Peripartum Cardiomyopathy: Review and Practice Guidelines

Leah Johnson-Coyle, Louise Jensen and Alan Sobey

Am J Crit Care 2012;21:89-98 doi: 10.4037/ajcc2012163
2012 American Association of Critical-Care Nurses
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C ardiovascular Critical Care

ERIPARTUM

CARDIOMYOPATHY:
REVIEW AND PRACTICE
GUIDELINES
By Leah Johnson-Coyle, RN, MN, Louise Jensen, RN, PhD, and Alan Sobey, MD

2012 American Association of Critical-Care Nurses

doi: http://dx.doi.org/10.4037/ajcc2012163

www.ajcconline.org

Peripartum cardiomyopathy, a type of dilated cardiomyopathy

of unknown origin, occurs in previously healthy women in the
final month of pregnancy and up to 5 months after delivery.
Although the incidence is lowless than 0.1% of pregnancies
morbidity and mortality rates are high at 5% to 32%. The
outcome of peripartum cardiomyopathy is also highly variable.
For some women, the clinical and echocardiographic status
improves and sometimes returns to normal, whereas for others, the disease progresses to severe cardiac failure and even
sudden cardiac death. In acute care, treatment may involve
the use of intravenous vasodilators, inotropic medications, an
intra-aortic balloon pump, ventricular-assist devices, and/or
extracorporeal membrane oxygenation. Survivors of peripartum
cardiomyopathy often recover from left ventricular dysfunction;
however, they may be at risk for recurrence of heart failure
and death in subsequent pregnancies. Women with chronic
left ventricular dysfunction should be managed according to
guidelines of the American College of Cardiology Foundation
and the American Heart Association. (American Journal of
Critical Care. 2012;21(2):89-98)

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eripartum cardiomyopathy (PPCM) is a type of dilated cardiomyopathy of unknown

origin. It occurs in previously healthy women in the final month of pregnancy and
up to 5 months after delivery.1 Although the incidence is lowless than 0.1% of
pregnanciesmorbidity and mortality rates are high, ranging from 5% to 32%.2,3
For some women, the clinical and echocardiographic status improve and may
return to normal, whereas for others, PPCM progresses to cardiac failure and even sudden
cardiac death.4 In severe cases, women experience a rapid deterioration in health, show no
improvement with medical therapy, and may require cardiac transplantation or die of heart
failure, thromboembolic events, and/or cardiac arrhythmias.5 Thus, initial severity of left ventricular dysfunction or dilatation is not necessarily predictive of long-term functional outcome.5
In this article, we review PPCM and present guidelines for practice.

Epidemiology
The reported incidence of PPCM varies because
the diagnosis is not always consistent and a comparison with age-matched nonpregnant women does
not exist.4,6,7 Reported incidences range from 1 in
299 live births in Haiti8 to 1 in 2229 live births in
Southern California9 to 1 in 4000 live births in the
United States.4 The wide variation most likely is the
result of geographic differences and
reporting patterns.10 Also, limited access
to echocardiography in some areas
may lead to overestimation of PPCM.11
Several risk factors predispose a
woman to PPCM, including increased
maternal age, multiparity, multiple
pregnancies, and pregnancies complicated by preeclampsia and gestational
hypertension.4,6,12 Although PPCM
occurs more frequently in women at
the upper and lower extremes of child-bearing ages
and in older women of higher parity,4,13 the disease
has also been reported in 24% to 37% of young
primigravid women.3,6,14 In contrast, the results of a
large population-based study from Haiti suggested
that multiparity and increasing maternal age are not
risk factors.8 Demakis et al12 and Brar et al15 found

Initial severity
of left ventricular
dysfunction is
not necessarily
predictive of
long-term outcome.

About the Authors

Leah Johnson-Coyle is a nurse practitioner in cardiac
sciences and Alan Sobey is an intensive care physician
in the cardiovascular surgery intensive care unit at the
Mazankowski Alberta Heart Institute, University of Alberta
Hospital, Edmonton, Alberta, Canada. Louise Jensen is
a professor in the Faculty of Nursing at the University of
Alberta in Edmonton.
Corresponding author: Louise Jensen, RN, PhD, Professor,
Faculty of Nursing, 3rd Floor, Edmonton Clinic Health
Academy, University of Alberta, Edmonton, AB, Canada
T6G 1C9 (e-mail: louise.jensen@ualberta.ca).

90

that African American women were 2.9 times more

likely to have PPCM than were white women and 7
times more likely than were Hispanic women. The
greater incidence of hypertension in African Americans may influence this finding.4,7

Etiology
PPCM is distinguished from other forms of
cardiomyopathies by its occurrence during pregnancy.16 Precise mechanisms that lead to PPCM
remain poorly defined. Many etiological processes
have been suggested: viral myocarditis, abnormal
immune response to pregnancy, maladaptive response
to hemodynamic stresses of pregnancy, stress-activated
cytokines, excessive prolactin excretion, and prolonged tocolysis.4,10,17,18 Also, a familial predisposition
to PPCM has been reported.19-21 Although underlying genetic variants common to dilated cardiomyopathies are being proposed,22 a genetic basis specific
to PPCM has not been systematically studied.23 The
European Society of Cardiology currently classifies
PPCM as a nonfamilial, nongenetic form of dilated
cardiomyopathy.24

Viral Myocarditis
Viral myocarditis has been proposed as the main
mechanism for PPCM and was first reported by
Goulet et al.25 This proposal was later supported by
Melvin et al,26 who found myocarditis during endomyocardial biopsy in 3 women with PPCM. The biopsy
specimens had dense lymphocytic infiltration with
a variable amount of myocytic edema, necrosis, and
fibrosis. Others27 have also reported an association
between PPCM and viral myocarditis. In a study by
Felker et al,28 62% of women with PPCM had
myocarditis or borderline myocarditis on biopsy;
however, clinical outcomes did not differ between
women with and without myocarditis.

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Abnormal Immune Response

An abnormal immune response to fetal microchimerism (harboring of fetal cells in maternal circulation) has been studied as a cause for PPCM.29
Other researchers4,6,16,18 support this theory that during pregnancy fetal cells released into the maternal
bloodstream are not rejected by the mother because
of the natural immunosuppresion that occurs during pregnancy. However, after delivery, women lose
the increased immunity, and if fetal cells reside on
cardiac tissue when the fetus is delivered, a pathological autoimmune response can occur, leading to
PPCM in the mother after birth.
Abnormal Hemodynamic Response
During pregnancy, blood volume and cardiac
output increase.4 In addition, afterload decreases
because of relaxation of vascular smooth muscle.13
These changes cause a brief, and reversible, hypertrophy of the left ventricle to meet the needs of the
mother and fetus.2 This transient left ventricular
dysfunction during the third trimester and early
postpartum period resolves shortly after birth in a
normal pregnancy.2,18 Pearson et al4 suggested that
PPCM might be due, in part, to an exaggerated
decrease in left ventricular function when these
hemodynamic changes of pregnancy occur.
Apoptosis and Inflammation
An increased concentration of plasma inflammatory cytokines, specifically tumor necrosis factor a;
C-reactive protein; and Fas/Apo-1, a plasma marker
for apoptosis (programmed cell death), have been
identified in women with PPCM.3 Levels of Fas/Apo-1,
a ligand found on cell-surface proteins that plays a
key role in apoptosis, were higher in women with
PPCM than in healthy volunteers.3 Furthermore, these
Fas/Apo-1 levels were higher among women with
PPCM who died than among those with PPCM who
survived. However, a correlation between increased
plasma cytokine levels and left ventricular function
or outcomes has not been demonstrated. Van Hoeven
et al30 further concluded that ejection fraction at the
time of clinical findings suggestive of PPCM was the
strongest predictor of outcome.
Prolactin
Hilfiker-Kleiner et al16,31 have proposed a new
pathogenic mechanism for PPCM: excessive prolactin production. Levels of prolactin are associated
with increased blood volume, decreased blood
pressure, decreased angiotensin responsiveness, and
a reduction in the levels of water, sodium, and potassium.31 Prolactin also increases the level of circulating

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erythropoietin, and hence hematocrit levels.18 Hilfiker-Kleiner et al31 discovered that PPCM develops
in mice bred to have a cardiomyocyte-specific deletion of STAT3, a protein that plays a key role in
many cellular processes such as cell growth and
apoptosis. The deletion of STAT3 led to enhanced
expression of cardiac cathepsin D, promoting the
formation of a 16-kD form of prolactin. In women
with PPCM, STAT3 protein levels were low in the
heart, and serum levels of activated cathepsin D
and 16-kD prolactin were elevated.16,31
Selenium and Malnutrition
Nutritional disorders, such as deficiencies in
selenium and other micronutrients, were thought
to play a role in the pathogenesis of PPCM.12,26 Deficiencies of selenium increase cardiovascular susceptibility to viral infections, hypertension, and
hypocalcemia. However, Fett et al32 concluded that
neither low serum levels of selenium nor deficiencies of other micronutrients (vitamins A, B12, C, E,
and b-carotene), played a significant role in the
development of PPCM in Haitian women. In contrast, women with PPCM from the
Sahelian region of Africa had low
levels of selenium.33

Viral myocarditis
has been
proposed as the
main mechanism
for peripartum
cardiomyopathy.

Prolonged Tocolysis
Prolonged tocolysis refers to
the use of tocolytic agents (b-sympathomimetic drugs) for more
than 4 weeks.18 The association
between tocolytic therapies and
heart failure appears to be unique
to pregnancy. Tocolytic agents are used for the management of various other conditions without the
occurrence of signs and symptoms of heart failure
like those experienced by pregnant women. Such
signs and symptoms may develop in pregnant
women as a result of normal physiological changes
that occur, including an increase in circulating
blood volume.18 Lampert et al34 found an association between use of tocolytic therapies and development of pulmonary edema in pregnant women and
proposed a link between chronic use of b-sympathomimetic medications and PPCM.

Clinical Manifestations and Diagnosis

Features of a normal pregnancy include increased
blood volume, increased metabolic demands, mild
anemia, changes in vascular resistance associated
with mild ventricular dilatation, and increased cardiac output.11 Thus, the onset of PPCM can easily be
maskedand missedbecause the manifestations

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can mimic those of mild heart failure. Women with

PPCM most commonly have dyspnea, dizziness,
chest pain, cough, neck vein distension, fatigue,
and peripheral edema.4,10,13 Women can also have
arrhythmias, embolic events due to the dilated,
dysfunctional left ventricle, and acute myocardial
infarction due to decreased perfusion to the coronary
arteries.4,10,35 They can also have other indications
typical of heart failure: hypoxia, jugular venous distention, S3 and S4 gallop, rales, and hepatomegaly.35
Blood pressure is often normal or decreased, and
tachycardia is common.20
PPCM was first defined in 1971 as the development of myocardial disease that occurs for the first
time toward the end or in the early stage of the
pregnancy.12 A modification of this classic definition
added a strict echocardiographic criterion.1 The National Heart, Lung, and
Blood Institute and the Office of Rare
Diseases workshop adopted the modified definition in 2000.4 In 2010, the
European Society of Cardiology Working Group on Peripartum Cardiomyopathy36 proposed a modification to
the existing definition of PPCM. PPCM
is defined as an idiopathic cardiomyopathy manifested as heart failure due
to left ventricular systolic dysfunction
toward the end of pregnancy or in the
months after delivery when no other
cause of heart failure is found. Thus,
PPCM is a diagnosis of exclusion, suggesting that a
broader definition would eliminate PPCM as a
missed diagnosis.36
The definitive diagnosis of PPCM depends on
echocardiographic identification of new-onset heart
failure during a limited period around parturition.
A diagnosis of PPCM requires the exclusion of other
causes of heart failure: myocardial infarction, sepsis,
severe preeclampsia, pulmonary embolism, valvular
diseases, and other forms of cardiomyopathy.17,37
Chest radiographs should be obtained in suspected cases of PPCM.35 Chest radiographs may be
helpful in acute pulmonary edema, but much less
so if no clinical evidence of pulmonary congestion
is revealed. Radiological indications of heart failure
such as cardiomegaly, pulmonary congestion, and
pleural effusions may be evident.35 However, diagnosing cardiomegaly on the basis of a chest radiograph in a pregnant patient is difficult because
the heart is pushed upward and laterally, giving the
false impression of cardiomegaly.
Electrocardiograms should also be obtained. In
PPCM, the tracings may be normal or may show

Magnetic
resonance images
can be used to
measure global
and segmental
contraction and
identify inflammatory processes.

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left ventricular hypertrophy, ST-T wave abnormalities,

dysrhythmias, Q-waves in the anteroseptal precordial leads, and prolonged PR and QRS intervals.4,38
Several laboratory tests should be performed: complete blood cell counts and serum levels of troponin,
urea, creatinine, and electrolytes.11,20 Liver function
tests should be done, and levels of thyroid-stimulating hormone should be measured. In the initial
evaluation, the serum level of troponin may be
helpful in ruling out myocardial infarction; however an increase in troponin in the acute phase of
PPCM, without myocardial infarction, can occur.35
Levels of B-type natriuretic peptide and N-terminal
pro-B-type natriuretic peptide can help in confirming the diagnosis.38,39
Unlike pulmonary artery catheterization,
echocardiography is noninvasive and allows serial
evaluations in pregnant women.1 Serial echocardiography with Doppler imaging is used to evaluate
and monitor regional and global left and right ventricular function, valvular structure and function,
possible pericardial pathological changes, and
mechanical complications.11 Findings in women
with PPCM are consistent with the findings in heart
failure: decreased ejection fraction, global dilatation, and thinned-out cardiac walls.4,11,38
Cardiac magnetic resonance imaging has been
suggested as a complementary tool in the diagnosis
and evaluation of women with PPCM.13,21,30 Such
imaging can be used to measure global and segmental myocardial contraction, can help in characterizing the pathogenesis of the disease, and can
reveal inflammatory processes.13 Baruteau et al21
maintain that because cardiac magnetic resonance
imaging can be used to distinguish inflammatory
from noninflammatory pathogenesis, it can be
helpful at the initial evaluation of a woman with
PPCM to determine the pathophysiology and to
guide further therapeutic options. Ntusi and Chin40
disagree, however, and do not see a benefit for
obtaining cardiac magnetic resonance images in all
women who have PPCM. Guidelines for diagnosis
of PPCM according to the American College of Cardiology Foundation (ACCF) and the American Heart
Association (AHA)39 are provided in Figures 1 and 2.

Management
Compensated Heart Failure
Management of PPCM is similar to standard
treatment for other forms of heart failure.4,39,41 However, no randomized clinical trials have been done
to evaluate these therapies specifically in PPCM.
Furthermore, careful attention should be paid to fetal
safety and to excretion of drug or drug metabolites

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during breastfeeding after delivery.4 The goals in

treating heart failure are to improve hemodynamic
status, minimize signs and symptoms, and optimize
the long-term outcomes. Treatment focuses on
reducing preload and afterload and increasing cardiac inotropy.2,4,35 Pearson et al4 reinforce that collaboration among medical specialists, including
obstetricians, cardiologists, perinatologists, and
neonatologists, is essential in care of women with
PPCM. Of note, polypharmacy may be required for
optimal management, to slow progression of heart
failure and to improve outcomes in women with left
ventricular systolic dysfunction.42 Medications should
be continued until evidence indicates improved
and/or resolved left ventricular dysfunction.4,35
Women with PPCM should be treated in the hospital
when they have evidence of hypotension, worsening
heart failure, altered mental status, and increased
work of breathing.42
Preload reduction is accomplished by administration of vasodilators, such as nitrates, most of
which are safe during pregnancy and breastfeeding.35
Loop diuretics are important for management of
signs and symptoms and for preload reduction,
although caution is warranted in antepartum women
because rapid changes in intravascular volume can
lead to a decrease in blood supply to the uterus and
therefore the fetus.35,43 Restriction of dietary sodium
is also helpful in preload reduction.2 Bed rest was
once standard care but is no longer recommended
because of the increased risk of thromboembolism.20
The current recommendation is light exercise such
as walking.4,10
Ideal medications intrapartum include hydralazine, nitrates, digoxin, and diuretics. Angiotensinconverting enzyme inhibitors are contraindicated
during pregnancy because of their teratogenicity,
but these medications are the mainstay of treatment
of PPCM after delivery for afterload reduction.4,13,38
Safe alternatives during pregnancy include hydralazine and nitrates.4,10 Aldosterone antagonists have
been effective when angiotensin-converting enzyme
inhibitors were not tolerated, but the antagonists
should not be used during pregnancy.41
b-Adrenergic antagonists, such as extended-release
metoprolol and carvedilol, have been approved for
use in PCCM and can improve survival.4,20,43 However, b-blockers should not be given in the early
stages of PPCM because they can decrease perfusion
in the acute decompensated phase of the disease.35
Pearson et al4 have proposed that carvedilol be used
in postpartum women who continue to have signs
and symptoms of heart failure and have echocardiographic evidence of left ventricular compromise

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Woman with signs and symptoms of heart failure who is

In last month of pregnancy or
Within 5 months postpartum

Signs and symptoms of heart failure

Dyspnea
Fatigue (at rest or exertion)
Neck vein distention
Exercise intolerance
Peripheral edema
Weight gain (water retention)
Chest pain

Cough
Heart palpitations/tachycardia
Sudden weight gain, fluid retention
Arrhythmias
Paroxysmal nocturnal dyspnea
Hepatomegaly
Weakness

Diagnostic testing
Complete family history, to identify possible familial association
Serum tests
Complete blood cell count with differential
Creatinine and urea levels
Electrolyte levels, including magnesium and calcium
Levels of cardiac enzymes, including troponin
Level of B-type natriuretic peptide and/or N-terminal
pro-B-type natriuretic protein
Liver function and level of thyroid-stimulating hormone
Chest radiograph
Electrocardiogram
Transthoracic echocardiogram
Cardiac magnetic resonance imaging and/or endomyocardial
biopsy (when indicated)

Figure 1 Evaluation of peripartum cardiomyopathy.

after more than 2 weeks of therapy. Digoxin, an

inotropic agent, is also safe during pregnancy and
should be considered for women with left ventricular systolic dysfunction and an ejection fraction of
less than 40% who have signs and symptoms of
heart failure while receiving standard therapy.42
Guidelines for management of compensated heart
failure in PPCM are presented in Table 1.
Decompensated Heart Failure
In pregnant women with acute decompensating heart failure, management begins with the
ABCs (airway, breathing, circulation).35 Assessment
of the airway is critical because pregnancy or recent
pregnancy with associated third spacing of excess
intravascular volume can result in a suboptimal airway.35 Women with impending respiratory failure
from pulmonary edema require rapid initiation of
supported ventilation.44 Endotracheal intubation is

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Diagnostic criteria for peripartum cardiomyopathy

All 4 of the following:
Classic
1. Development of cardiac failure in the last month of pregnancy or
within 5 months postpartum
2. No identifiable cause for the cardiac failure
3. No recognizable heart disease before the last month of
pregnancy
Additional
1. Strict echocardiographic indication of left ventricular dysfunction:
a. Ejection fraction <45%
and/or
b. Fractional shortening <30%
c. End-diastolic dimension >2.7 cm/m2

Yes: Meets criteria for

diagnosis for peripartum
cardiomyopathy

No: Consider other cause

Consultation with cardiologist, obstetrician, perinatologist

If diagnosis is made before the woman gives birth: involve
anesthesiology and neonatology also, and consider transfer to
a high-risk perinatal center

Figure 2 Diagnosis of peripartum cardiomyopathy.

Based on Pearson et al4 and Sliwa et al.36

often required; however, attempts involving noninvasive ventilation may obviate intubation.44 Noninvasive ventilation must be used with caution because
of the high risk for aspiration. Breathing is supported
with supplemental oxygen to relieve signs and symptoms related to hypoxemia and is assessed via continuous pulse oxymetry. Women should have cardiac
monitoring, including ST-segment monitoring when
available.13,35 Blood pressure should be monitored
with noninvasive blood pressure cuffs until arterial
catheters are placed. Venous and arterial access
should be obtained early so that medications can
be administered promptly and monitoring can be
streamlined.35 Some clinicians39 advocate for the use
of pulmonary artery catheters in women whose heart
failure is refractory; however, this logic has been
questioned because many of the drugs used to treat
PPCM produce benefits by mechanisms that cannot
be assessed by measurement of short-term changes
in hemodynamic status. Pulmonary artery catheters
may be beneficial in patients with heart failure, but
little information is available on their use in
women with PPCM.

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In antepartum women, fetal heart rate monitoring should be started early because abnormalities in
fetal heart rate tracings are common when maternal
oxygenation and circulation are compromised.35 Medical stabilization of the mothers condition is critical
and may result in resolution of fetal distress and prevent the need for emergency cesarean delivery that
most likely would be poorly tolerated by the mother.35
Women with acute heart failure benefit from
intravenous administration of positive inotropic
agents such as dobutamine and milrinone, none of
which are contraindicated in pregnancy.44 Positive
inotropic agents improve cardiac performance, facilitate diuresis, preserve end-organ function, and promote clinical stability.13,17,39 Dobutamine requires
b-receptors for its inotropic effects, whereas milrinone
does not, an important distinction in planning care
for a patient who is being treated with b-blocking
drugs.39 Furthermore, milrinone has vasodilating
properties for both the systemic and the pulmonary
circulation, a mechanism that may be a marked
benefit over other inotropic agents. In women with
systolic blood pressure less than 90 mm Hg, dobutamine may be preferred over milrinone.44 Vasodilatory
drugs such as nitroglycerin and nitroprusside also
may be of benefit.35,39 Nitroprusside should be used
with caution in pregnant women because the toxic
effects of thiocyanate can be harmful to the fetus.20,42
Clinicians should not focus therapy on a specific blood pressure value that might or might not
indicate hypotension; rather, they should focus on
signs and symptoms associated with poor cardiac
output and hypoperfusion, such as cold clammy
skin, cool upper and lower extremities, decreased
urine output, and altered mental status.39 Inotropic
agents are of greatest value in women who have
relative hypotension and an intolerance or no
response to vasodilators and diuretics.42 Regardless,
if invasive monitoring of hemodynamic status is
used, once the clinical status of the woman has
stabilized, every effort should be made to devise an
oral regimen that can maintain symptomatic improvement and reduce the subsequent risk of any deterioration in her condition.42
Left ventricular thrombus is common in women
with PPCM whose ejection fraction is less than
35%.2,38 Warfarin should be given to postpartum
women whose ejection fraction is 35% or less, and
heparin or a low-molecular-weight heparin should
be given to women who are pregnant and have a
similar ejection fraction.20,35 Anticoagulation therapy
should be continued until left ventricular function
is normal according to echocardiographic findings.13,39 Arrhythmias should be aggressively treated

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Table 1 Management of compensated heart failure in peripartum

cardiomyopathya

to minimize thrombus formation and to optimize

cardiac function.4,10
Immunosuppressive and anti-inflammatory
therapies have not improved the outcome in PPCM
and, in general, are not recommended.45 Because of
the various mechanisms of PPCM, immunosuppresion most likely would not help all women.13,35,45
In a case report, Jahns et al46 stated that bromocriptine, a dopamine antagonist that inhibits prolactin secretion, prevented the expected deterioration
in the size of the left ventricle and systolic function
when given in addition to standard heart failure
therapy in a woman with PPCM. The treatment of
STAT3-deficient mice with bromocriptine also prevented the development of PPCM in a study by
Hilfiker-Kleiner et al.16 The results of assessments of
the therapeutic effects of prolactin blockade with
bromocriptine are promising, and trials are being
done in women with PPCM.16,31 In a case study, de
Jong et al47 argue that the benefit of using cabergoline, another potent dopamine receptor antagonist
like bromocriptine, is the long half-life, 14 to 21
days, of cabergoline, so a single dose is often enough.
Medical therapy can be unsuccessful in women
with PPCM, and mechanical cardiovascular support
with an intra-aortic balloon pump or ventricular
assist devices may be required.48,49 Left ventricular
assist devices can be a bridge to recovery or to transplantation.13,49-51 Use of short-term extracorporeal
membrane oxygenation has also been of benefit in
women with PPCM whose heart failure was refractory to medical therapy and who had persistent pulmonary edema with hypoxemia.48,50 Extracorporeal
membrane oxygenation can also serve as a bridge
to left ventricular assist devices in patients with
refractory cardiogenic shock despite use of an intraaortic balloon pump and full inotropic support.51
Women in whom maximal medical management is unsuccessful may be candidates for cardiac
transplantation.48 According to one study,14 cardiac
transplantation was necessary in 4% of women with
PPCM. In another study52 in which 69 women underwent cardiac transplantation for PPCM, the investigators concluded that heart transplantation is a
practical therapeutic option for women with PPCM
who have advanced heart failure and signs and
symptoms unresponsive to medical therapies. The
risk of organ rejection in women with PPCM does
not appear to be higher than the risk in women of
similar age who have a history of pregnancy and
undergo transplantation for other causes. However,
in an earlier study, Koegh et al48 found that the incidence of biopsy-proven early rejection, necessitating
increased cytolytic therapy, was marginally higher in

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Nonpharmaceutical therapies
Low-sodium diet: limit of 2 g sodium per day
Fluid restriction: 2 L/day
Light daily activity: if tolerated (eg, walking)
Oral pharmaceutical therapies
Antepartum management of peripartum cardiomyopathy
b-blocker
Carvedilol (starting dose 3.125 mg twice a day, target dose
25 mg twice a day)
Extended-release metoprol (starting dose 0.125 mg daily, target
dose 0.25 mg daily)
Vasodilator
Hydralazine (starting dose 10 mg 3 times a day, target dose 40 mg
3 times a day)
Digoxin (starting dose 0.125 mg daily, target dose 0.25 mg daily)
Monitor serum levels
Thiazide diuretic (with caution)
Hydrochlorothiazide (12.5-50 mg daily)
May also consider loop diuretic with caution
Low-molecular-weight heparin if ejection fraction <35%
Postpartum management of peripartum cardiomyopathy
Angiotensin-converting enzyme (ACE) inhibitor
Captopril (starting dose 6.25-12.5 mg 3 times a day,
target dose 25-50 mg 3 times a day)
Enalapril (starting dose 1.25-2.5 mg 2 times a day,
target dose 10 mg 2 times a day)
Ramipril (starting dose 1.25-2.5 mg 2 times a day,
target dose 5 mg 2 times a day)
Lisinopril (starting dose 2.5-5 mg daily, target dose
25-40 mg daily)
Angiotensin-receptor blocker (if ACE inhibitor not tolerated)
Candesartan (starting dose 2 mg daily, target dose 32 mg daily)
Valsartan (starting dose 40 mg twice a day, target dose 160 mg
twice a day)
Consider nitrates or hydralazine if woman is intolerant to ACE
inhibitor and angiotensin-receptor blocker
Loop diuretic
Furosemide intravenously or by mouthdosing considerations
should be made on the basis of creatinine clearance
Glomerular filtration rate >60 mL/min per 1.73 m2:
furosemide 20-40 mg every12-24 h
Glomerular filtration rate <60 mL/min per 1.73 m2:
furosemide 20-80 mg every 12-24 h
Vasodilator
Hydralazine (starting dose 37.5 mg 3 or 4 times a day, target dose
40 mg 3 times a day)
Isorbide dinitrate (starting dose 20 mg 3 times a day, target dose
40 mg 3 times a day)
Aldosterone antagonist
Spironolactone (starting dose 12.5 mg daily, target dose
25-50 mg daily)
Eplerenone (starting dose 12.5 mg daily, target dose 25-50 mg daily)
b-blocker as above
Warfarin if ejection fraction <35%

aBased

in part on Jessup et al39 and Heart Failure Society of America.42

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Table 2 Management of decompensated heart failure in

peripartum cardiomyopathya
Airway
Intubate promptly upon distress for increased work of breathing
to prevent complications with difficult airway later in treatment
Breathing
Provide supplemental oxygen
Maintain continuous pulse oximetry to monitor SaO2
Measure arterial blood gases (if available) every 4-6 h until
breathing is stable
Circulation
Start cardiac and blood pressure monitoring
Insert arterial catheter for accurate blood pressure monitoring
and blood sampling
Obtain central venous access with central venous pressure
monitoring
In antepartum women, obtain fetal monitoring
Pharmacological management of acute heart failure in peripartum
cardiomyopathy
Intravenous loop diuretic (caution is advised in antepartum
women)
Furosemide: dosing considerations should be made on the
basis of creatinine clearance
Glomerular filtration rate >60 mL/min per 1.73 m2:
furosemide 20-40 mg intravenously every 12-24 h
Glomerular filtration rate <60 mL/min per 1.73 m2:
furosemide 20-80 mg intravenous every12-24 h
In severe fluid overload, consider furosemide infusion or
ultrafiltration
Vasodilator
Nitroglycerin infusion 5-10 g/min, titrate to clinical status and
blood pressure
Nitroprusside 0.1-5 g/kg per minute, use with caution in
antepartum women
Positive inotropic agents
Milrinone 0.125-0.5 g/kg per minute
Dobutamine 2.5-10 g/kg per minute

Avoid b-blockers in the acute phase, as they can decrease perfusion

Heparin sodium, alone or with oral warfarin (Coumadin) therapy
Monitor oxygenation with arterial blood gases every 4-6 h until
patients condition is stable
Consider endomyocardial biopsy; if proven viral myocarditis,
consider immunosuppresive medications (eg, azathioprine,
corticosteroids)
Every effort should be made to devise an oral regimen that can
maintain symptomatic improvement and reduce the subsequent
risk of worsening clinical status

If no improvement clinically:
Consider cardiac magnetic resonance imaging
Perform endomyocardial biopsy to detect viral myocarditis
(if not previously completed)
Assist devices:
Intra-aortic balloon pump
Left ventricular assist devices
Extracorporeal membrane oxygenation
Transplantation
If a woman remains refractory to therapy, consult your institutions
guidelines for bromocriptine or cabergoline administration for
suppression of prolactin production
aBased

96

in part on Jessup et al39 and Heart Failure Society of America.42

women with PPCM than in women with dilated

cardiomyopathy. Table 2 presents guidelines for management of decompensated heart failure in PPCM.

Outcomes of PPCM
Prognosis of PPCM is positively related to the
recovery of ventricular function.17 Failure of heart
size to return to normal is associated with increased
mortality and morbidity.4 Women with persistent
left ventricular dysfunction are less likely to survive
and recover normal cardiac function than are women
with improved left ventricular function. A fractional
shortening less than 20% and a left ventricular
diastolic dimension of 6 cm or greater at the time
of diagnosis are associated with a more than 3-fold
higher risk for persistent cardiac dysfunction.53
Sliwa et al3 found that ejection fraction was the
strongest predictor of outcome in women with PPCM.
Abboud et al17 reported that 50% of women with
PPCM recover baseline ventricular function within
6 months of delivery. In contrast, Ntusi and Mayosi18
found that only 30% of women with PPCM have
complete recovery of cardiac function; most have
partial recovery. Medical therapy as outlined in the
ACCF/AHA guidelines39 should be continued when
a woman does not recover function. When appropriate, implantation of defibrillators to prevent sudden
cardiac death and use of cardiac revascularization
therapy should be considered.
Reported mortality rates for PPCM vary widely.
In a study by Sliwa et al,3 the mortality rate in 29
women was 32%, whereas in a large populationbased study in Haiti by Fett et al,8 the mortality rate
was 15.8%. In a study of 123 women by Elkayam
et al,5 the rate was 9% at a mean follow-up time of
24 months. Brar et al15 concluded that mortality
rates associated with PPCM were lower than initially
reported at 2.5%, and Mielniczuk et al9 reported a
mortality rate of 1.36% to 2.05%. Earlier diagnosis,
coupled with modern management of heart failure,
most likely has an important influence on the mortality associated with PPCM.9,15 Although rates have
improved, mortality remains extremely high in
women with PPCM.
One of the most frequently cited issues for
women who survive PPCM is whether or not they
can safely become pregnant again.5,14 No clearly
established recommendations for future pregnancies
in these women exist.20 Left ventricular recovery and
function are considered the most reliable prognostic
factors and predictors of survival in subsequent
pregnancies.20 Future pregnancies are not recommended in women with persistent heart failure,
because the heart most likely would not be able to

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tolerate the increased cardiovascular workload associated with the pregnancy.5,13 Women whose cardiomyopathy appears to have resolved are a more
difficult group to counsel.4 Because multiparity has
been associated with PPCM, subsequent pregnancies can increase the risk for recurrent episodes of
PPCM, irreversible cardiac damage and decreased
left ventricular function, worsening of a womans
clinical condition, and even death.4,14
Williams et al35 have suggested that dividing
women into 2 categories (recovered vs nonrecovered
left ventricular function) is most appropriate for
counseling on future pregnancy. Even though the
cardiac function has normalized in the group of
women with recovered cardiac function, the left
ventricular contractile reserve may remain impaired,
and recurrence of PPCM is still possible.4,5 The subset of women with persistent left ventricular systolic
dysfunction should be counseled against subsequent pregnancies; the risks are 19% higher for
maternal death than among women with PPCM
whose heart failure has resolved.35

Conclusion
PPCM affects previously healthy women in the
final month of pregnancy and up to 5 months after
delivery.4 The diagnosis is based on 4 criteria.1,4 For
some women, the clinical and echocardiographic
status improve rapidly and sometimes return to
normal. In other women, the clinical condition rapidly worsens, no improvement occurs with medical
therapy, and chronic heart failure from persistent
ventricular dysfunction develops.5 No single explanation of the pathogenesis of PPCM is relevant for
all women; the disease has a multifactorial origin.
In acute care, treatment may involve the use of
intravenous vasodilators, inotropic medications, an
intra-aortic balloon pump, ventricular assist devices,
and/or extracorporeal membrane oxygenation.20,50
Survivors of PPCM often recover from left ventricular dysfunction; however, they may be at risk for
recurrence of heart failure and death in subsequent
pregnancies. Women with chronic left ventricular
dysfunction should be managed according to
ACCF/AHA guidelines.39 Careful assessment of risk
factors in pregnant women could help in the prevention of PPCM. Tools to stratify women by risk who
have recovered from PPCM are needed to predict
the risk of future pregnancies.
eLetters
Now that youve read the article, create or contribute to an
online discussion on this topic. Visit www.ajcconline.org
and click Submit a response in either the full-text or
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FINANCIAL DISCLOSURES
None reported.
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3. Sliwa K, Skudicky D, Bergemann A, Candy G, Puren A,
Sareli P. Peripartum cardiomyopathy: analysis of clinical
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8. Fett JD, Christie LG, Carraway RD, Murphy JG. Five-year
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9 Mielniczuk LM, Williams K, Davis DR, et al. Frequency of
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10. Ro A, Frishman W. Peripartum cardiomyopathy. Cardiol
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11. Sliwa K, Tibazarwa K, Hilfiker-Kleiner D. Management of
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12. Demakis JG, Rahimtoola S, Sutton GC, et al. Natural course
of peripartum cardiomyopathy. Circulation. 1971;44(6):
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13. Ramaraj R, Sorrell VL. Peripartum cardiomyopathy: causes,
diagnosis, and treatment. Cleve Clin J Med. 2009;76(5):
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14. Elkayam U, Akhter MW, Singh H, et al. Pregnancy-associated
cardiomyopathy: clinical characteristics and a comparison
between early and late presentation. Circulation. 2005;111
(16):2050-2055.
15. Brar SS, Khan SS, Sandhu GK, et al. Incidence, mortality,
and racial differences in peripartum cardiomyopathy. Am
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16. Hilfiker-Kleiner D, Sliwa K, Drexler H. Peripartum cardiomyopathy: recent insights in its pathophysiology. Trends Cardiovasc Med. 2008;18(5):173-179.
17. Abboud J, Murad Y, Chen-Scarabelli C, Saravolatz L,
Scarabelli TM. Peripartum cardiomyopathy: a comprehensive review. Int J Cardiol. 2007;118(3):295-303.
18. Ntusi NB, Mayosi BM. Aetiology and risk factors of peripartum cardiomyopathy: a systematic review. Int J Cardiol.
2009;131(2):168-179.
19. Pearl W. Familial occurrence of peripartum cardiomyopathy.
Am Heart J. 1995;129(2):421-422.
20. Moioli M, Menada MV, Bentivoglio G, Ferrero S. Peripartum
cardiomyopathy. Arch Gynecol Obstet. 2010;281(2):183-188.
doi:10.1007/s00404-009-1170-5.
21. Baruteau AE, Leurent G, Martins R, et al. Peripartum cardiomyopathy in the era of cardiac magnetic resonance
imaging: first results and perspectives. Int J Cardiol. 2010;
144(1):143-145.
22. van Spaendonck-Zwarts KY, van Tintelen P, van Veldhuisen
DJ, et al. Peripartum cardiomyopathy as a part of familial
dilated cardiomyopathy. Circulation. 2010;121:2169-2175.
23. Burkett EL, Hershberger RE. Clinical and genetic issues in
familial dilated cardiomyopathy. J Am Coll Cardiol. 2005;
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24. Elliott P, Andersson B, Arbustini E, et al. Classification of
the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial
and Pericardial Disease. Eur Heart J. 2008;29(2):270-276.
25. Goulet B, McMillan T, Bellet S. Idiopathic myocardial degeneration associated with pregnancy and especially the puer-

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pernium. Am J Med Sci. 1937;194(2):185-199.

26. Melvin KR, Richardson PJ, Olsen EG, Daly K, Jackson G.
Peripartum cardiomyopathy due to myocarditis. N Engl J
Med. 1982;307(12):731-734.
27. Midei MG, DeMent SH, Feldman AM, Hutchins GM, Baughman KL. Peripartum myocarditis and cardiomyopathy.
Circulation. 1990;81:922-928.
28. Felker GM, Jaeger CJ, Klodas E, et al. Myocarditis and
long-term survival in peripartum cardiomyopathy. Am
Heart J. 2000;140(5):785-791.
29. Ansari AA, Fett JD, Carraway RE, Mayne AE, Onlamoon N,
Sundstrom JB. Autoimmune mechanisms as the basis for
human peripartum cardiomyopathy. Clin Rev Allergy
Immunol. 2002;23:301-324.
30. van Hoeven KH, Kitsis RN, Katz SD, Factor SM. Peripartum
versus idiopathic dilated cardiomyopathy in young women
a comparison of clinical, pathological and prognostic factors. Int J Cardiol. 1993;40(1):57-65.
31. Hilfiker-Kleiner D, Kaminski K, Podewski E, et al. A cathepsin
D-cleaved 16 kDa form of prolactin mediates postpartum
cardiomyopathy. Cell. 2007;128(3):589-600.
32. Fett J, Ansara A, Sundstrom J, Combs G Jr. Peripartum
cardiomyopathy: a selenium disconnection and an autoimmune connection. Int J Cardiol. 2002;86(2):311-316.
33. Cnac A, Simonoff M, Moretto P, Djibo A. A low plasma
selenium is a risk factor for peripartum cardiomyopathy: a
comparative study in Sahelian Africa. Int J Cardiol. 1992;
36(1):57-59.
34. Lampert MB, Hibbard J, Weinert L, Briller J, Lindheimer M,
Lang RM. Peripartum heart failure associated with prolonged
tocolytic therapy. Am J Obstet Gynecol. 1992;168(2):493-495.
35. Williams J, Mozurkewich E, Chilimigras J, Van De Ven C.
Critical care in obstetrics: pregnancy-specific conditions.
Best Pract Res Clin Obstet Gynaecol. 2008;22(5):825-846.
36. Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al; Heart Failure
Association of the European Society of Cardiology Working
Group on Peripartum Cardiomyopathy. Current state of
knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement
from the Heart Failure Association of the European Society
of Cardiology Working Group on Peripartum Cardiomyopathy. Eur J Heart Fail. 2010;12(8):767-778.
37. Pyatt JR, Dubey G. Peripartum cardiomyopathy: current
understanding, comprehensive management review and
new developments. Postgrad Med J. 2011;87(1023):34-39.
38. Lata I, Gupta R, Sahu S, Singh H. Emergency management
of decompensated peripartum cardiomyopathy. J Emerg
Trauma Shock. 2009;2(2):124-128.
39. Jessup M, Abraham W, Casey D, et al. 2009 Focused update:
ACCF/AHA guidelines for the diagnosis and management
of heart failure in adults: a report of the American College
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40. Ntusi NB, Chin A. Characterisation of peripartum cardiomyopathy by cardiac magnetic resonance imaging. Eur Radiol.
2009;19(6):1324-1325.
41. Carlin AJ, Alfirevic Z, Gyte ML. Interventions for treating
peripartum cardiomyopathy to improve outcomes for
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CD008589. doi:10.1002/14651858.CD008589.pub2.
42. Heart Failure Society of America. Executive summary:
HFSA 2006 comprehensive heart failure practice guideline.
J Card Fail. 2006;12(1):10-38.
43. Egan DJ, Bisanzo MC, Hutson HR. Emergency department
evaluation and management of peripartum cardiomyopathy.
J Emerg Med. 2009;36(2):141-147.
44. Arnold JM, Liu P, Demers C, et al; Canadian Cardiovascular
Society. Canadian Cardiovascular Society consensus conference recommendation on heart failure 2006: diagnosis
and management. Can J Cardiol. 2006;22(1):23-45.
45. McNamara DM, Holubkov R, Starling, RC, et al. Controlled
trial of intravenous immune globulins in recent-onset
dilated cardiomyopathy. Circulation. 2001;103:2254-2259.
46. Jahns BG, Stein W, Hilfiker-Kleiner D, Pieske B, Emons G.
Peripartum cardiomyopathya new treatment option by
inhibition of prolactin secretion. Am J Obstet Gynecol.
2008;199(4):e5-e6.
47. de Jong JS, Rietveld K, van Lochem LT, Bouma BJ. Rapid left
ventricular recovery after cabergoline treatment in a patient
with peripartum cardiomyopathy. Eur J Heart Fail. 2009;1(2):
220-222.
48. Keogh A, Macdonald P, Spratt P, Marshman D, Larbalestier R,
Kaan A. Outcome in peripartum cardiomyopathy after heart
transplantation. J Heart Lung Transplant. 1994;13(2):202-207.
49. Smith IJ, Gillham MJ. Fulminant peripartum cardiomyopathy
rescue with extracorporeal membranous oxygenation. Int
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50. Palanzo DA, Baer LD, El-Banayosy A, et al. Successful treatment of peripartum cardiomyopathy with extracorporeal
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51. Gavaert S, van Belleghem Y, Bouchez S, et al. Acute and
critically ill peripartum cardiomyopathy and bridge to
therapeutic options: a single center experience with intraaortic balloon pump, extra-corporeal membrane oxygenation and continuous-flow left ventricular assist devices. Crit
Care. 2011;15(2):R93.
52. Rasmusson K, de Jong M, Doering L. Update on heart failure
management. current understanding of peripartum cardiomyopathy. Prog Cardiovasc Nurs. 2007;22(4):214-216.
53. Chapa JB, Heiberger HB, Weinert L, Decara J, Lang RM, Hibbard JU. Prognostic value of echocardiography in peripartum
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Letters
Letters are welcome and encouraged. They should raise points of current interest in the care of critical or high acuity patients or address
topics that previously have appeared in the American Journal of Critical Care. Please be concise; letters are subject to editing for length and
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Delirium Diagnosis: What You Do

With the Information Matters Most
The articles by Guenther et al1 and Gesin et al2
published in the January edition of the American
Journal of Critical Care are important contributions to
the discussion of how best to identify delirium in the
intensive care unit (ICU).
Gesin et al performed a comprehensive evaluation of a multifaceted education program. Guenther
et al reported the first study to identify the false-positive rate of subjective delirium assessments compared to an objective standard. However, both
papers fall into the common trap of confusing a
disease entity with the results of a diagnostic test.
Delirium is a pathophysiologic process, the
mechanisms of which are poorly understood and the
manifestations of which are protean, fleeting, and
influenced by baseline cognitive state, environment,
and method of assessment. As a result, comparisons
of diagnostic methods for detecting delirium will
inevitably produce different results,1 and training in a
particular diagnostic method will inevitably improve
agreement with other assessors using that method.2
In delirium diagnosis, it most important for
clinicians and researchers to identify a diagnostic
strategy that (1) identifies patients at higher risk of
adverse outcome, independent of other markers of
disease severity, and (2) identifies patients who will
benefit from therapy. Most methods of delirium
diagnosis, including unstructured subjective assessments,3 identify patients with poor outcomes; however no published study has ever convincingly
demonstrated one method does this more effectively
or efficiently than another. Only the Intensive Care
Delirium Screening Checklist (ICDSC) has ever
identified patients who benefitted from an intervention,4 and then only as a inclusion criterion for a
clinical trial, with no demonstration of comparative
diagnostic effectiveness. With this background, the
studies of Guenther et al and Gesin et al warrant
further consideration.
In a study of 160 patients, Guenther et al1 report
the paired comparison of 436 subjective assessments
made by bedside nurses and assessments made using
the Confusion Assessment Method for the ICU
(CAM-ICU). In 161 unreported assessments, the
CAM-ICU could not be performed as the RASS score

www.ajcconline.org

was -4 or -5. It would be interesting to know if the

bedside nurses were able to make any subjective
assessments in these patients. It is unclear whether
the subjective assessments were made in the course
of the usual clinical duties of the bedside nurses, and
whether they made a single snapshot assessment
or drew on observations made over the course of a
nursing shift. Such considerations are important, as
delirium fluctuates over time and the effort expended
in making an assessment must surely be influenced
by other clinical responsibilities. In any case, the
CAM-ICU was positive for delirium in 6.4% of assessments in which the subjective assessment was negative, whereas the subjective assessment was positive
in 9.6% of cases when the CAM-ICU was negative.
From this, the authors conclude that use of objective criteria helped detect delirium in more
patients.1(pe12) Only an analysis of paired observations is presented, rather than the overall patient
incidence of delirium, so it is impossible to know if
this statement is true; however, it is clearly not correct to conclude that the CAM-ICU detected delirium in more assessments. Indeed, as the authors
point out in their results section, the contrary is
true. More importantly, the authors conclude that
subjective assessments identifying delirium in
patients where the CAM-ICU was negative were
mistakes, and they express concern that 8 patients
were given antipsychotic medications or sedatives
though they were not delirious.1(pe18) They imply
that the CAM-ICU is the only correct method for
identifying delirium, and a positive CAM-ICU
should be the only indication for anti-delirium medication. These assumptions are not justified by any
published evidence.
The term CAM-ICU delirium does not necessarily universally equate to the pathophysiological
condition being sought, just as the result of an IQ
test does not necessarily equate to a persons intelligence or capacity to train in an occupation. Perhaps
the bedside nurse had observed features during his
or her shift that were not present at the time of the
CAM-ICU assessment? Perhaps the features
observed required treatment to prevent self-extubation? Concluding a bedside nurse was wrong to
administer sedation to an agitated patient who
could neither be safely extubated nor calmed by
reassurance or analgesia, simply because their

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151

CAM-ICU was negative, ignores the realities of ICU

practice. There is every possibility that patients
treated according to subjective impressions, rather
than their CAM-ICU diagnosis, ultimately had better
outcomes. Unfortunately, no published study has
yet answered this question.
In their 3-phase educational study of an educational intervention involving 20 nurses in a single
centre, Gesin et al2 report an effective educational
strategy that improved interrater reliability when clinical nurses were trained in the ICDSC. It is important
to show that diagnostic tools developed in a research
environment can be taught to clinicians, and that
effective methods for teaching are described in the literature. The reported results are perhaps not too surprisingjust as showing education in a foreign
language might be expected to improve communication with someone who speaks that language. However, in their discussion, Gesin et al2 introduce the
same thinking as Guenther et althat the ICDSC
improves the ability of nurses to evaluate patients
correctly for delirium.2(pe8) Not only is there no evidence that the ICDSC always correctly diagnoses
the pathophysiological entity that is delirium, there
is nothing to suggest that the methods used by the
nurses in their preeducation phase would not have
led to better patient outcomes than after they had
mastered the ICDSC. The argument is analogous to
that classically used to demonstrate the difference
between precision and accuracy. Training in the
ICDSC is shown to produce a more precise assessment, but there is nothing to suggest that in the
process the diagnosis has not become less accurate.
Once again, concentration on process rather than
outcome has led to overstatement of the importance of a studys results.
Discussion of how to diagnose delirium is not a
moot academic point. As recently identified,5 making
a diagnosis can be as beneficial or harmful as administering a powerful medication, yet while we subject
drugs to extensive trials, many diagnostic strategies,
such of those for delirium, enter practice with little
understanding of their comparative effects on patient
outcomes. Both papers conclude that education on
delirium monitoring should be performed such that
the CAM-ICU or the ICDSC can be more faithfully
implemented. However, as Gesin et al point out, one
cannot extrapolate results from studies using the
CAM-ICU to results of studies using the ICDSC.2(pe8)
Embarking on extensive education initiatives
when it is unsure which diagnostic tool provides the
greatest patient benefit is putting the cart before
the horse. A better strategy would be to perform a
multicenter, real-world study comparing outcomes
of patients treated according to various diagnoses.
We could then be sure we were teaching the most

152

effective diagnostic strategy. To do otherwise risks

much wasted effort.
MICHAEL READE, MBBS, MPH, DPHIL, FANZCA, FCICM
Brisbane, Queensland, Australia
FINANCIAL DISCLOSURES
None Reported
REFERENCES
1. Guenther U, Weykam J, Andorfer U, Theuerkauf N, Popp
J, Ely EW, Putensen C. Implications of Objective vs Subjective Delirium Assessment in Surgical Intensive Care
Patients. Am J Crit Care. 2012;21:e12-e20.
2. Gesin G, Russell BB, Lin AP, Norton HJ, Evans SL, Devlin JW.
Impact of a delirium screening tool and multifaceted education on nurses knowledge of delirium and ability to
evaluate it correctly. Am. J. Crit Care. 2012;21:e1-e11.
3. Reade MC, Eastwood GM, Peck L, Bellomo R, Baldwin I.
Routine use of the Confusion Assessment Method for the
Intensive Care Unit (CAM-ICU) by bedside nurses may
underdiagnose delirium. Crit Care Resusc. 2011;13:217-224.
4. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of
quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010;38:419-427.
5. Godlee F. Who should define disease? BMJ. 2011;342:d2974.

doi: http://dx.doi.org/10.4037/ajcc2012826

Response:
On behalf of my coauthors I would like to thank
Dr Reade for his comments and questions. He asks
if nurses were able to make subjective delirium
assessments on patients who had RASS scores of -4
and -5 and were thus rated as unable to assess by
the CAM-ICU raters. The answer is that it was left to
the nurses discretion not to rate patients if they
were comatose. No patients who had RASS scores
of -4 or -5 were subjectively rated by the nurses.
Reade points out a sentence in our abstract
regarding the use of objective criteria with the
CAM-ICU allowing detection of delirium in more
patients,1(pe12) that we could have more clearly
stated as follows: While the overall delirium incidence found with the CAM-ICU was lower than
subjectively rated, objective criteria helped detect
delirium in a significant number of patients who
were subjectively rated non-delirious.
He states that we implied, that the CAM-ICU
is the only correct method for identifying delirium.
This was not our intention. In fact, we emphasized
that the CAM-ICU is not a gold standard for diagnosis of delirium.1(pe18) The truth is that most of the
world uses a subjective and variable method by
which to pay attention to delirium, and thus subjectivity is part of usual care in many ICUs. Our
methodology, chosen a priori and based on previous literature showing that subjectivity misses
hypoactive delirium,2 was to consider a formal and
validated mechanism as the formal and definitive
approach to study discrepancy between the two. At
the same time, however, we clearly stated the fact

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that the CAM-ICU can miss cases of delirium. We

would like to take the opportunity to emphasize,
that any other validated delirium instrument might
have served a similar purpose as a comparator to
variable and loose subjective guestimates.
Reade criticizes the expression CAM-ICU delirium, because CAM-ICU positivity does not necessarily universally equate to the pathophysiological
condition being sought. . . . The expression CAMICU delirium was only chosen to express exactly
what Reade pointed out: delirium assessment was
done with the CAM-ICU in our study. It is true,
however, that out of the nearly dozen DSM-IV validation studies of the CAM-ICU, it has been absolutely
consistent that CAM-ICU specificity is exceedingly
high. Better said, although sometimes the CAM-ICU
may miss some delirium (eg, patients with lower
severity of illness, whose inattention is better diagnosed with a 10- to 30-minute instrument), when it
is positive it is highly likely to represent delirium in
all patient populations studied to date.
Reade stated that concluding a bedside nurse
was wrong to administer sedation . . . simply
because their CAM-ICU was negative . . . ignores
the realities of ICU practice. The reality in many
countries is that drugs must be prescribed by physicians. So, it is the physicians responsibility to verify
or exclude delirium, pain, or other reasons for disorientation such as an underlying dementia. It is
also a reality of ICU practice that physicians mostly
rely on the nurses subjective clinical impressions,
because they are present at the bedside much more
often than physicians.
We agree with Reade that it would be interesting to determine whether or not patients treated
according to subjective impressions have better outcomes as compared to those treated according to
objective delirium criteria.
ULF GUENTHER, MD
Bonn, Germany

Response:

Despite the lack of strong evidence demonstrating that screening for delirium at the bedside using
a validated instrument improves patient outcome,
recent European and North American consensus
guidelines advocate that patients admitted to the
ICU be routinely screened for delirium using either
the ICDSC or the CAM-ICU.1,2 Realizing that bedside delirium screening is not a replacement for a
formal diagnostic evaluation by either a psychiatrist
or neurologist, it nevertheless remains an efficient,
low-risk assessment that will help ICU clinicians
address reversible causes for delirium (when delirium is suspected), avoid treatments for agitation
known to worsen delirium (eg, benzodiazepines),
and promote regular interdisciplinary discussion
regarding the cognitive status of all patients.
Despite questions that remain surrounding the
psychometric properties of the ICSDC and the CAMICU and how one instrument compares to the other,
it is well established that if adequate education is
not provided to ICU clinicians when either of these
instruments are implemented into practice, the performance of each will be less than what has been
observed in formal psychometric evaluations.3-5
Our study was not designed to answer the important questions surrounding the identification of
delirium in the ICU that Reade raises. Instead,
knowing that the ICDSC identifies delirium nearly
as well as a psychiatrist using DSM-IV criteria, we
sought to measure the impact of using the ICDSC,
with or without a multifaceted educational strategy,
on the level of knowledge of ICU nurses regarding
delirium and its assessment and the ability of nurses
to use the ICDSC correctly.6
We did not aim to determine whether use of
the ICDSC identifies delirium correctly. Whereas
the rate of delirium detected in our study was
reported, this was not a focus and we caution readers not to make conclusions surrounding it. Many
of the questions Reade and others have raised surrounding the benefit and accuracy of using currently available delirium screening instruments
require further investigation.7,8
Until this research is completed, we feel our
study provides ICU clinicians with valuable insight
regarding how nurses evaluate delirium when education and a validated instrument are not used, the
intensity of any pedagogical strategy that should
be employed to support ICU delirium screening
efforts, and the members of the ICU team who are
best suited to deliver education in this area.
GAIL GESIN, PHARMD; JOHN W. DEVLIN, PHARMD
Charlotte, North Carolina; Boston, Massachusetts

We thank Dr Reade for his insightful comments

regarding recognition of delirium in the ICU and
for highlighting important areas for future research.

FINANCIAL DISCLOSURES
None Reported

FINANCIAL DISCLOSURES
None Reported
REFERENCE
1. Guenther U, Weykam J, Andorfer U, Theuerkauf N, Popp J,
Ely EW, Putensen C. Implications of Objective vs Subjective Delirium Assessment in Surgical Intensive Care
Patients. Am J Crit Care. 2012;21:e12-e20.
2. Spronk PE, Riekerk B, Hofhuis J, Rommes JH: Occurrence
of delirium is severely underestimated in the ICU during
daily care. Intensive Care Med. 2009;35:1276-80

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Correction
In the March 2012 article by Johnson-Coyle and
colleagues, Peripartum Cardiomyopathy: Review and
Practice Guidelines (Am J Crit Care. 2012;21[2]:89-98),
Table 1, p. 95, line10 should have read, Extendedrelease metroprolol (starting dose 12.5 mg/daily,
titrated up to 200 mg daily). We regret the error.
doi: http://dx.doi.org/10.4037/ajcc2012737

www.ajcconline.org

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