-
count the patient’s age, the fact that the
ventricular septal defect was restrictive
and uncommitted to the aorta, and that
the subpulmonary obstruction was com-
plex, we considered it safer to proceed
with a Senning atrial switch with ventric-
ular-septal-defect patch closure. The im-
mediate postoperative transesophageal
echocardiography showed a good result,
with only a minimal flow gradient on the
systemic venous return and normal flow
on the pulmonary venous channel. Sub-
sequently, the patient was monitored
with an internal jugular central venous
catheter and an indwelling right radial
artery catheter. No left atrial catheter was
inserted. The postoperative course was
uneventful, with the patient having stable
hemodynamic parameters after receiving
a low dose of inotropic and vasodilator
drugs and undergoing extubation on the
first postoperative day. The child was dis-
charged from hospital on the tenth post-
operative day with minimal diuretic
treatment and receiving antiplatelet
doses of aspirin. Transthoracic echocar-
diography at discharge showed normal
ventricular function, no intracardiac
shunt, and patent systemic and pulmo-
nary venous channels.
Five days later, the child was admitted
to the emergency room with a medical
history of progressive cardiorespiratory
distress, with hemodynamic instability
and cardiac tamponade, secondary to
massive right pleural and pericardial ef-
fusions. There were no clinical signs of
dehydration and no biological signs of
hypercoagulability. He underwent an
emergent percutaneous pericardial and
pleural drainage. A large amount of chy-
lous fluid (86% of lymphocytes and pos-
itive Soudan screening) was evacuated.
Transthoracic and transesophageal echo-
cardiographs documented the presence of
a large thrombus, firmly attached at the

Pediatr Crit Care Med 2007 Vol. 8, No. 3 279


Figure 1. Transesophageal echocardiography
showing a large partly occlusive thrombi (ar-
rows) across the pulmonary venous channel.
ECG, electrocardiogram.
Figure 2. Transesophageal echocardiography
documenting a horseshoe-shaped thrombi (ar-
row) partly occluding blood flow from the pul-
monary veins. BPM, beats per minute; ECG, elec-
trocardiogram.
distal insertion of the pulmonary venous
channel, with a significant mean gradient
of 15 mm Hg (Figs. 1, 2). The systemic
venous return was free from obstruction,
and tricuspid diastolic flow was not al-
tered.
Taking into account the potential
risks of surgical thrombectomy, the tech-
nical difficulty in reaching the Senning
baffle and the need for another extracor-
poreal circulation in the early postopera-
tive period and after obtaining a written
informed consent and Institutional Re-
view Board approval, thrombolysis was
instituted with rt-PA (Actilyse, Boehr-
inger Ingelheim, Basel, Switzerland). We
administered a continuous infusion at 0.6
mg·kg·hr for 6 hrs (5, 6), then decreased
it to 0.3 mg·kg·hr because of bleeding at
the insertion sites of pericardial and pleu-
ral drains. No other complications of
thrombolysis were noted, and there were
no clinical signs of systemic thromboem-
bolization. The fibrinogen level stayed
within the normal range (⬎100 mg/dL),
confirming the absence of systemic fi-
280
Figure 3. Transthoracic echocardiography after
therapy with recombinant tissue-type plasmino-
gen activator documenting a thrombi-free pul-
monary venous channel (arrow).
brinolysis. Serial cardiac ultrasounds
showed a progressive lysis of the throm-
bus. The rt-PA infusion was stopped after
36 hrs, because the thrombus had nearly
disappeared and the pulmonary venous
flow had returned to the normal pattern.
A heparin infusion at 15 IU·kg·hr was
then instituted after a 10 IU/kg bolus,
adjusted for a partial thromboplastin
time of 35–50 secs. Anticoagulation ther-
apy was maintained for a 6-wk period
with oral acenocoumarol, followed by an-
tiplatelet therapy with aspirin.
The final outcome was favorable, with
complete lysis of the thrombus and nor-
malization of the flow in the pulmonary
venous return. At 3-month follow-up,
echocardiography showed no residual
thrombus (Fig. 3).
DISCUSSION
Left atrial thrombi are a rare compli-
cation following surgery for congenital
heart disease (1, 2), when not associated
with central catheters or hypercoagula-
bility status (3). Moreover, thrombi in the
pulmonary venous channel early after a
Senning repair for D-transposition of the
great arteries very seldom are described
in the literature (7). Our patient pre-
sented with massive chylothorax and chy-
lopericardium. This was thought to be
secondary to the high venous pressure
owing to significant obstruction of the
pulmonary venous return caused by the
thrombus, generating a hemodynamic
compromise. As a matter of fact, the chy-
lothorax disappeared concomitantly with
the thrombus. At admission, the two
treatment options were surgical throm-
bectomy or systemic thrombolysis. Vigi-
lant thrombolysis was accepted as a rea-
sonable noninvasive alternative, whereas
surgical risks were deemed significantly
high because of technical difficulties im-
posed by inflammatory tissues and adher-
ences, difficulty in reaching the left
atrium after the Senning procedure, and
the need for a second cardiopulmonary-
bypass procedure (8).
Recently, there has been some in-
creasing interest in rt-PA as the recom-
mended treatment for children with crit-
ical thrombotic compromise of organs or
limbs (9). rt-PA is thought to have less
systemic fibrinolytic activity than strep-
tokinase and urokinase, because of its
relatively specific action on plasminogen-
bound fibrin, leading to less hemorrhagic
complications. It has been recommended
for thrombolysis of prosthetic heart
valves, even in children (10), while a few
authors have described successful lysis of
intracardiac thrombi after cardiac sur-
gery or catheterization (1, 2, 4), as well as
in preterm babies (11). As far as we are
aware, there are no recognized universal
guidelines for dosage of rt-PA (3, 5, 6):
some groups giving an initial intravenous
bolus (1, 2, 5, 6), and others directly
initiating the intravenous infusion (3– 6).
Its most commonly described side effect
is hematic oozing of the wound or at the
catheter-insertion sites, whereas severe
hemorrhage has been reported in rare
cases (1, 3). Nevertheless, monitoring of
fibrinogen levels is required with any dos-
ing regimen, the goal being to maintain
this level at ⬎100 mg/dL (9, 11), to re-
duce the risk of active bleeding. Other
potential complications include throm-
boembolism and stroke, particularly
when the thrombi are mobile and situ-
ated in the left side of the heart or when
surgical correction is not complete, al-
lowing for right-to-left embolization. All
cited authors reported a complete resolu-
tion of the intracardiac thrombi with
rt-PA (1– 4).
In our case, rt-PA was started with
an infusion rate of 0.6 mg·kg·hr, allow-
ing a rapid reduction in the size of the
thrombi, and then reduced to 0.3
mg·kg·hr because of local blood oozing.
There was no systemic hemorrhage, ev-
idence of systemic fibrinogenolysis, or
clinical embolic episode. The result was
excellent, with complete resolution of the
thrombus and normalization of the he-
modynamic profile.
CONCLUSION
In our case, thrombolysis with rt-PA
was an effective therapeutic alternative
for left nonmobile intracardiac thrombi
Pediatr Crit Care Med 2007 Vol. 8, No. 3
following open-heart surgery. Although
there is a potential risk for serious bleed-
ing or embolic complications, rt-PA
could be considered as an alternative to
surgical thrombectomy, particularly in
the early postoperative period, when the
surgical risks and the need for a close
cardiopulmonary bypass are to be taken
into account. Further studies are manda-
tory, to better assess the safety of this
approach in such a context and to estab-
lish clearer dose recommendations.
REFERENCES
1. Kehl HG, Kececioglu D, Kotthof S, et al: Left
atrial thrombus in a 10-month-old boy—
Successful thrombolysis with recombinant
tissue-type plasminogen activator after open-
heart surgery: Review of the literature. In-
tensive Care Med 1996; 22:968 –971
Pediatr Crit Care Med 2007 Vol. 8, No. 3
2. Asante-Korang A, Asreeram N, McKay R, et
al: Thrombolysis with tissue-type plasmino-
gen activator following cardiac surgery in
children. Int J Cardiol 1992; 35:317–322
3. Schermer E, Streif W, Genser N, et al:
Thrombolysis with recombinant tissue-type
plasminogen activator (rt-PA) in 13 children:
A case series. Wien Klin Wochenschr 2000;
112:927–933
4. Herron SB, Lax D, Zamora R: Successful
thrombolysis of acute left atrial thrombi in 2
pediatric patients following interventional
cardiac catheterization. J Invasive Cardiol
2004; 16:35–39
5. Michelson AD, Bovill E, Monagle P, et al:
Antithrombotic therapy in children. Chest
1998; 114:748S–769S
6. Leaker M, Massicotte MP, Brooker LA, et al:
Thrombolytic therapy in pediatric patients: A
comprehensive review of the literature.
Thromb Haemost 1996; 76:132–134
7. Ebeid MR, Gaymes CH, McMullan MR, et al:
Catheter management of occluded superior
baffle after atrial switch procedures for trans-
position of great vessels. Am J Cardiol 2005;
95:782–786
8. Chaikof EL, Dodson TF, Salam AA, et al:
Acute arterial thrombosis in the very young.
J Vasc Surg 1992; 16:428 – 435
9. Monagle P, Chan A, Massicotte P, et al: Anti-
thrombotic therapy in children: The 7th ACCP
Conference on Antithrombotic and Thrombo-
lytic Therapy. Chest 2004; 126(Suppl 3):
645S– 687S
10. Serpi M, Schmidt KG, Kreuz W, et al:
Thrombolysis of prosthetic heart valve
thrombosis using recombinant tissue plas-
minogen activator (rt-PA) in infancy and
childhood. Z Kardiol 2001; 90:191–196
11. Rimensberger PC, Humbert JR, Beghetti M:
Management of preterm infants with intra-
cardiac thrombi: Use of thrombolytic agents.
Paediatr Drugs 2001; 3:883– 898
281
Editorials
Critical pertussis may model organ failure in critical illness and
injury*
I n this issue of Pediatric Critical
Care Medicine, Dr. Namachivayam
and colleagues (1), pediatric critical
care investigators from Melbourne,
Australia, present a descriptive retrospec-
tive report on 49 children admitted to the
pediatric intensive care unit during a
20-yr period. Of these, seven infants
(14%) died, and six of these were in the
cohort requiring any form of circulatory
support. Only 18 of the 49 (about 37%) of
these required intubation and mechani-
cal ventilation. All seven fatalities oc-
curred in this group, so that the risk of
death increased to 38% in children re-
quiring intubation and any mechanical
ventilatory support. Of interest would be
any data confirming a change in mortal-
ity rate in recent years from critical per-
tussis, as compared with death rates from
other life-threatening illnesses and inju-
ries in very young babies.
In the United States, the overall mor-
tality rate in pediatric critical care units
has plummeted to 1.5–1.8%, and a large
proportion of children admitted emer-
gently with critical illness and injury ei-
ther have special healthcare needs at ad-
mission or will have such needs and
disabilities at discharge (2). Unfortu-
nately, critical pertussis mortality has not
uniformly decreased to the same degree.
To quantify the persistence of critical per-
tussis as a source of mortality and mor-
bidity, the National Institute of Child
Health and Human Development Collab-
orative Pediatric Critical Care Research
Network is undertaking a descriptive,
prospective cohort study with the Centers
for Disease Control and Prevention. Vari-
ables of interest in the pediatric intensive
*See also p. 207.
Key Words: organ failure; G proteins;
immunophenotyping
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: ‘10.1097/01.PCC.0000265500.59962.B8
288
care unit will be recorded, including the
need for extracorporeal membrane oxy-
genation, evidence of pulmonary hyper-
tension, and pediatric logistic organ dys-
function (PELOD) score. In addition, the
project will evaluate the status of chil-
dren with critical pertussis at 1 yr after
admission to the pediatric intensive care
unit for confirmed pertussis.
At least 400,000 children die world-
wide of pertussis annually. Most pertus-
sis-induced critical illness and fatalities
occur in very young infants (3), an im-
munologically immature cohort present-
ing challenges in sepsis and organ failure
(4). Bordetella pertussis pathogenesis is
characterized by the presence of a com-
plex of several physiologically active
agents with diverse properties. Pertussis
toxin (PT), now understood as a major
virulence factor, effects changes in the
immune system, both in T-cell popula-
tions/phenotypes and in immunoglobu-
lins (IgE, IgA, and IgG) (5– 8). The trans-
lational significance of this recent work
in animal (mouse) models remains un-
clear for infants with pertussis illness and
progressive organ system failure. Fur-
ther, the immunomodulatory effects of
PT are demonstrated as independent of
the adenosine diphosphate–ribosyltrans-
ferase activity known to modify
guanosine triphosphate– binding regula-
tory proteins and thus signal transduc-
tion (5).
Immunomodulatory PT effects are not
yet quantitated in cohorts of infants with
critical pertussis. One report of patho-
logic findings in infants dying of pertussis
implicated multiple organ system failure
and uniformly present pulmonary hyper-
tension and pulmonary hemorrhage (9).
Remarkably, this same report did not find
traditional clinical variables (cough,
whoop, fever, cyanosis) to be significantly
predictive of fatal outcome in hospital-
ized children with pertussis. Rather, the
level of leukocytosis, and the decision to
admit the child to the pediatric critical
care unit, presumably in the presence of
organ failure, were the most strongly pre-
dictive of death in that cohort. In the
report by Dr. Namachivayam and col-
leagues (1) reviewed here, a striking find-
ing is the lack of association of critical
pertussis prevalence and mortality with
prematurity at birth.
The disease is associated with leuko-
cytosis, characterized by lymphocytosis,
and a prominence of small lymphocytes
with cleaved nuclei. Reports suggest that
L-selectin activity is lost across several
immunologic cell lines, yet the relevance
for critical organ failure of altered or lost
L-selectin activity remains incompletely
understood, as does the effect of develop-
ment on immune function and the organ
failure phenotype; there may be a relative
immunoparalysis induced by B. pertussis
in an immature host that explains the
fulminant course of pertussis-induced
critical illness in very young infants (10 –
12). Studies have indicated that the lym-
phocytosis is uniform across B and T cells
(13), but extensive functional immuno-
phenotyping reports from critically ill in-
fants have not been a prominent feature
of recent pertussis literature. Although
the Th-1 phenotype seems to be prefer-
entially increased (12), definitive under-
standing of functional immunomodula-
tion in pertussis pathogenesis remains
incomplete (14, 15). The temporal initia-
tion or failure of the phenotype switch to
Th-2 in the presence of organ failure and
the relationship to altered signal trans-
duction (possibly due to the adenosine
diphosphate–ribosylating effects of the
PT subunit) are not well understood at
present. Disruption of signal transduc-
tion via cell cycle signaling in the hetero-
trimeric G protein system dismantles cel-
lular stress responses and is followed by
diverse biological effects, not limited to
acceleration of cyclic guanosine mono-
phosphate– dependent phosphodiesterase
activity and inhibition of adenyl cyclase
(14). One author suggests that one or
more of these downstream, diverse tissue
effects may singly or in cohort represent
a “point of no return” and irreversibility
in critical organ failure (15). G-protein
Pediatr Crit Care Med 2007 Vol. 8, No. 3
uncoupling and signal disruption might
be a common pathway of organ-failure
induction utilized by diverse agents, es-
pecially in view of recent work implicat-
ing small interfering RNA in pathogene-
sis (15, 16).
Data now emerging in studies of crit-
ical pertussis may inform understanding
how immune signal disruption relates to
the point of irreversibility/“no return” for
a given organ system or tissue bed. For
example, the ability to consume oxygen
and substrate is characteristically mea-
sured in sepsis by oxygen consumption
and the concept of supply dependency
(17, 18). The temporal relationship of
these events to signal disruption remains
unknown, but where oxygen is no longer
consumed, despite adequate supply, the
viability of tissues and cells may be in
doubt. Implementation of circulatory
support and extracorporeal membrane
oxygenation may be informed by such
data and family conferences and decision
making enabled.
Recognition of lymphocytic apoptosis
as an antecedent to sepsis and multiple
organ failure has recently emerged (19).
In critical pertussis, the characteristic
lymphocytosis and loss of L-selectin ac-
tivity may be a harbinger of immunosup-
pression, inapparent in cell counts. Fur-
ther, the developmental trajectory may
affect any immunomodulation, as lym-
phocyte populations are known to vary in
children of different ages and to vary
markedly with development in animal
models (20, 21). The detrimental cellular
effects of PT (as differentiated from the
other substances present in active B. per-
tussis infection) are only recently de-
scribed. Translational application of re-
cent work in the genomics of the critical
illness phenotype has not been carried
out in the setting of documented critical
pertussis in a homogeneous cohort of hu-
man infants but might be informative.
Downstream tissue effects of PT in criti-
cal and fatal pertussis may model organ
failure due to disruption of signal trans-
duction and immunoparalysis or down-
regulation. The model of G protein sys-
tem disruption and immune cell
Pediatr Crit Care Med 2007 Vol. 8, No. 3
dysfunction in critical pertussis may lead
us to understand more clearly how organ
failure occurs in a wider context of criti-
cal illness and injury.
Carol E. Nicholson, MS, MD, FAAP
National Institutes of Health
NICHD/NCMRR
Bethesda, MD
REFERENCES
1. Namachivayam P, Shimizu K, Butt W: Per-
tussis: Severe clinical presentation in pediat-
ric intensive care and its relation to out-
come. Pediatr Crit Care Med 2007;
8:207–211
2. Nicholson CE: Pediatric critical care for chil-
dren with congenital neurodevelopmental di-
agnoses. Pediatr Crit Care Med 2004;
5:407– 408
3. Centers for Disease Control and Prevention
(CDC): National, state, and urban area vacci-
nation coverage among children aged 19 –35
months: United States, 2004. MMWR Morb
Mortal Wkly Rep 2005; 545:717–721
4. Stoll BJ, Hansen N, Fanaroff AA, et al: Late-
onset sepsis in very low birth weight neo-
nates: The experience of the NICHD Neonatal
Research Network. Pediatrics 2002; 110(2 Pt
1):285–291
5. Ryan M, McCarthy L, Rappuoli R, et al: Per-
tussis toxin potentiates Th1 and Th2 re-
sponses to co-injected antigen: Adjuvant ac-
tion is associated with enhanced regulatory
cytokine production and expression of the
co-stimulatory molecules B7-1, B7-2 and
CD28. Int Immunol 1998; 10:651– 662
6. Fujimoto C, Yu CR, Shi G, et al: Pertussis
toxin is superior to TLR ligands in enhancing
pathogenic autoimmunity, targeted at a neo-
self antigen, by triggering robust expansion
of Th1 cells and their cytokine production.
J Immunol 2006; 177:6896 – 6903
7. Cassan C, Piaggio E, Zappulla JP, et al: Per-
tussis toxin reduces the number of splenic
Foxp3⫹ regulatory T cells. J Immunol 2006;
177:1552–1560
8. Tonon S, Badran B, Benghiat FS, et al: Per-
tussis toxin activates adult and neonatal na-
ive lymphocytes. Eur J Immunol 2006; 36:
1794 –1804
9. Halperin SA, Wang EE, Law B, et al: Epide-
miological features of pertussis in hospital-
ized patients in Canada, 1991–1997: Report
of the Immunization Monitoring
Program–Active (IMPACT). Clin Infect Dis
1999; 28:1238 –1243
10. Hodge G, Hodge S, Markus C, et al: A marked
decrease in L-selectin expression by leuko-
cytes in infants with Bordetella pertussis in-
fection: Leukocytosis explained? Respirology
2003; 8:157–162
11. Barnard A, Mahon BP, Watkins J, et al: Th1/
Th2 cell dichotomy in acquired immunity to
Bordetella Pertussis: Variables in the in vivo
priming and in vitro cytokine detection tech-
niques affect the classification of T-cell sub-
sets as Th1, Th2 or Th0. Immunology 1996;
87:372–380
12. Mills KH, Barnard A, Watkins J, et al: Cell-
mediated immunity to Bordetella pertussis:
Role of Th-1 cells in bacterial clearance in a
murine respiratory infection model. Infect
Immun 1993; 61:399 – 410
13. Mattoo S, Cherry JD: Molecular pathogene-
sis, epidemiology, and clinical manifestations
of respiratory infections due to Bordetella
Pertussis and other Bordetella subspecies.
Clin Microbiol Rev 2005; 18:326 –382
14. Forse RA: Biology of heterotrimeric G-
protein signaling: Signal transduction in
critical care medicine. Crit Care Med 2000;
28(4 Suppl):N53–N59
15. Sodhi A, Montaner S, Gutkind JS: Viral hi-
jacking of G-protein-coupled-receptor sig-
naling networks. Nat Rev Mol Cell Biol 2004;
5:998 –1012
16. Anderson S, Lundkvist A, Haller O, et al:
Type I-interferon inhibits Crimean-Congo
hemorrhagic fever virus in human target
cells. J Med Virol 2006; 78:216 –222
17. Mathru M, Solanki DR, Woodson LC, et al:
Splanchnic oxygen consumption is impaired
during severe and acute normovolemic ane-
mia in anesthetized humans. Anesthesiology
2006; 105:37– 44
18. Icx BE, Rigolet M, Van Der Linden PJ: Car-
diovascular and metabolic response to acute
normovolemic anemia: Effects of anesthesia.
Anesthesiology 2000; 93:1011–1016
19. Felmet KA, Hall MW, Clark RS, et al: Pro-
longed lymphopenia, lymphoid depletion,
and hypoprolactinemia in children with nos-
ocomial sepsis and multiple organ failure.
J Immunol 2005; 174:3765–3772
20. Halnon NJ, Jamieson B, Plunkett M, et al:
Thymic function and impaired maintenance
of peripheral T cell populations in children
with congenital heart disease and surgical
thymectomy. Pediatr Res 2005; 57:42– 48
21. Hulstaert F, Hannet I, Deneys V, et al: Age-
related changes in human blood lymphocyte
subpopulations: II. Varying kinetics and of
percentage and absolute count measure-
ments. Clin Immunol Immunopathol 1994;
70:152–158
289
Organ donation after cardiac death: The subtle line between
patient and donor care*
. . . and the intensive care unit physician voiced: “But on the one extreme I feel like we’re being asked to set up an organ bank
business and on the other side we’re in the business of hospital and protecting life and saving life. And I feel like there’s a conflict
of interest built into this.”
T he physician’s concerns re-
ported in the article by Dr.
Curley and colleagues (1) in
this issue of Pediatric Critical
Care Medicine highlight two crucial
points concerning donation after cardiac
death (DCD). First, health care providers
are uncomfortable about the interface be-
tween their daily clinical practices in-
cluding end-of-life care and DCD. Sec-
ond, they express the risk of conflict of
interest as a major ethical concern.
DCD is one of the most controversial
issues in the field of organ donation in
adult and pediatric intensive care. DCD oc-
curs when organs are recovered from a
donor who does not meet the criteria for
brain death but is declared dead following
irreversible cessation of circulatory and re-
spiratory function. On one hand, DCD can
increase the number of organs available for
donation and may satisfy families’ requests
for some patients who do not fulfill brain
death criteria. But, on the other hand,
many healthcare providers are reluctant to
participate in this procedure, claiming that
DCD is ethically unacceptable (2).
Dr. Curley and colleagues (1) present
the results of a qualitative study on the
extent to which a DCD program was ac-
cepted in their institution by its pediatric
staff. This outstanding article is of crucial
importance for different reasons.
The study is crucial because this field
has not yet been documented in pediat-
rics. The reason is understandable: DCD
*See also p. 212.
Key Words: death, pediatric intensive care; critical
care; children; donation after cardiac death; organ
donation
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262879.96446.66
290
from children is scarce. For instance,
among the 1,530 pediatric donors ⬍12
yrs of age who provided a liver graft be-
tween January 1, 2000, and December 31,
2004, only 15 came from DCD (3). It is
not certain that the number of organs
recovered from pediatric DCD will sub-
stantially increase in the future for sev-
eral reasons. First, the main causes of
death in DCD are trauma and anoxia,
both of which are preventable. Second,
the quality of the organs recovered from
DCD might be poorer than those har-
vested from brain-dead donors (3). Third,
some data suggest that the medical com-
munity is still unsure about whether
DCD is an ethically acceptable practice
(2, 4). Therefore, it is not certain that the
number of pediatric DCD programs will
increase considerably in the future, un-
like adult DCD programs.
The study points out two major issues.
First, staff members are uncomfortable
with medical practices at the interface
between daily clinical practices and DCD.
Second, this uneasiness is partly ex-
plained by ethical concerns and more
specifically the risk of conflict of interest.
The main aim of the authors was to
explore whether pediatric caregivers con-
sider that a DCD program is consistent
with their mission. As one surgeon said
in the article, “You realize the real con-
cern here is of giving the impression that
we’re going to be killing kids for their
organs.” This worry is consistent, with
recent data showing that care providers
are hesitant to perform medical tasks that
they consider to be outside the focus of
their practice (4). They identify their role
with either patient or donor care in DCD
practice and thus become uncomfortable
with participating in care that crosses the
boundary. This line between care includ-
ing end-of-life care and DCD raises the
question of ethical values of pediatric
staff and therefore of an institution. Al-
though we often consider the ethical val-
ues held by our unit or our ward, we do
not often examine the ethical values of
our institution and the different groups
of professionals involved in programs
with ethical concerns. In this study, the
88 interviewed were purposely sampled to
represent key members of the hospital
community who would be directly in-
volved in a DCD program. The inter-
viewed voiced “making it happen” for
families who desire to participate in or-
gan donation. However, they raised vari-
ous ethical issues. The different groups of
professionals prioritized them differently.
This means that the ethical values differ
among the categories of caregivers. These
data were confirmed in a national survey
recently published by Mandell et al (4). It
appears that caregivers question the prac-
tices and motives of colleagues from
other specialties who participate in organ
donation. For instance, critical care
nurses think it essential that they con-
tinue their end-of-life care in the operat-
ing room. In contrast, perioperative
nurses consider critical care providers in
the operating room to be intrusive (4).
Thus, communication among specialties
is crucial to anticipate the risk of misun-
derstanding and to enhance the accep-
tance of such a sensitive program. The
article by Dr. Curley and colleagues (1)
provides us with some key points to facil-
itate this interdisciplinary dialogue.
As previously mentioned, one of the
major ethical issues among many in DCD
is the risk of conflicts of interest. This
risk appears along the successive steps of
the process, especially when DCD candi-
dates are identified and when cardiac
death is diagnosed.
Identifying DCD Candidates
The question of the prognosis is cru-
cial when identifying DCD candidates.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Donors after cardiac death are usually
classified based on the Maastricht criteria
(5, 6). According to this classification,
category I concerns patients who are dead
on arrival, and category II concerns pa-
tients who die after unsuccessful resusci-
tation. In both cases, the prognosis is not
a question since the patient is dead. But
in the example provided by Dr. Curley
and colleagues (1), the patient, Michael,
belongs to category III, one that corre-
sponds to patients dying after life support
withdrawal. In other words, parents and
doctors consider removing an organ from
a patient who is not dead (i.e., either
brain-dead or cardiac-dead). In the sce-
nario proposed in the article, we only
know that “Michael had suffered a cata-
strophic head injury with preservation of
apneustic breathing.” The conflict of in-
terest is clear: to take advantage of the
situation and to withdraw life support
abusively, either to satisfy the parents’
request or the need for transplantation.
To avoid this risk of conflict of interest,
some countries, such as France, have
limited DCD programs to patients falling
under Maastrich categories I, II, and IV
(cardiac death in brain-dead donor).
Diagnosing Cardiac Death
The diagnosis of brain death is based
on strict criteria. But we do not have any
clear definition of cardiac death. How
long must the heart be in arrest before we
declare the patient dead? Too short and it
might be impossible to predict the irre-
versibility of the cardiac arrest. Too long
Parental presence during bedside pediatric intensive care unit rounds*
H ospitalization is a stressful
experience for children and
their family, particularly in
the setting of an intensive
care unit. The literature suggests that trau-
matic stress symptoms are common
*See also p. 220.
Key Words: pediatric intensive care unit; bedside
rounds; bedside teaching; open rounds; parental presence
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262880.86252.9B
Pediatr Crit Care Med 2007 Vol. 8, No. 3
and we might recover poor-quality or-
gans. Time pressure at this step of the
process is considerable, since premorbid
procedures are necessary to preserve or-
gan function. In some centers, antemor-
tem interventions are used to minimize
the consequences of warm ischemia dur-
ing the period of withdrawal of treat-
ment, declaration of death, and organ
harvest. These interventions may include
the antemortem administration of drugs
such as heparin or the placement of vas-
cular catheters used for in situ organ
preservation. The conflict of interest is
obvious. Doctors could decide cardiac
death prematurely after the last cardiac
beat in order to harvest good-quality or-
gans. Therefore, scientific and legal cri-
teria similar to those for the declaration
of brain death are mandatory for the di-
agnosis of cardiac death.
Conclusion
This groundbreaking study raises sev-
eral ethical points. It provides new infor-
mation on what pediatric staff members
believe to be essential elements of a
model pediatric DCD program. It appears
that care providers are ready to accept
such a program but with some condi-
tions. Various firewalls should be estab-
lished to avoid any conflict of interest
that could appear along the donation pro-
cess. Among them, there must be a clear
separation between patient and donation
interests. National legislative agencies
would play a crucial role in establishing
strict criteria for cardiac death and stan-
among parents of children in the pediatric
intensive care unit and that such symptoms
may persist long after discharge (1). Pro-
viding information to family members of a
critically ill child and means to alleviate
their anxieties about their sick child make
them more effective partners in the
care of the child, which may have a pos-
itive effect on the child’s recovery (2).
Flow of accurate and detailed informa-
tion among healthcare providers is the cor-
nerstone of good healthcare delivery. This
is why most pediatric intensive care units
have adopted multidisciplinary bedside
rounds that include physicians, nurses, re-
dardized procedures to guarantee full im-
partiality along the DCD process. Uni-
form national guidelines must create a
crystal-clear line between end-of-life care
and DCD. Without these guarantees, ac-
ceptance of DCD programs either by care-
givers or by society at large might remain
minimal.
Denis Devictor, MD, PhD
Department of Pediatrics
Pediatric Intensive Care
Unit
Hôpital de Bicêtre
Le Kermlin-Bicêtre, France
REFERENCES
1. Curley MAQ, Harrison CH, Craig N, et al:
Pediatric staff perspectives on organ donation
after cardiac death in children. Pediatr Crit
Care Med 2007; 8:212–219
2. Doig CJ, Rocker G: Retrieving organs from
non-heart-beating organ donors: A review of
medical and ethical issues. Can J Anesth 2003;
50:1069 –1076
3. Merion R, Pelletier S, Goodrich N, et al: Do-
nation after cardiac death as a strategy to
increase deceased donor liver availability. Ann
Surg 2006; 244:555–562
4. Mandell S, Zamudio S, Seem D, et al: National
evaluation of healthcare provider attitudes to-
ward organ donation after cardiac death. Crit
Care Med 2006; 34:2952–2958
5. Koostra G: Statement on non-heart-beating
donor programs. Transplant Proc 1995; 27:
2965
6. Koostra G, Kievit JK, Heineman E: The non-
heart-beating donor. Br Med Bull 1997; 53:
844 – 853
spiratory therapists, physiotherapists, nu-
tritionists, and other ancillary services.
Multidisciplinary rounds have proven to be
efficient and useful, both to the patients
and the healthcare team. However, studies
on the effects of parental involvement in
rounds on critical care patients, particu-
larly children, are limited.
Parents of children in critical care
units usually wait eagerly for information
about their child’s condition (2) and sel-
dom get the opportunity to see the treat-
ing physician. Usually, nurses act as facil-
itators for information flow between the
patient’s family and the healthcare team
291
Donors after cardiac death are usually
classified based on the Maastricht criteria
(5, 6). According to this classification,
category I concerns patients who are dead
on arrival, and category II concerns pa-
tients who die after unsuccessful resusci-
tation. In both cases, the prognosis is not
a question since the patient is dead. But
in the example provided by Dr. Curley
and colleagues (1), the patient, Michael,
belongs to category III, one that corre-
sponds to patients dying after life support
withdrawal. In other words, parents and
doctors consider removing an organ from
a patient who is not dead (i.e., either
brain-dead or cardiac-dead). In the sce-
nario proposed in the article, we only
know that “Michael had suffered a cata-
strophic head injury with preservation of
apneustic breathing.” The conflict of in-
terest is clear: to take advantage of the
situation and to withdraw life support
abusively, either to satisfy the parents’
request or the need for transplantation.
To avoid this risk of conflict of interest,
some countries, such as France, have
limited DCD programs to patients falling
under Maastrich categories I, II, and IV
(cardiac death in brain-dead donor).
Diagnosing Cardiac Death
The diagnosis of brain death is based
on strict criteria. But we do not have any
clear definition of cardiac death. How
long must the heart be in arrest before we
declare the patient dead? Too short and it
might be impossible to predict the irre-
versibility of the cardiac arrest. Too long
Parental presence during bedside pediatric intensive care unit rounds*
H ospitalization is a stressful
experience for children and
their family, particularly in
the setting of an intensive
care unit. The literature suggests that trau-
matic stress symptoms are common
*See also p. 220.
Key Words: pediatric intensive care unit; bedside
rounds; bedside teaching; open rounds; parental presence
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262880.86252.9B
Pediatr Crit Care Med 2007 Vol. 8, No. 3
and we might recover poor-quality or-
gans. Time pressure at this step of the
process is considerable, since premorbid
procedures are necessary to preserve or-
gan function. In some centers, antemor-
tem interventions are used to minimize
the consequences of warm ischemia dur-
ing the period of withdrawal of treat-
ment, declaration of death, and organ
harvest. These interventions may include
the antemortem administration of drugs
such as heparin or the placement of vas-
cular catheters used for in situ organ
preservation. The conflict of interest is
obvious. Doctors could decide cardiac
death prematurely after the last cardiac
beat in order to harvest good-quality or-
gans. Therefore, scientific and legal cri-
teria similar to those for the declaration
of brain death are mandatory for the di-
agnosis of cardiac death.
Conclusion
This groundbreaking study raises sev-
eral ethical points. It provides new infor-
mation on what pediatric staff members
believe to be essential elements of a
model pediatric DCD program. It appears
that care providers are ready to accept
such a program but with some condi-
tions. Various firewalls should be estab-
lished to avoid any conflict of interest
that could appear along the donation pro-
cess. Among them, there must be a clear
separation between patient and donation
interests. National legislative agencies
would play a crucial role in establishing
strict criteria for cardiac death and stan-
among parents of children in the pediatric
intensive care unit and that such symptoms
may persist long after discharge (1). Pro-
viding information to family members of a
critically ill child and means to alleviate
their anxieties about their sick child make
them more effective partners in the
care of the child, which may have a pos-
itive effect on the child’s recovery (2).
Flow of accurate and detailed informa-
tion among healthcare providers is the cor-
nerstone of good healthcare delivery. This
is why most pediatric intensive care units
have adopted multidisciplinary bedside
rounds that include physicians, nurses, re-
dardized procedures to guarantee full im-
partiality along the DCD process. Uni-
form national guidelines must create a
crystal-clear line between end-of-life care
and DCD. Without these guarantees, ac-
ceptance of DCD programs either by care-
givers or by society at large might remain
minimal.
Denis Devictor, MD, PhD
Department of Pediatrics
Pediatric Intensive Care
Unit
Hôpital de Bicêtre
Le Kermlin-Bicêtre, France
REFERENCES
1. Curley MAQ, Harrison CH, Craig N, et al:
Pediatric staff perspectives on organ donation
after cardiac death in children. Pediatr Crit
Care Med 2007; 8:212–219
2. Doig CJ, Rocker G: Retrieving organs from
non-heart-beating organ donors: A review of
medical and ethical issues. Can J Anesth 2003;
50:1069 –1076
3. Merion R, Pelletier S, Goodrich N, et al: Do-
nation after cardiac death as a strategy to
increase deceased donor liver availability. Ann
Surg 2006; 244:555–562
4. Mandell S, Zamudio S, Seem D, et al: National
evaluation of healthcare provider attitudes to-
ward organ donation after cardiac death. Crit
Care Med 2006; 34:2952–2958
5. Koostra G: Statement on non-heart-beating
donor programs. Transplant Proc 1995; 27:
2965
6. Koostra G, Kievit JK, Heineman E: The non-
heart-beating donor. Br Med Bull 1997; 53:
844 – 853
spiratory therapists, physiotherapists, nu-
tritionists, and other ancillary services.
Multidisciplinary rounds have proven to be
efficient and useful, both to the patients
and the healthcare team. However, studies
on the effects of parental involvement in
rounds on critical care patients, particu-
larly children, are limited.
Parents of children in critical care
units usually wait eagerly for information
about their child’s condition (2) and sel-
dom get the opportunity to see the treat-
ing physician. Usually, nurses act as facil-
itators for information flow between the
patient’s family and the healthcare team
291
(3–5). In a recent survey in a pediatric
intensive care unit, including parental in-
volvement in bedside rounds was per-
ceived to decrease parental anxiety and
enhance trust between the parents and
the staff (6). Another survey done in a
trauma center showed that the presence
of family during rounds was successful in
enhancing communication between par-
ents and staff and in decreasing parental
anxiety (7).
Although parental involvement in
rounds provides an opportunity for par-
ents to meet the physicians and get in-
formation about their child, it may have
potential problems, such as prolonging
the duration of rounds, inhibiting train-
ees from asking questions, thus decreas-
ing the amount of bedside teaching, and
possibly creating a higher level of anxiety
in parents because of misinterpretation of
technical information that is exchanged
at rounds. Another concern about having
parents join rounds is the potential for
privacy violation.
In this issue of Pediatric Critical Care
Medicine, Phipps and colleagues (8) re-
port on the effect of the presence of fam-
ily members during rounds on the dura-
tion of the round, time spent on teaching,
and satisfaction of staff and family mem-
bers in a pediatric intensive care unit.
The study was a prospective, blinded ob-
servational study in a 12-bed pediatric
intensive care unit that cares for medical
and surgical patients. The duration of
rounds and time spent on education with
and without parental presence was com-
pared in 89 cases. The perception of staff
and parents about the rounds was deter-
mined through a self-administered ques-
tionnaire. A total of 81 family members
and 187 staff responded to the survey. In
this study, there was no significant differ-
ence in the time spent on rounds or ed-
292
ucation. In addition, there was no con-
cern about patient confidentiality.
In this study, the family asked the med-
ical team questions 28% of the time, and
the medical team asked the family ques-
tions 32% of the time, suggesting that the
family was actively involved in the rounds.
However there is no assessment of the
quality of questions or information re-
ceived. Was the dialogue useful? Is it pos-
sible that staff asked questions to the family
just to make them feel involved?
Although this work is commendable,
there are certain important aspects that
could affect the generalizability of the
results. The authors do not describe the
complexity and severity of illness of their
patients; neither do they discuss the level
of knowledge and education of the family
members. Parents of critically ill children
with complex and multiple medical prob-
lems require more explanation and time
compared with parents of children with
less complex problems. Similarly, edu-
cated parents are more likely to ask ques-
tions in a group setting and demand elab-
orate answers to their questions
compared with less educated parents.
This study was carried out in a critical
care unit where the presence of family
members during rounds is an accepted
regular practice. Thus, the measured ef-
fects on education and staff satisfaction
may not be as apparent as in a unit where
parental attendance of rounds is being
introduced as a new practice.
There are many social and cultural
differences that influence the attitudes,
behaviors, and perceptions of parents
during a child’s illness. These differences
also influence the interrelationship and
communication between parents and
staff. Studies of the effects of parental
involvement in bedside rounds have been
limited to Western countries. Thus, their
applicability to other societies should be
interpreted with caution. Future studies
should focus on assessing the quality of
information exchanged between the par-
ents and staff during rounds, the effect of
parental involvement in bedside rounds
on the quality of staff education, and the
outcome of the children.
Avedis Kalloghlian, MD, FRCPC
Section of Cardiac Surgical
Intensive Care
King Faisal Heart Institute
King Faisal Specialist
Hospital and Research
Centre
Riyadh, Saudi Arabia
REFERENCES
1. Bulluffi et al: Traumatic stress in parents of
children admitted to the pediatric intensive
care unit. Pediatr Crit Care Med 2004;
5:547–553
2. Farrell MW, Frost C: The most important
needs of parents of critically ill children: Par-
ents’ perceptions. Intensive Crit Care Nurs
1992; 8:130 –139
3. Curley MAQ: Effects of the nursing mutual
participation model of care and parental stress
in the pediatric intensive care unit. Heart
Lung 1988; 17:682– 688
4. Whitmer M, Hughes B, Hurst SM, et al:
Innovative solutions: Family conference
progress note. Dimens Crit Care Nurse
2005; 24:83– 88
5. Board R: Stressors and stress symptoms of
mothers with children in PICU. J Pediatr Nurs
2003; 18:195–202
6. Kleiber et al: Open bedside rounds for families
with children in pediatric intensive care units.
Am J Crit Care 2006; 15:492– 496
7. Schiller WR, Anderson BF: Family as a mem-
ber of the trauma rounds: A strategy for max-
imized communication. J Trauma Nurs 2003;
10:93–101
8. Phipps LM, Bartke CN, Spear DA, et al: Assess-
ment of parental presence during bedside pe-
diatric intensive care unit rounds: Effect on
duration, teaching, and privacy. Pediatr Crit
Care Med 2007; 8:220 –224
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Can policy spoil compassion?*
I n this issue of Pediatric Critical
Care Medicine, Dr. Okhuysen-
Cawley and colleagues (1) discuss
an important and controversial
matter for critical care physicians and all
of medicine: should institutional policies
dictate care when patients or families re-
quest interventions the providers deem
“inappropriate”? Illustrated with five
cases, the authors outline a formal pro-
cedure, consistent with the Texas Ad-
vance Directives Act, for reviewing care
when physicians think therapies consti-
tute “medically inappropriate” treatment
and families disagree. The process in-
volves case examination and, if the med-
ical determination is confirmed, further
discussions with the family, attempts to
find alternative sources of treatment, and
finally, formal notification of the family
that the doctors and hospital plan to
withdraw ongoing interventions.
Virtually all pediatric intensivists have
found themselves administering treat-
ments they perceived as simply “wrong.”
That assessment may arise from a belief
that therapy will not achieve intended
aims, that the burdens of treatment out-
weigh any benefits, or from a less clear,
but no less powerful, sense that the inter-
ventions are not “worth it.” The key ethical
question, when medical personnel and fam-
ilies disagree, involves how to decide which
view prevails. Dr. Okhuysen-Cawley and
colleagues (1) think professional values,
duly considered in a formal process, de-
serve more weight than personal beliefs or
feelings of patients and families.
Such an approach has some attrac-
tions. The methodical formality could
lead to greater consistency, even stan-
dardization, of decisions and replace hap-
hazard or emotion-driven decisions by
professionals. Some high-expense, low-
yield treatments might be reduced. Some
*See also p. 225.
Key Words: futility; medical ethics; end-of-life care
The authors have not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000264316.47451.6E
Pediatr Crit Care Med 2007 Vol. 8, No. 3
parents might experience relief from bur-
dens associated with making end-of-life
decisions.
On the other hand, the recommended
approach presents some problems and
depends on claims and assumptions that
may not stand up to careful scrutiny. Dr.
Okhuysen-Cawley and colleagues (1) em-
phasize how the need for analgesia and
sedation influenced thinking regarding
the value of continued life support. All
patients deserve scrupulous attention to
symptom control/palliative care, regard-
less of the prognosis. In the 21st century,
virtually every ventilated patient can have
his or her discomfort or agitation elimi-
nated, although not necessarily without
impaired consciousness. The most im-
portant issue, then, has to do with decid-
ing what characterizes a patient’s care as
inappropriate. The article itself demon-
strates just how difficult this may be-
come. The authors review the histories of
“five ventilator-dependent, irreversibly ill
children for whom no additional thera-
peutic options . . . were available.” In
each of these cases, the medical staff de-
termined that the children met the Texas
statutory definition of having an “irre-
versible” condition that “will produce
death within six months, even with avail-
able life-sustaining treatment.” The fact
that one patient lived for 2.5 yrs after the
physicians’ determination that he met
the law’s criteria should give readers and
all critical care practitioners pause.
We see two crucial issues here. First,
despite our advanced technology, we still
have very flawed crystal balls. A mistaken
prediction 20% of the time seems a high
margin of error, given the life and death
stakes in these cases. Like it or not, we
have not yet achieved diagnostic and
prognosticating certainty or objectivity
(2, 3). In this setting, can we accurately
identify all relevant cases and avoid er-
roneous inclusion of cases? Second, the
decisions under consideration have an
inherently value-laden, subjective char-
acter. We live in a morally and reli-
giously pluralistic society with a wide
diversity of beliefs about the value of
continued human biological existence.
How can we justify the assumption in
the Texas law that professionals’ value
judgments, no matter how carefully
made, deserve privilege over opposing
values held by families?
For many reasons, some having to do
with theology, some with secular philos-
ophy, and some with complicated histor-
ical, social, and political factors, different
individuals and groups attach different
meaning to the continued application of
medical technologies, even in the ab-
sence of patient consciousness (4, 5). This
issue could not have been any starker
than in the Schiavo case (6). Some fam-
ilies want to preserve life when doctors,
nurses, and others just do not understand
it or like it. When that happens, we must
reflect very carefully before we cast aside
the meanings nonprofessionals attach to
our medical treatments. Declaring treat-
ments inappropriate and stopping them
over the objections of patients and fami-
lies involves the exercise of social and
economic authority that may deeply of-
fend families and highlight status differ-
ences between those with power (i.e.,
doctors, hospital administrators, and law-
yers) and those currently and historically
downtrodden. This is the stuff of coercion
and risks destruction of trust in health-
care professionals and the systems in
which they work.
The article by Dr. Okhuysen-Cawley
and colleagues (1) assumes that parents
experience excessive burdens when asked
to participate in end-of-life decision mak-
ing. That may be true for some families,
but not all experience and data support
this assumption. In the 1970s, Duff and
Campbell (7) showed that parents of new-
borns with birth defects could and did
come to terms with participating in such
decisions. Benfield et al. (8) noted better
psychosocial outcomes in parents of crit-
ically ill newborns when families partici-
pated actively in decisions than when par-
ents could or would not participate. In a
study of parental perspectives on end-of-
life decision making, Meert et al. (9) re-
ported that 20% of parents thought they
had too little decision-making authority.
Our data from parents of children in pe-
diatric intensive care units indicates par-
293
ents overwhelmingly want a role in end-
of-life decision making (10).
We worry that overriding family deci-
sions, with resulting patient deaths, may
have negative effects on bereavement.
Coming to terms with the death of one’s
child cannot be easy in a society that
employs intensive care readily and has
remarkably low—at least from a global
perspective— childhood mortality. Be-
reaved parents routinely feel angry and
powerless even when their cognitive ex-
perience suggests doctors did “every-
thing” possible. If parents cannot con-
vince themselves that everything was
done, the additional layer of helplessness
and lack of positive regard for healthcare
providers could complicate and deepen
the psychological burdens.
On balance, we wonder who really
gains and loses if formality and bureau-
cracy substitute for compassion and com-
promise. The cost savings, in the long
run, cannot amount to more than a tiny
fraction of pediatric critical care spending
in any period. Although healthcare pro-
viders can feel great anguish from provid-
ing treatment they do not believe in, the
Community-acquired methicillin-resistant Staphylococcus aureus:
A new scourge so virulent even extracorporeal membrane
oxygenation may not help?*
I t seems to be a fact of life that
whenever you solve one problem,
another arrives to take its place.
So it seems with medicine, as well.
Two reports (1, 2) in this issue of Pediat-
ric Critical Care Medicine highlight this
by discussing the rising virulence of the
Staphylococcus aureus (SA) species in
previously healthy children of such sever-
*See also pp. 231 and 282.
Key Words: extracorporeal membrane oxygen-
ation; infection; sepsis; septic shock; children; antibi-
otic resistance; nosocomial infections; extracorporeal
life support; pediatrics; intensive care
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262884.02605.84
294
ideals of professionalism suggest the im-
portance of putting aside personal beliefs,
convenience, and even risk in many in-
stances. Working harder on relationships
and understanding in these cases should
teach tolerance and empathy, reinforcing
the moral nature of caring for others,
including others we do not like or with
whom we disagree.
Joel Frader, MD
General Academic Pediatrics
Children’s Memorial Hospital
Chicago, IL
Kelly Michelson, MD
Division of Critical Care
Medicine
Children’s Memorial Hospital
Chicago, IL
REFERENCES
1. Okhuysen-Cawley R, McPherson M, Jefferson
L, et al: Institutional policies on determina-
tion of medically inappropriate interven-
tions: Use in five pediatric patients. Pediatr
Crit Care Med 2007; 8:225–230
2. Truog RD, Brett AS, Frader J: The problem
with futility. N Engl J Med 1992; 326:
1560 –1564
ity as to lead to extracorporeal membrane
oxygenation (ECMO) support.
In years past, the intensive care unit
harbored many children who were previ-
ously healthy and developed acute, over-
whelming sepsis, shock, multiple-organ
failure, and even death from common
pathogens. With the advent of vaccines to
common precipitating pathogens, such
as the Haemophilus influenzae, Strepto-
coccus pneumoniae, and Neisseria men-
ingitidis species, the incidence of such
diseases and associated mortality have be-
come relatively infrequent (3). The prev-
alence of H. influenzae, for example, has
dropped 95% since conjugate vaccine be-
came widespread in the United States in
the 1990s. The epidemiology of many in-
tensive care units has become dominated
by children with underlying chronic dis-
ease, genetic disorders, immune compro-
mise, or other comorbid conditions who
3. Frader J, Watchko J: Physicians and medical
futility: Experience in pediatrics. In: Medical
Futility and the Evaluation of Life-Sustain-
ing Interventions. Zucker MB, Zucker HD,
Capron A (Eds). Boston, Cambridge Univer-
sity Press, 1997, pp 48 –57
4. Kopaczynski G: Initial reactions to the Pope’s
March 20, 2004 allocution. Natl Cathol Bio-
eth Q 2004; 4:473– 482
5. Dorff EN: End-of-life: Jewish perspectives.
Lancet 2005; 366:862– 865
6. Bloche G: Managing conflict at the end of
life. N Engl J Med 2005; 352:2371–2373
7. Duff RS, Campbell GM: Moral and ethical
dilemmas in the special-care nursery. N Engl
J Med 1973; 289:890 – 894
8. Benfield DG, Leib SA, Vollman JH: Grief re-
sponse of parents to neonatal death and par-
ent participation in deciding care. Pediatrics
1978; 62:171–177
9. Meert KL, Thurston CS, Sarnaik AP: End-of-
life decision-making and satisfaction with
care: Parental perspectives. Pediatr Crit Care
Med 2000; 1:179 –185
10. Michelson K, Koogler T, Frader J: Forgoing
life-sustaining therapies in critically ill chil-
dren: Who decides? Pediatr Crit Care Med In
Press [to be presented at the 5th World Con-
gress on Pediatric Critical Care, Geneva,
Switzerland, June 24 –28, 2007]
then develop an acute illness that re-
quires intensive care (4). These patients
often harbor different types of pathogens
to which vaccines are not yet available, or
they are infected with “common” bacteria
that have become resistant to the antibi-
otics used to treat them in the past. The
evolution of such antibiotic resistance is
largely our own fault—widespread and
perhaps inappropriate antibiotic use has
fostered the rise of vancomycin-resistant
enterococci, methicillin-resistant SA
(MRSA), and extended spectrum ␤-lacta-
mase species. These pathogens easily
spread throughout the healthcare envi-
ronment and have created epidemics
within neonatal intensive care units,
chronic care facilities, and other areas.
Although they cause many headaches in
infection control and patient cohorting
and even lead some units to refuse in-
fected admissions or transfers from “epi-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
ents overwhelmingly want a role in end-
of-life decision making (10).
We worry that overriding family deci-
sions, with resulting patient deaths, may
have negative effects on bereavement.
Coming to terms with the death of one’s
child cannot be easy in a society that
employs intensive care readily and has
remarkably low—at least from a global
perspective— childhood mortality. Be-
reaved parents routinely feel angry and
powerless even when their cognitive ex-
perience suggests doctors did “every-
thing” possible. If parents cannot con-
vince themselves that everything was
done, the additional layer of helplessness
and lack of positive regard for healthcare
providers could complicate and deepen
the psychological burdens.
On balance, we wonder who really
gains and loses if formality and bureau-
cracy substitute for compassion and com-
promise. The cost savings, in the long
run, cannot amount to more than a tiny
fraction of pediatric critical care spending
in any period. Although healthcare pro-
viders can feel great anguish from provid-
ing treatment they do not believe in, the
Community-acquired methicillin-resistant Staphylococcus aureus:
A new scourge so virulent even extracorporeal membrane
oxygenation may not help?*
I t seems to be a fact of life that
whenever you solve one problem,
another arrives to take its place.
So it seems with medicine, as well.
Two reports (1, 2) in this issue of Pediat-
ric Critical Care Medicine highlight this
by discussing the rising virulence of the
Staphylococcus aureus (SA) species in
previously healthy children of such sever-
*See also pp. 231 and 282.
Key Words: extracorporeal membrane oxygen-
ation; infection; sepsis; septic shock; children; antibi-
otic resistance; nosocomial infections; extracorporeal
life support; pediatrics; intensive care
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262884.02605.84
294
ideals of professionalism suggest the im-
portance of putting aside personal beliefs,
convenience, and even risk in many in-
stances. Working harder on relationships
and understanding in these cases should
teach tolerance and empathy, reinforcing
the moral nature of caring for others,
including others we do not like or with
whom we disagree.
Joel Frader, MD
General Academic Pediatrics
Children’s Memorial Hospital
Chicago, IL
Kelly Michelson, MD
Division of Critical Care
Medicine
Children’s Memorial Hospital
Chicago, IL
REFERENCES
1. Okhuysen-Cawley R, McPherson M, Jefferson
L, et al: Institutional policies on determina-
tion of medically inappropriate interven-
tions: Use in five pediatric patients. Pediatr
Crit Care Med 2007; 8:225–230
2. Truog RD, Brett AS, Frader J: The problem
with futility. N Engl J Med 1992; 326:
1560 –1564
ity as to lead to extracorporeal membrane
oxygenation (ECMO) support.
In years past, the intensive care unit
harbored many children who were previ-
ously healthy and developed acute, over-
whelming sepsis, shock, multiple-organ
failure, and even death from common
pathogens. With the advent of vaccines to
common precipitating pathogens, such
as the Haemophilus influenzae, Strepto-
coccus pneumoniae, and Neisseria men-
ingitidis species, the incidence of such
diseases and associated mortality have be-
come relatively infrequent (3). The prev-
alence of H. influenzae, for example, has
dropped 95% since conjugate vaccine be-
came widespread in the United States in
the 1990s. The epidemiology of many in-
tensive care units has become dominated
by children with underlying chronic dis-
ease, genetic disorders, immune compro-
mise, or other comorbid conditions who
3. Frader J, Watchko J: Physicians and medical
futility: Experience in pediatrics. In: Medical
Futility and the Evaluation of Life-Sustain-
ing Interventions. Zucker MB, Zucker HD,
Capron A (Eds). Boston, Cambridge Univer-
sity Press, 1997, pp 48 –57
4. Kopaczynski G: Initial reactions to the Pope’s
March 20, 2004 allocution. Natl Cathol Bio-
eth Q 2004; 4:473– 482
5. Dorff EN: End-of-life: Jewish perspectives.
Lancet 2005; 366:862– 865
6. Bloche G: Managing conflict at the end of
life. N Engl J Med 2005; 352:2371–2373
7. Duff RS, Campbell GM: Moral and ethical
dilemmas in the special-care nursery. N Engl
J Med 1973; 289:890 – 894
8. Benfield DG, Leib SA, Vollman JH: Grief re-
sponse of parents to neonatal death and par-
ent participation in deciding care. Pediatrics
1978; 62:171–177
9. Meert KL, Thurston CS, Sarnaik AP: End-of-
life decision-making and satisfaction with
care: Parental perspectives. Pediatr Crit Care
Med 2000; 1:179 –185
10. Michelson K, Koogler T, Frader J: Forgoing
life-sustaining therapies in critically ill chil-
dren: Who decides? Pediatr Crit Care Med In
Press [to be presented at the 5th World Con-
gress on Pediatric Critical Care, Geneva,
Switzerland, June 24 –28, 2007]
then develop an acute illness that re-
quires intensive care (4). These patients
often harbor different types of pathogens
to which vaccines are not yet available, or
they are infected with “common” bacteria
that have become resistant to the antibi-
otics used to treat them in the past. The
evolution of such antibiotic resistance is
largely our own fault—widespread and
perhaps inappropriate antibiotic use has
fostered the rise of vancomycin-resistant
enterococci, methicillin-resistant SA
(MRSA), and extended spectrum ␤-lacta-
mase species. These pathogens easily
spread throughout the healthcare envi-
ronment and have created epidemics
within neonatal intensive care units,
chronic care facilities, and other areas.
Although they cause many headaches in
infection control and patient cohorting
and even lead some units to refuse in-
fected admissions or transfers from “epi-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
demic” sites, the bacteria involved rarely
are lethal to a healthy host.
The most ubiquitous of these new-age
organisms is MRSA. The rise of MRSA in
health care has led to a specific descrip-
tion of the source: HA-MRSA, or health-
care-acquired MRSA. More recent is the
rise of MRSA within urban zones, so
called CA-MRSA (community-acquired
MRSA) (5,6). Once rare, CA-MRSA is ex-
ceedingly common. In the metropolitan
Washington, DC, area where I live, 50%
of the population is estimated to be col-
onized with MRSA. HA-MRSA and CA-
MRSA often inhabit people without caus-
ing overt disease, but a dangerous rise in
highly virulent CA-MRSA now seems to
be taking place. The “new” type of CA-
MRSA being reported seems different
from in past years. It attacks seemingly
healthy children, frequently adolescents,
with a ferocity that quickly develops into
a lethal spiral of multiple organ failure,
despite all common medical measures.
Also perplexing, the subtype of MRSA fre-
quently cultured from those with severe
and acute illness often is not the same as
that found in the same patients’ nasopha-
rynges or in the surrounding commu-
nity. It is unclear what causes this form
of CA-MRSA to become so invasive in the
seemingly healthy host. Some research-
ers have noted virulence factors that are
not shared with the more common forms
of HA-MRSA or CA-MRSA (7–9). As the
authors note, the presence of genes that
encode factors, such as Pantan-Valentine
leukocidin, has been noted in patients
with severe necrotizing pneumonia, one
of the more lethal presentations of CA-
MRSA and SA in general. Others have
noted that the strains of CA-MRSA–
labeled USA300 seem to be associated
with virulence, as well. Exotoxins pro-
duced by SA also have been associated
with toxic shock syndrome, purpura ful-
minans, and necrotizing pneumonia. The
shock produced by these toxins is be-
lieved to be mediated by a massive in-
crease in tumor necrosis factor-␣ and tu-
mor necrosis factor-␤ activity. Further
research probably will identify virulence
factors that are either genetically based
or represent some other mutation to ac-
count for what we see in current cases of
CA-MRSA or the overwhelming sepsis
noted from even methicillin-sensitive SA
in the report by Stroud et al (2). For now,
however, we are left with what to do
about it. As with H. influenzae, perhaps
advances in research will lead to a vaccine
with just as dramatic an effect as we saw
Pediatr Crit Care Med 2007 Vol. 8, No. 3
15 yrs ago when the Haemophilus influ-
enzae type b vaccine came into use. If so,
then another mutated pathogen likely
will take its place.
Infection-control programs to limit
infection spread, educate about antibiotic
resistance and appropriate antibiotic use,
reduce nosocomial infection rates, and
improve overall patient care are currently
huge initiatives in many centers, and
such programs are long overdue. The
Surviving Sepsis Campaign, aimed at
early recognition and the treatment of
sepsis, also has shown promising results
in improving overall mortality from sep-
sis. What is not so encouraging, however,
is the outcome when commonly used
measures fail to reverse the progressive
downhill course of the patient.
As outlined in the current reviews,
ECMO has been used as another tech-
nique to support the septic patient, in-
cluding those with staphylococcal disease
(10, 11). By providing additional oxygen
delivery and cardiorespiratory support to
the patient via the ECMO circuit, toxic
ventilator settings and vasoactive infu-
sions may be reduced, providing an opti-
mized milieu for organ recovery. Addi-
tionally, the driving pressure provided by
the ECMO circuit may allow the use of
other adjunct therapies, such as renal
replacement or plasma exchange, with
minimal adverse hemodynamic effects to
the patient. The rise in the use of ECMO
in such severely ill patients represents a
paradigm shift in pediatric intensive care.
Ten to 20 yrs ago, sepsis and multiple
organ failure often were listed as exclu-
sion criteria for ECMO consideration.
This belief was based on the assumption
that infected patients likely could not be
cleared of their acute disease. Because
the components of the ECMO circuit it-
self would become colonized with the in-
fecting pathogen, eradication could not
occur and the patient would never sur-
vive. We now have evidence that this fear
was false. Many infected patients, even
those harboring organisms such as Can-
dida that are extremely hard to clear from
indwelling catheters and plastic, have
been successfully treated with ECMO and
survived (12, 13). Comparisons between
ECMO-treated patients with and without
sepsis have confirmed that ECMO can be
associated with good outcomes (14). The
latest recommendations from the Society
of Critical Care Medicine and the Associ-
ation of American Physicians regarding
support measures for pediatric patients in
septic shock include ECMO as a therapy
that should be considered in cate-
cholamine-resistant shock (3).
Despite the recommendations that
ECMO during severe sepsis may help, the
experience with ECMO in patients pre-
senting with SA is discouraging overall.
As can be seen from the two reports in
this issue (1, 2), there is a spectrum of
disease with SA that has gone from the
“simple” soft-tissue and skin infections
seen in the past to a more aggressive
form in which pneumonia, arthritis, and
bone pain lead to overwhelming septic
shock. It is interesting that the survivors
noted in the Arkansas series both had
methicillin-sensitive SA, despite their
overwhelming illness. In contrast, all pa-
tients in the Vanderbilt series had CA-
MRSA and only one third survived. The
review by Creech et al. (1) of the Extra-
corporeal Life Support Organization
(ELSO) registry and MRSA patients found
a 50% death rate, with a biphasic distri-
bution of disease at ages ⬍2 yrs and in
adolescents. Mortality was highest in
children ⬎5 yrs of age. This fact also is a
strange feature of severe MRSA infec-
tions; historically, the majority of sepsis
deaths in children occur in infants. A
similar review of the ELSO database re-
garding SA in two time frames from
1995–1999 and 2000 –2005 was presented
in abstract form a few months ago (15).
This review noted an increase of ⬎200%
in patients treated with ECMO who were
identified as infected with SA and an in-
crease in MRSA cases of ⬎350% between
the early and late time periods. Mortality
of patients with SA as well as those with
MRSA increased to ⬎50% in the more
recent time frame. It is difficult to draw
conclusions from these data, as informa-
tion is not provided on subtypes of SA or
MRSA, comorbid conditions, and other
factors. What is consistent, however, is
that mortality with this pathogen is high
and morbidity is frequent. Anecdotal re-
ports from other ECMO clinicians also
have noted the high morbidity and mor-
tality of patients with SA, and especially
those with CA-MRSA who present mor-
tally ill with established organ failure,
even from the time of initial medical
care. The presentation and clinical course
are reminiscent of the days when H. in-
fluenzae and N. meningitidis brought
seemingly healthy children to death’s
door in a matter of hours.
In addition to insight on SA and
MRSA, the case reports within these arti-
cles provide other interesting discussion
points. The use of factor VIIa for refrac-
295
tory bleeding is a controversial and
timely topic among ECMO clinicians. The
report by Stroud et al. (2) found it useful
in a patient without observed adverse ef-
fects, such as circuit thromboses. Other
reports have noted similar success, but
massive thrombosis and death also have
been described with the use of factor VIIa.
This topic needs more examination, with
perhaps a guideline from ELSO regarding
refractory bleeding. The articles (1, 2)
also stimulate discussion of when pa-
tients should receive ECMO, when lung
recovery should be deemed sufficient to
discontinue ECMO, and what ventilator
settings start and stop ECMO treatment.
Some clinicians would consider a mean
airway pressure of 26 on high-frequency
ventilation a place to start ECMO, not to
discontinue it.
The ELSO registry has become an im-
portant source of data on patient popula-
tions, complications, and outcomes. It
also illustrates current use of ECMO and
allows comparisons between patient pop-
ulations or time frames. As both articles
correctly point out, however, the ELSO
registry fails to capture many details that
might allow even more specific compari-
sons of patients, treatment techniques,
and long-term outcomes. The lack of dis-
criminatory data within the ELSO regis-
try hampers efforts to provide complete
descriptions of patients, their underlying
disease, and changes that occur over
time. Such critique of the database is
timely, as ELSO currently is revising the
registry into a Web-based format that will
be able to fill in some of the identified
gaps. Although care needs to be taken to
not make data collection so exhaustive
that it is impractical, the ability to more
closely follow which patients are being
treated with ECMO and their clinical
course is imperative as medicine moves
forward. As one example, there remains
controversy as to the usefulness of ECMO
in patients with high cardiac-output fail-
ure as compared with those in a vasocon-
296
stricted, low cardiac-output state. By fol-
lowing selected parameters such as
vasoactive use and organ failure over
time, both before and during the ECMO
course, meaningful data that may identify
outcome differences between groups may
be obtained to guide future treatment.
Correlating data obtained on MRSA (and
other) patients receiving ECMO, who
should represent the sickest end of the
spectrum, with that of patients who de-
velop less destructive disease is another
area for research and collaboration. Al-
though it is unlikely that data within
ELSO will be able to solve the mystery of
the current rise in virulence in patients
infected with SA, it remains an important
forum to foster discussion and raise
awareness of changes that are taking
place in extracorporeal support.
Heidi J. Dalton, MD, FCCM
Pediatric Critical Care and
Extracorporeal Membrane
Oxygenation
Children’s National
Medical Center
The George Washington
University
Washington, DC
REFERENCES
1. Creech CB Jr, Johnson BG, Bartilson RE, et
al: Increasing use of extracorporeal life sup-
port in methicillin-resistant Staphylococcus
aureus sepsis in children. Pediatr Crit Care
Med 2007; 8:231–235
2. Stroud MH, Okhuysen-Cawley R, Jaquiss R,
et al: Successful use of extracorporeal mem-
brane oxygenation in severe necrotizing
pneumonia caused by Staphylococcus au-
reus. Pediatr Crit Care Med 2007; 8:282–287
3. Carcillo JA, Fields AI, American College of
Critical Care Medicine Task Force Commit-
tee Members: Clinical practice parameters
for hemodynamic support of pediatric and
neonatal patients in septic shock. Crit Care
Med 2002; 30:1365–1378
4. Randolph AG, Wypij D, Venkataraman ST, et
al: Effect of mechanical ventilator weaning
protocols on respiratory outcomes in infants
and children: A randomized controlled trial.
JAMA 2002; 288:2561–2568
5. Chambers HF: Community-associated
MRSA-resistance and virulence converge.
N Engl J Med 2005; 352:1485–1487
6. Okuma K, Iwakawa K, Turnidge JD, et al: Dis-
semination of new methicillin-resistant Staph-
ylococcus aureus clones in the community.
J Clin Microbiol 2002; 40:4289 – 4294
7. Gillet Y, Issartel B, Vanhems P, et al: Associ-
ation between Staphylococcus aureus strains
carrying gene for Panton-Valentine leukoci-
din and highly lethal necrotizing pneumonia
in young immunocompetent patients. Lan-
cet 2002; 359:753–759
8. McGowan JE, Miller LG: Community-
acquired methicillin-resistant Staphylococ-
cus aureus: Right here, right now. ISMR
Update 2006; 1:4-12
9. Huang YC, Chou YH, Su LH, et al: Methicillin-
resistant Staphylococcus aureus colonization
and its association with infection among in-
fants hospitalized in neonatal intensive care
units. Pediatrics 2006; 118:469 – 474
10. Fortenberry JD, Paden ML: Extracorporeal
therapies in the treatment of sepsis: Experi-
ence and promise. Semin Pediatr Infect Dis
2006; 17:72–79
11. Brown KL, Ridout DA, Shaw M, et al: Health-
care-associated infection in pediatric patients
on extracorporeal life support: The role of
multidisciplinary surveillance. Pediatr Crit
Care Med 2006; 7:546 –550
12. Minette MS, Ibsen LM: Survival of candida
sepsis in extracorporeal membrane oxygen-
ation. Pediatr Crit Care Med 2005;
6:709 –711
13. Roy BJ, Rycus P, Conrad SA, et al: The
changing demographics of neonatal extra-
corporeal membrane oxygenation patients
reported to the Extracorporeal Life Support
Organization (ELSO) registry. Pediatrics
2000; 106:1334 –1338
14. Meyer DM, Jessen ME: Results of extracorpo-
real membrane oxygenation in children with
sepsis. Ann Thorac Surg 1997; 63:756-761
15. Paden MI, Okhuysen-Cawley RS, Rycus P, et
al: Increased frequency of primary Staphylo-
coccus aureus infections in ECMO patients.
23rd Annual Children’s National Medical
Center Symposium on ECMO and Advanced
Therapies for Respiratory Failure, Keystone,
CO, 2007
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Rapid response systems: Is yet another before-and-after trial
needed?*
O ne of the hottest debates in
health care in 2006 was
whether rapid response sys-
tems (RRS) should be imple-
mented at every hospital. Although the
Institute for Healthcare Improvement’s
100,000 Lives Campaign successfully
marketed success stories and prompted
coalitions and individual hospitals to take
on the initiative, peer-reviewed reports
have been more ambivalent. Although a
consensus conference report (1) on the
topic defined terminology, summarized
the literature, and strongly supported
RRS, the authors had to rely largely on
single-center before-and-after trials to
draw their conclusions. Investigators for
the MERIT trial, a 23-hospital, cluster-
randomized clinical trial of medical
emergency teams (METs), reported that
their data failed to show a difference be-
tween intervention and control hospitals
(2). Winters et al. (3) authored a powerful
and skeptical take on METs that cau-
tioned the healthcare community regard-
ing what may be unjustified optimism
and “overreading” the data and called for
better data. Many following the debate
were left to resolve nagging questions:
Why are the data regarding METs incon-
sistent? Should hospitals spend effort and
money to introduce the intervention? At
the heart of the debate may be the question
of whether it is possible to conduct a study
in which an entire hospital is the unit of
randomization. And if it is impossible, what
types of trials do constitute proof of benefit
(or lack thereof)?
Although the best study design for sys-
tems analysis in hospitals remains to be
determined, one might rely on other data
that may help chip away at the question by
*See also p. 236.
Key Words: cardiopulmonary arrest; pediatrics;
rapid response system; medical emergency team
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262891.55713.8B
Pediatr Crit Care Med 2007 Vol. 8, No. 3
adding details. For example, are physician-
led teams more effective than teams with-
out them? Is success with METs confined
to medical and surgical patients outside the
intensive care unit? Might pediatric, obstet-
ric, and psychiatric patients also benefit?
Into this milieu, Dr. Brilli and col-
leagues (4) add their report, appearing in
this issue of Pediatric Critical Care Med-
icine, of a MET program at an academic
pediatric institution in the United States.
The only previous report of METs for
pediatric patients is by Tibballs et al. (5),
who in a preliminary report of yet an-
other before-and-after trial described
mortality benefit at a hospital in Austra-
lia. Dr. Brilli and colleagues, in the first
report of the response to a MET interven-
tion in the United States, did not show a
mortality benefit but did show a decrease
in cardiopulmonary arrests and “prevent-
able” cardiopulmonary arrests when
compared with pre-implementation data.
(The result does raise the question of
whether their system merely postpones
death.) Nevertheless, a report again using
before-and-after trial design is in a sense
disheartening. Let us suppose that Win-
ters et al. (3) were correct and a random-
ized clinical trial is the gold standard for
measuring interventions in hospital sys-
tems. If so, then this report adds little to
the literature. We must instead wait for a
better level of evidence for answers. On
the other hand, if one believes that per-
forming a randomized clinical trial where
the whole hospital is the unit of random-
ization is impossibly confounded, then
each report (positive or negative) may
add to our understanding. (At this time,
reporting negative trials should certainly
be encouraged.) Individuals holding this
perspective would suggest that if the in-
tervention has a similar impact in dispar-
ate patient populations, or distant geog-
raphies, then perhaps it is more likely to
be effective in fact rather than in theory.
Dr. Brilli and colleagues’ results do mir-
ror those of Tibballs et al. but also results
from interventions in adult hospital pop-
ulations in Australia (6, 7) and the United
States (8). Of course, if only positive trials
are reported, a literature bias will result.
Are before-and-after trials of poor
value? When studying systems or quality
improvement targets, the before-and-
after trial is the common standard. When
one looks at the “run” charts (events per
unit time, over a long observation pe-
riod), one looks for a change in events (or
behaviors) timed to an intervention that
is sustained. Because there is a back-
ground event rate that is fairly consistent
(whether it is medication errors, equip-
ment failures, or cardiac arrests), one can
usually detect interventions that are suc-
cessful. Some of Dr. Brilli and colleagues’
figures show this effect nicely.
One of the problems pediatricians have
encountered in planning and implement-
ing a rapid response system is the lack of a
simple set of call-triggering criteria. At
least one reason for this is that there are
age-specific normal ranges for vital signs.
Having different criteria for a number of
age ranges might create so much confusion
that over- and underrecognition of crisis
may result. Like Tibballs et al. (5), Dr. Brilli
and colleagues (4) added the criterion “par-
ent or caregiver worry” about the patient.
Although one might think such vague cri-
teria might have no impact, their data sug-
gest that calling for help when worried
seems to decrease cardiac arrest events.
This is good news for those who have been
unable to agree on more objective criteria
for children. For those who want some
guidance for objective criteria, Dr. Brilli
and colleagues have noted the physiologic
abnormalities that existed when the call
was made.
Those hospitals successfully imple-
menting an RRS that do not discern out-
come benefit should publish their find-
ings. Their results may depend on the
benefit of the intervention or the success
of the implementation process. Dr. Brilli
and colleagues have assisted those con-
templating RRS in a pediatric setting by
providing a detailed description of their
process for changing process. Comparing
the details of their methods to unsuccess-
297
ful studies will perhaps help us deduce
what about RRS is beneficial and if RRS is
in fact a lifesaver. Although the question,
“Are rapid response systems effective in
preventing unexpected death outside the
intensive care unit?” is not yet answered
in a way to satisfy all those following the
literature, this report adds weight to what
we know. In the meantime, for those
waiting to act, the scale has tipped a little
more toward “try it.”
Michael A. DeVita, MD
Critical Care Medicine and
Internal Medicine
University of Pittsburgh
School of Medicine
Pittsburgh, PA
Transhepatic approach as an alternative long-term central venous
access in critically ill children with complex congenital heart
disease: A new angle to an old problem?*
P ediatric patients with complex
congenital heart disease often
are critically ill and have pro-
longed intensive care stays in-
volving long-term administration of
drugs and fluids, sampling of blood, or
hyperalimentation. In some cases, tradi-
tional percutaneous access to the femo-
ral, subclavian, or internal jugular veins
may not be available as a consequence of
previous indwelling central venous cath-
eters, cardiac catheterization procedures,
venous anatomy, or related surgical pro-
cedures (e.g., Glenn shunt). In addition,
patients with a functionally single ventri-
cle may require multiple and staged in-
terventions in the future, and preserva-
tion of the patency of the inferior and
superior caval veins in these patients is
necessary for future cardiac surgeries and
catheterizations. Achieving and main-
*See also p. 248.
Key Words: central venous access; transhepatic ap-
proach; congenital heart disease; children; complication
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
achang@choc.org
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262883.94031.0F
298
REFERENCES
1. DeVita MA, Bellomo R, Hillman K, et al: Find-
ings of the First Consensus Conference on
Medical Emergency Teams. Crit Care Med
2006; 34:2463–2478
2. MERIT Study Investigators: Introduction of
the medical emergency team (MET) system: A
cluster-randomised controlled trial. Lancet
2005; 385:2091–2097
3. Winters B, Pham J, Pronovost PJ: Rapid re-
sponse teams—Walk, don’t run. JAMA 2006;
296:1645–1647
4. Brilli RJ, Gibson R, Luria JW, et al: Implemen-
tation of a medical emergency team in a large
pediatric teaching hospital prevents respira-
tory and cardiopulmonary arrests outside the
intensive care unit. Pediatr Crit Care Med
2007; 8:236 –246
taining vascular access is the penultimate
challenge in this special population.
The clinical use of central venous ac-
cess devices, or central venous catheters,
was first described by Aubaniac (1) in
1952 for cannulating the subclavian vein
and resuscitating wounded soldiers on
the battlefield. Central venous catheters
have now become indispensable in mod-
ern-day medical practice and can be di-
vided into the following: a) percutane-
ously inserted non-tunneled catheters
(subclavian, internal jugular, and femo-
ral); b) peripherally inserted central cath-
eters; c) tunneled catheters (nonvalved,
Hickman/Broviac; valved, Groshong); and
d) totally implantable (port) catheters (2).
Currently, peripherally inserted central
catheters appear to be the preferred
method of establishing long-term central
venous access in cardiac patients (3). The
use of peripherally inserted central cath-
eters was associated with lower rates of
complication compared with other tun-
neled central venous catheters (3– 6).
Furthermore, they allowed for early hos-
pital discharge (7).
However, in the setting of difficult pe-
ripheral venous access or when preserva-
tion of vessels is important, alternatives
to peripherally inserted central catheters
and traditional tunneled catheters may be
5. Tibballs J, Kinney S, Duke T, et al: Reduction
of paediatric in-patient cardiac arrest and
death with a medical emergency team: Pre-
liminary results. Arch Dis Child 2006; 90:
1148 –1152
6. Buist MD, Moore GE, Bernard SA, et al: Effects
of a medical emergency team on reduction of
incidence of and mortality from unexpected
cardiac arrests in hospital: Preliminary study.
BMJ 2002; 324:387–390
7. Bellomo R, Goldsmith D, Ushino S, et al: A
prospective before-and-after trial of a medical
emergency team. Med J Aust 2003; 179:
283–287
8. DeVita MA, Braithwaite RS, Mahidhara R, et
al: Use of medical emergency team (MET) re-
sponses to reduce hospital cardiac arrests.
Qual Saf Health Care 2004; 13:251–254
needed. Unconventional procedures in-
volving the intercostal veins, the azygos,
and direct right atrial access have been
explored as a means of dealing with oc-
cluded veins (8 –10). In children requir-
ing prolonged and multiple central ve-
nous catheterizations, conventional
cannulation sites may become throm-
bosed or stenotic, thus limiting the abil-
ity to gain vascular access and posing a
life-threatening problem. Some studies
show that percutaneous inferior vena ca-
val cannulation via the translumbar or
transhepatic routes provides viable alter-
native routes for prolonged central ve-
nous access in those patients with diffi-
cult vascular access (11).
Percutaneous transhepatic cholangiog-
raphy has been available as an effective di-
agnostic procedure for decades (12). There
are several previous reports of use of the
transhepatic approach to obtain diagnostic
information about the portal venous sys-
tem (13), to localize occult neuroendocrine
tumors (14), and to perform embolization
procedures in patients with cirrhosis and
bleeding varices (15). In addition, the
transhepatic approach provided an effec-
tive and safe route for diagnostic and
interventional cardiac catheterization in
children (16). In small case series, the
hepatic vein was reported as a reusable
Pediatr Crit Care Med 2007 Vol. 8, No. 3
ful studies will perhaps help us deduce
what about RRS is beneficial and if RRS is
in fact a lifesaver. Although the question,
“Are rapid response systems effective in
preventing unexpected death outside the
intensive care unit?” is not yet answered
in a way to satisfy all those following the
literature, this report adds weight to what
we know. In the meantime, for those
waiting to act, the scale has tipped a little
more toward “try it.”
Michael A. DeVita, MD
Critical Care Medicine and
Internal Medicine
University of Pittsburgh
School of Medicine
Pittsburgh, PA
Transhepatic approach as an alternative long-term central venous
access in critically ill children with complex congenital heart
disease: A new angle to an old problem?*
P ediatric patients with complex
congenital heart disease often
are critically ill and have pro-
longed intensive care stays in-
volving long-term administration of
drugs and fluids, sampling of blood, or
hyperalimentation. In some cases, tradi-
tional percutaneous access to the femo-
ral, subclavian, or internal jugular veins
may not be available as a consequence of
previous indwelling central venous cath-
eters, cardiac catheterization procedures,
venous anatomy, or related surgical pro-
cedures (e.g., Glenn shunt). In addition,
patients with a functionally single ventri-
cle may require multiple and staged in-
terventions in the future, and preserva-
tion of the patency of the inferior and
superior caval veins in these patients is
necessary for future cardiac surgeries and
catheterizations. Achieving and main-
*See also p. 248.
Key Words: central venous access; transhepatic ap-
proach; congenital heart disease; children; complication
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
achang@choc.org
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262883.94031.0F
298
REFERENCES
1. DeVita MA, Bellomo R, Hillman K, et al: Find-
ings of the First Consensus Conference on
Medical Emergency Teams. Crit Care Med
2006; 34:2463–2478
2. MERIT Study Investigators: Introduction of
the medical emergency team (MET) system: A
cluster-randomised controlled trial. Lancet
2005; 385:2091–2097
3. Winters B, Pham J, Pronovost PJ: Rapid re-
sponse teams—Walk, don’t run. JAMA 2006;
296:1645–1647
4. Brilli RJ, Gibson R, Luria JW, et al: Implemen-
tation of a medical emergency team in a large
pediatric teaching hospital prevents respira-
tory and cardiopulmonary arrests outside the
intensive care unit. Pediatr Crit Care Med
2007; 8:236 –246
taining vascular access is the penultimate
challenge in this special population.
The clinical use of central venous ac-
cess devices, or central venous catheters,
was first described by Aubaniac (1) in
1952 for cannulating the subclavian vein
and resuscitating wounded soldiers on
the battlefield. Central venous catheters
have now become indispensable in mod-
ern-day medical practice and can be di-
vided into the following: a) percutane-
ously inserted non-tunneled catheters
(subclavian, internal jugular, and femo-
ral); b) peripherally inserted central cath-
eters; c) tunneled catheters (nonvalved,
Hickman/Broviac; valved, Groshong); and
d) totally implantable (port) catheters (2).
Currently, peripherally inserted central
catheters appear to be the preferred
method of establishing long-term central
venous access in cardiac patients (3). The
use of peripherally inserted central cath-
eters was associated with lower rates of
complication compared with other tun-
neled central venous catheters (3– 6).
Furthermore, they allowed for early hos-
pital discharge (7).
However, in the setting of difficult pe-
ripheral venous access or when preserva-
tion of vessels is important, alternatives
to peripherally inserted central catheters
and traditional tunneled catheters may be
5. Tibballs J, Kinney S, Duke T, et al: Reduction
of paediatric in-patient cardiac arrest and
death with a medical emergency team: Pre-
liminary results. Arch Dis Child 2006; 90:
1148 –1152
6. Buist MD, Moore GE, Bernard SA, et al: Effects
of a medical emergency team on reduction of
incidence of and mortality from unexpected
cardiac arrests in hospital: Preliminary study.
BMJ 2002; 324:387–390
7. Bellomo R, Goldsmith D, Ushino S, et al: A
prospective before-and-after trial of a medical
emergency team. Med J Aust 2003; 179:
283–287
8. DeVita MA, Braithwaite RS, Mahidhara R, et
al: Use of medical emergency team (MET) re-
sponses to reduce hospital cardiac arrests.
Qual Saf Health Care 2004; 13:251–254
needed. Unconventional procedures in-
volving the intercostal veins, the azygos,
and direct right atrial access have been
explored as a means of dealing with oc-
cluded veins (8 –10). In children requir-
ing prolonged and multiple central ve-
nous catheterizations, conventional
cannulation sites may become throm-
bosed or stenotic, thus limiting the abil-
ity to gain vascular access and posing a
life-threatening problem. Some studies
show that percutaneous inferior vena ca-
val cannulation via the translumbar or
transhepatic routes provides viable alter-
native routes for prolonged central ve-
nous access in those patients with diffi-
cult vascular access (11).
Percutaneous transhepatic cholangiog-
raphy has been available as an effective di-
agnostic procedure for decades (12). There
are several previous reports of use of the
transhepatic approach to obtain diagnostic
information about the portal venous sys-
tem (13), to localize occult neuroendocrine
tumors (14), and to perform embolization
procedures in patients with cirrhosis and
bleeding varices (15). In addition, the
transhepatic approach provided an effec-
tive and safe route for diagnostic and
interventional cardiac catheterization in
children (16). In small case series, the
hepatic vein was reported as a reusable
Pediatr Crit Care Med 2007 Vol. 8, No. 3
site of cannulation in patients with no
other alternative for maintaining long-
term central venous access (17).
Until now, there has been very limited
data on evaluating the transhepatic cen-
tral venous catheter features such as the
duration of use, reasons for removal, and
complications in children with complex
congenital disease. In this issue of Pedi-
atric Critical Care Medicine, Dr. Qureshi
and colleagues (18) describe their study
on the utility and safety of transhepatic
Broviac placement in critically ill chil-
dren with complex congenital heart dis-
ease. Although this is a single-institution,
retrospective study, it does add more con-
vincing data to the literature regarding
the use of the transhepatic Broviac as a
central venous access in children whose
veins are occluded or need to be pre-
served for future use.
The great concern about using trans-
hepatic central venous access also comes
from the safety and efficacy of its use. In
this study, an average catheter life of 36
days provided prolonged uninterrupted
intravenous access. The complication
rate of the technique itself was 8.8% and
appears to be higher compared with the
standard approaches reported. Although
the rates of catheter-related infection and
thrombus formations were not frequent,
the late catheter complications may be
underestimated. First, the incidence rate
of complications may be underestimated
because of the retrospective nature of this
study. Second, the authors defined
thrombus formation as a clot seen by
echocardiography in the heart or inferior
vena cava, or on catheter tips, and this
may not reflect the true rates. A prospec-
tive study using venography or ultra-
sound in all patients after the removal of
such catheters might accurately deter-
mine the true rate of venous thrombosis
associated with their use. Third, the in-
consistent use of terms and definitions is
one of the main problems in interpreting
the literature concerning infectious com-
plications of central venous catheters.
The “gold standard” for diagnosing cath-
eter-related infection remains a positive
Pediatr Crit Care Med 2007 Vol. 8, No. 3
blood culture drawn from the infected
central venous catheter, supported by an-
other culture, preferably taken from a
peripheral vessel, from which the same
organism is cultured (2). Finally, the
small sample size is one of the limitations
of this study.
The transhepatic approach provides an
alternative long-term central venous ac-
cess in selected pediatric cardiac patients
with difficult vascular access. Transhe-
patic Broviac catheters should be placed by
personnel experienced with transhepatic
access. As almost all of the presently pub-
lished studies are single-institution studies,
there is a need for larger prospective, ran-
domized, multicenter studies with cost-
effective analyses to evaluate the safety and
efficacy of transhepatic Broviac catheter
placement for long-term central venous ac-
cess in critically ill children with complex
congenital heart disease.
Lin-Hua Tan, MD
Surgical Intensive Care Unit
Children’s Hospital
Zhejiang University School
of Medicine
Hangzhou, Zhejiang
China
Anthony C. Chang, MD
Heart Institute
Children’s Hospital of
Orange County
Orange, CA
REFERENCES
1. Aubaniac R: Subclavian intravenous injec-
tion: Advantages and technique. Press Med
1952; 60:1456
2. De Jonge RC, Polderman KH, Gemke RJ:
Central venous catheter use in the pediatric
patient: Mechanical and infectious complica-
tions. Pediatr Crit Care Med 2005;
6:329 –339
3. Thiagarajan RR, Ramamoorthy C, Gettmann
T, et al: Survey of the use of peripherally
inserted central venous catheters in chil-
dren. Pediatrics 1997; 99:E4
4. Dubois J, Garel L, Tapiero B, et al: Peripher-
ally inserted central catheters in infants and
children. Radiology 1997; 204:622– 626
5. Foo R, Fujii A, Harris JA, et al: Complications
in tunneled CVL versus peripherally inserted
central venous catheter lines in very low
birth weight infants. J Perinatol 2001; 21:
525–530
6. Smith JR, Friedell ML, Cheatham ML, et al:
Peripherally inserted central catheters revis-
ited. Am J Surg 1998; 176:208 –211
7. Crowley JJ: Vascular access. Tech Vasc Interv
Radiol 2003; 6:176 –181
8. Solomon BA, Solomon J, Shlansky-Goldberg
R: Percutaneous placement of an intercostal
central venous catheter for chronic hyperali-
mentation guided by transhepatic venogra-
phy. JPEN J Parenter Nutr 2001; 25:42– 44
9. Meranze SG, McLean GK, Stein EJ, et al:
Catheter placement in the azygos system: An
unusual approach to venous access. AJR
Am J Roentgenol 1985; 144:1075–1076
10. Oram-Smith JC, Mullen JL, Harken AH, et al:
Direct right atrial catheterization for total
parenteral nutrition. Surgery 1978; 83:
274 –276
11. Cheatham JP, McCowan TC, Fletcher SE:
Percutaneous translumbar cardiac catheter-
ization and central venous line insertion: An
alternative approach in children with con-
genital heart disease. Cathet Cardiovasc In-
terv 1999; 46:187–192
12. Olbert F, Gaudernak T, Miess F: Percutane-
ous transhepatic cholangiography. Radiol
Clin Biol 1972; 41:453– 465
13. Burcharth F: Percutaneous transhepatic por-
tography: I. Technique and application. AJR
Am J Roentgenol 1979; 132:177–182
14. Vinik AI, Delbridge L, Moattari R, et al:
Transhepatic portal vein catheterization for
localization of insulinomas: A 10-year expe-
rience. Surgery 1991; 109:1–11
15. Lunderquist A, Vang J: Sclerosing injection
of esophageal varices through transhepatic
selective catheterization of the gastric coro-
nary vein: A preliminary report. Acta Radiol
Diagn 1974; 15:546 –550
16. Shim D, Lloyd TR, Cho KJ, et al: Transhe-
patic cardiac catheterization in children:
Evaluation of efficacy and safety. Circulation
1995; 92:1526 –1530
17. De Csepel J, Stanley P, Padua EM, et al:
Maintaining long-term central venous access
by repetitive hepatic vein cannulation. J Pe-
diatr Surg 1994; 29:56 –57
18. Qureshi AM, Rhodes JF, Appachi E, et al:
Transhepatic Broviac catheter placement for
long-term central venous access in critically
ill children with complex congenital heart
disease. Pediatr Crit Care Med 2007;
8:248 –253
299
Calcium: A double-edged sword*
C alcium is essential for myo-
cardial excitation-contraction
coupling (EC). Many believe
that hypocalcemia is associ-
ated with decreased cardiac contractility,
decreased cardiac index, and hypoperfu-
sion. Therefore, it seems axiomatic that
giving calcium to correct hypocalcemia
must improve myocardial function, car-
diac output, and, thus, clinical outcomes.
The satisfying increase in blood pressure
following a calcium bolus in children hy-
potensive from myriad causes, often in
our cardiac intensive care units, encour-
ages us to believe that calcium is good for
the heart and circulation and surely hy-
pocalcemia should be vigorously cor-
rected.
Not so fast. For years, suspicion has
been smoldering that it is not so simple.
Contraction band necrosis, characterized
by calcium deposition in necrotic myo-
cardium, occurs following head trauma
and postischemic reperfusion and is seen
at postmortem in acute and chronic heart
failure (1). Its presence suggests that cal-
cium deposition in the myocardium may
lead to myocyte death, especially in hy-
peradrenergic states. Certainly calcium is
implicated in other cell death situations,
notably in cerebral cell death, and cal-
cium deposition accompanies neuronal
injury of varying etiologies including
ischemia, trauma, and neurodegenerative
disease (2, 3).
In this issue of Pediatric Intensive
Care Medicine, Dr. Dyke and colleagues
(4) suggest that in infants following car-
diac surgery, giving calcium to treat hy-
pocalcemia is detrimental. They demon-
strated that in the first 3 days following
surgery, infants who received total cal-
cium supplementation ⬎1 SD above the
mean given for the entire group (170, SD
241 mg/kg) had greater morbidity (odds
*See also p. 254.
Key Words: calcium metabolism; cardiac surgery;
apoptosis; outcomes research; excitation-contraction
coupling; postoperative myocardial function
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000264315.37398.0B
300
ratio, 7.6) and mortality (odds ratio, 5.8)
than those who received less than this
amount.
There are problems with this article.
First of all, we should remember Dr.
Johnson’s observation that “It is incident
to physicians, I am afraid, beyond all
other men, to mistake subsequence for
consequence” (5). Dr. Dyke and col-
leagues (4) report that infants who re-
ceived the most calcium supplementation
subsequently had worse outcomes.
Whether the need for calcium (hypocal-
cemia) reflected a pathologic state on the
way to morbidity and mortality or
whether giving calcium caused one is not
resolved by this article. We are given
morbidity and mortality information but
no physiologic data and little information
about other treatments the infants may
have received. The authors claim to test
the hypothesis that hypocalcemia is bad
and that giving calcium to correct hy-
pocalcemia is therefore good. Alas, be-
cause the authors did not present the
calcium concentration data, we do not
know how hypocalcemic the children
where, only that an intensivist believed
that they were. Furthermore, we do not
know whether the hypocalcemia was ac-
tually corrected. It may be that calcium
supplementation only “fed” a calcium
sink in patients who were (and remained)
hypocalcemic because they were so ill.
The hypothesis that correcting hypocal-
cemia is desirable was not tested. Rather,
the hypothesis that calcium supplemen-
tation is bad for you (the null hypothesis)
appears not to have been refuted by these
data.
In corroboration of these observations
by Dr. Dyke and colleagues (4), we ob-
served that bolus calcium (also given to
correct hypocalcemia in infants following
cardiac surgery), although initially fol-
lowed by increased blood pressure, was
also followed by an echocardiographically
demonstrated decreased shortening frac-
tion and cardiac output (6). The salutary,
but short-lived, effect on blood pressure
was the result of increased systemic vas-
cular resistance but was accompanied by
depression in cardiac output for up to 30
mins following the calcium bolus.
How can calcium be so bad for us?
The central and critical role of cal-
cium in EC is well described, wherein the
action potential depolarizes the myocyte,
causing voltage gated calcium channel
mediated calcium release and giving rise
to calcium-induced calcium release by
triggering the ryanodine (RyR2) recep-
tors on the sarcoplasmic reticulum (7).
The binding of calcium to troponin C
leads to troponin-1 phosphorylation and
a conformational change in troponin and
tropomyosin that permits the actin-
myosin cross-bridging leading to con-
traction (8). Intracellular calcium con-
tent rises rapidly during phase two of the
action potential, 100-fold from 10⫺7 M to
10⫺5 M (serum ionized calcium concen-
tration is approximately 10⫺3 M). We also
know that calcium re-uptake or seques-
tration mediated by sarcoendoplasmic re-
ticulum reuptake calcium-adenosine
triphosphatase (SERCA) is essential dur-
ing diastole and that failure of this mech-
anism leads to negative lusitropy and di-
astolic dysfunction— compromising
cardiac function even further. In short,
the amount of calcium released deter-
mines systolic function. The amount of
calcium taken up from the cytosol deter-
mines diastolic function. Calcium fluxes
play a critical role in chronotropy, inot-
ropy, and lusitropy, and we only incom-
pletely understand the regulation of this
delicate but very rapid dance.
Calcium does much more. Derange-
ments in calcium release and compart-
mentalization can also be cytotoxic. Cal-
cium overload leads to necrotic cell death
in the heart. It has become increasingly
clear that calcium also plays a critical
role in apoptosis, and apoptosis has re-
cently been suggested as contributing to
many cardiac diseases such as myocardial
infarction, ischemia-reperfusion injury,
end-stage heart failure, adriamycin car-
diotoxicity, and cardiac arrhythmias (9,
10). Calcium is central to apoptosis sig-
naling (9 –11). Evidence links cal-
cineurin, calcium/calmodulin-dependent
protein kinase (CaMKII) pathways, mito-
chondrial calcium pathways, and the
family of Bcl-2 proteins all in calcium-
modulated apoptosis (9, 11). The dual
Pediatr Crit Care Med 2007 Vol. 8, No. 3
role of calcium is clear: essential to sur-
vival and function and a ruthless de-
stroyer that signals cell death.
Another double-edged sword, inti-
mately linked with calcium metabolism,
is ␤-adrenergic receptor (BAR) stimula-
tion. ␤-blockade is acutely detrimental to
cardiac function but also has an impor-
tant role in treating heart failure. BAR1
receptor activation modulates EC by
phosphorylation of a) voltage gated cal-
cium channel leading to flooding the cell
with extracellular calcium; b) the sarco-
plasmic RyR2 receptor, mediating sarco-
plasmic reticulum release of calcium; and
c) phospholamban-mediated calcium re-
uptake via SERCA mechanisms (12). In
the hyperadrenergic state, these calcium-
mediated steps are perturbed and cause a
RyR2-mediated low-grade calcium leak
during diastole leading to diastolic dys-
function and a SERCA-mediated failure of
re-uptake and calcium depletion during
systole, thus impairing both systolic and
diastolic function (12). The effect of acute
calcium supplementation in this setting
might well be to augment these patho-
logic processes and worsen cardiac func-
tion. Finally, it has recently been demon-
strated that BAR1 stimulation (through a
non-protein kinase A phosphorylation
pathway) can activate CaMKII-mediated
apoptosis (13) suggesting that excess
BAR1 activity leads to apoptosis (12, 13).
This pathway up-regulates calcium re-
lease and, as in calcineurin-mediated ap-
optosis, increases intracellular calcium as
the final pathway to apoptosis. Also, con-
traction band necrosis results from the
perturbed interaction between cat-
echolamines and calcium (1). Clearly
there is complex, intricate, and vital
cross-talk between these calcium signal-
ing pathways. How calcium supplemen-
tation could aggravate the dysfunctional
hyperadrenergic state is still unclear, but
the occurrence of calcium deposition in
the myocytes, contraction band necrosis,
and the linking of adrenergic, calcium-
mediated apoptotic pathways suggests a
fatal downward spiral.
A word of caution. Dr. Dyke and col-
leagues (4) studied infants. The research
cited here is from many species, usually
mature animals. It is known that aspects
of EC coupling, sarcoplasmic reticulum
function, and receptor activity all un-
dergo distinct developmental changes,
and these are most marked in the neona-
tal period (8, 14). Whether Dr. Dyke and
colleagues’ observations are unique to in-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
fants with surgical heart disease, or
whether the data cited here apply to in-
fants, is uncertain. Nevertheless, this
confusing and expanding repertoire of
cross-talk in crucial pathways that seem
to be double-edged—the adrenergic path-
way, the calcium-dependent processes,
and perhaps many other therapeutic
pathways—may suggest that we should
expect contrary outcomes from appar-
ently beneficial therapies, such as treat-
ing hypocalcemia and noticing a nearly
six-fold increase in mortality with larger
calcium doses (3).
What are the implications of these ob-
servations? Perhaps calcium metabolism
in the failing heart now looks more like a
minefield than a sensible target for ther-
apeutic endeavor. Flooding damaged,
permeable cells with calcium, especially
in the setting of a hyperadrenergic state,
must be harmful. What are the implica-
tions for this on other calcium-dependent
therapies? Levosimendan is a “calcium
sensitizing” (prolonging effects of intra-
cellular calcium) inotropic therapeutic
agent that has short-term salutary ef-
fects. Nevertheless, in such a complex
setting, what else is “sensitized” to cal-
cium may also be of concern. Milrinone,
on the other hand, seems to have salutary
effects on calcium re-uptake via the sar-
coplasmic reticulum, which mediates its
lusitropic effect (15). Could this mecha-
nism also decrease cytosolic calcium and
perhaps put a damper on calcium-
mediated apoptotic events?
Intensivists must remain observant.
We are often lulled into the risks of “sub-
sequent ergo consequent” (post hoc, ergo
propter hoc) thinking (5) or, worse, re-
joicing with the short-term, apparently
beneficial effects of our therapies while
missing the long-term, perhaps negative
effects. The complex process of support-
ing cardiovascular function in the inten-
sive care unit in the short run, without
increasing morbidity and mortality,
whether from calcium supplementation,
adrenergic agents, or other common
therapies, requires outcome studies be-
yond merely observing the initial benefi-
cial effect, such as this one by Dr. Dyke
and colleagues (4).
As for the matter of calcium supple-
mentation in infants following cardiac
surgery, it must be remembered that cal-
cium is a double-edged sword, necessary
for survival but capable of great harm.
Calcium is also a very sharp and long
sword, piercing to the very heart of the
matter in ways we are just beginning to
understand.
Randall C. Wetzel, MB, BS
Children’s Hospital of Los
Angeles
Los Angeles, CA
REFERENCES
1. Baroldi G, Mittleman R, Parolini M, et al:
Myocardial contraction bands: Definition,
quantification and significance in forensic
pathology. Int J Legal Med 2001; 115:
142–151
2. Mattson MP: Neuronal life-and-death signal-
ing, apoptosis, and neurodegenerative disor-
ders. Antioxid Redox Signal 2006; 8:11–12
3. Chinopoulos C, Adam-Vizi V: Calcium, mito-
chondria and oxidative stress in neuronal
pathology. Novel aspects of an enduring
theme. FEBS J 2006; 273:433– 450
4. Dyke PC, Yates AR, Cua CL, et al: Increased
calcium supplementation is associated with
morbidity and mortality in the infant post-
operative cardiac patient. Pediatr Crit Care
Med 2007; 8:254 –257
5. Johnson S: Review of Dr. Lucas’s essay on
waters. Literary Magazine 1756; ii:39
6. Castillo W, Quintos M, Wong P, et al: Cal-
cium chloride infusion in infants following
cardiac surgery does not improve hemody-
namics. Crit Care Med 2003; 31:A156
7. Xu L, Meissner G: Mechanism of calmodulin
inhibition of cardiac sarcoplasmic reticulum
Ca2⫹ release channel (raynodine receptor).
Biophys J 2004; 86:797– 804
8. Epstein D, Wetzel R: Cardiovascular physiol-
ogy and shock. In: Critical Heart Disease in
Infants and Children. Nichols DN (Ed). Phil-
adelphia, Mosby Elsevier, 2006, pp 20 –27
9. Rizzuto R, Pinton P, Ferrari D, et al: Calcium
and apoptosis: Facts and hypotheses. Onco-
gene 2003; 22:8619 – 8627
10. Gustafsson A, Gottlieb R: Mechanisms of ap-
optosis in the heart. J Clin Immunol 2003;
23:447– 459
11. Orrenius S, Zhivotovsky B, Nicotera P: Reg-
ulation of cell death: The calcium-apoptosis
link. Nat Rev Mol Cell Biol 2003; 4:552–565
12. Marks A: Calcium and the heart: A question
of life and death. J Clin Invest 2003; 111:
597– 600
13. Zhu W, Wang S, Chakir K, et al: Linkage of
b1-adrenergic stimulation to apoptotic heart
cell death through protein kinase A-indepen-
dent activation of Ca2⫹/calmodulin kinase
II. J Clin Invest 2003; 111:617– 625
14. Hoch M, Netz H: Heart failure in pediatric
patients. Thorac Cardiovasc Surg 2005;
53(Suppl 2):S129 –S134
15. Yano M, Kohno M, Ohkusa T, et al: Effect of
milrinone on left ventricular relaxation and
Ca2⫹ uptake function of cardiac sarcoplas-
mic reticulum. Am J Physiol Heart Circ
Physiol 2000; 279:H1898 –H1905
301
Patency of the ductus arteriosus in the newborn—Now you want
it, now you don’t*
T he ductus arteriosus (Botalli)
is arguably one of the most
important blood vessels in the
first months of the existence
of a human being. In fetal life, the ductus
constitutes one of two escape routes for
blood which, exiting from the right ven-
tricle, is to a large extent denied entry
into the lungs due to their high blood
flow resistance. When premature closure
of the ductus occurs in utero, remodeling
of the pulmonary vasculature ensues, re-
sulting in therapy-resistant pulmonary
hypertension after birth (1, 2). Thus, in-
trauterine closure of the ductus is clearly
an undesirable event.
After birth, the ductus typically closes
functionally in a few hours, but perma-
nent closure takes a little longer (3). In
the majority of cases, such closure is a
normal and highly desirable event. How-
ever, postpartum closing of the ductus
can be catastrophic in infants with con-
genital heart disease, when the nature of
the malformation is such that mainte-
nance of circulation through either the
systemic or the pulmonary vascular beds
depends on shunting of blood through
the ductus. In this scenario, neonatolo-
gists and cardiologist apply their best ef-
forts to keep the ductus open, most com-
monly as a stop-gap measure through the
action of drugs, but recently also occa-
sionally through insertion of intravascu-
lar stents when longer term palliation is
needed (4).
On the other hand, when babies are
born very prematurely (before 30 wks of
gestation), neonatologist are frequently
confronted with the opposite problem.
The ductus, apparently closed for the first
*See also p. 258.
Key Words: heparin; indomethacin; patent ductus
arteriosus; peripherally inserted central venous cathe-
ter; very low birthweight infant
The author has not disclosed any potential con-
flicts of interest.
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262886.67502.2B
302
few hours and days, reopens; and because
of the lower blood flow resistance in the
lungs, a left-to-right shunt through the
ductus leads to more blood flow through
the lungs than some believe is good for
the baby, although agreement on the
right course of action in persistent duc-
tus arteriosus (PDA) of premature infants
is by no means unanimous (3, 5– 8).
Thus, although some neonatal intensive
care policies require closing of all signif-
icant PDAs in very premature infants,
others have a more expectant approach.
In this issue of Pediatric Critical Care
Medicine, Drs. Ojala and Lehtonen (9)
report on an apparent association be-
tween use of heparin-containing infu-
sates in peripherally inserted central ve-
nous catheters (PICC) and failed attempts
to close the ductus arteriosus with indo-
methacin. A change in policy in the neo-
natal intensive care unit of the Turku
University Central Hospital called for the
addition of heparin 0.6 IU/mL to paren-
teral solutions infused through PICCs.
Previously, PICCs had been flushed with
heparin every 12 hrs, but infusates were
not heparinized. Hospital policy on PDAs
called for early medical closure in the
presence of any ductal shunt as observed
by echocardiography. During the index
period, which lasted approximately 12
wks, the rate of failed attempts to close
the PDA with indomethacin increased to
70% from a preindex rate of 25%. When
this was noted, the neonatal intensive
care unit reverted to their previous policy
regarding heparin and PICCs, and the
rate of failed ductal closures fell to 6.4%.
The difference between the index and the
pre- and postindex periods was highly sig-
nificant.
The findings from this study are po-
tentially of great importance to practic-
ing neonatologists and reconfirm the
great value of retrospective, observational
studies in medicine. The authors are to
be commended for their systematic ob-
servation, which led to early recognition
of this possible association. Indeed, if the
data presented had been the result of a
sufficiently powered, prospective, ran-
domized, controlled study, there is little
doubt that many of us would have been
compelled to reconsider our policies re-
garding heparin, total parenteral nutri-
tion, and PICC catheters. The authors
also present good physiologic, biochemi-
cal, and pharmacologic arguments to
suggest that this apparent association
may, in fact, be a causal relationship.
However, the study raises some ques-
tions which, in my view, need to be an-
swered before a widespread change in
policy can be recommended. As with
many retrospective and observational
studies, there is a danger in small num-
bers. Thus, although the only significant
difference between the index period vs.
the baseline and postindex periods was
the increased rate of failed ductal closure,
a number of nonsignificant differences
may potentially have contributed to the
results and might have been statistically
significant given a larger population size
(i.e., sufficient power).
The index period infants were smaller,
were more immature (25.6 wks of gesta-
tion vs. 27.4 wks preindex and 28.3 wks
postindex), had been exposed to more
preterm rupture of membranes, and had
a higher rate of significant PDAs. The
latter fact is noteworthy and would seem
to be compatible with the vasodilatory
effects of heparin (10, 11). It is also wor-
risome that the index period infants had a
higher rate of grade 3– 4 intraventricular
hemorrhages, raising the question
whether heparin infusion in the PICCs
may have contributed to this or whether
this was primarily an effect of the chil-
dren being more immature and sicker.
All of these uncertainties need to be re-
solved.
Reports like that of Drs. Ojala and
Lehtonen often highlight issues other
than those that were the primary intent
of the authors. Unfortunately, the article
does not say what percentage of the very
low birthweight infants received PICCs
and thus were at risk. However, it appears
to have been a fairly common procedure.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
In contrast, in my own unit we tend to
use such tools only exceptionally. Most of
our very low birthweight infants will get
an umbilical venous catheter initially, in
addition to a peripheral intravenous cath-
eter that is used for drugs. By the time
our guidelines call for removal of the
umbilical venous catheter (7 days, with
exceptions up to 10 days permitted in
unusual circumstances), the great major-
ity of infants receive sufficient volume by
nasogastric tube that we elect to give the
additional fluids and nutrition needed by
peripheral intravenous catheter and thus
avoid the use of PICCs. Indeed, data from
the Norwegian Extreme Prematurity
Study showed that 92% of extremely low
birthweight infants received full enteral
feeding with human milk within the third
week of life (12). This shows how differ-
ences in practices and procedures may
expose our infants to different risks and
suggests that the “background tapestry”
in multicenter studies is likely to have a
very intricate pattern.
In a recent study, Shah et al. (13)
compared the effect of heparin infusion
0.5 IU/kg/hr vs. placebo on the duration
of PICC patency. They found a signifi-
cantly increased rate of catheter occlu-
sion in the placebo group, clearly an un-
desirable situation if the PICC is truly
needed. Their study population appears
reasonable comparable to that of Drs.
Ojala and Lehtonen, with a majority of
premature infants. Their report does not
include any mention of problems with
PDAs, but this issue appears not to have
been in focus. As the Turku infants are
reported to have received 80 –100 mL/kg/
day of fluids during indomethacin treat-
ment for PDA (9), they would have re-
ceived ⬇2.5 IU/kg/hr of heparin (60 IU/
kg/day) with the reported heparin
concentration in the total parenteral nu-
trition, which is six times more than the
10 IU/kg/day given during the pre- and
postindex periods and five times more
than the infants in the Shah et al. (13)
study. Is it possible that the inhibitory
effect of heparin on efforts to close a PDA,
Pediatr Crit Care Med 2007 Vol. 8, No. 3
if reproducible, could be related to the
dose and/or concentration?
Another issue that may be discussed
relative to this report is the policy of
closing all significant PDAs. As already
noted, there is no agreement on this pol-
icy, and even for those who lean toward
closing PDAs in premature infants, there
is uncertainty about which criteria must
be fulfilled before closure is indicated. In
a recent review, Laughon et al. (6) opined
that therapies designed to close the duc-
tus arteriosus “should not be considered
standard of care at any time until these
therapies are proven to decrease long-
term clinical morbidities in randomized,
placebo-controlled trials.” To paraphrase
the bard: To close or not to close? That is
the question.
Finally, it is notable that the phenom-
enon described by Drs. Ojala and Leh-
tonen may have occurred because two
separate clinical routines—adding hepa-
rin to total parenteral nutrition and de-
ciding to close all PDAs—were combined,
resulting in coadministration of two dif-
ferent drugs. Thus, this study illustrates
the need to make pediatric and neonatal
pharmacology and pharmacotherapy a
major research area in the years to come.
The practice of neonatology has made
tremendous strides in the past decades,
but our map is still full of uncharted
territories. The need for carefully con-
trolled, prospective, randomized trials in
many areas is clear for us all to see.
Thor Willy Ruud Hansen,
MD, PhD
Department of Pediatrics,
Rikshospitalet-
Radiumhospitalet HC
Faculty of Medicine,
University of Oslo
Oslo, Norway
REFERENCES
1. Levin DL, Hyman AI, Heymann MA, et al:
Fetal hypertension and the development of
increased pulmonary vascular smooth mus-
cle: A possible mechanism for persistent pul-
monary hypertension of the newborn infant.
J Pediatr 1978; 92:265–269
2. Morin FC III: Ligating the ductus arteriosus
before birth causes persistent pulmonary hy-
pertension in the newborn lamb. Pediatr Res
1989; 25:245–250
3. Evans N: Current controversies in the diag-
nosis and treatment of patent ductus arteri-
osus in preterm infants. Adv Neonatal Care
2003; 3:168 –177
4. Boucek MM, Mashburn C, Kunz E, et al:
Ductal anatomy: A determinant of successful
stenting in hypoplastic left heart syndrome.
Pediatr Cardiol 2005; 26:200 –205
5. Fowlie PW: Managing the baby with a patent
ductus arteriosus. More questions than an-
swers? Arch Dis Child Fetal Neonatal Ed
2005; 90:F190
6. Laughon MM, Simmons MA, Bose CL: Pa-
tency of the ductus arteriosus in the prema-
ture infant: Is it pathologic? Should it be
treated? Curr Opin Pediatr 2004; 16:146 –151
7. Van Overmeire B, Chemtob S: The pharma-
cologic closure of the patent ductus arterio-
sus. Semin Fetal Neonat Med 2005; 10:
177–184
8. Bancalari E, Claure N, Gonzalez A: Patent
ductus arteriosus and respiratory outcome in
premature infants. Biol Neonate 2005; 88:
192–201
9. Ojala TH, Lehtonen L: A preliminary re-
port—Heparin counteracts indomethacin ef-
fect on ductus arteriosus in very low birth-
weight infants. Pediatr Crit Care Med 2007;
8:258 –260
10. Tangphao O, Chalon S, Moreno HJ Jr, et al:
Heparin-induced vasodilation in human
hand veins. Clin Pharmacol Ther 1999; 66:
232–238
11. Tasatargil A, Golbasi I, Sadan G, et al: Un-
fractioned heparin produces vasodilatory ac-
tion on human internal mammary artery by
endothelium-dependent mechanisms. J Car-
diovasc Pharmacol 2005; 45:114 –119
12. Rønnestad A, Abrahamsen TG, Medbø S, et
al: Late-onset septicemia in a Norwegian na-
tional cohort of extremely premature infants
receiving very early full human milk feeding.
Pediatrics 2005; 115:e269 – e276
13. Shah PS, Kalyn A, Satodia P, et al: A random-
ized, controlled trial of heparin versus pla-
cebo infusion to prolong the usability of pe-
ripherally placed percutaneous central
venous catheters (PCVCs) in neonates: The
HIP (Heparin infusion for PCVC) study. Pe-
diatrics 2007; 119:284 –291
303
Computerized physician order entry: Friend or foe?*
I ntensive care is a complex envi-
ronment in which many high-risk
decisions are taken, unclear tasks
are distributed, unwritten orders
are given, and difficult protocols should
be followed. Clinicians of varying levels of
education, expertise, and experience con-
front these challenges every minute of
every 24 hrs. That is why so many near-
mistakes and real errors are made in this
environment every day. Moreover, the pa-
tients involved, certainly those receiving
pediatric intensive care, are particularly
vulnerable to iatrogenic failures, because
of their unstable condition and depen-
dency on devices and medication. Adverse
drug events are estimated to injure or kill
thousands of people in hospitals every
year. Although controversy surrounds
the mortality approximations, it is clear
that medical errors and accidental inju-
ries happen too often and that we should
work with combined efforts to overcome
these systemic failures.
One of the means most frequently ad-
vocated for improving safety in prescrib-
ing and delivering drugs is a computer-
ized physician order entry system
(CPOE). CPOE is a means of eliminating
many of the problems inherent in manual
order writing (e.g., illegible handwriting,
incomplete orders, wrong dosages). It
also includes various levels of decision
support, ranging from dose and allergy
checking to drug-drug interaction check-
ing and more complex clinically driven
rules (1). CPOE is widely viewed as cru-
cial for reducing prescribing errors and
saving billions in annual costs. In a 2002
survey, only 10% of the included hospi-
tals had CPOE (2). Many hospital admin-
istrations have yet to implement such a
system and, thus, can learn from the ex-
*See also p. 268.
Key Words: computerized physician order entry;
medication error; drug safety; implementation
For information regarding this article, E-mail:
j.a.hazelzet@erasmusmc.nl
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262885.52560.B9
304
periences of those that already have con-
verted.
There are very few studies in the
medical literature addressing the ques-
tion of whether CPOE changes patients’
medical outcome. Several studies per-
formed with systems designed in the
1970s and 1980s dealt only with antibi-
otic administration by CPOE and show
some benefit in both cost savings and
patient outcomes (3). In 2005, a study
of the pediatric intensive care unit in
Pittsburgh showed an increased mortal-
ity after the implementation of CPOE
(4). A 2006 study analyzing the imple-
mentation of the same system in a Se-
attle pediatric intensive care unit could
not confirm this finding (5). These two
studies generated much debate, which
compared them and tried to learn les-
sons for other implementations (6, 7).
In this issue of Pediatric Critical Care
Medicine, Keene and colleagues (8) de-
scribe the implementation of CPOE in
the neonatal and pediatric intensive
care units of the Montefiore Medical
Center in New York. They compared
mortality before and after the imple-
mentation during two 6-month periods
before CPOE and one 6-month period
immediately after CPOE was initiated.
Only patients admitted from the emer-
gency or operating rooms or as trans-
fers from other institutions directly to
pediatric or neonatal intensive care
were included. There was no difference
in mortality before and after the imple-
mentation. To compare severity of ill-
ness before and after implementation,
the authors used the Pediatric Risk of
Mortality III score; however, they only
used the laboratory components of this
score, which is a limitation of this
study. Furthermore, only 12% of their
patients were transferred from other in-
stitutions, whereas the study by Han et
al. (4) concerned only transported pa-
tients.
This implementation seems to have
been carefully planned in multidisci-
plinary workgroups to ensure that CPOE
was tailored to each unit. This phase re-
quired approximately 1 yr. Before imple-
mentation, each unit performed exten-
sive in-service training, both in person
and online. The curriculum included a
mandatory training session for all per-
sonnel (4 hrs for nurses and 2 hrs for
physicians, which is an interesting differ-
ence). Furthermore, trained specialists
were on call at all hrs for the first weeks
of implementation.
Implementing CPOE is a change pro-
cess and should be considered as such.
The term sociotechnical approach is of-
ten used (9), because implementing de-
pends more on the organizational context
than on a specific technology (7). This
means that we should also put effort into
understanding the local sociotechnical
dimensions before implementation and
use this knowledge in preparation for it.
Many reported experiences describe the
importance of medical leadership and
physician advisory groups in all phases
(5, 10, 11). As already stated, the ulti-
mate goal of CPOE is to decrease the
number of medication errors; it is not
obvious that this will happen all by it-
self (12, 13). We must learn from im-
plementation failures, as well as from
scientifically sound reports about suc-
cessful conversions, to have optimal ef-
ficacy of our CPOE. The reported prac-
tical experiences also can be very
helpful (14, 15).
Jan A. Hazelzet, MD, PhD,
FCCM
Erasmus Medical Center
Rotterdam, The
Netherlands
REFERENCES
1. Bates DW, Gawande AA: Improving safety
with information technology. N Engl J Med
2003; 348:2526 –2534
2. Ash JS, Gorman PN, Seshadri V, et al: Com-
puterized physician order entry in U.S. hos-
pitals: Results of a 2002 survey. J Am Med
Inform Assoc 2004; 11:95–99
3. Berger RG, Kichak JP: Computerized physi-
cian order entry: Helpful or harmful? J Am
Med Inform Assoc 2004; 11:100 –103
4. Han YY, Carcillo JA, Venkataraman ST, et al:
Unexpected increased mortality after imple-
mentation of a commercially sold computer-
ized physician order entry system. Pediatrics
2005; 116:1506 –1512
Pediatr Crit Care Med 2007 Vol. 8, No. 3
 5. Del Beccaro MA, Jeffries HE, Eisenberg MA,
et al: Computerized provider order entry im-
plementation: No association with increased
mortality rates in an intensive care unit. Pe-
diatrics 2006; 118:290 –295
6. Sittig DF, Ash JS, Zhang J, et al: Lessons
from “unexpected increased mortality after
implementation of a commercially sold com-
puterized physician order entry system.” Pe-
diatrics 2006; 118:797– 801
7. Ammenwerth E, Talmon J, Ash JS, et al:
Impact of CPOE on mortality rates—Contra-
dictory findings, important messages. Meth-
ods Inf Med 2006; 45:586 –593
8. Keene A, Ashton L, Shure D, et al: Mortality
before and after initiation of a computerized
physician order entry system in a critically ill
Testing the waters*
Science . . . requires testing of its ideas . . . to see if predictions are borne out by experiment . . . the testing of theories can be
considered to distinguish science from other creative fields.—DC Giancoli, Physics, Upper Saddle River, NJ, Prentice Hall,
1995, p 3
F or the most part, pediatric in-
tensivists behave as an inde-
pendent bunch, similar to a
community of cats. On the
other hand, critical care therapeutics
from adult experience frequently migrate
into the pediatric intensive care unit
(PICU), often with meager evidence of
either safety or efficacy in children. In
this respect, the metaphor is more appro-
priately sheep rather than cats. This be-
havior likely reflects burgeoning pediat-
ric critical care clinical and outcomes
research, compared with more estab-
lished adult research in these areas. No
example better exemplifies this situation
than the use of corticosteroids as adjunc-
tive therapy for severe sepsis. Interest-
ingly, the origins of rigorous clinical re-
*See also p. 276.
Key Words: adrenal insufficiency; corticotropin
stimulation test; cortisol; free cortisol; hydrocortisone;
sepsis; children; hyperglycemia; gluconeogenesis; ev-
idence-based medicine
Salary support for Dr. Zimmerman was provided,
in part, by 1 U10 HD049945, Collaborative Pediatric
Critical Care Research Network, National Institutes of
Health/National Institutes of Child Health and Human
Development.
For information regarding this article, E-mail:
jerry.zimmerman@seattlechildrens.org
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262882.51753.D3
Pediatr Crit Care Med 2007 Vol. 8, No. 3
pediatric population. Ped Crit Care Med
2007; 8:268 –271
9. Stoop AP, Berg M: Integrating quantitative
and qualitative methods in patient care in-
formation system evaluation: Guidance for
the organizational decision maker. Methods
Inf Med 2003; 42:458 – 462
10. Ash JS, Bates DW: Factors and forces affect-
ing EHR system adoption: Report of a 2004
ACMI discussion. J Am Med Inform Assoc
2005; 12:8 –12
11. Ash JS, Stavri PZ, Kuperman GJ: A consen-
sus statement on considerations for a suc-
cessful CPOE implementation. J Am Med In-
form Assoc 2003; 10:229 –234
12. Koppel R, Localio AR, Cohen A, et al: Neither
panacea nor black box: Responding to three
search in adult critical care can be traced
to the 1980s, when several randomized,
double-blinded, placebo-controlled trials
were conducted to assess high-dose,
short-duration methylprednisolone for
septic shock. Although these studies
demonstrated no benefit, and perhaps
harm, they established a new, more rig-
orous standard for attempting to gener-
ate evidence-based critical care medicine
(1–3).
In this issue of Pediatric Critical Care
Medicine, Menon and Lawson (4) report
survey data regarding views of Canadian
pediatric intensivists on the question of
adjunctive corticosteroid therapy for chil-
dren with severe sepsis. This type of in-
formation is vital in terms of eventual
interventional trial design. Completed
survey data were received from 84% (59/
70) of intensivists practicing in 16 ter-
tiary PICUs in Canada during 2004. More-
over, survey data also were received from
75% (43/57) of pediatric endocrinologists
who provided consultation in Canadian
PICUs during this interval. The authors
acknowledge that the survey did not
distinguish among absolute adrenal in-
sufficiency (e.g., congenital adrenal hy-
perplasia), so-called relative adrenal in-
sufficiency (in the setting of severe stress,
such as sepsis), and inadequate adrenal
reserve (requires a corticotrophin stimu-
lation test).
Journal of Biomedical Informatics papers on
computerized physician order entry systems.
J Biomed Inform 2005; 38:267–269
13. Koppel R, Metlay JP, Cohen A, et al: Role of
computerized physician order entry systems
in facilitating medication errors. JAMA 2005;
293:1197–1203
14. Massachusetts Technology Collaborative:
CPOE lessons learned in community hospitals.
Online at: www.masstech.org/ehealth/CPOE_
lessonslearned.pdf. Accessed February 12,
2007
15. Baldwin G: Bringing order to CPOE: 10 make
or break steps (and 5 myths). HealthLeaders
Media 2005; also online at www.healthleade
rsmedia.com/magazine/view_magazine_
feature.cfm?content_id⫽74158
Although opinions varied widely, most
Canadian pediatric intensivists would use
a serum cortisol concentration ⬍138 nM
(5 ␮g/dL) as their definition of adrenal
insufficiency, while Canadian pediatric
endocrinologists prefer a definition of se-
rum cortisol ⬍500 nM (⬍18.1 ␮g/dL)
after standard-dose corticotropin adrenal
stimulation. Interestingly, 12% of the in-
tensivists preferred to diagnose (and
treat) adrenal insufficiency using clinical
findings only. Without pediatric evidence
of either safety or efficacy, 51% of Cana-
dian pediatric intensivists would treat
sepsis-related hypotension with cortico-
steroids. Surprisingly, 81% of Canadian
pediatric endocrinologists would never or
only occasionally prescribe corticoste-
roids for this same indication.
In a related investigation conducted in
the United Kingdom, Hildebrandt and
colleagues (5) surveyed their pediatric in-
tensivist colleagues regarding the use of
adjunctive corticosteroids for pediatric
severe sepsis. Among 25 PICUs, 13 (52%)
returned the mailed survey, and the au-
thors followed up with the other 12 units
by telephone. For severe sepsis, 76% of
the PICUs used corticosteroids regularly,
84% in the setting of vasoactive-inotropic
refractory hypotension associated with
sepsis. Usually (79%) hydrocortisone was
the corticosteroid of choice, and it was
administered without testing for adrenal
305
 5. Del Beccaro MA, Jeffries HE, Eisenberg MA,
et al: Computerized provider order entry im-
plementation: No association with increased
mortality rates in an intensive care unit. Pe-
diatrics 2006; 118:290 –295
6. Sittig DF, Ash JS, Zhang J, et al: Lessons
from “unexpected increased mortality after
implementation of a commercially sold com-
puterized physician order entry system.” Pe-
diatrics 2006; 118:797– 801
7. Ammenwerth E, Talmon J, Ash JS, et al:
Impact of CPOE on mortality rates—Contra-
dictory findings, important messages. Meth-
ods Inf Med 2006; 45:586 –593
8. Keene A, Ashton L, Shure D, et al: Mortality
before and after initiation of a computerized
physician order entry system in a critically ill
Testing the waters*
Science . . . requires testing of its ideas . . . to see if predictions are borne out by experiment . . . the testing of theories can be
considered to distinguish science from other creative fields.—DC Giancoli, Physics, Upper Saddle River, NJ, Prentice Hall,
1995, p 3
F or the most part, pediatric in-
tensivists behave as an inde-
pendent bunch, similar to a
community of cats. On the
other hand, critical care therapeutics
from adult experience frequently migrate
into the pediatric intensive care unit
(PICU), often with meager evidence of
either safety or efficacy in children. In
this respect, the metaphor is more appro-
priately sheep rather than cats. This be-
havior likely reflects burgeoning pediat-
ric critical care clinical and outcomes
research, compared with more estab-
lished adult research in these areas. No
example better exemplifies this situation
than the use of corticosteroids as adjunc-
tive therapy for severe sepsis. Interest-
ingly, the origins of rigorous clinical re-
*See also p. 276.
Key Words: adrenal insufficiency; corticotropin
stimulation test; cortisol; free cortisol; hydrocortisone;
sepsis; children; hyperglycemia; gluconeogenesis; ev-
idence-based medicine
Salary support for Dr. Zimmerman was provided,
in part, by 1 U10 HD049945, Collaborative Pediatric
Critical Care Research Network, National Institutes of
Health/National Institutes of Child Health and Human
Development.
For information regarding this article, E-mail:
jerry.zimmerman@seattlechildrens.org
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000262882.51753.D3
Pediatr Crit Care Med 2007 Vol. 8, No. 3
pediatric population. Ped Crit Care Med
2007; 8:268 –271
9. Stoop AP, Berg M: Integrating quantitative
and qualitative methods in patient care in-
formation system evaluation: Guidance for
the organizational decision maker. Methods
Inf Med 2003; 42:458 – 462
10. Ash JS, Bates DW: Factors and forces affect-
ing EHR system adoption: Report of a 2004
ACMI discussion. J Am Med Inform Assoc
2005; 12:8 –12
11. Ash JS, Stavri PZ, Kuperman GJ: A consen-
sus statement on considerations for a suc-
cessful CPOE implementation. J Am Med In-
form Assoc 2003; 10:229 –234
12. Koppel R, Localio AR, Cohen A, et al: Neither
panacea nor black box: Responding to three
search in adult critical care can be traced
to the 1980s, when several randomized,
double-blinded, placebo-controlled trials
were conducted to assess high-dose,
short-duration methylprednisolone for
septic shock. Although these studies
demonstrated no benefit, and perhaps
harm, they established a new, more rig-
orous standard for attempting to gener-
ate evidence-based critical care medicine
(1–3).
In this issue of Pediatric Critical Care
Medicine, Menon and Lawson (4) report
survey data regarding views of Canadian
pediatric intensivists on the question of
adjunctive corticosteroid therapy for chil-
dren with severe sepsis. This type of in-
formation is vital in terms of eventual
interventional trial design. Completed
survey data were received from 84% (59/
70) of intensivists practicing in 16 ter-
tiary PICUs in Canada during 2004. More-
over, survey data also were received from
75% (43/57) of pediatric endocrinologists
who provided consultation in Canadian
PICUs during this interval. The authors
acknowledge that the survey did not
distinguish among absolute adrenal in-
sufficiency (e.g., congenital adrenal hy-
perplasia), so-called relative adrenal in-
sufficiency (in the setting of severe stress,
such as sepsis), and inadequate adrenal
reserve (requires a corticotrophin stimu-
lation test).
Journal of Biomedical Informatics papers on
computerized physician order entry systems.
J Biomed Inform 2005; 38:267–269
13. Koppel R, Metlay JP, Cohen A, et al: Role of
computerized physician order entry systems
in facilitating medication errors. JAMA 2005;
293:1197–1203
14. Massachusetts Technology Collaborative:
CPOE lessons learned in community hospitals.
Online at: www.masstech.org/ehealth/CPOE_
lessonslearned.pdf. Accessed February 12,
2007
15. Baldwin G: Bringing order to CPOE: 10 make
or break steps (and 5 myths). HealthLeaders
Media 2005; also online at www.healthleade
rsmedia.com/magazine/view_magazine_
feature.cfm?content_id⫽74158
Although opinions varied widely, most
Canadian pediatric intensivists would use
a serum cortisol concentration ⬍138 nM
(5 ␮g/dL) as their definition of adrenal
insufficiency, while Canadian pediatric
endocrinologists prefer a definition of se-
rum cortisol ⬍500 nM (⬍18.1 ␮g/dL)
after standard-dose corticotropin adrenal
stimulation. Interestingly, 12% of the in-
tensivists preferred to diagnose (and
treat) adrenal insufficiency using clinical
findings only. Without pediatric evidence
of either safety or efficacy, 51% of Cana-
dian pediatric intensivists would treat
sepsis-related hypotension with cortico-
steroids. Surprisingly, 81% of Canadian
pediatric endocrinologists would never or
only occasionally prescribe corticoste-
roids for this same indication.
In a related investigation conducted in
the United Kingdom, Hildebrandt and
colleagues (5) surveyed their pediatric in-
tensivist colleagues regarding the use of
adjunctive corticosteroids for pediatric
severe sepsis. Among 25 PICUs, 13 (52%)
returned the mailed survey, and the au-
thors followed up with the other 12 units
by telephone. For severe sepsis, 76% of
the PICUs used corticosteroids regularly,
84% in the setting of vasoactive-inotropic
refractory hypotension associated with
sepsis. Usually (79%) hydrocortisone was
the corticosteroid of choice, and it was
administered without testing for adrenal
305
sufficiency 42% of the time. For PICUs
that undertook laboratory testing for ad-
renal sufficiency, there was wide varia-
tion for what was considered abnormal.
Although all units regarded their pre-
scribed dose of corticosteroids as stress or
physiologic, significant variability in dos-
ing also was reported.
Czaja and Zimmerman (6) conducted
a similar informal survey of pediatric in-
tensivists who subscribe to the PICUList
e-mail-forum digest. The questionnaire
was posted at http://pedsccm.wustl.edu/
research/trials/shipss_questionnaire.doc.
Respondents numbered 65. In describing
why a physician would prescribe cortico-
steroids to children with severe sepsis,
62% cited adult evidence, 8% cited pedi-
atric evidence, and 30% cited personal
preference. Nearly half of the respondents
(48%) ordered no cortisol laboratory test-
ing before prescribing corticosteroids for
sepsis, whereas 21% relied on random
cortisol levels and 31% preferred cortico-
tropin stimulation testing. Again, despite
lack of pediatric evidence for safety and
efficacy of adjunctive corticosteroid ther-
apy for severe sepsis, 68% of respondents
noted that they would not participate in a
clinical trial examining this question if a
bailout study design was not used (i.e.,
administration of corticosteroids at the
discretion of the primary intensivist as a
life-saving measure).
Several pediatric studies have linked
increasing sepsis severity with decreasing
random baseline serum cortisol levels (7–
13). Two pediatric investigations have re-
ported that children exhibiting a subop-
timal increase in serum cortisol after
corticotropin administration require
more intense hemodynamic resuscita-
tion, but no relationship to mortality
could be established (9, 13). Admittedly,
relatively small numbers of children were
included in each of these pediatric inves-
tigations. Despite a transition from in-
dustrial corticosteroid dosing for severe
sepsis to the currently popular low-dose,
stress-dose, or physiologic-replacement
corticosteroid dose, controversy contin-
ues to abound regarding the benefit of
even this approach. Initial, small, adult
trials using this tactic appeared to dem-
onstrate hastened resolution of septic
shock associated with decreased mortal-
ity (14 –18). Subsequently, a substantially
larger trial with 299 subjects demon-
strated faster resolution of organ dys-
function, including septic shock, and sig-
nificantly reduced mortality in an a priori
defined subgroup with ⬍9 ␮g/dL (250
306
nM) increment in serum cortisol after
standard-dose corticotropin administra-
tion (74% of the total subjects enrolled)
(19). Unfortunately, this investigation
was subsequently found to be flawed by a
report that a significant number of sub-
jects had received etomidate for sedation
during intubation (20). Etomidate inhib-
its 11-␤ hydroxylase, the rate-limiting
enzyme in cortisol synthesis (21, 22).
A definitive trial, CORTICUS, was de-
signed and conducted as a logical follow-up
(23). Although results of this pivotal study
have only been reported in abstract form
(24), it appears that even stress-dose hydro-
cortisone is not a panacea for adults with
septic shock. Three small corticosteroid in-
terventional trials in pediatric sepsis are
also inconclusive (25–27).
Multiple studies have confirmed that
stress-dose corticosteroids hasten resolu-
tion from septic shock (14, 15, 18, 28 –
30). However, as illogical as it seems,
resolution of septic shock may not be a
clinically meaningful surrogate marker
for mortality associated with sepsis. This
was ascertained in the definitive trial of a
nonselective inhibitor of inducible nitric
oxide synthase; it hastened resolution of
septic shock but was associated with in-
creased mortality (31–33). In fact, corti-
costeroid supplementation for recalci-
trant septic shock may hasten resolution
of septic shock (34 –36), but its pro-
nounced gluconeogenic activity may aug-
ment hyperglycemia that, if inadequately
controlled, may contribute to increased
morbidity and mortality (37– 41).
It remains unclear whether the cor-
rect population is being targeted for cor-
ticosteroid supplementation during sep-
sis. Identifying this population would
maximize the beneficial effects of corti-
costeroids, while minimizing adverse ef-
fects. Herein likely lies the value of the
correct test to identify the target popula-
tion. Among intensive care providers, this
testing has traditionally involved two
points of view: a) a stress such as severe
sepsis should be sufficient stimulus for
adrenal stimulation and, accordingly, a
random serum cortisol should suffice to
identify those individuals not mounting
an appropriate adrenal stress response
(42); and b) formal corticotropin stimu-
lation testing best identifies individuals
likely to benefit from corticosteroid sup-
plementation (36). The latter approach is
made more complex by arguments for
standard-dose (145 ␮g/m2, 250 ␮g maxi-
mum) vs. low-dose corticotropin (1 ␮g)
(43). A recent study in adults indicates
that individuals with a random baseline
serum cortisol of ⬍10 ␮g/dL (278 nM) or
those with an increment ⬍9 ␮g/dL (250
nM) after standard dose corticotropin are
likely to benefit from corticosteroid sup-
plementation, but those with a random
baseline level ⬎44 ␮g/dL (1,222 nM) or
those with an increment ⬎16.8 ␮g/dL
(467 nM) after standard-dose cortico-
tropin appear cortisol sufficient and are
unlikely to benefit from cortisol supple-
mentation (44). Overriding all of this is
an evolving consensus among endocri-
nologists that free (rather than total) cor-
tisol more closely reflects the degree of
stress and best identifies patients who are
most likely to benefit from corticosteroid
supplementation (45, 46).
Studies such as the one presented by
Menon and Lawson (4) should remind
pediatric intensivists that we have an ac-
ademic and, more importantly, patient
responsibility to generate our own evi-
dence-based medicine regarding the ra-
tional use of adjunctive corticosteroid for
severe pediatric sepsis.
Jerry J. Zimmerman, MD,
PhD, FCCM
Pediatric Critical Care
Medicine
Seattle Children’s Hospital
University of Washington
School of Medicine
Seattle, WA
REFERENCES
1. Sprung CL, Caralis PV, Marcial EH, et al: The
effects of high-dose corticosteroids in pa-
tients with septic shock: A prospective, con-
trolled study. N Engl J Med 1984; 311:
1137–1143
2. Bone RC, Fisher CJ Jr, Clemmer TP, et al:
Early methylprednisolone treatment for sep-
tic syndrome and the adult respiratory dis-
tress syndrome. Chest 1987; 92:1032–1036
3. The Veterans Administration Systemic Sepsis
Cooperative Study Group: Effect of high-dose
glucocorticoid therapy on mortality in pa-
tients with clinical signs of systemic sepsis.
N Engl J Med 1987; 317:659 – 665
4. Menon K, Lawson, M: Identification of adre-
nal insufficiency in pediatric critical illness.
Pediatr Crit Care Med 2007; 8:276-278
5. Hildebrandt T, Mansour M, Al Samsam R:
The use of steroids in children with septice-
mia: Review of the literature and assessment
of current practice in PICUs in the UK. Pae-
diatr Anaesth 2005; 15:358 –365
6. Czaja A, Zimmerman J: Endpoints/treatment
algorithms for RCTs of steroids in pediatric
sepsis. Abstr. Crit Care Med 2004; 32:A127
7. Riordan FA, Thomson AP, Ratcliffe JM, et al:
Admission cortisol and adrenocorticotrophic
hormone levels in children with meningo-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
 coccal disease: Evidence of adrenal insuffi-
ciency? Crit Care Med 1999; 27:2257–2261
8. Auletta JJ, O’Riordan MA, Nieder ML: Infec-
tions in children with cancer: A continued
need for the comprehensive physical exami-
nation. J Pediatr Hematol Oncol 1999; 21:
501–508
9. Hatherill M, Tibby SM, Hilliard T, et al: Ad-
renal insufficiency in septic shock. Arch Dis
Child 1999; 80:51–55
10. Van Woensel JB, Biezeveld MH, Alders AM, et
al: Adrenocorticotropic hormone and corti-
sol levels in relation to inflammatory re-
sponse and disease severity in children with
meningococcal disease. J Infect Dis 2001;
184:1532–1537
11. De Kleijn ED, Joosten KF, Van Rijn B, et al:
Low serum cortisol in combination with
high adrenocorticotrophic hormone concen-
trations are associated with poor outcome in
children with severe meningococcal disease.
Pediatr Infect Dis J 2002; 21:330 –336
12. Joosten KF, de Kleijn ED, Westerterp M, et
al: Endocrine and metabolic responses in
children with meningococcal sepsis: Striking
differences between survivors and nonsurvi-
vors. J Clin Endocrinol Metab 2000; 85:
3746 –3753
13. Pizarro CF, Troster EJ, Damiani D, et al:
Absolute and relative adrenal insufficiency in
children with septic shock. Crit Care Med
2005; 33:855– 859
14. Bollaert PE, Charpentier C, Levy B, et al:
Reversal of late septic shock with supraphysi-
ologic doses of hydrocortisone. Crit Care
Med 1998; 26:645– 650
15. Briegel J, Forst H, Haller M, et al: Stress
doses of hydrocortisone reverse hyperdy-
namic septic shock: A prospective, random-
ized, double-blind, single-center study. Crit
Care Med 1999; 27:723–732
16. Yildiz O, Doganay M, Aygen B, et al: Physio-
logical-dose steroid therapy in sepsis. Crit
Care 2002; 6:251–259
17. Keh D, Boehnke T, Weber-Cartens S, et al:
Immunologic and hemodynamic effects of
“low-dose” hydrocortisone in septic shock: A
double-blind, randomized, placebo-con-
trolled, crossover study. Am J Respir Crit
Care Med 2003; 167:512–520
18. Oppert M, Schindler R, Husung C, et al:
Low-dose hydrocortisone improves shock re-
versal and reduces cytokine levels in early
hyperdynamic septic shock. Crit Care Med
2005; 33:2457–2464
19. Annane D, Sebille V, Charpentier C, et al:
Effect of treatment with low doses of hydro-
cortisone and fludrocortisone on mortality in
Pediatr Crit Care Med 2007 Vol. 8, No. 3
patients with septic shock. JAMA 2002; 288:
862– 871
20. Annane D: Corticosteroids for patients with
septic shock. JAMA 2003; 289:43– 44
21. Annane D: Etomidate and intensive care phy-
sicians. Intensive Care Med 2005; 31:1454
22. Den Brinker M, Joosten KF, Liem O, et al:
Adrenal insufficiency in meningococcal sep-
sis: Bioavailable cortisol levels and impact of
interleukin-6 levels and intubation with eto-
midate on adrenal function and mortality.
J Clin Endocrinol Metab 2005; 90:5110 –5117
23. Hadassah Medical Organization European
Society of Intensive Care Medicine, Interna-
tional Sepsis Forum, The Gorham Founda-
tion: Corticosteroid therapy of septic
shock— corticus. Online at: clinicaltrials.
gov. Accessed February 15, 2007
24. Palencia E: Hidrocortisona en el shock sép-
tico: Primeros resultados del CORTICUS. Re-
vista Electronica de Medicina Intensiva
2006; 6:A43
25. Min MUT, Aye M, Shwe TN, et al: Hydrocor-
tisone in the management of dengue shock
syndrome. Southeast Asian J Trop Med Pub-
lic Health 1975; 6:573–579
26. Sumarmo, Talogo W, Asrin A, et al: Failure of
hydrocortisone to affect outcome in dengue
shock syndrome. Pediatrics 1982; 69:45– 49
27. Slusher T, Gbadero D, Howard C, et al: Ran-
domized, placebo-controlled, double blinded
trial of dexamethasone in African children
with sepsis. Pediatr Infect Dis J 1996; 15:
579 –583
28. Annane D: Cortisol replacement for severe
sepsis and septic shock: What should I do?
Crit Care 2002; 6:190 –191
29. Celkan T, Ozkan A, Apak H, et al: Bacteremia
in childhood cancer. J Trop Pediatr 2002;
48:373–377
30. Annane D, Briegel J, Keh D, et al: Clinical
equipoise remains for issues of adrenocorti-
cotropic hormone administration, cortisol
testing, and therapeutic use of hydrocorti-
sone. Crit Care Med 2003; 31:2250 –2251
31. Bakker J, Grover R, McLuckie A, et al: Ad-
ministration of the nitric oxide synthase in-
hibitor NG-methyl-L-arginine hydrochloride
(546C88) by intravenous infusion for up to
72 hours can promote the resolution of
shock in patients with severe sepsis: Results
of a randomized, double-blind, placebo-
controlled multicenter study. Crit Care Med
2004; 32:1–12
32. Watson D, Grover R, Anzueto A, et al: Car-
diovascular effects of the nitric oxide syn-
thase inhibitor NG-methyl-L-arginine hydro-
chloride (546C88) in patients with septic
shock: Results of a randomized, double-
blind, placebo-controlled multicenter study.
Crit Care Med 2004; 32:13–20
33. Lopez A, Lorente JA, Steingrub J, et al: Mul-
tiple-center, randomized, placebo-con-
trolled, double-blind study of the nitric oxide
synthase inhibitor 546C88: Effect on survival
in patients with septic shock. Crit Care Med
2004; 32:21–30
34. Annane D: Replacement therapy with hydro-
cortisone in catecholamine-dependent septic
shock. J Endotoxin Res 2001; 7:305–309
35. Annane D, Bellissant E, Sebille V, et al: Im-
paired pressor sensitivity to noradrenaline in
septic shock patients with and without im-
paired adrenal function reserve. Br J Clin
Pharmacol 1998; 46:589 –597
36. Annane D, Sebille V, Troche G, et al: A
3-level prognostic classification in septic
shock based on cortisol levels and cortisol
response to corticotropin. JAMA 2000; 283:
1038 –1045
37. Faustino EV, Apkon M: Persistent hypergly-
cemia in critically ill children. J Pediatr
2005; 146:30 –34
38. Srinivasan V, Spinella PC, Drott HR, et al:
Association of timing, duration, and intensity
of hyperglycemia with intensive care unit
mortality in critically ill children. Pediatr
Crit Care Med 2004; 5:329 –336
39. Van den Berghe G: How does blood glucose
control with insulin save lives in intensive
care? J Clin Invest 2004; 114:1187–1195
40. Van den Berghe G, Wouters P, Weekers F, et
al: Intensive insulin therapy in critically ill
patients. N Engl J Med 2001; 345:1359 –1367
41. Van den Berghe GH: Role of intravenous
insulin therapy in critically ill patients. En-
docr Pract 2004; 10(Suppl 2):17–20
42. Marik PE, Zaloga GP: Adrenal insufficiency
during septic shock. Crit Care Med 2003;
31:141–145
43. Sarthi MLR, Vivekananhan S, Arora N: Adre-
nal status in children with septic shock using
low dose stimulation test. Pediatr Crit Care
Med 2007; 8:23–28
44. Annane D, Maxime V, Ibrahim F, et al: Diag-
nosis of adrenal insufficiency in severe sepsis
and septic shock. Am J Respir Crit Care Med
2006; 174:1319 –1326
45. Hamrahian AH, Oseni TS, Arafah BM: Mea-
surements of serum free cortisol in critically
ill patients. N Engl J Med 2004; 350:
1629 –1638
46. Arafah BM: Hypothalamic pituitary adrenal
function during critical illness: Limitations
of current assessment methods. J Clin Endo-
crinol Metab 2006; 91:3725–3745
307
Letter to the Editor
Can somatostatin derivatives really be
suggested in the treatment of
chylothorax?
To the Editor:
With great interest I read the article by
Helin and colleagues (1) about octreotide
therapy in infants and children. In my opin-
ion, it is a very brief, incomplete review that
does not include studies published about
the treatment of children with somatosta-
tin and its derivatives.
Helin and colleagues (1) tried to give
an overview about the published data.
From this overview, they conclude that
treating children with this medication is
safe and should be included as a first-line
treatment. In the literature, it is very well
documented that most patients can be
treated with conservative therapy, includ-
ing fat-free nutrition and total parenteral
nutrition (2, 3). We (3) published a suc-
cess rate of 74.9% with this treatment
strategy, and Chan et al. (2) reported a
rate of 71%. Although somatostatin and
its derivatives have not shown severe side
effects in the small patient groups pub-
lished thus far, it is too early to suggest
treating patients before attempting con-
servative treatment.
The two big, retrospective studies (2,
3) published in the last 2 yrs were not
mentioned by Helin and colleagues (1).
They showed a maximal success rate of
50% when patients were treated with so-
matostatin or octreotide (2, 3).
Helin and colleagues (1) suggest ad-
ministering higher doses for greater du-
rations, and they try to support this opin-
ion with their experience in three cases.
The time for resolution of chylothorax
ranged from 1 to 12 days. I dare to say
that in the patient in whom chylous ef-
fusion decreased after 12 days, it might
be more the effect of the natural way of
chylothorax than the success of soma-
tostatin. In two publications, our group
(3, 4) showed the greatest number of pa-
tients with chylothorax treated with so-
matostatin, and I still find it very impor-
tant to exploit conservative treatment
options before using somatostatin. I fully
agree with the authors’ last sentence,
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
308
that we need a prospective, multicenter,
controlled trial to answer the many un-
acknowledged questions.
The author has not disclosed any po-
tential conflicts of interest.
Vera Bernet-Buettiker, MD, Depart-
ment of Neonatology and Intensive
Care, University Children’s Hospital,
Zurich, Switzerland
REFERENCES
1. Helin RD, Angeles ST, Bhat R: Octreotide
therapy for chylothorax in infants and chil-
dren: A brief review. Pediatr Crit Care Med
2006; 7:576 –579
2. Chan EH, Russel JL, Williams WG, et al: Post-
operative chylothorax after cardiothoracic
surgery in children. Ann Thorac Surg 2005;
80:1864 –1871
3. Cannizzaro V, Frey B, Bernet-Buettiker V:
Role of somatostatin in a treatment algorithm
for chylothorax in children. Eur J Cardiotho-
rac Surg 2006; 30:49 –53
4. Buettiker V, Hug MI, Burger R, et al: Soma-
tostatin: A new therapeutic option for the
treatment of chylothorax. Intensive Care Med
2001; 27:1083–1086
DOI: 10.1097/01.PCC.0000262799.34181.80
The authors reply:
We appreciate the interest in our arti-
cle (1) expressed by Dr. Bernet-Buettiker
and would like the opportunity to reply to
her comments. As stated in the title, this
work was intended only to provide a brief
review. We focused on octreotide and in-
tentionally refrained from any extended
discussion of somatostatin. No informa-
tion regarding somatostatin dosing was
included in our summary table. We did
not include the study by Chan et al. (2)
because octreotide dosing was not re-
ported in a standardized manner (i.e., mi-
crograms per kilogram), but rather in
micrograms per hour.
We chose octreotide because we
think that it may be superior to soma-
tostatin. Octreotide has a longer half-
life, is more potent, is synthetic, and
can be administered as a continuous
intravenous infusion, as an intermit-
tent intravenous dose, or subcutane-
ously. The longer half-life of octreotide
is a tangible benefit because it allows
the option for intermittent dosing, and
a drug with greater potency may be
more concentrated and allow for better
control over total fluid intake—a fact
that is of particular importance to our
smaller patients. Although the intrave-
nous route appears to be used most
frequently (3), situations do arise in
critically ill patients where intravenous
access sites are limited and require
multiple continuous drug infusions.
Such patients include those who have
undergone cardiac surgery or newborns
with congenital chylothorax, often as-
sociated with nonimmune hydrops fe-
talis. In these patients, an option to
administer the drug subcutaneously
may be beneficial.
In addition, Dr. Bernet-Buettiker and
colleagues (4) have previously asserted
that traditional, supportive measures
should be used before surgical measures
or somatostatin (and by implication, oc-
treotide). The literature suggests that ap-
proximately 80 – 85% of patients may be
managed with conservative measures (2,
4, 5). A first-line conservative/supportive
approach therefore appears reasonable.
However, several points deserve mention.
First, the results mentioned above (2, 4,
5) are derived overwhelmingly from post-
operative surgical heart patients. The ex-
tent to which these results can be gener-
alized to other causes of chylothorax
(especially congenital chylothorax) is un-
certain. Next, thoracostomy tubes are
portals of entry for infection and are pain-
ful. In addition, in patients with congen-
ital chylothorax or patients who are crit-
ically ill and not being enterally fed,
conservative measures are limited to par-
enteral nutrition and assisted ventilation,
thoracostomy tube drainage, and replace-
ment of protein, clotting factors, and
electrolytes. Although protein, clotting
factors, and electrolytes can be replaced,
the high rate of fluid production in chy-
lothorax often makes replacement chal-
lenging and exposes these patients to
multiple infusions, vascular access issues,
and the potential for medical errors. In
other words, conservative measures are
not necessarily benign. Lastly, as we in-
dicate in our article, octreotide appears to
be a safe drug.
The precise role of octreotide in man-
agement of chylothorax remains unclear.
Dose-response relationships have not
been adequately delineated, and random-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Letter to the Editor
Can somatostatin derivatives really be
suggested in the treatment of
chylothorax?
To the Editor:
With great interest I read the article by
Helin and colleagues (1) about octreotide
therapy in infants and children. In my opin-
ion, it is a very brief, incomplete review that
does not include studies published about
the treatment of children with somatosta-
tin and its derivatives.
Helin and colleagues (1) tried to give
an overview about the published data.
From this overview, they conclude that
treating children with this medication is
safe and should be included as a first-line
treatment. In the literature, it is very well
documented that most patients can be
treated with conservative therapy, includ-
ing fat-free nutrition and total parenteral
nutrition (2, 3). We (3) published a suc-
cess rate of 74.9% with this treatment
strategy, and Chan et al. (2) reported a
rate of 71%. Although somatostatin and
its derivatives have not shown severe side
effects in the small patient groups pub-
lished thus far, it is too early to suggest
treating patients before attempting con-
servative treatment.
The two big, retrospective studies (2,
3) published in the last 2 yrs were not
mentioned by Helin and colleagues (1).
They showed a maximal success rate of
50% when patients were treated with so-
matostatin or octreotide (2, 3).
Helin and colleagues (1) suggest ad-
ministering higher doses for greater du-
rations, and they try to support this opin-
ion with their experience in three cases.
The time for resolution of chylothorax
ranged from 1 to 12 days. I dare to say
that in the patient in whom chylous ef-
fusion decreased after 12 days, it might
be more the effect of the natural way of
chylothorax than the success of soma-
tostatin. In two publications, our group
(3, 4) showed the greatest number of pa-
tients with chylothorax treated with so-
matostatin, and I still find it very impor-
tant to exploit conservative treatment
options before using somatostatin. I fully
agree with the authors’ last sentence,
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
308
that we need a prospective, multicenter,
controlled trial to answer the many un-
acknowledged questions.
The author has not disclosed any po-
tential conflicts of interest.
Vera Bernet-Buettiker, MD, Depart-
ment of Neonatology and Intensive
Care, University Children’s Hospital,
Zurich, Switzerland
REFERENCES
1. Helin RD, Angeles ST, Bhat R: Octreotide
therapy for chylothorax in infants and chil-
dren: A brief review. Pediatr Crit Care Med
2006; 7:576 –579
2. Chan EH, Russel JL, Williams WG, et al: Post-
operative chylothorax after cardiothoracic
surgery in children. Ann Thorac Surg 2005;
80:1864 –1871
3. Cannizzaro V, Frey B, Bernet-Buettiker V:
Role of somatostatin in a treatment algorithm
for chylothorax in children. Eur J Cardiotho-
rac Surg 2006; 30:49 –53
4. Buettiker V, Hug MI, Burger R, et al: Soma-
tostatin: A new therapeutic option for the
treatment of chylothorax. Intensive Care Med
2001; 27:1083–1086
DOI: 10.1097/01.PCC.0000262799.34181.80
The authors reply:
We appreciate the interest in our arti-
cle (1) expressed by Dr. Bernet-Buettiker
and would like the opportunity to reply to
her comments. As stated in the title, this
work was intended only to provide a brief
review. We focused on octreotide and in-
tentionally refrained from any extended
discussion of somatostatin. No informa-
tion regarding somatostatin dosing was
included in our summary table. We did
not include the study by Chan et al. (2)
because octreotide dosing was not re-
ported in a standardized manner (i.e., mi-
crograms per kilogram), but rather in
micrograms per hour.
We chose octreotide because we
think that it may be superior to soma-
tostatin. Octreotide has a longer half-
life, is more potent, is synthetic, and
can be administered as a continuous
intravenous infusion, as an intermit-
tent intravenous dose, or subcutane-
ously. The longer half-life of octreotide
is a tangible benefit because it allows
the option for intermittent dosing, and
a drug with greater potency may be
more concentrated and allow for better
control over total fluid intake—a fact
that is of particular importance to our
smaller patients. Although the intrave-
nous route appears to be used most
frequently (3), situations do arise in
critically ill patients where intravenous
access sites are limited and require
multiple continuous drug infusions.
Such patients include those who have
undergone cardiac surgery or newborns
with congenital chylothorax, often as-
sociated with nonimmune hydrops fe-
talis. In these patients, an option to
administer the drug subcutaneously
may be beneficial.
In addition, Dr. Bernet-Buettiker and
colleagues (4) have previously asserted
that traditional, supportive measures
should be used before surgical measures
or somatostatin (and by implication, oc-
treotide). The literature suggests that ap-
proximately 80 – 85% of patients may be
managed with conservative measures (2,
4, 5). A first-line conservative/supportive
approach therefore appears reasonable.
However, several points deserve mention.
First, the results mentioned above (2, 4,
5) are derived overwhelmingly from post-
operative surgical heart patients. The ex-
tent to which these results can be gener-
alized to other causes of chylothorax
(especially congenital chylothorax) is un-
certain. Next, thoracostomy tubes are
portals of entry for infection and are pain-
ful. In addition, in patients with congen-
ital chylothorax or patients who are crit-
ically ill and not being enterally fed,
conservative measures are limited to par-
enteral nutrition and assisted ventilation,
thoracostomy tube drainage, and replace-
ment of protein, clotting factors, and
electrolytes. Although protein, clotting
factors, and electrolytes can be replaced,
the high rate of fluid production in chy-
lothorax often makes replacement chal-
lenging and exposes these patients to
multiple infusions, vascular access issues,
and the potential for medical errors. In
other words, conservative measures are
not necessarily benign. Lastly, as we in-
dicate in our article, octreotide appears to
be a safe drug.
The precise role of octreotide in man-
agement of chylothorax remains unclear.
Dose-response relationships have not
been adequately delineated, and random-
Pediatr Crit Care Med 2007 Vol. 8, No. 3
ized controlled trials are needed to fur-
ther evaluate the drug’s efficacy. In our
article, we summarized the collective ex-
perience with octreotide for chylothorax
in infants and children and proposed a
dosing framework that might be useful to
others wishing to conduct such trials.
Radley D. Helin, DO, FAAP, University
of Illinois Medical Center, Chicago, IL;
Rama Bhat, MD, FAAP, Department of
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Pediatrics, University of Illinois at Chi-
cago, Chicago, IL
REFERENCES
1. Helin RD, Angeles ST, Bhat R: Octreotide
therapy for chylothorax in infants and chil-
dren: A brief review. Pediatr Crit Care Med
2006; 7:576 –579
2. Chan EH, Russel JL, Williams WG, et al: Post-
operative chylothorax after cardiothoracic
surgery in children. Ann Thorac Surg 2005;
80:1864 –1871
3. Buettiker V, Hug MI, Burger R, et al: Soma-
tostatin: A new therapeutic option for the
treatment of chylothorax. Intensive Care Med
2001; 27:1083–1086
4. Cannizzaro V, Frey B, Bernet-Buettiker V: The
role of somatostatin in the treatment of per-
sistent chylothorax in children. Eur J Cardio-
thorac Surg 2006; 30:49 –53
5. Beghetti M, La Scala G, Belli D, et al: Etiology
and management of pediatric chylothorax.
J Pediatr 2000; 136:653– 658
DOI: 10.1097/01.PCC.0000263238.46778.02
309
Abstract Translations

Pediatric Critical Care Medicine is proud to present translations of selected abstracts into Chinese, French, Italian, Japanese,
Portuguese, and Spanish. We sincerely thank the following for their important work on these translations: Xun-mei Fan,
MD, and Hao-xun Tang, MD (Chinese), Jacques Lacroix, MD, and Jean-Christophe Mercier, MD (French), Giuseppe A.
Marraro, MD (Italian), Hirokazu Sakai, MD (Japanese), Francisco Cunha, MD, and José Manuel Aparício, PhD, MD
(Portuguese), and Eduardo Schnitzler, MD, Santiago Campos, MD, and Pablo G. Minces, MD (Spanish).

DOI:10.1097/01.pcc.0000268245.53242.ba

310 Pediatr Crit Care Med 2007 Vol. 8, No. 3

PEDIATRIC STAFF PERSPECTIVES ON ORGAN DONATION AF-
TER CARDIAC DEATH IN CHILDREN OPINIONS DE L’ÉQUIPE
PÉDIATRIQUE SUR LE DON D’ORGANE APRÈS DÉCÈS CARDI-
AQUE CHEZ L’ENFANT
Martha A.Q. Curley, RN, PhD, FAAN; Charlotte H. Harrison, JD, MPH, MTS;
Nancy Craig, RRT; Craig W. Lillehei, MD, FAAP, FACS; Anne Micheli, RN, MS;
Peter C. Laussen, MBBS
Résumé
Objectifs: Les objectifs de ce projet sont de décrire si l’équipe pédiatrique
croit ou non qu’un programme de don d’organe après décès cardiaque (DCD)
puisse être compatible avec la mission et les valeurs essentielles d’un hôpital
pédiatrique et d’identifier si l’équipe médicale considère comme essentielle
l’acceptabilité d’un tel programme.
Méthodes: Etude qualitative dans laquelle les données proviennent de
l’équipe médicale pédiatrique pendant huit réunions conduites dans un
hôpital d’enfants de Mars à Avril 2005.
Mesures et Résultats principaux: 88 membres de l’équipe médicale ont
participé. Six thèmes majeurs ont émergé de l’analyse qualitative des don-
nées: 1) identifier les enfants qui pourraient être candidats DCD; 2) prendre
en compte les meilleurs intérêts de l’enfant en train de mourir; 3) approcher
les parents quant au programme DCD; 4) préparer les parents à la mise en
œuvre du programme DCD chez leur enfant; 5) le besoin de pratiquer bien la
procédure DCD; et 6) maintenir l’intégrité du programme. Les thèmes
étaient utilisés pour construire un cadre conceptuel décrivant le modèle
pédiatrique du programme DCD. Le staff pédiatrique a exprimé de nom-
breuses réserves. Cependant, ils ont identifié que “faire en sorte que cela
arrive pour les familles” qui expriment le désir de participer à un don
d’organe consttuait la raison principale d’adoption du programme.
Conclusions: Cette étude fournit un cadre pour comprendre les perspectives
du staff pédiatrique sur les programmes DCD chez l’enfant. Les résultats
suggèrent plusieurs éléments possible qui peuvent aider à cadrer un dia-
logue interdisciplinaire et informer les pratiques institutionnelles dans la
mise en œuvre d’un programme pédiatrique DCD.
ASSESSMENT OF PARENTAL PRESENCE DURING BEDSIDE PEDIATRIC IN-
TENSIVE CARE UNIT ROUNDS: THE IMPACT ON DURATION, TEACHING,
AND PRIVACY EVALUATION DE LA PRÉSENCE PARENTALE PENDANT LES
VISITES AU LIT DU MALADE DANS L’UNITÉ DE SOINS INTENSIFS: SON
IMPACT SUR LA DURÉE DES VISITES, LA QUALITÉ DE L’ENSEIGNEMENT
ET L’INTIMITÉ DU PATIENT
Lorri M. Phipps MSN, CPNP, Cheryl N. Bartke MSN, CPNP, Debra A. Spear RN, CCRN,
Linda F. Jones RN, CCRN, Carolyn P. Foerster, RN, BSN, CCRN, Marie E. Killian RN, BSN,
CCRN, Jennifer R. Hughes RN, BSN, Joseph C. Hess RN, BSN, David R. Johnson PhD, and
Neal J. Thomas MD, MSc
Résumé
Objectif: Très peu d’articles dans la littérature ont évalué les effets de la présence d’un
membre de la famille pendant les visites au lit du malade dans l’Unité de Soins Intensifs
(USI) pédiatrique. Nous avons fait l’hypothèse que, par comparaison aux visites sans
présence de membres de la famille, la présence parentale pendant les visites du matin
augmenterait le temps passés à la visite, diminuerait le temps consacré par les médecins
à l’enseignement ou à l’éducation, augmenterait l’insatisfaction médicale, créerait plus de
stress familial et violerait l’intimité du patient dans notre USI ouverte.
Type d’étude: Prospective, en aveugle.
Lieu d’étude: USI pédiatrique de 12 lits.
Participants: 105 admissions ont été étudiées. 81 membres de la famille ont rempli un
questionnaire, de même que 187 membres du staff médical.
Interventions: Les investigateurs ont documenté la présence parentale et le temps alloué
à la présentation, à l’enseignement et pour rèpondre aux questions. Des questionnaires
concernant les objectifs, l’enseignement dispensé et l’intimité des visites étaient distri-
bués aux participants.
Paramètres mesurés: Le temps passé en visite, le temps consacré à l’enseignement, la
perception par l’équipe médicale et la famill e de l’impact de la présence parentale sur les
visites.
Résultats: Il n’y avait pas de différence significative dans la durée des visites, en présence
ou en absence de membres de la famille. Il n’y avait pas non plus de différence dans le
temps consacré à l’enseignement par le consultant, en présence ou absence des membres
de la famille. Globalement, les parents rapportaient que l’équipe médicale avait passé un
temps approprié pour discuter avec eux de leur enfant et qu’ils n’étaient pas mécontents
de cette discussion. Les parents ne ressentaient pas que leur propre intimité ou celle de
leur enfant avaient été violées pendant les visites. La majorité des membres de l’équipe
médicale rapportaient que la présence de la famille au cours des visites était bénéfique.
Conclusions: La présence parentale au cours des visites n’apparaı̂t pas interférer avec le
processus éducationnel et de communication. Les parents rapportent être satisfaits de
leur participation aux visites, et les violations de leur intimité n’apparaissent pas con-
stituer un problème de leur point de vue.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
INCREASING USE OF EXTRACORPOREAL LIFE SUPPORT IN MRSA
SEPSIS IN CHILDREN AUGMENTATION DE L’UTILISATION DE
L’ASSISTANCE RESPIRATOIRE EXTRA-CORPORELLE DANS LES SEP-
SIS À STAPHYLOCOQUE AUREUS MÉTHICILLIN-RÉSISTANTS CHEZ
L’ENFANT
C. Buddy Creech, MD, MPH, Belinda Johnson, RN, Randall Bartilson, RN, Ed-
mund Yang, MD, PhD, Frederick Barr, MD, MSCI
Introduction: Les cas rapportés d’infections fulminantes à Staphylococcus aureus
méthicilline-résistants (SARM) communautaires nécessitant l’utilisation d’une as-
sistance respiratoire extra-corporelle (AREC) sont apparus, mais la fréquence
d’utilisation de l’AREC pour des staphylococcies sévères est inconnue.
Objectifs: Décrire la fréquence et les caractéristiques des enfants avec infections à
SARM nécessitant une AREC à partir des bases de données locales et internation-
ales.
Méthodes: Les raisons pour l’utilisation de l’AREC chez les enfants âgés de 0 à 18
ans étaient déterminées à la fois dans le système d’information de l’Hôpital
d’Enfants Vanderbilt et dans la base de données de l’Extracorporeal Life Support
Organization (ELSO) pendant les années 1994 –2005. Les caractéristiques dé-
mographiques, le management ventilatoire, et les paramètres de l’état cardiopul-
monaire chez les sujet subissant une AREC avec un diagnostic préalable
d’infection à Staphylococcus aureus et à SARM étaient analysées.
Résultats: Trois sujets avec sepsis à SARM nécessitant l’AREC ont été identifié à
Vanderbilt depuis 2000. Avant cette date, aucun cas dû à SARM n’était rapporté.
Tous étaient des adolescents auparavant sains avec une pneumonie nécrotique
sévère associée à une infection cutanée ou des parties molles, et deux d’entre eux
sont décédés. 45 patients nécessitant l’AREC pour une infection à SARM étaient
identifiés dans la base de données internationale ELSO, dont prés de la moitié était
rapportée dans les deux dernières années passées (20/45). L’âge médian était de
2,4 ans (IC 0,36 – 14 ans), avec des pics notés dans l’enfance et dans l’adolescence.
Chez les sujets ELSO avec SARM, la survie à la sortie de l’hôpital était plus élevée
chez les nourrissons et les jeunes enfants âgés de 1 à 4 ans, respectivement de 65%
et de 71%, et la plus faible chez les 5–9 ans et les 13–18 ans, respectivement de 0%
et de 31%. II n’y avait aucune différence statistiquement significative dans les
paramétres de ventilation pré-AREC, les paramètres cardiopulmonaires, ou la
fréquence des complications entre les survivant et les non-survivants.
Conclusions: L’utilisation de l’AREC pour une infection à SARM apparaı̂t aug-
menter à la fois localement et internationalement. La mortalité élevée, notamment
chez les adolescents, est préoccupante et souligne le problème croissant posé par ce
pathogène.
IMPLEMENTATION OF A MEDICAL EMERGENCY TEAM IN A
LARGE PEDIATRIC TEACHING HOSPITAL PREVENTS RESPIRA-
TORY AND CARDIOPULMONARY ARRESTS OUTSIDE THE ICU
PRÉVENTION DES ARRÊTS CARDIAQUES ET RESPIRATOIRES
PAR LA MISE EN PLACE D’UNE ÉQUIPE MÉDICALE
D’INTERVENTION DANS UN LARGE HÔPITAL UNIVERSITAIRE
PÉDIATRIQUE
Richard J. Brilli, MD, FCCM, FAAP, Rosemary Gibson, RN, CNS, Joseph W.
Luria, MD, FAAP, T. Arthur Wheeler, MS, MBA, Julie Shaw, MSN, MBA,
RN, Matt Linam, MD, John Kheir, MD, Patricia McLain, RN, Tammy Ling-
sch, RN, Amy Hall, RN, Mary McBride, MD
Résumé
Objectif: Nous avons mis en place une équipe médicale d’intervention (EMI)
dans notre hôpital pédiatrique. L’objectif est de réduire la survenue d’arrêts
respiratoires et d’arrêts cardiaques en dehors des unités de soins intensifs
(USI) de plus de 50% dans les 6 mois suivant la mise en place de l’EMI.
Méthodes: Les dossiers des patients qui ont nécessité une réanimation car-
dio-pulmonaire (RCP) en dehors de l’USI étaient revus rétrospectivement
avant la mise en place de l’EMI, afin de déterminer les critères d’appel de
l’EMI. Les appels étaient ensuite prospectivement définis comme des arrêts
respiratoires ou des arrêts cardiaques. Les arrêts qui auraient pu être
prévenus étaient prospectivement définis. L’incidence des arrêts avant et
après EMI étaient comparée.
Résultats: 25 arrêts sont intervenus avant la mise en place de l’EMI, par
comparaison à 6 après cette mise en place. L’incidence des arrêts respira-
toires ⫹ arrêts cardiaques post-EMI était de 0,11 p.mille patients-jours par
comparaison à une incidence pré-EMI de 0,27 p.mille, RR 0,42 [IC95%
0-0,89], p ⫽ 0,03. La prévalence p.mille admissions a diminué de 1,54 avant-
EMI à 0,62 après EMI (RR 0,41 [IC95% 0-0,86], p⫽0,02). Pour les arrêts qui
auraient pu être prévenus, l’incidence était de 0,04 p.mille patients-jours
contre 0,14 p.mille (RR 0,27 [IC95% 0-0,94], p ⫽ 0,04). II n’y avait pas de
différence entre l’incidence des arrêts cardio-respiratoires avant et aprés
EMI. Pour les arrêts survenant en dehors de l’USI, la mortalité pré-EMI
était de 0,12 p.mille patients-jours, par comparaison à 0,06 p.mille post EMI
(RR 0,48 [IC95% 0-1,4], p ⫽ 0,13). La mortalité globale pour les arrêts
survenus en dehors de l’USI était de 42% (15 sur 36 enfants).
Conclusions: La mise en place d’une EMI est associée à une réduction du
risque d’arrêt respiratoire et d’arrêt cardiaque survenant en dehors des
unités de soins intensifs dans un large hôpital d’enfants universitaire.
311
PEDIATRIC STAFF PERSPECTIVES ON ORGAN DONATION AF-
TER CARDIAC DEATH IN CHILDREN
IL PUNTO DI VISTA DELLO STAFF MEDICO SULLA DONAZIONE
D’ORGANO DOPO MORTE CARDIACA NEL BAMBINO
Martha A.Q. Curley, RN, PhD, FAAN; Charlotte H. Harrison, JD, MPH,
MTS; Nancy Craig, RRT; Craig W. Lillehei, MD, FAAP, FACS; Anne Micheli,
RN, MS; Peter C. Laussen, MBBS
Riassunto
Obiettivi: Gli scopi dello studio furono quelli di descrivere se lo staff medico credeva che
un programma di una donazione in età pediatrica dopo morte cardiaca poteva essere
compatibile con la missione medica e con gli interessi di un ospedale pediatrico, e di
identificare che cosa lo staff considerava essenziale per la formulazione di un programma
di questo tipo.
Metodi: Studio qualitativo condotto in un ospedale pediatrico da marzo ad aprile 2005, nel
quale furono raccolti i dati dallo staff clinico durante 8 gruppi di studio focalizzati
sull’argomento.
Misurazioni e risultati principali: Presero parte allo studio 88 membri dello staff.
Dall’analisi qualitativa dei dati emersero 6 temi principali: 1) identificazione dei bambini
che potevano essere candidati per DCD; 2) considerare i migliori interessi per il bambino
morente; 3) avvicinare i genitori sul DCD; 4) preparare i genitori per la DCD del loro
bambino; 5) effettuare correttamente la DCD; e 6) mantenere l’integrità del programma.
Furono impiegati specifici temi per costruire uno schema concettuale che descrivesse un
modello del programma pediatrico di DCD. Lo staff pediatrico pose numerose problema-
tiche. In ogni caso, essi identificarono che “è di chiara pertinenza della famiglia” la scelta
e il desiderio di partecipare nella donazione d’organo, come primo motivo per partecipare
al programma di donazione.
Conclusioni: Questo studio fornisce un modello per capire il punto di vista dello staff
pediatrico sul programma di DCD nei bambini. I risultati forniscono parecchi elementi
che possono essere utili per iniziare un dialogo interdisciplinare e strutturare le pratiche
istituzionali necessarie per definire un modello di programma di DCD.
Parole chiave: Donatore d’organo a cuore non battente, donazione d’organo, trapianto,
sospensione del supporto vitale, bambino, genitori, gruppo di studio, analisi qualitativa.
ASSESSMENT OF PARENTAL PRESENCE DURING BEDSIDE PE-
DIATRIC INTENSIVE CARE UNIT ROUNDS: THE IMPACT ON DU-
RATION, TEACHING, AND PRIVACY
VALUTAZIONE DELLA PRESENZA DEI FAMILIARI DURANTE IL
GIRO AL LETTO DEL PAZIENTE IN TERAPIA INTENSIVA PEDI-
ATRICA: IMPATTO SULLA DURATA, L’INSEGNAMENTO E LA
RISERVATEZZA
Lorri M. Phipps, MSN, CPNP, Cheryl N. Bartke, MSN, CPNP, Debra A. Spear,
RN, CCRN, Linda F. Jones, RN, CCRN, Carolyn P. Foerster, RN, BSN, CCRN,
Marie E. Killian, RN, BSN, CCRN, Jennifer R. Hughes, RN, BSN, Joseph C.
Hess, RN, BSN, David R. Johnson, PhD, and Neal J. Thomas, MD, MSc
Riassunto
Obiettivo: Esiste poca letteratura che valuta l’effetto della presenza di un membro della
famiglia del paziente durante il giro al letto del paziente in Terapia Intensiva Pediatrica
(PICU). Abbiamo ipotizzato che, quando il giro è effettuato senza la presenza dei familiari,
la presenza del genitore potrebbe far aumentare il tempo impiegato per il giro, ridurre la
possibilità dell’insegnamento dello staff medico, aumentare l’insoddisfazione dello staff,
creare più ansia nei membri della famiglia e violare la riservatezza del paziente.
Disegno: Studio prospettico, cieco, di osservazione.
Ambiente: PICU di 12 posti letto in ambiente accademico.
Partecipanti: Sono state studiate 105 accettazioni. 81 membri della famiglia completarono il
questionario. 187 questionari sono stati completati dallo staff medico.
Interventi: I ricercatori hanno documentato la presenza dei parenti e il tempo impiegato
per la presentazione del caso, l’insegnamento e la risposta alle domande poste. I ques-
tionari che facevano riferimento agli obiettivi, all’insegnamento e alla riservatezza furono
distribuiti ai partecipanti.
Misurazioni: Tempo speso nell’effettuare il giro, tempo speso nell’insegnamento, percezione della
famiglia e dello staff sull’impatto che ha la presenza dei parenti sul giro al letto del paziente.
Risultati: Non ci fu differenza significativa nel tempo impiegato per effettuare il giro
rispetto alla presenza o meno di un membro della famiglia (p ⫽ NS) né ci fu significativa
differenza nel tempo impiegato nell’insegnamento (p ⫽ NS). I genitori riferirono che il
team medico spese un sufficiente periodo discutendo del loro bambino ed essi non inter-
vennero nella discussione. I genitori non ebbero la sensazione che la riservatezza del
proprio bambino fosse violata durante il giro. La maggior parte dei medici riferirono che
la presenza dei familiari durante il giro fu di beneficio.
Conclusioni: La presenza dei genitori durante il giro non sembra interferire sul processo
di insegnamento e di comunicazione. I genitori riferirono di essere rimasti soddisfatti
della partecipazione e che dal loro punto di vista non ci fosse stata la percezione che la
riservatezza del bambino fosse stata violata.
Parole chiave: Pediatria, Giro medico, Giro al letto del malato, PICU, Presenza dei genitori.
312
INCREASING USE OF EXTRACORPOREAL LIFE SUPPORT IN
MRSA SEPSIS IN CHILDREN
AUMENTO DELL’IMPIEGO DEL SUPPORTO EXTRACORPOREO
(ECLS) NELLA SEPSI MRSA NEL BAMBINO
C. Buddy Creech, MD, MPH, Belinda Johnson, RN, Randall Bartilson, RN,
Edmund Yang, MD, PhD Frederick Barr, MD, MSCI
Riassunto
Conoscenze di base: Sono stati pubblicati casi di infezioni fulminanti da Staphylococcus
aureus (CA-MRSA) che hanno richiesto un supporto extracorporeo (ECLS) ma la fre-
quenza dell’impiego della ECLS nelle forme gravi di patologia da stafilococco non è
conosciuta.
Obiettivo: Descrivere la frequenza e le caratteristiche dei bambini con infezioni MRSA che
hanno richiesto la ECLS mediante l’impiego di database nazionali ed internazionali.
Metodi: I motivi dell’impiego della ECLS nei bambini di età tra 0 - 18 anni furono
determinati sia dalle cartelle cliniche del Vanderbilt Children’s Hospital sia dal database
dell’Extracorporeal Life Support Organization (ELSO) per gli anni compresi tra il 1994 e
il 2005. Furono analizzati le caratteristiche demografiche, il trattamento ventilatorio e le
condizioni cardiopolmonari dei soggetti sottoposti a ECLS che avevano avuto una diagnosi
pre-ECLS di infezione da Staphylococcus aureus e MRSA.
Risultati: Tre soggetti con sepsi e MRSA, che hanno richiesto la ECLS, sono stati
identificati al Vanderbilt dal 2000. Prima di questa epoca non sono stati riscontrati casi
di MRSA. Tutti e tre gli adolescenti erano sani prima della comparsa di una grave
polmonite necrotizzante associata ad infezione della cute o dei tessuti molli e due di essi
sono deceduti. 45 pazienti che hanno richiesto la ECLS per infezione da MRSA furono
identificati nel International ELSO Database di cui circa la metà si riferivano agli ultimi
due anni (20/45). L’età media fu di 2.4 anni (IQ range: 0.36 y - 14 y), con picchi più elevati
nel lattante e nell’adolescente. Nei soggetti sottoposti ad ELSO per MRSA, la sopravvi-
venza alla dimissione fu maggiore nei lattanti e nei bambini più piccoli che avevano un’età
compresa tra 1-4 anni (65% e 71%, rispettivamente) e più bassa nei bambini tra 5-9 anni
e tra 13-18 anni (0% e 31%, rispettivamente). Non ci furono significative variazioni
statistiche nel modello ventilatorio impiegato in fase pre-ECLS, nelle condizioni car-
diopolmonari, o nella frequenza di complicanze tra sopravvissuti e non sopravvissuti.
Conclusioni: L’impiego del ECLS per infezione MRSA sembra essere in aumento sia
localmente sia a livello internazionale. L’alta incidenza di mortalità, particolarmente nei
bambini più grandi appare preoccupante ed evidenzia il crescente rischio a cui espone
questo patogeno.
Parole chiave: Staphylococcus, sepsi, ECMO, MRSA, adolescenti, ECLS.
IMPLEMENTATION OF A MEDICAL EMERGENCY TEAM IN A
LARGE PEDIATRIC TEACHING HOSPITAL PREVENTS RESPIRA-
TORY AND CARDIOPULMONARY ARRESTS OUTSIDE THE ICU
LO SVILUPPO DI UN GRUPPO PER L’EMERGENZA MEDICA IN UN
GRANDE OSPEDALE D’INSEGNAMENTO PREVIENE L’ARRESTO
RESPIRATORIO E CARDIOPOLMONARE FUORI DALLA TERAPIA
INTENSIVA
Richard J. Brilli, MD, FCCM, FAAP, Rosemary Gibson, RN, CNS, Joseph W.
Luria, MD, FAAP, T. Arthur Wheeler, MS, MBA, Julie Shaw, MSN, MBA,
RN, Matt Linam, MD, John Kheir, MD, Patricia McLain, RN, Tammy Ling-
sch, RN, Amy Hall, RN, Mary McBride, MD
Riassunto
Obiettivo: Implementare un Medical Emergency Team (MET) all’interno di un ospedale
pediatrico. Lo scopo specifico fu quello di ridurre l’incidenza della frequenza dell’arresto
respiratorio e cardiorespiratorio, in ambiente esterno alle terapie intensive, del 50% nei
sei mesi successivi all’implementazione del MET.
Metodi: Sono state riviste le cartelle cliniche dei pazienti che hanno richiesto una rian-
imazione cardiorespiratoria all’esterno dell’area intensiva prima dell’implementazione
del MET, al fine di definire i codici di attivazione per il MET. I codici facevano riferimento
prospetticamente ad arresto respiratorio e cardiorespiratorio. I codici di previsione del
MET furono definiti prospetticamente. Fu rilevata l’incidenza dei codici prima e dopo
l’implementazione del MET.
Risultati: 25 codici si presentarono nel periodo pre-MET in confronto a 6 che fecero seguito
all’implementazione del MET. Il codice di frequenza (arresti respiratori ⫹ arresti cardio-
respiratori) post-MET fu dello 0.11 per 1000 pazienti per giorni rispetto al basale di 0.27:
risk ratio 0.42 (95% CI 0 – 0.89; p ⫽ 0.03). La frequenza del codice per 1000 accettazioni
diminuı̀ da 1.54 (livello basale) a 0.62 (post MET): risk ratio 0.41 (0 – 0.86; p ⫽ 0.02). Per
i codici in cui era prevedibile il MET, la frequenza del codice post-MET fu 0.04 per 1000
pazienti per giorni rispetto al basale di 0.14: risk ratio of 0.27 (95% CI 0 – 0.94; p ⫽ 0.04).
Non ci fu differenza nell’incidenza dell’arresto cardiorespiratorio pre e post MET. Per i
codici fuori della terapia intensiva, la frequenza di mortalità pre-MET fu di 0.12 per 1000
giorni rispetto a 0.06 post MET: risk ratio 0.48 (95% CI 0 – 1.4, p ⫽ 0.13). La frequenza
di mortalità totale per i codici fuori dalla terapia intensiva fu del 42% (15 su 36 pazienti).
Conclusioni: La creazione di un MET si associa con una riduzione del rischio di arresto
respiratorio e cardiorespiratorio all’esterno della area intensiva in un grande ospedale
pediatrico di terzo livello.
Parole chiave: Arresto cardiorespiratorio, arresto respiratorio, pediatria, bambino, sis-
temi a rapida risposta, gruppo di emergenza medica.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
Pediatr Crit Care Med 2007 Vol. 8, No. 3 313
PEDIATRIC STAFF PERSPECTIVES ON ORGAN DONATION AF-
TER CARDIAC DEATH IN CHILDREN
PERSPECTIVAS DO PESSOAL CLÍNICO PEDIÁTRICO SOBRE A
DOAÇÃO DE ÓRGÃOS APÓS MORTE CARDÍACA
Martha A.Q. Curley, RN, PhD, FAAN; Charlotte H. Harrison, JD, MPH,
MTS; Nancy Craig, RRT; Craig W. Lillehei, MD, FAAP, FACS; Anne Micheli,
RN, MS; Peter C. Laussen, MBBS
Resumo
Objectivo: O objectivo deste trabalho é descrever se o pessoal clı́nico pediátrico acredita,
ou não, que um programa de doação de órgãos após morte cardı́aca (DOMC) pode ser
enquadrado na missão e nos valores essenciais de um hospital pediátrico, bem como
identificar os itens que o pessoal considera essenciais para a aceitação de um programa
deste tipo.
Métodos: Estudo qualitativo, em que os dados foram recolhidos durante a realização de 8
reuniões de grupo, entre o pessoal clı́nico de um hospital pediátrico, entre Março e Abril
de 2005.
Resultados: Participaram 88 membros do pessoal clı́nico. A análise qualitativa dos dados
evidenciou seis temas principais: 1) identificação de crianças candidatas a DOMC; 2)
consideração de quais são os melhores interesses da crianças em morte eminente; 3)
aproximação aos pais em relação à DOMC; 4) preparação dos pais para a DOMC dos seus
filhos; 5) necessidade de um correcto funcionamento do programa de DOMC; e 6) ma-
nutenção da integridade do programa. Estes temas principais foram usados para con-
struir uma metodologia conceptual para descrever um modelo pediátrico. O pessoal clı́nico
mencionou numerosos receios. Contudo, estes identificaram “a necessidade de corre-
sponder às famı́lias” que manifestaram o desejo de participar na doação de órgãos como
sendo a principal razão para a adopção deste tipo de programa.
Conclusões: Este estudo providencia uma metodologia para o conhecimento das perspec-
tivas do pessoal clı́nico pediátrico em relação a programas de DOMC em crianças. Os
resultados sugerem vários itens que podem ser úteis para o diálogo interdisciplinar e para
a formação de práticas institucionais, no desenho de programas de DOMC.
ASSESSMENT OF PARENTAL PRESENCE DURING BEDSIDE PE-
DIATRIC INTENSIVE CARE UNIT ROUNDS: THE IMPACT ON DU-
RATION, TEACHING, AND PRIVACY
AVALIAÇÃO DA PRESENÇA PARENTAL DURANTE AS PASSA-
GENS DE TURNO Á CABECEIRA DOS DOENTES, NA UNIDADE DE
CUIDADOS INTENSIVOS PEDIÁTRICOS: IMPACTO NA DURAÇÃO,
ENSINO E PRIVACIDADE
Lorri M. Phipps, MSN, CPNP, Cheryl N. Bartke, MSN, CPNP, Debra A. Spear,
RN, CCRN, Linda F. Jones, RN, CCRN, Carolyn P. Foerster, RN, BSN, CCRN,
Marie E. Killian, RN, BSN, CCRN, Jennifer R. Hughes, RN, BSN, Joseph C.
Hess, RN, BSN, David R. Johnson, PhD, and Neal J. Thomas, MD, MSc.
Resumo
Objectivo: Existe uma escassez de literatura que avalie os efeitos da presença de um elemento
da famı́lia durante as passagens de turno na Unidade de Cuidados Intensivos Pediátricos
(UCIP). Os autores colocam a hipótese de quando se comparam com as mesmas passagens de
turno sem familiares, a presença parental durante as passagens matinais poderá aumentar
o tempo gasto nas mesmas, diminuir o tempo de educação/ensino médico, aumentar a
insatisfação da equipa clı́nica, criar maior desconforto nos elementos da famı́lia e violar a
privacidade do doente (a unidade dos autores é uma UCIP aberta).
Desenho: Estudo prospectivo, cego e de observação.
Local: UCIP académica com 12 camas.
População: Foram estudadas 105 admissões. Completaram o inquérito 81 familiares.
Foram preenchidos pela equipa médica 187 inquéritos.
Intervenções: Os investigadores documentaram a presença parental e o tempo utilizado
para a apresentação, ensino e colocação de questões. Inquéritos referindo-se à percepção
dos objectivos, ensino e privacidade das passagens foram distribuı́dos aos participantes.
Medidas: Tempo dispendido nas passagens, no ensino nas mesmas, percepção pela equipa
médica e famı́lia do impacto da presença parental nas passagens de turno
Resultados: Não se observaram diferenças significativas entre o tempo gasto nas passa-
gens de turno, com a presença ou ausência de membros da famı́lia do doente (p⫽NS). Não
se observaram diferenças significativas entre o tempo gasto no ensino pelo médico re-
sponsável na presença ou ausência de familiares (p⫽NS). Globalmente os familiares
referiram que a equipa médica despendeu uma quantidade apropriada de tempo dis-
cutindo sobre a sua criança, não tendo ficado aborrecidos com a referida discussão. Os pais
não consideram que a sua privacidade, bem como a do seu filho, tenha sido violada
durante as passagens. A maioria dos elementos da equipa médica referiu que a presença
dos familiares durante as passagens foi benéfica.
Conclusões: A presença parental nas passagens de turno não parece interferir com o
processo de comunicação bem como de educação. Os pais referem satisfação com a
participação nas passagens de turno e as violações da privacidade não parecem ser uma
preocupação, no ponto de vista dos familiares.
314
INCREASING USE OF EXTRACORPOREAL LIFE SUPPORT IN
MRSA SEPSIS IN CHILDREN
AUMENTO DA UTILIZAÇÃO DO SUPORTE DE VIDA EXTRA-COR-
PORAL EM CRIANÇAS COM SEPSIS POR MRSA
C. Buddy Creech, MD, MPH, Belinda Johnson, RN, Randall Bartilson, RN,
Edmund Yang, MD, PhD, Frederick Barr, MD, MSCI
Resumo
Introdução: Têm sido descritos casos pediátricos de infecções fulminantes por Staphylo-
coccus aureus meticilino-resistente (MRSA) com origem na comunidade, com necessidade
de suporte de vida extra-corporal (SVEC), mas a frequência da utilização de SVEC para
apresentações graves de doença estafilocócica é desconhecida.
Objectivo: Descrever a frequência e as caracterı́sticas das crianças com infecções por
MRSA com necessidade de SVEC, usando bases de dados locais e internacionais.
Métodos: O motivo da utilização do SVEC em crianças com idade entre 0-18 anos foi
determinado através do sistema de registo clı́nico do “Vanderbilt Children’s Hospital” e da
base de dados da “Extracorporeal Life Support Organozation” (ELSO), durante os anos de
1994-2005. Foram incluı́das as crianças submetidas a SVEC, com diagnóstico pré-SVEC
de infecção por Staphylococcus aureus e MRSA, em relação a caracterı́sticas demográfi-
cas, parâmetros ventilatórios e medidas do estado cárdiopulmonar.
Resultados: No hospital de Vanderbilt, foram identificados, desde 2000, três crianças com
sepsis por MRSA que necessitaram de SVEC. Antes dessa data não foi descrito nenhum
caso devido a MRSA. Todos eram adolescentes previamente saudáveis com pneumonia
necrosante associada a infecções da pele/tecidos moles e dois deles faleceram. Na base de
dados internacional da ELSO foram identificados 45 crianças com necessidade de SVEC
por infecção por MRSA, com quase metade identificados nos últimos dois anos (20/45). A
mediana da idade foi de 2,4 anos (P25-P75: 0,36-14 anos), com picos observados nos
lactentes e adolescentes. Nas crianças com MRSA do registo da ELSO a sobrevivência
hospitalar foi mais alta em lactentes e crianças com idades 1-4 anos (65% e 71%,
respectivamente) e mais baixa no grupo dos 5-9 anos e 13-18 anos (0% e 31%, respectiva-
mente). Não se verificaram diferenças com significado estatı́stico, entre os sobreviventes
e os falecidos, nos parâmetros ventilatórios pré-SVEC, estado cárdiopulmonar ou frequên-
cia de complicações.
Conclusões: O uso de SVEC para infecções por MRSA parece estar a aumentar quer
localmente quer a nı́vel internacional. As elevadas taxas de mortalidade, em particular
em crianças mais velhas, são preocupantes e realçam os crescentes problemas com
infecções por este patogéneo.
IMPLEMENTATION OF A MEDICAL EMERGENCY TEAM IN A
LARGE PEDIATRIC TEACHING HOSPITAL PREVENTS RESPIRA-
TORY AND CARDIOPULMONARY ARRESTS OUTSIDE THE ICU
A IMPLEMENTAÇÃO DE UMA EQUIPA DE EMERGÊNCIA MÉDICA
NUM HOSPITAL PEDIÁTRICO ESCOLAR PREVINE PARAGENS
RESPIRATÓRIAS E CÁRDIO-PULMONARES FORA DA UCI
Richard J. Brilli, MD, FCCM, FAAP, Rosemary Gibson, RN, CNS, Joseph W.
Luria, MD, FAAP, T. Arthur Wheeler, MS, MBA, Julie Shaw, MSN, MBA,
RN, Matt Linam, MD, John Kheir, MD, Patricia McLain, RN, Tammy Ling-
sch, RN, Amy Hall, RN, Mary McBride, MD
Resumo
Objectivo: Os autores implementaram uma Equipa de Emergência Médica (EEM) no seu
hospital pediátrico. O objectivo especı́fico foi o de reduzir os “códigos” (paragem respira-
tória e cárdio-pulmonar) fora das unidades de cuidados intensivos (UCI) em 50% num
perı́odo superior a 6 meses após a implementação da EEM.
Métodos: Os registos de doentes que necessitaram de reanimação cárdio-respiratória fora
da UCI foram revistos, antes da implementação da EEM, de modo a determinar critérios
de activação para a EEM. Os “códigos” foram definidos, prospectivamente, como paragens
respiratórias ou cárdio-pulmonares. “Códigos prevenı́veis pela EEM” foram definidos
prospectivamente. A incidência de “códigos” pré e pós implementação da EEM foram
registados.
Resultados: Ocorreram 25 “códigos” durante a fase pré implementação da EEM compara-
tivamente aos 6 “códigos” ocorridos após a implementação da EEM. A frequência dos
“códigos” (paragens respiratórias ⫹ paragens cárdio-pulmonares) após-EEM foi de 0,11
por 1000 doentes comparativamente à linha de base de 0,27: razão de risco 0,42 (IC95%:
0 - 0,89; p⫽0,03). A frequência dos “códigos” por 1000 admissões diminuiu de 1,54 (valor
basal) para 0,62 (após-EEM): razão de risco 0,41 (IC95%: 0 - 0,86; p⫽0,02). Relativamente
aos “códigos prevenı́veis pela EEM”, a frequência dos “códigos” após-EEM foi de 0,04 por
1000 dias de internamento comparativamente ao valor de base de 0,14: razão de risco de
0,27 (IC95%: 0 - 0,94; p⫽0,04). Não houve diferença na incidência de paragens cárdio-
pulmonares antes e depois da EEM. Para “códigos” fora da UCI a taxa de mortalidade
pré-EEM foi de 0,12 por 1000 dias comparativamente a 0,06 após perı́odo de EEM: razão
de risco 0,48 (IC95%: 0 - 1,4; p⫽0,13). A taxa de mortalidade global para “códigos” fora da
UCI foi de 42% (15 dos 36 doentes).
Conclusões: A implementação de uma EEM esta associada a uma redução do risco de
paragens respiratórias e cárdio-pulmonares fora das áreas de cuidados crı́ticos, num
grande hospital pediátrico terciário.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
PEDIATRIC STAFF PERSPECTIVES ON ORGAN DONATION AF-
TER CARDIAC DEATH IN CHILDREN
PERSPECTIVAS DEL EQUIPO MÉDICO SOBRE LA DONACIÓN DE
ÓRGANOS LUEGO DE LA MUERTE CARDÍACA EN NIÑOS
Martha A.Q. Curley, RN, PhD, FAAN; Charlotte H. Harrison, JD, MPH,
MTS; Nancy Craig, RRT; Craig W. Lillehei, MD, FAAP, FACS; Anne Micheli,
RN, MS; Peter C. Laussen, MBBS
Resumen
Objetivos: los objetivos de este proyecto fueron describir si el equipo médico consideraba,
o no, que el programa de donación, luego de la muerte cardı́aca (DCD) podrı́a estar de
acuerdo con la misión y los valores centrales del hospital e identificar qué es considerado
esencial por parte del equipo médico, para la aceptabilidad del programa.
Métodos: es un estudio cualitativo en el cual la información fue obtenida del equipo médico
a partir de ocho grupos especı́ficos, llevado a cabo en el hospital de niños entre marzo y
abril de 2005.
Mediciones y principales resultados: participaron 88 miembros del equipo médico. Hubo
seis temas principales que surgieron del análisis cualitativo: 1) la identificación de los
niños candidatos para DCD; 2) la consideración de los mejores intereses del niño muri-
ente; 3) el abordaje de los parientes sobre el DCD; 4) la preparación de los parientes para
el DCD del niño; 5) la necesidad de realizar el DCD correctamente; 6) el mantenimiento
de la integridad del programa.. Estos temas fueron utilizados para construir un marco
conceptual para la descripción del modelo pediátrico de DCD. El equipo médico manifestó
numerosas preocupaciones. Sin embargo, identificaron como la principal razón para la
adopción del programa que éste serı́a en beneficio de las familias que manifestaran un
deseo de participar en la donación de órganos.
Conclusiones: este estudio brinda un marco para el entendimiento de las perspectivas del
equipo médico sobre los programas pediátricos de DCD. Los resultados sugieren diversos
posibles elementos que pueden ser de ayuda para un diálogo multidisciplinario ası́ como
para la información de las prácticas institucionales en el diseño de un programa pedi-
átrico de DCD.
ASSESSMENT OF PARENTAL PRESENCE DURING BEDSIDE PE-
DIATRIC INTENSIVE CARE UNIT ROUNDS: THE IMPACT ON DU-
RATION, TEACHING, AND PRIVACY
EVALUACIÓN DE LA PRESENCIA DE LOS PADRES JUNTO A LA
CAMA DEL PACIENTE DURANTE LAS RECORRIDAS DE SALA EN
LA UNIDAD DE CUIDADOS INTENSIVOS PEDIÁTRICOS: IM-
PACTO EN LA DURACIÓN, LA DOCENCIA Y LA PRIVACIDAD
Lorri M. Phipps, MSN, CPNP, Cheryl N. Bartke, MSN, CPNP, Debra A. Spear,
RN, CCRN, Linda F. Jones, RN, CCRN, Carolyn P. Foerster, RN, BSN, CCRN,
Marie E. Killian, RN, BSN, CCRN, Jennifer R. Hughes, RN, BSN, Joseph C.
Hess, RN, BSN, David R. Johnson, PhD, and Neal J. Thomas, MD, MSc
Resumen
Objetivo: existe poca literatura que evalúe los efectos de la presencia de un familiar junto a la
cama del paciente durante las recorridas de sala en la Unidad de Cuidados Intensivos
Pediátricos (PICU). Nuestra hipótesis es que, en comparación con las recorridas sin los
familiares, la presencia de los padres durante las recorridas médicas matinales provocarı́a un
incremento del tiempo de las recorridas, disminuirı́a el aporte de enseñanza/educación médi-
cas, aumentarı́a la insatisfacción del grupo médico, se provocarı́a más estrés en los familiares
y se vioları́a la privacidad de los pacientes en las unidades abiertas.
Diseño: estudio observacional, prospectivo y cegado.
Ubicación: una PICU académica con 12 camas.
Participantes: se estudiaron 105 internaciones. Ochenta y un familiares complet-
aron la encuesta y se completaron 187 respuestas médicas al estudio.
Intervenciones: los investigadores documentaron la presencia de los padres y el tiempo
asignado a la presentación, a la docencia y a las respuestas de preguntas. Se distribuy-
eron, entre los participantes, encuestas sobre la percepción de objetivos, docencia, y
privacidadde las recorridas.
Mediciones: se evaluó el tiempo empleado en las recorridas, en la enseñanza durante las
mismas, y en la percepción, tanto por parte de los médicos como de los familiares sobre la
presencia de los padres en ellas.
Resultados: no hubo diferencias significativas en el tiempo empleado en las recorridas con
la presencia de los familiares o sin ellos. (p⫽NS). Tampoco hubo diferencias significativas
en el tiempo empleado para la enseñanza por parte de los médicos de planta (p⫽NS). En
general, los pacientes respondieron que los médicos dedicaron una cantidad de tiempo
adecuada para discutir sobre su hijo y no se sintieron molestos por el debate. No hubo una
percepción, por parte de los padres, en el sentido de que tanto su propia privacidad como
la de su hijo hubiese sido violada durante las recorridas. La mayorı́a de los miembros del
equipo médico informaron que la presencia familiar en las recorridas fue beneficiosa.
Conclusiones: la presencia de los padres en las recorridas de sala no parece interferir con
los procesos educativos ni de comunicación. Los padres manifestaron su satisfacción por
participar en las recorridas y, desde su perspectiva, no parece haber habido preocupación
con respecto a la violación de su privacidad.
Pediatr Crit Care Med 2007 Vol. 8, No. 3
INCREASING USE OF EXTRACORPOREAL LIFE SUPPORT IN
MRSA SEPSIS IN CHILDREN
AUMENTO DE LA UTILIZACIÓN DEL SOPORTE VITAL EXTRA-
CORPÓREO EN LOS NIÑOS CON SEPSIS POR MRSA
C. Buddy Creech, MD, MPH, Belinda Johnson, RN, Randall Bartilson, RN,
Edmund Yang, MD, PhD Frederick Barr, MD, MSCI
Resumen
Antecedentes: aun cuando han surgido informes de casos pediátricos de infecciones ful-
minantes asociadas a Staphylococcus aureus meticilino-resistente (CA-MRSA) de la co-
munidad que requirieron soporte vital extracorpóreo (ECLS), la frecuencia del uso de
ECLS en las formas clı́nicas severas de enfermedad estafilocócica es desconocida.
Objetivo: describir la frecuencia y las caracterı́sticas de los niños con infección por MRSA
que requirieron ECLS, utilizando bases de datos locales e internacionales.
Métodos: las razones para la utilización de ECLS en niños de 0 a 18 años de edad fueron
tomadas del sistema de registros médicos del Hospital de Niños de Vanderbilt y de la base
de datos de la Organización de Soporte Vital Extracorpóreo (ELSO) durante el perı́odo
1994-2005. Se incluyeron las caracterı́sticas demográficas, el manejo ventilatorio y las
mediciones del estado cardiopulmonar en los sujetos bajo ECLS con diagnóstico pre-ECLS
de infección por Staphylococcus aureus y MRSA.
Resultados: desde el año 2000 se identificaron tres pacientes con sepsis por MRSA que
requirieron ECLS en Vanderbilt. No hubo informes de casos por MRSA previos. Todos
resultaron adolescentes previamente sanos con neumonı́a necrosante severa y con infección
de piel o partes blandas. Dos de ellos fallecieron. En la base de datos de la ELSO Internacional
se identificaron cuarenta y cinco pacientes que requirieron ECLS por infección causada por
MRSA. Aproximadamente la mitad de éstos (20/45) fueron comunicados en los últimos dos
años. La mediana de la edad fue 2,4 años (rango de IQ: 0,36 años -14 años), observándose
picos en la infancia y en la adolescencia. En los pacientes del ELSO con MRSA, la sobrevida
al egreso fue mayor en la infancia y en los niños jóvenes, cuyas edades eran 1 - 4 años (65 %
y 71 %, respectivamente) y menor en las edades comprendidas entre 5 - 9 y 13 - 18 años (0 %
y 31 %, respectivamente). No hubo diferencias estadı́sticamente significativas en los
parámetros ventilatorios pre-ECLS, en el estado cardiopulmonar o en la frecuencia de
complicaciones entre los sobrevivientes y los no sobrevivientes.
Conclusiones: la utilización de ECLS en los pacientes con infección por MRSA parece estar
aumentando, tanto a nivel local como internacional. Las altas tasa de mortalidad, par-
ticularmente en los pacientes mayores, son preocupantes y resaltan el problema creciente
de este patógeno.
IMPLEMENTATION OF A MEDICAL EMERGENCY TEAM IN A
LARGE PEDIATRIC TEACHING HOSPITAL PREVENTS RESPIRA-
TORY AND CARDIOPULMONARY ARRESTS OUTSIDE THE ICU
LA IMPLEMENTACIÓN DE UN EQUIPO DE EMERGENCIAS MÉDI-
CAS EN UN GRAN HOSPITAL PEDIÁTRICO DOCENTE PREVIENE
LOS PAROS CARDIOPULMONAR FUERA DE LA UNIDAD DE
CUIDADOS INTENSIVOS
Richard J. Brilli, MD, FCCM, FAAP, Rosemary Gibson, RN, CNS, Joseph W.
Luria, MD, FAAP, T. Arthur Wheeler, MS, MBA, Julie Shaw, MSN, MBA,
RN, Matt Linam, MD, John Kheir, MD, Patricia McLain, RN, Tammy Ling-
sch, RN, Amy Hall, RN, Mary McBride, MD
Resumen
Objetivo: hemos implementado un Equipo de Emergencias Médicas (MET) en nuestro
hospital de niños autónomo. El objetivo especı́fico fue reducir un 50 % la tasa de códigos
de llamado (paro respiratorio o cardiopulmonar) fuera de las Unidades de Cuidados
Intensivos (ICUs) durante más de 6 meses luego de la implementación del MET.
Métodos: se revisaron los registros de los pacientes que requirieron reanimación cardio-
respiratoria fuera de las áreas crı́ticas antes de la implementación del MET para deter-
minar los criterios de activación de este equipo. En forma prospectiva se definieron los
códigos como paro respiratorio o paro cardiopulmonar. Se definieron, prospectivamente,
códigos prevenibles por el MET. Se registró la incidencia de los códigos antes y después de
la implementación del MET.
Resultados: durante en la etapa basal pre MET ocurrieron 25 códigos, en comparación con
los 6 que siguieron a la implementación del MET. La tasa de códigos (paros cardı́acos ⫹
paros respiratorios) pos MET fue 0,11 por 1000 pacientes dı́as, en comparación con una
tasa basal de 0,27: tasa de riesgo 0,42 (IC 95% 0-0,89; p ⫽ 0,003). La tasa de códigos por
1000 internaciones disminuyó de 1,54 (basal) a 0,62 (pos MET): tasa de riesgo 0,41 (IC
95% 0-0,86; p ⫽ 0,02). Para los códigos prevenibles por el MET, la tasa de códigos pos MET
fue 0,04 por 1000 pacientes dı́a, en comparación con el valor basal de 0,14: tasa de riesgo
0,27 (IC 95% 0-0,94; p ⫽ 0,04). No hubo diferencias en la incidencia de paro cardiopul-
monar pre y pos MET. Para los códigos fuera de la ICU, la tasa mortalidad pre MET fue
0,12 por 1000 dı́as, en comparación con 0,06 del perı́odo pos MET: tasa de riesgo 0,48 (IC
95% 0-1,4; p ⫽ 0,13). La tasa de mortalidad global para los códigos fuera de la ICU fue
42% (15 de 36 pacientes).
Conclusiones: la implementación de un MET está asociada a una reducción en el riesgo de
paro respiratorio o cardiopulmonar fuera de las áreas crı́ticas en un gran hospital
pediátrico terciario.
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