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Recruitment Maneuvers and Positive

End-Expiratory Pressure Titration in Morbidly


Obese ICU Patients
Massimiliano Pirrone, MD1,2; Daniel Fisher, RRT3; Daniel Chipman, RRT3; David A. E. Imber, BA1;
Javier Corona, MD1,4; Cristina Mietto, MD1,2; Robert M. Kacmarek, RRT, PhD1,3; Lorenzo Berra, MD1

Objective: The approach to applying positive end-expiratory pressure in morbidly obese patients is not well defined. These patients
frequently require prolonged mechanical ventilation, increasing
the risk for failed liberation from ventilatory support. We hypothesized that lung recruitment maneuvers and titration of positive
end-expiratory pressure were both necessary to improve lung volumes and the elastic properties of the lungs, leading to improved
gas exchange.
Design: Prospective, crossover, nonrandomized interventional study.
Setting: Medical and surgical ICUs at Massachusetts General
Hospital.
Patients: Critically ill, mechanically ventilated morbidly obese
(body mass index > 35kg/m2) patients (n = 14).

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA.
2
Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Universit degli Studi di Milano, Milan, Italy.
3
Respiratory Care Services, Massachusetts General Hospital, Boston, MA.
4
Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
This work was performed at Massachusetts General Hospital, Boston, MA.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF
versions of this article on the journals website (http://journals.lww.com/
ccmjournal).
Supported, in part, by the Department of Anesthesia, Critical Care and
Pain Medicine, Massachusetts General Hospital.
Dr. Pirrones institution received grant support from the Department of
Anesthesia to cover study-related expenses. Mr. Fisher received educational grant from Hollister. Dr. Kacmarek has received grants from Covidien
and Venner Medical. He consulted for Covidien on mechanical ventilators. His institution received grant support (research grants from Venner
Medical and Covidien). Dr. Berra received support for travel from E-motion
(visit to the laboratory located in Tel Aviv, Israel). He and his institution
received grant support from the National Institutes of Health (T32 training
grant). His institution received grant support from Endoclear, LLC (Endoclear, LLC supported research-related expenses and provided devices for
a study on endotracheal tube cleaning devices). The remaining authors
have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: lberra@partners.org
Copyright 2016 by the Society of Critical Care Medicine and Wolters
Kluwer Health, Inc. All Rights Reserved.
DOI: 10.1097/CCM.0000000000001387
1

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Interventions: This study evaluated two methods of titrating positive end-expiratory pressure; both trials were done utilizing positive end-expiratory pressure titration and recruitment maneuvers
while measuring hemodynamics and respiratory mechanics. Measurements were obtained at the baseline positive end-expiratory
pressure set by the clinicians, at zero positive end-expiratory pressure, at best positive end-expiratory pressure identified through
esophageal pressure measurement before and after a recruitment
maneuver, and at best positive end-expiratory pressure identified
through a best decremental positive end-expiratory pressure trial.
Measurements and Main Results: The average body mass index
was 50.716.0kg/m2. The two methods of evaluating positive endexpiratory pressure identified similar optimal positive end-expiratory
pressure levels (20.74.0 vs 21.33.8cm H2O; p = 0.40). Endexpiratory pressure titration increased end-expiratory lung volumes
(117mL/kg; p < 0.01) and oxygenation (8650 torr; p <
0.01) and decreased lung elastance (55cm H2O/L; p < 0.01).
Recruitment maneuvers followed by titrated positive end-expiratory
pressure were effective at increasing end-expiratory lung volumes
while decreasing end-inspiratory transpulmonary pressure, suggesting an improved distribution of lung aeration and reduction of overdistension. The positive end-expiratory pressure levels set by the
clinicians (11.62.9cm H2O) were associated with lower lung volumes, worse elastic properties of the lung, and lower oxygenation.
Conclusions: Commonly used positive end-expiratory pressure by
clinicians is inadequate for optimal mechanical ventilation of morbidly obese patients. A recruitment maneuver followed by endexpiratory pressure titration was found to significantly improve
lung volumes, respiratory system elastance, and oxygenation. (Crit
Care Med 2016; 44:300307)
Key Words: lung compliance; mechanical ventilation; obesity;
positive end-expiratory pressure; pulmonary gas exchange;
respiratory mechanics

besity is a worldwide public health issue. The current


prevalence in the United States is 34.9% with a body
mass index (BMI) greater than 30kg/m2 (1). One of
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Clinical Investigations

the greatest challenges in caring for obese patients in the ICU


is optimization of mechanical ventilation (2). Many of these
patients cannot be weaned from mechanical ventilation and
therefore require prolonged respiratory support (3). Diagnostic imaging often is not feasible and the commonly used
assumptions for titration of ventilatory pressures may not be
applicable to patients with a significantly elevated BMI (4, 5).
Morbidly obese patients are characterized by reductions of
total lung capacity, functional residual capacity (FRC), and the
vital capacity (6). Low FRC increases the risk of expiratory flow
limitation and early airway closure. Expiratory flow limitation
can lead to gas trapping, resulting in auto-positive end-expiratory pressure (auto-PEEP) and dynamic pulmonary hyperinflation, two common sources of increased work of breathing
and patient-ventilator asynchrony (7). The reduction of FRC
in morbidly obese patients is due to the cephalad displacement
of the diaphragm caused by the weight of intra-abdominal
contents, resulting in collapse of lung tissue in dependent
zones of the lung. It has been observed that transpulmonary
pressure (the difference between airway pressure and pleural
pressure) is frequently negative in obese patients, resulting in
atelectasis (8). In mechanically ventilated obese patients, positive end-expiratory pressure (PEEP) applied to match autoPEEP levels improves respiratory mechanics and gas exchange
and minimizes expiratory flow limitation without increasing
plateau pressure (Pplat) (9). Additionally, the adoption of a sitting position has been shown to lower the PEEP requirements
for the reversal of expiratory flow limitation and the restoration of FRC (10). The application of adequate PEEP levels in
mechanically ventilated obese patients should prevent atelectasis and optimize respiratory mechanics. However, the optimal
level of PEEP required in morbidly obese ICU patients remains
unclear.
We hypothesized that PEEP levels selected by the ICU team
in critically ill, morbidly obese patients (11) may not be adequate for maintaining end-expiratory lung volume (EELV),
resulting in atelectasis and hypoxemia. We additionally investigated the effects of two approaches for titrating PEEP (a decremental PEEP trial and an end-expiratory transpulmonary
pressure [Ptpe] approach). We evaluated these two approaches
in each patient to establish the effect of the approach on EELV,
respiratory mechanics, and gas exchange. Some results of this
study were presented in the form of an abstract (44th Society
of Critical Care Medicine Congress) (12).

MATERIAL AND METHODS


Population and Study Protocol
The inclusion criteria were as follows: age older than 18 years,
BMI more than 35kg/m2, and absence of a diagnosis of acute
respiratory distress syndrome as defined by the Berlin criteria (13). The study was approved by Partners Institutional
Review Board (IRB 2013P001413) and registered at http://
www.clinicaltrials.gov (NCT 02105220). The enrolled subjects or surrogates provided written informed consent prior
to any study maneuver. After consent, a nasogastric tube with
Critical Care Medicine

an esophageal balloon (Avea GS SmartCath; Carefusion, Yorba


Linda, CA) was positioned and inflated with 2mL of air (14).
Esophageal pressure (Pes) was used as a surrogate of pleural
pressure. Patients were then connected to a mechanical ventilator (Engstrm Carestation; GE Healthcare, Madison, WI),
sedated, and paralyzed with cisatracurium. Mechanical ventilation was switched to volume-control mode. Subjects EELVs
and respiratory mechanics were studied at clinically set PEEP
(baseline PEEP), zero PEEP (ZEEP), lowest PEEP level with a
positive Ptpe without a recruitment maneuver (RM), lowest
PEEP level with a positive Ptpe after a RM, best decremental
PEEP after a RM, and best decremental PEEP with the head of
bed elevated to 30 degrees. Gas exchange measurements were
performed only at the baseline PEEP level and at the two differently titrated PEEP levels, both after RM, to limit the number of arterial punctures to a minimum. Blood, airway, and Pes
were continuously recorded throughout the study. After the
study procedure, the attending physician was informed of the
study results and free to decide whether to keep baseline PEEP
levels or adjust them according to the results.
PEEP Titration Techniques and RMs
Lowest PEEP With Positive Ptpe. PEEP was progressively
increased in a stepwise manner until it matched or was slightly
greater than the Pes at end expiration, resulting in Ptpe between
zero and +2cm H2O (15).
Best Decremental PEEP. A decremental trial was performed
as described by Kacmarek and Villar (16). PEEP was increased
to a level 4cm H2O higher than the PEEP level identified with
the transpulmonary pressure approach. After 2 minutes, Pplat
and PEEP were measured with end-inspiratory and end-expiratory pauses. The delta pressure (Pplat PEEP) was then calculated, and PEEP was decreased by 2cm H2O. The procedure
was repeated for at least five decrements, until the PEEP level
with the lowest delta pressure was determined, thus identifying
the best decremental PEEP. The PEEP set was the best decremental PEEP plus 2cm H2O (17).
RM. RMs were performed in a stepwise fashion. The
patients ventilatory mode was switched to pressure control
ventilation, with PEEP of 15cm H2O, respiratory rate of 10
breaths/min, inspiratory/expiratory ratio of 1:1, and a pressure control level of +15cm H2O. Every 30 seconds, PEEP was
increased by 5cm H2O. We progressively increased PEEP to
30cm H2O + 15cm H2O of pressure control. The total duration of the RM was 2 minutes.
EELV Estimation and Gas Exchange
EELV was estimated by the 10% oxygen/nitrogen wash-in/
wash-out technique. This technique is based on gas dilution
within a constant volume. At baseline, nitrogen volume is
equal to the N2 fraction of the intrathoracic gas volume. With
constant Co2 production, if the intrathoracic oxygen fraction
is changed by 10%, after 2 minutes intrathoracic gases will
reach a new equilibrium with a new N2 fraction and a new N2
volume. Volume of distribution, or EELV, was then calculated
as N2(mL)/Fio2. EELV was measured twice for every study
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301

Pirrone et al

step, and the results were averaged. Gas exchange was measured through arterial blood gas analysis. Pao2/Fio2 was used as
a measure of oxygenation.
Statistical Analysis
We anticipated enrolling a total of 14 (13 + 10% possible dropouts) subjects. Sample size calculations showed that 13 patients
were needed in order to detect a predicted increase in EELV of at
least 300mL 300mL after PEEP titration with a power of 0.9
and a two-sided p value of less than 0.05. The estimated PEEP at
which the Ptpe would be 0cm H2O was based on the observations
made by Behazin et al (8) on Pes in obese patients. They observed
an average end-expiratory Pes of 12.5cm H2O with no significant
PEEP applied. They also showed a chest wall elastance/respiratory
system elastance ratio of 0.16. The application of 15cm H2O of
PEEP would result in an increase of 2.5cm H2O of Pes (18), resulting in an Ptpe of 0cm H2O. We based our sample size calculation
on the results reported by Pelosi et al (19). They showed that an
Table 1.

Characteristics of Study Patients

Total number of patients enrolled

14

Age, mean sd, yr

54.015.7
6 (42.9)

Female, n (%)
Height, mean sd, cm

170.912.5

Weight, mean sd, kg

146.140.8

Body mass index, mean sd, kg/m

50.716.0

Thoracic circumference, mean sd, cm

144.823.3

Abdominal circumference, mean sd, cm

151.823.8

Simplified Acute Physiology Score II,


mean sd

34.618.1

Acute Physiology and Chronic Health


Evaluation II, mean sd

15.87.9

Intra-abdominal pressure,
mean sd, cm H2O

13.85.6

Admission
Medical, n (%)

7 (50)

Scheduled surgery, n (%)

5 (35.7)

Emergency surgery, n (%)

2 (14.3)

Primary diagnosis
Upper airway obstruction, n (%)

2 (14.3)

Volume overload, n (%)

1 (7.1)

Sepsis, n (%)

9 (64.3)

Pulmonary embolism, n (%)

1 (7.1)

Trauma, n (%)

1 (7.1)

Reason for intubation


Airway protection, n (%)

2 (14.3)

Respiratory failure, n (%)

12 (85.7)

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increase from a set PEEP of 10cm H2O to a PEEP of 15cm H2O


in obese patients would result in an increase in EELV of 300mL.
Continuous variables are expressed as mean sd. Normality
of data distribution was assessed with the Shapiro-Wilk test.
The overall differences in respiratory and hemodynamic variables at different PEEP levels were assessed by repeated-measures analysis of variance. Single changes of measured values
at different PEEP levels were compared using post hoc HolmBonferroni corrections for multiple comparisons. A p value of
less than 0.05 was considered statistically significant.

RESULTS
ICU patients were screened from surgical, neurologic, and
medical ICUs. Fourteen patients (eight men, six women) met
all the inclusion criteria and were enrolled in the study. ZEEP
maneuver was performed only on four patients, as deemed safe
by the attending physician. However, in one patient, desaturation prevented performing the EELV measurement at ZEEP.
Head of bed elevation to 30 degrees was not feasible in two
of the 14 patients because the elevation caused dysfunction of
the continuous venous-venous hemodialysis catheter in one
patient and the other patient required mandatory supine positioning after trauma surgery. The average error between the
two repeated EELV measurements was 8.77.8%.
Subjects were on average 54 years old and had an average
BMI of 50.7kg/m2, ranging from 35.2 to 91.8kg/m2. Twelve
patients were intubated for primary respiratory failure, nine of
whom were admitted with a primary diagnosis of sepsis. The
remaining two patients were intubated for airway obstruction.
Table 1 summarizes the characteristics of the patients.
PEEP Commonly Selected by the ICU Team Is
Lower Than Titrated PEEP, Resulting in Low EELV,
and Transpulmonary Pressure Cycles Into Negative
Values
As reported in Table 2, baseline PEEP levels were 9.1cm
H2O lower than PEEP levels that achieved a positive Ptpe
(p < 0.0001) and 9.7cm H2O lower than the best decremental PEEP (p < 0.0001). The PEEP levels identified with either
trial method were not significantly different (p = 0.37). EELV
increased after PEEP titration, reaching a significant difference
of 10.6mL/kg of ideal body weight (IBW) at the lowest PEEP
level with a positive Ptpe (p = 0.0004) and 11.1mL/kg IBW
at best decremental PEEP (p < 0.0001). The EELV difference
between baseline and best decremental PEEP with 30 degrees
of head of bed elevation was 19mL/kg IBW (p < 0.0001).
At baseline PEEP level, Ptpe values were negative (CI95 Ptpe:
9.1, 2.4cm H2O; end-inspiratory transpulmonary pressure
[Ptpi]: 1.3, +4.5cm H2O), exposing the lung to tidal cyclic
recruitment/derecruitment. At ZEEP, transpulmonary pressure was markedly negative (CI95 Ptpe: 14.2, 8.9cm H2O;
Ptpi: 7.7, +1.2cm H2O) and EELV was reduced. Both PEEP
trials were effective at restoring transpulmonary pressures to
positive values (CI95 lowest positive Ptpe PEEP: Ptpe: 0, 2.8cm
H2O; Ptpi: 4.7, 8.5cm H2O; CI95 best decremental PEEP: Ptpe:
1.0, 3.6cm H2O; Ptpi 6.0, 9.0cm H2O). Figures1 and 2 show
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Clinical Investigations

Table 2 . Respiratory Mechanics and Gas Exchange at Different Positive End-Expiratory


Pressure Levels

Baseline

Zero PEEPa

Lowest PEEP
With Positive
Ptpe

PEEP cm H2O

11.62.9

20.74.0b

20.74.0b

21.33.8b

21.53.7b

End-expiratory lung volume,


mL/kg ideal body weight

19.58.3

14.63.9

27.19.2

30.18.2b,c

30.68.7b

38.511.5b

Ppeak, cm H2O

34.65.8

22.44.9

41.76.0b

40.26.1b,c

40.45.2b

41.65.5b

Pplat, cm H2O

22.54.1

11.72.1

30.44.2b

29.14.1b,c

29.83.8b

30.83.2b

Pao2/Fio2, torr

17960

27067b

26672b

Ptpi, cm H2O

1.65.0

-3.22.8

8.12.5b

6.63.3b,c

7.52.6b

10.33.8b

Ptpe, cm H2O

-5.85.8

-11.51.7b

1.11.5b

1.42.4b

2.32.3b

4.23.8b

Elastance of the respiratory


system, cm H2O/L

23.26.8

23.21.3

22.15.1

17.94.0b,c

18.24.4b

20.85.2

Elastance of the lung, cm


H2O/L

17.86.8

18.41.6

16.83.6

12.43.4b,c

12.73.2b

15.15.3

5.42.9

4.81.0

5.62.8

5.62.2

5.52.7

5.72.9

18.86.1

16.83.0

17.56.1

17.46.2

16.57.3

17.27.4

Elastance of the chest wall,


cm H2O/L
Airway resistance, cm
H2O/L/s

Lowest PEEP
With Positive
Ptpe After RM

Best Decremental
PEEP After RM

Best Decremental
PEEPHead of
Bed 30 Degree

PEEP = positive end-expiratory pressure, Ptpe = end-expiratory transpulmonary pressure, RM = recruitment maneuver, Ppeak = peak airway pressure, Pplat =
plateau airway pressure, Ptpi = end-inspiratory transpulmonary pressure.
a
Zero PEEP (ZEEP) maneuver was performed only on four patients; end-expiratory lung volume at ZEEP was measured only in three of four patients. All data
presented as mean sd.
b
Statistically different from baseline (p < 0.0033).
c
Statistically different after recruitment maneuver (lowest PEEP with positive Ptpe versus lowest PEEP with positive Ptpe after RM, p < 0.05).
Patients were ventilated with a tidal volume of 6.61.2mL/kg of ideal body weight, respiratory rate of 22.66.8 breaths/min, minute volume ventilation of
9.83.3L/min, and an inspired oxygen fraction of 0.550.09.

the changes of EELV and transpulmonary pressure values


measured.
RMs Are Effective at Increasing EELV While Lowering
Ptpi
At the lowest PEEP level with a positive Ptpe, RMs increased
EELV by 3mL/kg IBW (p = 0.017). No change in Ptpe was
observed (p = 0.43). However, Ptpi decreased by 1.5cm H2O
(p = 0.01), suggesting a more favorable distribution of volume
among alveolar units. Indeed, a PEEP increase without a RM
did not significantly improve the elastance of the respiratory
system (Ers) (p = 0.37) or of the lung (p = 0.45) compared
with baseline PEEP level, while after a RM, Ers decreased by
4.2cm H2O/L (p = 0.0002), a change attributable to the 4.2cm
H2O/L decrease in lung elastance (El) (p < 0.0001). Chest
wall elastance (Ecw) did not differ before and after the RM
(p = 0.85). Only five of 14 patients experienced transient hypotension (systolic arterial blood pressure < 90mm Hg) during
the final steps of the RM.
Ecw Is Not Significantly Altered in Morbid Obesity
In the subgroup of four patients who were briefly ventilated
at ZEEP, the Ers increased by 5.7cm H2O/L (p = 0.055). Chest
wall elastance did not change (p = 0.90). A similar increase
Critical Care Medicine

in stiffness was observed in Ers and El (delta, 5.8cm H2O/L;


p=0.09). At the lowest PEEP level with positive Ptpe, Ers
decreased by 5.3cm H2O/L (p = 0.0007) when compared with
baseline. Similarly, a decrease in Ers of 5.0cm H2O/L was
observed at best decremental PEEP (p = 0.0016). A comparable
difference in El (5.4cm H2O/L; p = 0.003) at the lowest PEEP
level that achieved a positive Ptpe and at best decremental
PEEP was observed, as well as a difference in El (5.1cm H2O/L;
p = 0.004) at best decremental PEEP. Ecw did not change at any
of the different PEEP levels (p = 0.96) and remained within
physiologic values (Table2 and Fig.3). The significance of El
in determining the elastic properties of the respiratory system, together with EELV changes, suggests that lung aeration
plays a major role in the pathophysiology of critically ill obese
patients.
In Morbidly Obese Patients, Titrated PEEP Levels
Improve Oxygenation and Have Little Impact on
Hemodynamics
Pao2/Fio2 improved after PEEP titration (p < 0.0001). Pao2/
Fio2 increased by 91 torr from baseline to the lowest PEEP with
positive Ptpe (p = 0.0001) and 87 torr at the best decremental PEEP (p < 0.0001). Neither trial technique was superior;
both improved oxygenation following a RM (p = 0.28) (Table2
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Pirrone et al

and Fig.4). Systolic blood pressure and diastolic blood pressure did not change at any of the studied PEEP levels (p = 0.37
and p = 0.36), except for those five patients who experienced
transient hypotension during the RM (Table S2, Supplemental Digital Content 1, http://links.lww.com/CCM/B489). The
analysis of variance of the heart rate showed significance (p =
0.01), although post hoc adjusted comparisons did not reach
significance. The statistical signal was biased by the few heart
rate observations at ZEEP (Fig.5). Additionally, as detailed in
Tables S1 and S2 (Supplemental Digital Content 1, http://links.
lww.com/CCM/B489), we did not observe any relevant changes
in fluid management or creatinine at 24 hours in those patients
whose PEEP was increased based on the study findings.

DISCUSSION
The main findings of this study on morbidly obese critically ill
patients can be summarized as follows:
1. The PEEP level set by managing clinicians is considerably
less than that required to maintain Ptpe above 0cm H2O.
2. The Ecw in morbidly obese patients is not increased and is
not affected by lung recruitment in the setting of optimal
PEEP.
3. Lung RMs increase EELV and improve Ers and El while
markedly increasing oxygenation.
4. Determination of optimal PEEP in obese patients following
a lung RM is not significantly different, whether the PEEP
trial is done using a decremental PEEP trial without measurement of transpulmonary pressure or by using measurements of transpulmonary pressure to insure that the Ptpe is
greater than 0cm H2O.
5. Elevation of the head of the bed increases EELV and reduces
the optimal PEEP needed.
It has been previously reported that Ecw might be impaired
in obese patients, a possible cause of increased work of breathing and suboptimal mechanical ventilation (10, 20, 21).
However, the finding that our patients did not show significant alterations in Ecw supports the hypothesis that increased
abdominal fat acts like a mechanical weight requiring a high
level of PEEP to maintain physiologic EELV but does not cause
significant alterations in Ecw (22), leading to a right shift of the
respiratory system pressure-volume relationship (8, 23).
We measured EELV by nitrogen wash-in/wash-out technique
(24, 25). EELV was markedly reduced in our study population,
consistent with findings reported by others (6). Although PEEP
titration was effective at increasing EELV, it could not completely
reestablish the loss of lung volume. One possible explanation
was that our population was composed of critically ill patients
on mechanical ventilation, in whom normal respiratory system
function cannot be expected. In addition, titrated PEEP levels
were able to achieve a Ptpe greater than 0cm H2O. However, this
is a measure of a local phenomenon: lung tissue that lies below
the measurement level is not necessarily ventilated at positive
transpulmonary pressure throughout the tidal cycle.
At the PEEP levels set by clinicians, breathing occurred at
negative transpulmonary pressures for most of the tidal cycle,
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Figure 1. Changes in end-expiratory lung volumes at different positive


end-expiratory pressure (PEEP) levels. End-expiratory lung volume
(EELV) significantly increased from baseline after PEEP titration
(*p < 0.0005). Head of bed elevation at the same titrated PEEP
levels further increased EELV although resulted in an increase in lung
elastance (Fig.3). The recruitment maneuver (RM) was effective at
further increasing EELV (#p = 0.017) while reducing lung elastance
(Fig.3). **EELV at zero end-expiratory positive pressure (ZEEP) was
measured in three patients only. Data are presented as mean sd. *p
< 0.0005, paired t test baseline versus positive transpulmonary after
RM, baseline versus best decremental PEEP after RM, baseline versus
best decremental PEEP head of bed 30 degree with a Bonferroni-Holm
adjusted of 0.0033. #p = 0.017, paired t test positive transpulmonary
no RM versus positive transpulmonary after RM, of 0.05. IBW = ideal
body weight, baseline = PEEP level adopted by the clinical staff, positive
transpulmonary = lowest PEEP level at which the end-expiratory
transpulmonary pressure was positive, best decremental PEEP = 2cm
H2O above the PEEP at which the elastance of the respiratory system
was lowest, tested through a decremental PEEP trial.

resulting in cyclic collapse and reopening of alveoli (26). The


exposure to markedly negative end-expiratory pressure is the
pathophysiologic cause of distal airway closure and gas reabsorption, leading to atelectasis. The fact that atelectasis is the major
pathophysiologic alteration in obese patients is evidenced by low
EELV and by the increased Ers and El (Table2). As expected, this
phenomenon is more pronounced at ZEEP (Figs.13).
Shifting the respiratory cycle into positive transpulmonary
pressure by applying PEEP without performing a RM did not
prevent collapsed alveoli, even though EELV increased, since
El did not change. After a RM, however, we observed a second
increase in EELV and a reduction in Ers and El. These observations support the hypotheses that PEEP alone is not sufficient
to successfully recruit collapsed alveolar units (27) but instead
leads to a gain in EELV at the price of overdistension of already
aerated lung tissue (28). A pattern similar to that observed after
a PEEP increase without performing a RM was also observed
after elevating the head of the bed by 30 degrees, suggesting
that the upright positioning of obese patients lowers the PEEP
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Clinical Investigations

Figure 2. Changes in end-inspiratory transpulmonary pressure and


end-expiratory transpulmonary pressure. Transpulmonary pressures
cycle into negative values at commonly set (baseline) PEEP levels.
PEEP titration significantly increased end-expiratory and end-inspiratory
transpulmonary pressures (*p < 0.0004). However, end-inspiratory
transpulmonary pressure remained low after PEEP titration (positive
transpulmonary after recruitment maneuver [RM]: 95% CI, 4.688.48
cm H2O, best decremental PEEP after RM: 95% CI, 6.09.0cm H2O).
After the RM at positive transpulmonary PEEP level, the end-expiratory
pressure did not change (#p = 0.43), while the end-inspiratory pressure
significantly decreased (#p = 0.01). **Transpulmonary pressures at
zero end-expiratory positive pressure (ZEEP) were measured only
in four patients. Data presented as mean sd. *p < 0.0004, paired t
test baseline versus positive transpulmonary no RM, baseline versus
positive transpulmonary after RM, baseline versus best decremental
PEEP after RM, baseline versus best decremental PEEP head of bed
30 degree with a Bonferroni-Holm adjusted of 0.0033. #p = 0.43
and p = 0.01, paired t test positive transpulmonary no RM versus
positive transpulmonary after RM, of 0.05. Baseline = positive endexpiratory pressure (PEEP) level adopted by the clinical staff, positive
transpulmonary = lowest PEEP level at which the end-expiratory
transpulmonary pressure was positive, best decremental PEEP = 2cm
H2O above the PEEP at which the elastance of the respiratory system
was lowest, tested through a decremental PEEP trial.

requirements for optimal lung volume and gas exchange (9,


10). We did not test, however, the effects of an additional RM
after head of bed elevation.
Atelectasis during positive pressure ventilation can cause
ventilation/perfusion mismatch by two mechanisms. In supine
positioning, PEEP causes a displacement of blood flow from
the nondependent to the dependent regions of the lung (29).
In healthy subjects, this shift of blood flow is coupled to a shift
of ventilation from nondependent to dependent regions of the
lung. However, the dependent regions of the lungs of mechanically ventilated obese patients appear atelectatic at commonly
Critical Care Medicine

Figure 3. Chest wall, lung, and respiratory system variations at different


positive end-expiratory pressure (PEEP) values. Respiratory system
elastance did not significantly change after PEEP titration without
recruitment maneuver (RM) (p = 0.37). Titrated PEEP levels were able
to reduce respiratory system and lung elastance compared with baseline
(*p < 0.003). The RM significantly decreased respiratory system and
lung elastance (#p < 0.0002). No changes in chest wall elastance were
detected throughout the tested PEEP values (p = 0.96). **Elastances
at zero end-expiratory positive pressure (ZEEP) were measured only
in four patients. Data presented as mean sd. *p < 0.003, paired t test
baseline versus positive transpulmonary after RM, baseline versus best
decremental PEEP after RM with a Bonferroni-Holm adjusted of 0.0033.
#p < 0.0002, paired t test positive transpulmonary no RM versus positive
transpulmonary after RM, of 0.05. Chest wall elastance p = 0.96, analysis
of variance for repeated measures. Baseline = PEEP level adopted by the
clinical staff, positive transpulmonary = lowest PEEP level at which the endexpiratory transpulmonary pressure was positive, best decremental PEEP =
2cm H2O above the PEEP at which the elastance of the respiratory system
was lowest, tested through a decremental PEEP trial.

adopted PEEP levels due to high pleural pressure (Figs.1 and


2 and Table2). Consistently, at baseline levels of PEEP, we
observed a low Pao2/Fio2 ratio (Fig.4 and Table2). After a
RM followed by the application of titrated PEEP, we observed
a marked improvement in arterial oxygenation, EELV, and El
(Figs.1, 3 and 4 and Table2), indicating that the application of
PEEP after a RM is effective at keeping atelectatic areas open
and improving gas exchange in morbidly obese patients.
Under the hypothesis of an increased Ecw, we expected
to observe a markedly negative heart-lung interaction at
increased positive pressures in obese patients (3032).
However, Figure5 shows no significant variation of the measured hemodynamic parameters at the different PEEP levels studied. Positive airway pressure influences right heart
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305

Pirrone et al

Figure 4. Differences in oxygenation between baseline and differently


titrated positive end-expiratory pressure (PEEP) levels. Pao2/Fio2
significantly increased after PEEP titration and recruitment maneuvers
(RMs) compared with baseline (*p < 0.0001). No difference in
oxygenation was found between the two different titration techniques
(p = 0.28). Data presented as mean sd. *p < 0.0001, baseline versus
positive transpulmonary after RM, baseline versus best decremental PEEP
after RM, with a Bonferroni-Holm adjusted level of 0.016. Baseline =
PEEP level adopted by the clinical staff, positive transpulmonary = lowest
PEEP level at which the end-expiratory transpulmonary pressure was
positive, best decremental PEEP = 2cm H2O above the PEEP at which
the elastance of the respiratory system was lowest, tested through a
decremental PEEP trial.

function by increasing pericardial pressure and limiting the


diastolic filling of the heart (33). In addition, pericardial pressure increases linearly with pleural pressure in lung-healthy
subjects (33, 34). As noted in Table2 and reported by Behazin
et al (8), these patients show elevated pleural pressures at
baseline, no significant Ecw alteration, and high El. Increasing
PEEP to the level of a positive end-expiratory pleural pressure should not significantly influence pleural pressure. Only
five study patients showed transient hypotension during the
RM, when airway pressure was markedly higher than pleural
pressure (Table S2, Supplemental Digital Content 1, http://
links.lww.com/CCM/B489), but not at titrated PEEP levels.
There were no increases in vasopressor use at 24 hours in
those patients whose poststudy PEEP was increased, no signs
of increased fluid requirements (daily water balance), and no
worsening of kidney function (Tables S1 and S2, Supplemental
Digital Content 1, http://links.lww.com/CCM/B489).
There are some limitations in this study that the reader
should be aware of. First, patients were not subject to a randomized application of differently titrated PEEP levels. Second,
gas exchange evaluation could not be performed at every study
step, limiting the conclusions on the efficacy of RMs. The
results of this study increase the available knowledge on obese
respiratory pathophysiology, raising attention on the need of
306

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Figure 5. Heart rate and systolic and diastolic blood pressure changes
at different end-expiratory pressures. No significant differences were
observed between the tested PEEP values for systolic blood pressure
(p = 0.37, analysis of variance for repeated measures [rANOVA]), diastolic
blood pressure (p = 0.36, rANOVA), or heart rate (p = 0.01, rANOVA, no
significant differences in post hoc t test comparisons with a BonferroniHolm adjusted level of 0.0033). **Zero end-expiratory positive pressure
(ZEEP) maneuver and hemodynamic data collection were performed
only on four patients. Data presented as mean sd. Baseline = positive
end-expiratory pressure (PEEP) level adopted by the clinical staff,
positive transpulmonary = lowest PEEP level at which the end-expiratory
transpulmonary pressure was positive, best decremental PEEP = 2cm
H2O above the PEEP at which the elastance of the respiratory system
was lowest, tested through a decremental PEEP trial.

lung recruitment and PEEP titration in the management of


obese patients. Future studies should focus on the effects of
titrated PEEP on distribution of ventilation, perfusion, and
heart-lung interaction. Additionally, there is still a lack of solid
data on the management of the weaning process of morbidly
obese patients.

CONCLUSIONS
This study outlines the deleterious pathophysiologic effects of
commonly adopted PEEP levels in critically ill morbidly obese
patients. We have found that routinely set PEEP levels expose
this population to atelectasis and hypoxemia. Tailoring a ventilation strategy based on the implementation of RMs followed
by PEEP titration significantly improved respiratory mechanics and gas exchange.
February 2016 Volume 44 Number 2

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Clinical Investigations

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