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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
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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
Copyright 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Clinical Investigations
Copyright 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
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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.
14
54.015.7
6 (42.9)
Female, n (%)
Height, mean sd, cm
170.912.5
146.140.8
50.716.0
144.823.3
151.823.8
34.618.1
15.87.9
Intra-abdominal pressure,
mean sd, cm H2O
13.85.6
Admission
Medical, n (%)
7 (50)
5 (35.7)
2 (14.3)
Primary diagnosis
Upper airway obstruction, n (%)
2 (14.3)
1 (7.1)
Sepsis, n (%)
9 (64.3)
1 (7.1)
Trauma, n (%)
1 (7.1)
2 (14.3)
12 (85.7)
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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
February 2016 Volume 44 Number 2
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Clinical Investigations
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
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
23.26.8
23.21.3
22.15.1
17.94.0b,c
18.24.4b
20.85.2
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
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.
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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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Clinical Investigations
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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.
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
REFERENCES
www.ccmjournal.org
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