British Journal of Anaesthesia, xxx (xxx): xxx (xxxx)
doi: 10.1016/j.bja.2023.08.007
Advance Access Publication Date: xxx
Clinical Investigation
CLINICAL INVESTIGATION
Effect of driving pressure-guided positive end-expiratory pressure
on postoperative pulmonary complications in patients undergoing
laparoscopic or robotic surgery: a randomised controlled trial
Yoon Jung Kim1,2, Bo Rim Kim3
, Hee Won Kim2, Ji-Yoon Jung2
Jeoung-Hwa Seo1,2 , Won Ho Kim1,2
Hyun-Kyu Yoon1,2,*
1
, Hye-Yeon Cho1,2,
, Hee-Soo Kim1,2, Suhyun Hwangbo4
and
Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of
Korea, 2Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of
Korea, 3Department of Anesthesiology and Pain Medicine, Korea University College of Medicine, Korea University Guro
Hospital, Seoul, Republic of Korea and 4Department of Genomic Medicine, Seoul National University Hospital, Seoul,
Republic of Korea
*Corresponding author. E-mail: warren83@snu.ac.kr
Abstract
Background: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether
PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressureguided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery.
Methods: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or
robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the
comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg1 ideal
body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by prespecified clinical and radiological criteria) within 7 postoperative days after surgery.
Results: Some 384 patients (median age: 67 yr [inter-quartile range: 61e73]; 66 [18%] female) were randomised. Mean
(standard deviation) PEEP in patients randomised to individualised PEEP (n¼178) was 13.6 cm H2O (2.1). Individualised
PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard
PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There
was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP
(36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45e1.15]; P¼0.215). Pulmonary complications as a result of desaturation were
less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%],
risk ratio [95% CI], 0.28 [0.13e0.59]; P¼0.001).
Conclusions: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of
laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event
rate for the primary outcome.
Clinical trial registration: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).
Keywords: driving pressure; lung protective ventilation; pneumoperitoneum; positive end-expiratory pressure;
postoperative pulmonary complications
Received: 1 February 2023; Accepted: 1 August 2023
© 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com
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Kim et al.
Editor’s key points
Individualised PEEP determined by a driving
pressure-guided intervention might reduce pulmonary
complications
after
laparoscopic/robotic
abdominal surgery.
This single-centre study randomised 384 patients at
risk of postoperative pulmonary complications to
receive either driving pressure-guided PEEP or 5 cm
H2O fixed PEEP during surgery.
Individualised PEEP resulted in 3.7 cm H2O lower
mean driving pressure.
Pulmonary complications were lower than anticipated but similar between individualised vs standard
PEEP.
Optimal PEEP settings remain unclear for laparoscopic/robotic abdominal surgery.
Over the past few decades, laparoscopic and robotic techniques have become increasingly common approaches for
lower abdominal surgery, with the aim of accelerating postoperative recovery.1,2 The combination of pneumoperitoneum
with steep Trendelenburg positioning to facilitate lower
abdominal/pelvic surgery3 promotes atelectasis and reduces
lung compliance and arterial oxygenation.4 Postoperative
pulmonary complications (PPCs) are common in patients undergoing laparoscopic lower abdominal surgery.5 As PPCs
prolong hospitalisation and possibly increase mortality,6,7
optimising intraoperative mechanical ventilation strategies
may prevent these complications.
Intraoperative lung-protective ventilation is associated
with reduced PPC incidence.8 Positive end-expiratory pressure
(PEEP), a key component of lung-protective ventilation, prevents the closure of small airways and alveolar collapse;
thus, ventilationeperfusion mismatch and oxygenation are
improved.9 However, large multicentre randomised controlled
trials comparing two fixed PEEP values showed no clinically
significant differences in PPCs,10,11 which has prompted clinicians to focus on individualised adjustment of PEEP.12
Whereas many studies have investigated the effects of individualised PEEP on clinical outcomes,13e17 the role of individualised PEEP remains unclear. In particular, limited data exist
on the association between driving pressure-guided PEEP and
PPCs in laparoscopic or robotic lower abdominal surgery.
Therefore, in the present study, we investigated the impact
of driving pressure-guided PEEP on PPCs in patients scheduled
to undergo surgeries requiring pneumoperitoneum with the
steep Trendelenburg position. We hypothesised that driving
pressure-guided PEEP during surgery would decrease PPCs
within 7 postoperative days.
Methods
Study design
This single-centre, randomised controlled trial was approved by
the institutional review board of the Seoul National University
Hospital (Approval number: 2002-142-1104). The protocol of the
present study was registered at the clinical trial registry (http://
cris.nih.go.kr, principal investigator: H-KY, registration date:
April 6, 2020, registration number: KCT0004888), and written
informed consent was obtained from all patients before enrolment. This study was conducted in compliance with the Good
Clinical Practice guidelines, and the manuscript was written in
accordance with the applicable Consolidated Standards of
Reporting Trials (CONSORT) guidelines.
Inclusion criteria
The patients aged 18 yr with a moderate or high risk of PPCs
according to the Assess Respiratory Risk in Surgical Patients in
Catalonia (ARISCAT) risk score,6 scheduled to undergo laparoscopic or robotic surgery in the steep Trendelenburg position at a tertiary teaching hospital (Seoul National University
Hospital) between April 9, 2020 and September 2, 2022 were
eligible.
Exclusion criteria
We excluded patients with conversion to open surgery,
American Society of Anesthesiologists (ASA) physical status
classification 3, history of acute respiratory distress syndrome (ARDS), body mass index 35 kg m2, angina, heart
failure, increased intracranial pressure, pregnancy, and contraindications to the use of PEEP, including bronchopleural
fistula, hypovolemic shock, and right ventricular failure.
Randomisation and blinding
An investigator not involved in this study generated the
random sequence table with a one-to-one ratio using a computer program with a block size of two and four before patient
recruitment. The patients were randomly assigned to receive
either individualised PEEP based on driving pressure (individualised group) or a fixed PEEP of 5 cm H2O during surgery
(standard group). The random allocation sequence was sealed
in an opaque envelope and released to the attending anaesthesiologist immediately before the trial. The investigators
assessing the primary outcomes were blinded to the group
allocation. Both surgeons and patients were also unaware of
their respective group allocations. However, the attending
anaesthesiologists were not blinded to the study group
allocation.
Anaesthesia protocol
Peripheral pulse oximetry (SpO2), electrocardiography, and
noninvasive blood pressure monitoring were performed upon
entry to the operating room. After adequate preoxygenation,
anaesthesia was induced with a target-controlled infusion of
remifentanil (target effect-site concentration of 4 ng ml1) and
propofol bolus administration (1.0e2.0 mg kg1). Tracheal
intubation was performed after achieving adequate neuromuscular block. Mechanical ventilation started via the volumecontrolled ventilation mode with a fraction of inspired oxygen
(FiO2) of 0.4, tidal volume of 8 ml kg1 for ideal body weight,
PEEP of 5 cm H2O, and an inspiratory-to-expiratory (I:E) ratio of
1:2. The respiratory rate was adjusted to maintain an end-tidal
carbon dioxide (ETCO2) of 4.7e6.0 kPa. The bispectral index was
adjusted within 40e60, and the mean blood pressure was
maintained within 8e12 kPa (60e90 mm Hg). During the
pneumoperitoneum, the degree of neuromuscular block was
maintained as deep neuromuscular block, defined as a train-offour of 0 and post-tetanic count 4 using a neuromuscular
Driving pressure-guided individualised PEEP
monitoring device (TOF-Watch SX, Bluestar Enterprises,
Omaha, NE, USA). Extubation was performed after administering sugammadex. The protocol mentioned above was provided identically to patients in both groups.
Study protocol
Three clinicians, including two primary researchers (YJK and
H-KY) and another investigator who was not involved in
assessing postoperative clinical outcomes but was part of the
study team, were engaged in the intervention process. All
intervention processes, including recruitment manoeuvres
and decremental PEEP trials, were performed by one of the two
experienced researchers. During the intervention, the investigator recorded the intervention results and ensured the accuracy of the intervention process. In the individualised group,
the first recruitment manoeuvre was performed after achieving
the pneumoperitoneum with the steep Trendelenburg position. The volume-controlled ventilation mode was maintained
at a respiratory rate of 15 bpm and an I:E ratio of 1:1 during the
recruitment manoeuvre. At each 40-s increment, PEEP was
then increased from 5 to 20 cm H2O by 5 cm H2O. The recruitment manoeuvre was followed by a decremental PEEP trial,
which was initiated at a PEEP of 20 cm H2O. During this trial,
with the same respiratory rate and an I:E ratio of 1:2, PEEP was
sequentially reduced from 20 to 5 cm H2O by 2 cm H2O every 30
s. Driving pressure was measured by subtracting the PEEP from
the plateau pressure at the end of each step. Individualised
PEEP was defined as a PEEP that produced the lowest driving
pressure. A second recruitment manoeuvre was performed at
the end of the decremental PEEP trial. Individualised PEEP was
subsequently applied during the pneumoperitoneum. When
the pneumoperitoneum ended, another individualised PEEP
was determined using the abovementioned manner. The second individualised PEEP was maintained until the end of the
surgery. In the standard group, PEEP was initially set to 5 cm
H2O and maintained throughout the surgery.18
As an intraoperative rescue therapy, a recruitment
manoeuvre was performed if SpO2 decreased below 95% in the
two groups, where PEEP was increased stepwise from 5 to 20
cm H2O at an I:E ratio of 1:1, and FiO2 was increased by 0.1
subsequently. PEEP was increased by 2 cm H2O after the
recruitment manoeuvre if SpO2 remained below 95% under an
FiO2 of 1.0. If titration or application of PEEP interfered with the
surgery or caused severe haemodynamic instability, including
hypotension or bradycardia that did not respond with fluid
resuscitation and administration of vasoactive drugs, PEEP
was changed at the discretion of attending anaesthesiologists
and recorded. Ephedrine or phenylephrine was administered
in both groups to correct hypotension, defined as systolic
blood pressure (SBP) <12 kPa, at the discretion of the attending
anaesthesiologists. In the postanaesthesia care unit (PACU),
an arterial blood gas analysis was performed in room air. If
SpO2 decreased by less than 92% in room air, oxygen supply
was initiated through a nasal prong or facial mask in both
groups. FiO2 was increased if SpO2 was 95% or less despite
supplying oxygen.
Primary outcome
The primary outcome was a composite of pulmonary complications within 7 postoperative days.19 A composite of
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pulmonary complications included atelectasis, hypoxaemia,
ARDS, pneumonia, pleural effusion, bronchospasm, pneumothorax, aspiration pneumonia, early extubation failure or
requirement of reintubation, and postoperative requirements
for rescue manoeuvres (Supplementary Table S1). Atelectasis,
pleural effusion, and pneumothorax were diagnosed by
radiological reports, and others were determined by clinicians.
Secondary outcomes
Secondary outcomes included the length of hospital stay,
admission to the intensive care unit (ICU), length of ICU stay,
frequency of hypoxaemia (arterial partial pressure of oxygen
[PaO2] <8.0 kPa or SpO2 <90% at room air), and arterial blood gas
analyses. Arterial blood gas analysis was performed at the
following five time-points: 10 min after anaesthesia induction
(T1), 30 min after implementing pneumoperitoneum in the
steep Trendelenburg position (T2), 1 h after T2 (T3), 2 h after T2
(T4), and just before emergence in the operating room (T5). The
intraoperative ventilatory parameters, including peak inspiratory pressure, plateau pressure, tidal volume, PEEP, dynamic
and static compliances, mean blood pressure, and heart rate,
were automatically recorded at a 1-min interval in the electronic medical record (EMR) systems. All these records were
retrieved from the EMR systems by an investigator blinded to
the group assignment. Intraoperative hypotension was
defined as a time-weighted average (TWA) SBP of <12 kPa,
which was calculated as the area between the threshold (12
kPa) and the curve of the SBP measured at a 1-min interval
divided by the total duration of monitoring.
Sample size calculation
In a previous study on patients with moderate or high risk,
according to the ARISCAT risk index, PPC incidence was 51.2%
after major abdominal surgery using lung-protective ventilation.20 Assuming a significant difference as a 30% decrease in
PPC incidence with a two-sided type I error of 0.05 and a power
of 80%, 163 patients were required per group. The dropout rate
was expected to be up to 15%; therefore, 192 patients had to be
enrolled in each group, with 384 patients in total.
Statistical analysis
Primary analyses utilised per protocol analysis to obtain a more
precise estimate of the efficacy of driving pressure-guided
PEEP, including only patients who adhered to the predefined
PEEP individualisation protocol. Additionally, we conducted an
intention-to-treat analysis as a sensitivity analysis. We summarised the collected data as mean (standard deviation, SD) or
median (inter-quartile range) or the number of patients (percentage), as appropriate. The ShapiroeWilk test was used to
evaluate the normality of the data. Pearson c2 or Fisher’s exact
test was used to compare categorical data. Continuous data
were analysed using the Student t-test or ManneWhitney Utest, where appropriate. Because of cell sparsity, the PPC count
was deemed a categorical variable and compared using
Fisher’s exact test. We used repeated measures analysis of
variance (ANOVA) test for respiratory parameters and arterial
blood gas analysis results. To investigate the risk factors for
PPCs, we conducted a post hoc multivariate logistic regression
analysis with a stepwise selection using preoperative and
intraoperative variables. Statistical analyses were performed
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Kim et al.
using R software (version 4.1.3; R Foundation for Statistical
Computing, Vienna, Austria). P-values <0.05 were considered
statistically significant except for repeated measured
parameters.
Results
Participant characteristics
From April 2020 to September 2022, 384 subjects meeting the
inclusion criteria were enrolled (Table 1). Twenty-one patients
were excluded after allocation (Fig. 1). The final per protocol
analysis included the remaining 363 patients (178 and 185
patients in the individualised and standard PEEP groups,
respectively).
to -3.1 cm H2O]; P<0.001). The peak inspiratory and plateau
pressures were also higher with individualised PEEP (Fig. 2).
Primary outcome: postoperative pulmonary
complications
There was no difference in the incidence of PPCs within seven
postoperative days between individualised (25/178 [14.0%])
and standard (36/185 [19.5%]) PEEP (risk ratio [95% CI]: 0.72
[0.45e1.15], P¼0.215; Table 3). The incidence of each postoperative complication was also comparable between the two
groups. Among patients who developed PPCs within 7 postoperative days, most patients presented only one complication (22/25 [88.0%] and 28/36 [77.8%], respectively). The
intention-to-treat analysis findings were similar to the perprotocol analysis (Supplementary Table S4).
Effect of individualised driving pressure-guided PEEP
intervention
Secondary outcomes
The mean (SD) PEEP with individualised PEEP was 13.6 (2.1) cm
H2O (Table 2). Individualised PEEP resulted in lower driving
pressure than standard PEEP (14.7 [2.6] vs 18.4 [3.2] cm H2O,
mean difference [95% confidence interval, CI] -3.7 cm H2O [-4.3
The need for rescue interventions for episodes of acute desaturation was less frequent with individualised PEEP (8/178
[4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio
[95% CI], 0.28 [0.13e0.59]; P¼0.001). Although there was no
Table 1 Comparisons of preoperative subject characteristics between the two groups. Data are mean (standard deviation), median
(inter-quartile range), or n (%). APTT, activated partial thromboplastin time; ARISCAT, the Assess Respiratory Risk in Surgical Patients
in Catalonia; ASA-PS, American Society of Anesthesiologists physical status; eGFR, estimated glomerular filtration rate; FEV1, forced
expiratory volume in one second; FVC, forced vital capacity; INR, international normalised ratio.
Characteristics
Individualised
group (n¼178)
Standard group
(n¼185)
Standardised
mean difference
Age, yr (median [range])
Sex, n (%)
Female
Male
Height, cm
Weight, kg
Body mass index, kg m2
Current smoker, n (%)
ARISCAT risk score
Preoperative pulmonary function test
FVC, L
FEV1, L
FEV1/FVC, %
ASA-PS classification, n (%)
1
2
Comorbidities, n (%)
Hypertension
Diabetes mellitus
Respiratory disease
Chronic liver disease
Cardiac disease
Thyroid disease
Neurologic disease
Chronic kidney disease
Preoperative laboratory results
Haemoglobin, g dl1
Platelet, 1000 mm3
White blood cell count, 1 000 mm3
Prothrombin time, INR
Serum creatinine, mg dl1
eGFR, ml min1 1.73 m2
APTT, s
Serum albumin, g dl1
C-reactive protein, mg dl1
67 (39e83)
67 (38e87)
0.069
0.047
34 (19.1)
144 (80.9)
164.9 (7.1)
67.3 (9.3)
24.6 (23.0e26.3)
24 (13.5)
26.0 (26.0e26.0)
32 (17.3)
153 (82.7)
166.3 (6.9)
68.6 (9.5)
24.8 (23.0e26.6)
30 (16.2)
26.0 (26.0e26.0)
3.8 (0.7)
2.8 (0.5)
74.0 (7.6)
3.9 (0.8)
2.8 (0.6)
72.8 (7.4)
37 (20.8)
141 (79.2)
43 (23.2)
142 (76.8)
91 (51.1)
29 (16.3)
18 (10.1)
19 (10.7)
9 (5.1)
9 (5.1)
3 (1.7)
8 (4.5)
81 (43.8)
40 (21.6)
20 (10.8)
15 (8.1)
6 (3.2)
18 (9.7)
9 (4.9)
12 (6.5)
0.147
0.136
0.023
0.088
0.091
0.179
0.179
0.088
13.6 (13.0e14.3)
222.0 (189.0e252.5)
5.9 (5.0e6.6)
1.0 (0.1)
0.9 (0.8e1.0)
87.7 (77.2e93.6)
30.3 (3.1)
4.4 (4.3e4.6)
0.2 (0.3)
13.7 (13.0e14.6)
213.0 (186.0e253.0)
5.9 (5.1e7.0)
1.0 (0.1)
0.9 (0.8e1.0)
87.1 (76.9e91.8)
30.2 (2.8)
4.4 (4.2e4.6)
0.2 (0.4)
0.147
0.041
0.050
0.048
0.030
0.035
0.025
0.079
0.044
0.203
0.148
0.023
0.077
0.057
0.075
0.002
0.160
0.059
Enrollment
Driving pressure-guided individualised PEEP
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5
Assessed for eligibility
(n=518)
Excluded (n=134)
• Declined to participate (n=65)
• Other reasons (n=69)
Allocated to the standard group who received
a fixed PEEP of 5 cm H2O (n=192)
▪ Received allocated intervention (n=183)
▪ Did not receive allocated intervention (n=9)
• Change in surgical plan (n=5)
• Cancellation of surgery (n=3)
• Not meeting inclusion (n=1)
▪ Received allocated intervention (n=186)
▪ Did not receive allocated intervention (n=6)
• Change in surgical plan (n=3)
• Cancellation of surgery (n=2)
• Not meeting inclusion (n=1)
Follow-up
Lost to follow-up (n=0)
Discontinued intervention (n=5)
• Unavailable investigator (n=3)
• Protocol violation (n=1)
• Intraoperative massive bleeding (n=1)
Lost to follow-up (n=1)
• Incomplete records at ward (n=1)
Discontinued intervention (n=0)
Analysed (n=178)
• Excluded from analysis (n=0)
Analysed (n=185)
• Excluded from analysis (n=0)
Allocation
Allocated to the individualised group who
received driving pressure-guided PEEP (n=192)
Analysis
Randomised (n=384)
Fig 1. CONSORT flow diagram.
difference in time-weighted hypotension, the number of bolus
administrations of vasoactive drugs was more frequent with
individualised PEEP (2.1 [2.5] vs standard PEEP 1.5 [1.9];
P¼0.009).
Intraoperatively, PaO2 and SaO2 were higher with individualised PEEP (Fig. 3; Supplementary Table S2). Other postoperative clinical outcomes, including respiratory failure,
length of hospital stays, ICU admission, and postoperative
non-pulmonary complications were similar between the two
groups.
Post hoc analyses
Mean driving pressure (odds ratio [OR], 1.114, 95% CI,
1.024e1.212, P¼0.012), ARISCAT risk score (OR, 1.076, 95% CI,
1.014e1.142, P¼0.015), and intraoperative estimated blood loss
(OR, 1.001, 95% CI, 1.000e1.002, P¼0.023) were associated with
PPCs (Supplementary Table S3)
Discussion
In this randomised controlled trial, we failed to demonstrate
the beneficial effects of driving pressure-guided individualised
PEEP on PPCs for up to 7 days after surgery requiring pneumoperitoneum and steep Trendelenburg position. Although
individualised PEEP improved some intraoperative respiratory
and arterial blood gas variables, these benefits were not
translated into improved postoperative clinical outcomes.
The lack of difference in incidence of PPCs between groups
may be partly explained by several reasons. First, despite
enrolling patients with moderate-to-high risk based on the
ARISCAT risk score calculated using the expected duration of
surgery, a substantial proportion of patients (84%) had a score of
26, a borderline value for distinguishing between low- and
moderate-risk patients. Furthermore, ~61% of patients had
actual operation times of <180 min. This unintended inclusion
of a significant number of low-medium risk patients resulted in
our trial being underpowered. Moreover, unlike a previous
study, we excluded patients with an ASA physical status classification 3 because of considerations of patient safety.20 Second, the beneficial effects of intraoperative individualised PEEP
may disappear after extubation and not persist after surgery, as
reported in several previous studies.13,17,21 Thus, postoperative
measures, rather than only intraoperative intervention, may be
needed to prevent postoperative atelectasis or decruitment.20
Future well-powered randomised controlled trials to test this
hypothesis are warranted. Lastly, driving pressure may not
adequately represent the lung strain in laparoscopic or robotic
surgical patients because its calculation may be influenced by
the properties of the whole respiratory system.22 In robotic
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Kim et al.
Table 2 Comparisons of intraoperative and postoperative characteristics between the two groups. Data are mean (standard deviation),
median (inter-quartile range), or n (%). AUC, the area under the curve; CI, confidence interval; NA, not applicable; SBP, systolic blood
pressure; TWA, time-weighted average. *Indicates the fluid given the rest of the day of surgery, not including the intraoperative fluid
amount.
Characteristics
Type of surgery, n (%)
Prostatectomy
Gynaecologic surgery
Cystectomy
Colorectal surgery
Surgical modality, n (%)
Laparoscopic surgery
Robotic surgery
Anaesthesia time, min
Surgery time, min
Intra-abdominal pressure, kPa
Ventilatory parameters
Mean positive end-expiratory
pressure, cm H2O
Mean peak inspiratory pressure, cm
H 2O
Mean plateau pressure, cm H2O
Mean driving pressure, cm H2O
Mean tidal volume, ml
Mean respiratory rate, bpm
Intraoperative fluid management
Infused fluid volume, ml
Urine output, ml
Estimated blood loss, ml
Transfusion, n (%)
Medications
Number of bolus administrations of
vasoactive drugs
Number of bolus administrations of
ephedrine
Number of patients who received
ephedrine, n (%)
Cumulative dose of ephedrine, mg
Number of bolus administrations of
phenylephrine
Number of patients who received
phenylephrine, n (%)
Cumulative dose of
phenylephrine, ug
Intraoperative hypotension
AUC SBP <12 kPa, kPa min
TWA SBP <12 kPa, kPa
Rescue intervention because of
intraoperative
desaturation (95%), n (%)
Intraoperative subcutaneous
emphysema
Postoperative fluid status
intake, ml
Postoperative day 0*
Postoperative day 1
Postoperative day 2
Postoperative day 3
Output, ml
Postoperative day 0*
Postoperative day 1
Postoperative day 2
Postoperative day 3
P-value
Individualised
group (n¼178)
Standard group
(n¼185)
Risk ratio, mean, or
median difference
(95% CI)
129 (72.5)
32 (18.0)
16 (9.0)
1 (0.6)
133 (71.9)
30 (16.2)
21 (11.4)
1 (0.5)
1.01 (0.89e1.14)
1.11 (0.70e1.74)
0.79 (0.43e1.47)
1.04 (0.07e16.49)
29 (16.3)
149 (83.7)
167 (136e223)
135 (105e184)
2.0 (2.0e2.0)
27 (14.6)
158 (85.4)
180 (145e225)
143 (110e180)
2.0 (2.0e2.0)
1.11 (0.69e1.81)
0.98 (0.90e1.07)
-13 (-21 to 10)
-8 (-20 to 8)
0.00 (0.00e0.00)
0.284
0.359
0.646
13.6 (2.1)
5.1 (0.6)
8.5 (8.1e8.8)
<0.001
31.3 (3.9)
26.3 (3.6)
5.0 (4.2e5.8)
<0.001
27.7 (4.1)
14.7 (2.6)
483.2 (53.9)
14.3 (1.9)
22.9 (3.3)
18.4 (3.2)
494.5 (54.7)
13.7 (2.6)
4.8 (3.6e6.1)
-3.7 (-4.3 to -3.1)
-11.3 (-23 to 0.4)
0.6 (0.1e1.1)
<0.001
<0.001
0.058
0.005
1050 (750e1450)
219 (191)
240 (159)
0 (0.0)
1050 (800e1450)
223 (214)
339 (273)
1 (0.5)
0 (-175 to 200)
-5 (-70 to 61)
-99 (-147 to -52)
NA
0.598
0.892
<0.001
0.999
2.1 (2.5)
1.5 (1.9)
0.62 (0.15e1.09)
0.009
1.5 (1.6)
1.2 (1.4)
0.31 (-0.01 to 0.63)
0.054
112 (62.9)
103 (55.7)
1.13 (0.95e1.34)
0.194
8.7 (9.5)
0.6 (1.7)
6.5 (8.0)
0.3 (1.0)
2.17 (0.36e3.99)
0.31 (0.02e0.60)
0.019
0.034
37 (20.8)
31 (16.8)
1.24 (0.81e1.91)
0.396
27.2 (86.3)
9.2 (30.0)
17.99 (4.48e31.50)
0.008
3.8 (0.0e8.8)
0.02 (0.00e0.05)
8 (4.5)
3.2 (0.0e7.8)
0.01 (0.00e0.03)
30 (16.2)
0.60 (-0.93 to 2.53)
0.002 (-0.01 to 0.01)
0.28 (0.13e0.59)
0.192
0.159
0.001
11 (6.2)
12 (6.5)
0.95 (0.43e2.10)
>0.999
900.0 (700.0e1137.5)
3062.5 (2800.0e3370.0)
2250.0 (1742.5e2560.0)
2070.0 (1650.0e2550.0)
900.0 (700.0e1150.0)
3020.0 (2750.0e3400.0)
2200.0 (1785.0e2650.0)
1960.0 (1580.0e2550.0)
0 (-100 to 84)
42.5 (-80 to 157.5)
-50 (-275 to 170)
110 (-100 to 310)
0.837
0.600
0.918
0.345
670.0 (355.0e1145.0)
2372.5 (1845.0e2810.0)
1860.0 (1523.0e2240.0)
1687.5 (1190.0e2180.0)
670.0 (409.0e1010.0)
2305.0 (1695.0e2755.0)
1897.0 (1489.5e2420.0)
1582.5 (950.0e2260.0)
0 (-125 to 105)
67.5 (-153.5 to 259.5)
-37 (-200 to 134)
105 (-132 to 345)
0.727
0.421
0.857
0.476
0.881
0.762
abdominal surgery with pneumoperitoneum and Trendelenburg positioning, the chest wall primarily distributes the
increased airway pressure.23 This indicates that driving
pressure may be inaccurate as a surrogate marker of lung strain
when chest wall compliance changes.24 In this situation, direct
assessment of transpulmonary pressure may be necessary to
Driving pressure-guided individualised PEEP
40
*
b
*
Plateau pressure (cm H2O)
30
25
20
*
*
T2
T3
Time
T4
*
*
*
35
35
7
30
25
20
15
15
T1
T2
c
*
Driving pressure (cm H2O)
*
T3
Time
T4
*
*
T1
T5
d
T5
*
16
20
15
*
PEEP (cm H2O)
Peak inspiratory pressure (cm H2O)
a
-
12
*
8
10
T1
T2
T3
Time
T4
T5
T1
T2
Individualised
Standard
T3
Time
T4
T5
Fig 2. Intraoperative respiratory parameters recorded at the predefined five time-points; T1, 10 min after anaesthesia induction; T2, 30 min
after implementation of pneumoperitoneum in the steep Trendelenburg position; T3, 1 h after T2; T4, 2 h after T2; and T5 just before
emergence in the operating room. (a) Peak inspiratory pressure, (b) plateau pressure, (c) driving pressure, and (d) positive end-expiratory
pressure. *P<0.0001.
quantify the stress applied to the lung accurately. However, as
measuring transpulmonary pressure using an oesophageal
manometer may be invasive, the decision should be made based
on a careful evaluation of the risks and benefits.
Pneumoperitoneum with the steep Trendelenburg position
enhances surgical conditions in some laparoscopic or robotic
surgery. However, this approach causes the diaphragm to
move upward. Consequently, airway pressure increases and
chest wall compliance decreases.25 In our study, we found that
both plateau pressure and driving pressure were relatively
higher during pneumoperitoneum and the steep Trendelenburg position compared with previous open surgeries15,16 and
laparoscopic or robotic surgeries.26,27 Previous research has
shown a linear relationship between intraabdominal pressure
(IAP) during pneumoperitoneum and respiratory driving
pressure.28 The median IAP during pneumoperitoneum in the
present study was relatively higher at 2 kPa compared with a
previous multicentre study.29 Another study with an IAP of 2
kPa showed that when PEEP was set to 5 cm H2O or the IAPtargeted value, the median driving pressure reached as high
as 12 and 17 cm H2O, respectively, despite surgeries being
performed under a head-up tilt position.30 In summary,
increased IAP during pneumoperitoneum and steep Trendelenburg position could potentially contribute to the higher
plateau and driving pressures observed in this study. However,
previous studies have shown that increased plateau pressure
from elevated IAP does not always result in a proportional
increase in transpulmonary pressure.27 Additionally, when
chest wall compliance varies, driving pressure may not accurately reflect transpulmonary pressure.22 Therefore, relying
8
-
Kim et al.
Table 3 Comparisons of postoperative outcomes between the two groups. Data are mean (standard deviation), median (inter-quartile
range), or n (%). CI, confidence interval; ICU, intensive care unit; NA, not applicable; PACU, post-anaesthesia care unit; SaO2, arterial
oxygen saturation. *The percentage was calculated only in patients who developed postoperative complications. yMild respiratory
failure was defined as PaO2 <8 kPa or SpO2 <90% at room air.
Primary outcome (composite of
postoperative pulmonary
complications), n (%)
Hypoxaemia
Atelectasis
Pleural effusion
Pneumonia
Requirements for rescue manoeuvres
Count of postoperative pulmonary
complications
One complication, n (%)*
Two or more complications, n (%)*
PACU SaO2 at room air, %
Mild respiratory failurey, n (%)
Length of hospital stay, day
ICU admission, n (%)
Postoperative other complications, n (%)
Cardiac complication
Acute kidney injury
Deep vein thrombosis
Infection
Wound dehiscence
Anastomosis site leakage
Ileus
Postoperative bleeding
Postoperative blood transfusion, n (%)
Standard
group
Risk ratio or
mean difference
(n¼178)
(n¼185)
(95% CI)
25 (14.0)
36 (19.5)
0.72 (0.45e1.15)
0.215
4 (2.2)
16 (9.0)
2 (1.1)
0 (0.0)
6 (3.4)
7 (3.8)
29 (15.7)
1 (0.5)
1 (0.5)
10 (5.4)
0.59 (0.18e1.99)
0.57 (0.32e1.02)
2.08 (0.19e22.72)
NA
0.62 (0.23e1.68)
0.584
0.076
0.973
>0.999
0.491
0.147
22 (88.0)
3 (12.0)
95.9 (2.7)
4 (2.2)
6.3 (4.1)
0 (0.0)
15 (8.4)
1 (0.6)
9 (5.1)
0 (0.0)
4 (2.3)
0 (0.0)
3 (1.7)
8 (4.5)
0 (0.0)
2 (1.1)
28 (77.8)
8 (22.2)
95.3 (2.8)
4 (2.2)
7.1 (7.1)
3 (1.6)
16 (8.6)
2 (1.1)
20 (10.8)
1 (0.5)
1 (0.5)
1 (0.5)
4 (2.2)
5 (2.7)
1 (0.5)
3 (1.6)
1.13 (0.90e1.42)
0.54 (0.16e1.84)
0.59 (-0.02 to 1.21)
1.04 (0.26e4.09)
-0.81 (-2.00 to 0.38)
NA
0.97 (0.50e1.91)
0.52 (0.05e5.68)
0.47 (0.22e1.00)
NA
4.16 (0.47e36.84)
NA
0.78 (0.18e3.43)
1.66 (0.55e4.99)
NA
0.59 (0.12e4.10)
solely on plateau pressure and driving pressure may not provide an accurate assessment of lung stress or strain in this
surgical condition.
PEEP plays a critical role as an essential component of
modern intraoperative lung-protective ventilation.8 Previous
studies have explored different methods for individualised
a
*
b
Pa2 (kPa)
Pa2 (kPa)
6.5
6.0
5.5
P-value
Individualised
group
c
†
26
†
24
22
0.058
>0.999
0.181
0.260
>0.999
>0.999
0.068
>0.999
0.342
>0.999
>0.999
0.518
>0.999
>0.999
PEEP, including dynamic and static compliance, driving pressure, transpulmonary pressure, and electrical impedance
tomography.21,24,31e33 Still, it is unclear which method is superior for clinical outcomes. Although recent meta-analyses
found a reduction in PPCs with individualised PEEP,31,34 most
of the included studies had small sample sizes. Furthermore, no
Arterial oxygen
saturation (%)
Variables
†
†
20
18
†
99.5
†
†
†
99.0
98.5
98.0
5.0
T1 T2 T3 T4 T5
Time
T1 T2 T3 T4 T5
Time
Individualised
T1 T2 T3 T4 T5
Time
Standard
Fig 3. Intraoperative arterial blood gas analysis at the predefined five time-points: T1, 10 min after anaesthesia induction; T2, 30 min after
implementation of pneumoperitoneum in the steep Trendelenburg position; T3, 1 h after T2; T4, 2 h after T2; and T5 just before emergence
in the operating room. (a) Arterial partial pressure of carbon dioxide, (b) Arterial partial pressure of oxygen, and (c) Arterial oxygen
saturation. *P¼0.045. yP<0.0001.
Driving pressure-guided individualised PEEP
strong evidence supports consistent improvement in patientimportant outcomes with individualised PEEP.31 Therefore,
large-scale randomised controlled trials are needed to confirm
the effects of individualised PEEP on relevant clinical outcomes
in the future.
Driving pressure is widely recognised as a surrogate
parameter reflecting global lung strain.24 A robust association between driving pressure and survival was initially
reported in patients with ARDS.35 Many studies supported
the link between driving pressure and PPCs in surgical
patients.8,36e39 However, the clinical effectiveness of
modifying driving pressure as a therapeutic target remains
inconclusive. Contrary to previous randomised controlled
trials,14e16,26 a recent multicentre study in thoracic surgery
found no benefit in driving pressure-guided ventilation.39
Similarly, a multinational trial involving obese patients
showed no differences in PPCs despite lower driving pressure in the low PEEP group compared with the high PEEP
group.11 In line with these findings, our study did not
establish an association between driving pressure-guided
PEEP and PPCs, although higher driving pressure was
significantly associated with an increased risk of PPCs.
Therefore, future studies should prioritise exploring the
clinical utility of driving pressure-guided PEEP.
A low level of PEEP can be tolerated by most surgical patients. However, PEEP can induce changes in cardiac output,
leading to PEEP-induced haemodynamic deterioration in patients with comorbidities.40 A previous multicentred randomised study revealed that hypotension occurred more
frequently in the group receiving higher PEEP than in those
with lower PEEP.10 In the present study, most respiratory
variables were kept within safe limits, and severe haemodynamic instability or impairment in mechanical ventilation did
not occur in the individualised group. There was also no significant difference in TWA hypotension in the present study;
however, the individualised group showed higher incidences
of administration of vasoactive drugs and cumulative ephedrine doses. Therefore, monitoring whether PEEP-induced
haemodynamic instability occurs closely is necessary when
using individualised high PEEP.
This study had several limitations. Firstly, because the
study was conducted in a single tertiary teaching hospital,
institutional policy and patient severity could have affected
the results. Secondly, although we enrolled patients with a
moderate or high risk of PPCs based on the ARISCAT risk score,
the actual risk score was not as high as expected. As a result,
our study was underpowered to detect a significant difference
in the primary outcome. This could partly explain why most
subjects who developed PPCs had minor complications.
Thirdly, the intervention was manually performed for a relatively short time (40 s for recruitment and 30 s for the decremental PEEP trial). However, the intervention was conducted
by two experienced researchers, and an independent investigator ensured the accuracy of the intervention in this study.
Fourthly, in order to obtain a more precise estimate of the
efficacy of driving pressure-guided PEEP, we opted for per
protocol analysis. However, we acknowledge that this analysis could introduce biases and might not fully reflect realworld clinical practice, even the intention-to-treat analysis
confirmed similar results. Lastly, there was no consensus
regarding the strategy for driving pressure-guided ventilation.
However, as a decremental PEEP trial may reduce shear stress
by opening the alveoli even at low driving pressure,41 we
adopted this method for PEEP titration.
-
9
In summary, driving pressure-guided PEEP did not decrease
PPC incidence within seven postoperative days in patients
who underwent laparoscopic or robotic lower abdominal
surgery. Although driving pressure-guided PEEP improved
intraoperative lung mechanics and oxygenation profile, this
benefit was not translated into postoperative clinical outcomes. Future multicentre studies are needed to confirm our
results.
Authors’ contributions
Contributed to the conception and design of the study: H-KY,
BRK
Contributed to the acquisition of data or analysis and interpretation of data: H-KY, BRK, YJK, HWK, J-YJ, H-YC, J-HS, WHK,
H-SK
Contributed to drafting the manuscript or revising it critically
for important intellectual content: H-KY, YJK, SH
Contributed to revising of manuscript critically for important
intellectual content: all authors
Contributed to the final approval of the manuscript to be
submitted: H-KY, YJK
Agreed to be accountable for all aspects of the work in
ensuring that questions related to the accuracy or integrity of
any part of the work are appropriately investigated and
resolved: all authors
Declaration of interest
The authors declare that they have no conflicts of interest.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.bja.2023.08.007.
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Handling Editor: Gareth Ackland