Lung-protective perioperative mechanical ventilation - Chapter 5: Intraoperative ventilation strategies and patient outcomes following surgery: an international observational study (LAS VEGAS)

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Lung-protective perioperative mechanical ventilation

Hemmes, S.N.T.

Publication date

2015

Document Version

Final published version

Link to publication

Citation for published version (APA):

Hemmes, S. N. T. (2015). Lung-protective perioperative mechanical ventilation.

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Intraoperative Ventilation Strategies

and Patient Outcomes Following Surgery:

an International Observational Study

(LAS VEGAS)

Hemmes SNT, Gama de Abreu M, Pelosi P, Schultz MJ for the The LAS VEGAS Investigators for PROVE Network*, and the Clinical Trial Network of the European Society of Anaesthesiology *PROVE Network: the PROtective VEntilation Network

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Abstract

Background. Postoperative pulmonary complications (PPCs) increase morbidity and mortality

of surgical patients. The intraoperative ventilation strategy may affect occurrence of PPCs.

Objective. To describe practice of intraoperative ventilation and to determine associations

between ventilator settings and occurrence of PPCs.

Design, data source, setting and patients. Prospective observational study in adult patients

requiring invasive ventilation during general anaesthesia for surgery in 2013.

Measurements. The primary outcome measure was development of PPCs in the first five

postoperative days. A multivariable model was built to quantify the net effect of intraoperative

ventilation characteristics on the occurrence of PPCs, while controlling for other perioperative

risk factors.

Results. Data collection was complete in 8,241 patients (146 hospitals in 29 countries); PPCs

occurred in 861 (10.4%) patients, arising most commonly within three days after surgery. Median

tidal volume was 500.0 (454.2–550.5) mL resulting in 8.1 (7.2–9.1) mL/kg predicted body weight.

The positive end–expiratory pressure (PEEP) level was 4.0 (0.0–5.0) cm H2O. PEEP levels of 0 and

5 cm H2O were used most frequently. Recruitment manoeuvres were performed in < 10% of

patients. Increased levels of PEEP were independently associated with the occurrence of PPCs

(odds ratio 1.06 (95% CI) 1.01–1.12; p = 0.020)).

Limitations. The observational character of this study precludes causal inferences.

Conclusion. Low tidal volumes are frequently used, but PEEP levels above 5 cm H

2

O and

recruitment manoeuvres are seldom applied. Occurrence of PPCs is independently associated

with the use of increasing intraoperative PEEP levels.

Ch apt er 5 83

Introduction

Mechanical ventilation is often considered a harmless intervention during general anaesthesia

for surgery. However, ventilation can induce overdistension as well as repetitive opening and

closing of lung units, resulting in ventilator–induced lung injury and even the acute respiratory

distress syndrome (ARDS).

1

_{Several randomized controlled trials showed that ventilation with low}

tidal volumes (V

T

) is associated with improved outcome in patients with ARDS and in critically

ill patients without ARDS,

2–4

_{and this knowledge has profoundly changed ventilation practice in}

intensive care units.

5–7

Theoretically, surgery patients with uninjured lungs could also benefit from intraoperative

ventilation with low V

T

.

3

Three randomized controlled trials in patients planned for major

abdominal surgery showed that intraoperative ventilation with low V

T

and positive end–expiratory

pressures (PEEP) with recruitment manoeuvres reduced occurrence of postoperative pulmonary

complications (PPCs).

8-10

_{One metaanalysis, however, suggested that V}

T

, rather than PEEP, is

the major factor responsible for lung protection during intraoperative ventilation.

11

_{One recent}

multicentre audit in Australia showed that surgery patients remain to receive high V

T

(median

9.5 (8.5–10.4 mL/kg predicted body weight) and higher levels of PEEP (median 5.0 (4.0–5.0) cm

H

2

O).

12

Another study showed that the average size of V

T

during intraoperative ventilation is 7.8

± 1.5 mL/kg predicted body weight, and that > 60% of patients receive ≥ 5 cm H

2

O of PEEP.

13

Thus while there is controversy regarding V

T

, PEEP levels have increased, despite the fact that

PEEP may not protect against PPC, and maybe even cause harm.

11,14

We conducted the ‘Local ASsessment of VEntilatory management during General Anesthesia

for Surgery, LAS VEGAS’ study, an international multicentre prospective observational study, to

describe current intraoperative ventilation practice, and to determine associations between

ventilator settings and patient outcome. We hypothesized that V

T

< 10 mL/kg PBW and PEEP

levels ≥ 5 cm H

2

O were commonly used and both to be associated with a reduced occurrence

of PPCs.

Methods

Study design and sites

The LAS VEGAS study was co–sponsored and endorsed by the European Society of

Anaesthesiology (ESA), which assisted in developing the electronic case record forms, and

hosted the electronic database, without influencing study design, conduct, data analysis, and

final reporting. The Writing Committee drafted the manuscript, and the Steering Committee

provided revisions and comments. The study was registered at Clinicaltrials.gov (NCT01601223).

Study sites were recruited through the Clinical Trial Network of the ESA. Sites sought approval

from the respective Institutional Review Board (research ethics committee), and if required,

obtained written informed consent from individual patients. National coordinators assisted

local coordinators and monitored the study according to the ‘International Conference on

84

Harmonization (Good Clinical Practice) guidelines.

15

_{Local coordinators arranged regulatory}

approvals, monitored local researchers, and ensured integrity and timely completion of data

collection.

Study population and data collection

Adult patients receiving invasive ventilation during general anaesthesia for elective or non–

elective surgery were eligible for participation in the study, which ran for seven predefined

days in each country, selected by the national coordinator, in the period between January 14

th

and March 4

th

_{, 2013. Patients were excluded from participation if they were aged < 18 years, or}

scheduled for pregnancy related surgery, surgical procedures outside the operating room, or

procedures involving cardio-pulmonary bypass. Data from patients undergoing thoracic surgery

or one–lung ventilation during surgery, and those who had received ventilation at any time in

the previous 30 days were collected, but excluded from the present analysis. Centres performing

more than 180 surgical procedures per week were allowed to randomly select either 25% or

50% of their eligible patients for inclusion (ALEA Version 2.2 | AMC/ALEA). The randomization

procedure is described in the Supplement.

Baseline characteristics and preoperative risk factors for PPCs were identified from previous

studies.

16–19

_{During the intraoperative period we collected data describing ventilation settings}

and vital parameters hourly, and scored complications possibly related to ventilation, including

episodes of hypoxia, use of recruitment manoeuvres, airway pressure reduction, presence

of expiratory flow limitation, hypotension, use of vasoactive drugs, and new arrhythmias.

Postoperative residual curarisation with neuromuscular blocking agents (NMBAs), defined as

train–of–four stimulation (TOF) ratio < 0.9 was documented.

Outcomes

The following PPCs were scored daily from the day of surgery until hospital discharge or

postoperative day 5: 1) need for supplementary oxygen (due to PaO

2

< 60 mmHg or SpO

2

<

90% in room air, excluding oxygen supplementation given as standard care or as continuation

of preoperative therapy), 2) respiratory failure (PaO

2

< 60 mmHg or SpO

2

< 90% despite oxygen

therapy, or need for non-invasive mechanical ventilation), 3) unplanned new or prolonged

invasive or non–invasive mechanical ventilation, 4) acute respiratory distress syndrome, 5)

pneumonia, and 6) pneumothorax. Length of hospital stay and in–hospital mortality was censored

at postoperative day 28. Definitions of intraoperative complications, possible types of recruitment

manoeuvres, and postoperative complications are provided in eTables 1, 2 and 3. Patient data

were anonymized before entry onto a password secured, web–based electronic case record

form (OpenClinica, Boston, MA, USA).

Statistical analysis

Since the reported incidences of PPCs vary between 2.6% and 5.0%,

16,17

_{we anticipated that to}

provide a sample of at least 120 PPC events, enrolment of 4,800 or more patients was required.

This would allow up to 12 covariates in a logistic regression model for predicting PPCs.

20

Part of the statistical analysis plan was published previously.

21

_{Patients with incomplete data}

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PBW), PEEP and peak pressure level, or oxygen fraction in inspired air (F

i

O

2

) were censored. The

ventilation settings were examined for plausibility and excluded if: V

T

< 100 or > 1500 mL, V

T

<

2 or > 20 mL/kg PBW, PEEP > 30 cm H

2

O, peak pressure < 5 or > 70 cm H

2

O, and F

i

O

2

< 0.21 or

> 1.0. The remaining cohort included only complete data of main ventilation settings and the

primary endpoint.

Patient demographics, surgical characteristics, intraoperative characteristics, intraoperative

complications, PPCs, length of hospital stay and in–hospital mortality are presented using

descriptive statistics. Demographic data are presented as medians (with the 25 and 75%

quartiles). Hourly–collected intraoperative variables were averaged per patient and are presented

as medians (with the 25 and 75% quartiles). The occurrence of PPCs is presented as a collapsed

composite of PPCs in the first five postoperative days. We calculated Kaplan-Meier estimates

of survival curves, and we used log–rank tests to compare survival distributions in the overall

cohort and also in the subgroups of BMI (< 35 vs. ≥ 35 kg/m2), ARISCAT (< 26 vs. ≥ 26) and

laparoscopic vs. non–laparoscopic surgery. We considered PPC development as any PPC within

five postoperative days, and within one patient. We censored data used for Kaplan–Meier

estimates when patients did not have a PPC during the study period, or when patients were

lost to follow–up before the end of postoperative day 5.

A multivariable model was built to quantify the association between intraoperative ventilation

characteristics, including V

T

(expressed in mL/kg PBW), PEEP level, peak pressure, and F

i

O

2

, and

the occurrence of PPCs, while controlling for other known preoperative and intraoperative risk

factors for PPCs.

15–18

_{. We conducted multi–level analyses to adjust for clustering of the data.}

Therefore, generalized linear mixed model was used to determine predictors of PPC, by modelling

PPC as the dependent variable over time. Independent variables were selected according to

biologic plausibility, and when a p value less than 0.2 was found in the univariate analysis. Then,

the generalized linear mixed model was conducted with these selected predictor variables as

fixed effects, and centres where participants were treated (cluster) as a random effect. Effects

were expressed as an average odds ratio (OR) with their respective 95% confidence interval

(95% CI). The OR represents how the predictor affects outcome for the combined population

of all clusters instead of one specific cluster. In the multivariable model statistical significance

was set at a p value < 0.05.

Propensity scores for PPCs were estimated for each patient with logistic regression using 20

relevant baseline, intraoperative and postoperative characteristics (age, sex, BMI, ARISCAT,

19

preoperative SpO

2

, functional status, smoking, chronic obstructive pulmonary disease (COPD),

chronic comorbidity, respiratory infection < 30 days, preoperative anaemia, type of surgery,

planned duration of surgery, condition of surgery, type of incision, fluid intake, epidural

anaesthesia, use of and reversal of NMBAs, and postoperative residual curarisation) and

correcting for the clustering of the data. The propensity score reflects the propensity in the range

of 0 to 1 to present PPCs given a set of known variables, and is an attempt to adjust for potential

selection bias, confounding factors, and differences between groups. Patients with missing data

were excluded from the database. Based on the propensity score weighted estimators for the

clustered data we constructed a propensity score–matched cohort. Matching was performed

using nearest neighbour matching without replacement, with each patient with PPCs matched to

86

Figure 1. Data collection and selection of cohort for analysis

IRB: institutional review board; VT: tidal volume; mL: millilitres; kg: kilogram; PBW: predicted body weight; PEEP: positive

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three patients without PPCs. A calibre width of 0.15 of the standard deviation of the logit of the

propensity score was used for the development of matching. Absolute standardized differences

were computed to evaluate matching effectiveness.

22

A PROBIT regression analysis was used to characterize the dose–response relationship between

the intraoperative PEEP level and the probability of PPCs. A cubic term was used in the final

model for PEEP. The cubic term was chosen, because we hypothesized that the relationship

between PEEP and PPCs is curvilinear with low probability in low levels, some plateau, and high

probability in high levels. This was confirmed by the inspection of the residuals.

Post–hoc analyses were conducted for patients with body mass index (BMI) < versus ≥ 35 kg/

m

2

_{, for patients undergoing laparoscopic versus non–laparoscopic surgery, and patients with}

low versus high risk for PPCs, according to the Assess Respiratory Risk in Surgical Patients in

Catalonia risk (ARISCAT) score (< versus ≥ 26, respectively).

19

_{The chi square test for categorical}

variables and Mann–Whitney U test for continuous variables were performed to compare the

intraoperative ventilation strategies, intraoperative complications and PPCs within each subgroup.

Statistical significance was considered to be at p < 0.05. All analyses were performed with R

version 3.1 (http://www.R-project.org/).

Role of funding source

The European Society of Anaesthesiology supported LAS VEGAS. The funding sources had no

role in study design, data analysis or interpretation, or writing of the manuscript.

Results

Two hundred and nineteen centres in 38 countries expressed interest in participating in the

LAS VEGAS study. Of them, 73 in seven countries did not obtain formal approval from the local

Institutional Review Board, or had other reasons not to participate (figure 1). One centre used

the randomization program to reduce the number of patients to 50%, and another one to

25% of eligible patients. The list of participating centres, countries and respective numbers of

included patients is presented in eTable 4; hospital characteristics of participating centres are

given in eTable 5. In total 10,523 patients were recruited of whom 656 patients were excluded

due to ventilation preceding surgery, or thoracic surgery, and 1,540 patients had missing data in

main ventilation settings; in 86 patients the postoperative follow–up data was missed, yielding

8,241 patients for the analysis (figure 1). In the BMI subgroups an additional 18 patients were

excluded due to missing weight and/or height. Of 7,594 patients follow–up was complete until

the day of hospital discharge. Demographics and surgical characteristics of patients are shown

in table 1 and eTable 6.

Intraoperative ventilation characteristics

Anaesthetists preferred volume– over pressure–controlled ventilation. The pressure support

mode and combined modes of ventilation were seldom used (table 2). The most frequently

chosen V

T

was 500 mL, or 7 to 9 mL/kg PBW, with limited variation (figure 2, table 2). V

T

was

88

lower than 8 and higher than 10 mL/kg PBW in 46% and 12% of patients, respectively (figure 2).

The most frequently applied PEEP levels were 0 and 5 cm H

2

O (table 2, figure 2). PEEP levels were

lower than 2, 2 to 5 and ≥ 6 cm H

2

O in 30%, 61%, and 9% of patients, respectively. Recruitment

manoeuvres were applied in 9.5% of all patients.

Patient outcomes

The most frequent intraoperative complication was hypotension (table 3). PPCs occurred in 861

patients (10.4%), arising most commonly within three days after surgery (figure 3). The need

for supplemental oxygen arose in 700 patients (8.5%), and 138 patients developed respiratory

Figure 2. Distribution of intraoperative ventilation settings

Tidal volume size (expressed in mL and in mL/kg predicted body weight, PBW), level of PEEP (cm H2O), and peak pressure

(cm H2O) presented for the whole group; patients with body mass index (BMI) lower than 35 kg/m2 versus equal or higher

than 35 kg/m2_{; patients undergoing laparoscopic versus non–laparoscopic surgery; and patients with a low versus high risk}

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failure (1.7%). ARDS, pneumonia, and pneumothorax occurred in less than 1% of patients (table

4). Patients who developed PPCs experienced a longer stay in hospital and greater mortality

(eFigure 1 and 2).

The occurrence of PPCs was associated with increasing PEEP and peak pressure levels, and not

associated with V

T

(table 5 and eTable 7). PPCs were also associated with patient age above 50

years, preoperative oxygen saturation ≤ 90%, current smoking, recent respiratory infection, and

preoperative anaemia. PPCs were associated with the following surgery characteristics: urgent

or emergency surgery, planned duration of surgery longer than two hours, abdominal incision,

intraoperative events (fluid administration of 2,000 mL or more, hypoxemia, use of vasoactive drugs),

postoperative residual curarisation, and no reversal of neuromuscular blockade (table 5 and eTable

7). The categorization of PEEP and tidal volume in tertiles did not change the results (eTable 8).

The characteristics of the propensity score matched cohort are show in eTable 9. Patients

developing PPCs experienced more intraoperative complications, including hypoxemia, hypotension,

arrhythmias, and need for vasoactive drugs (eTable 9). In the propensity score matched cohort,

PEEP levels and peak pressure were associated with the development of PPCs (table 6).

Figure 4 and eFigure 4 respectively show the association between levels of PEEP and peak

pressure with the occurrence of PPCs.

Post–hoc analyses

In patients with BMI ≥ 35 kg/m

2

_{, V}

T

was higher (table 2, figure 2, eFigure 3). Also,

F

i

O

2

, peak

airway pressures and PEEP levels were higher (table 2) and recruitment manoeuvres more often

used. The most frequent intraoperative complication was hypotension and need for vaso–active

drugs, followed by de–saturation.

In laparoscopic vs. non–laparoscopic surgery, and in patients with ARISCAT scores

19

_{≥ 26 vs. <}

26, V

T

sizes were comparable, but peak airway pressures as well as levels of PEEP were higher,

and recruitment manoeuvres more frequently applied (table 3). F

i

O

2

was higher in laparoscopic

surgery, and lower in patients with ARISCAT ≥ 26.

The occurrence of PPCs was higher in patients with a BMI ≥ 35 kg/m

2

_{, and those with an ARISCAT}

score ≥ 26 (table 4).

In patients with BMI ≥ 35 kg/m

2

_{, higher PEEP levels and peak pressures were independently}

associated with the occurrence of PPCs (table 5). Also in patients with ARISCAT score ≥ 26, higher

PEEP levels were independently associated with the occurrence of PPCs (table 5). Age > 50 years,

urgent or emergency surgery, planned duration of surgery longer than two hours, intraoperative

de–saturation, postoperative residual curarisation, and no reversal of neuromuscular blockade

were consistently associated with PPCs (table 5 and eTables 10, 11, 12).

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Va ria bl e Al l p atien ts BM I < 3 5 BM I ≥ 3 5 N on la pa ro sc op ic La pa ro sc op ic AR IS CA T < 2 6 AR IS CA T ≥ 2 6 M ale se x 45 .0 (3 71 1/8 24 1) 46 .4 (4 02 0/7 50 7) 30 .4 (2 18 /7 16 ) 47 .6 (3 15 7/6 63 6) 34 .5 (5 54 /1 60 5) 43 .7 (2 66 4/6 09 7) 48 .8 (1 04 7/2 14 4) Ag e (y ea rs) 54 .0 (4 0.0 – 6 6.0 ) 54 .0 (4 0.0 – 6 6.0 ) 54 .0 (4 3.0 – 6 3.0 ) 54 .0 (4 1.0 – 6 7.0 ) 50 .0 (3 7.0 – 6 3.0 ) 50 .0 (3 7.0 – 6 3.0 ) 63 .0 (5 1.0 – 7 2.0 ) ≤ 5 0 44 .1 (3 63 5/8 23 9) 44 .2 (3 32 1/7 50 6) 43 .1 (3 08 /7 15 ) 42 .3 (2 80 6/6 63 4) 51 .7 (8 29 /1 60 5) 51 .5 (3 13 7/6 09 6) 23 .2 (4 98 /2 14 3) 51 – 8 0 52 .2 (4 30 4/8 23 9) 52 .0 (3 90 3/7 50 6) 55 .0 (3 93 /7 15 ) 53 .8 (3 57 1/6 63 4) 45 .7 (7 33 /1 60 5) 46 .7 (2 84 9/6 09 6) 67 .9 (1 45 5/2 14 3) > 8 0 3.6 (3 00 /8 23 9) 3.8 (2 82 /7 50 6) 2.0 (1 4/7 15 ) 3.9 (2 57 /6 63 4) 2.7 (4 3/1 60 5) 1.8 (1 10 /6 09 6) 8.9 (1 90 /2 14 3) BM I (k g/m 2) 26 .2 (2 3.4 – 3 0.0 ) 25 .8 (2 3.0 – 2 8.8 ) 38 .3 (3 6.2 – 4 1.4 ) 26 .1 (2 3.3 – 2 9.7 ) 26 .9 (2 3.5 – 3 1.2 ) 26 .1 (2 3.2 – 2 9.7 ) 26 .8 (2 3.7 – 3 0.5 ) Unde rw eig ht (< 1 8.5 ) 2.4 (1 94 /8 22 3) 2.6 (1 94 /7 50 7) ---2.3 (1 51 /6 62 3) 2.7 (4 3/1 60 0) 2.3 (1 38 /6 08 5) 2.6 (5 6/2 13 8) No obe sit y (1 8.5 – 2 4.9 ) 37 .1 (3 05 1/8 22 3) 40 .6 (3 05 1/7 50 7) ---37 .8 (2 50 6/6 62 3) 34 .1 (5 45 /1 60 0) 38 .6 (2 34 7/6 08 5) 32 .9 (7 04 /2 13 8) Ov er w eig ht (≥ 2 5.0 - 29 .9 ) 35 .5 (2 91 7/8 22 3) 38 .9 (2 91 7/7 50 7) ---36 .2 (2 40 0/6 62 3) 32 .3 (5 17 /1 60 0) 35 .1 (2 13 3/6 08 5) 36 .7 (7 84 /2 13 8) Obe sit y Cla ss 1 (3 0.0 to 3 4.9 ) 16 .3 (1 34 5/8 22 3) 17 .9 (1 34 5/7 50 7) ---16 .0 (1 06 1/6 62 3) 17 .8 (2 84 /1 60 0) 16 .0 (9 76 /6 08 5) 17 .3 (3 69 /2 13 8) Obe sit y Cla ss 2 (3 5.0 to 3 9.9 ) 5.7 (4 64 /8 22 3) ---64 .8 (4 64 /7 16 ) 5.3 (3 51 /6 62 3) 7.1 (1 13 /1 60 0) 5.4 (3 29 /6 08 5) 6.3 (1 35 /2 13 8) M or bid obe sit y (≥ 4 0) 3.1 (2 52 /8 22 3) ---35 .2 (2 52 /7 16 ) 2.3 (1 54 /6 62 3) 6.1 (9 8/1 60 0) 2.7 (1 62 /6 08 5) 4.2 (9 0/2 13 8) AS A p hy sic al st at us cl as sific atio n sy st em A SA 1 29 .5 (2 42 6/8 22 9) 31 .5 (2 36 0/7 49 7) 8.7 (6 2/7 14 ) 29 .0 (1 92 1/6 62 9) 31 .6 (5 05 /1 60 0) 35 .8 (2 17 7/6 08 9) 11 .6 (2 49 /2 14 0) A SA 2 49 .2 (4 05 1/8 22 9) 48 .5 (3 63 5/7 49 7) 57 .6 (4 11 /7 14 ) 48 .5 (3 21 4/6 62 9) 52 .3 (8 37 /1 60 0) 49 .6 (3 01 9/6 08 9) 48 .2 (1 03 2/2 14 0) A SA 3 19 .6 (1 61 5/8 22 9) 18 .5 (1 38 4/7 49 7) 31 .5 (2 25 /7 14 ) 20 .5 (1 36 2/6 62 9) 15 .8 (2 53 /1 60 0) 13 .9 (8 44 /6 08 9) 36 .0 (7 71 /2 14 0) A SA 4 1.6 (1 34 /8 22 9) 1.5 (1 16 /7 49 7) 2.1 (1 5/7 14 ) 1.9 (1 29 /6 62 9) 0.3 (5 /1 60 0) 0.8 (4 7/6 08 9) 4.1 (8 7/2 14 0) A SA 5 0.0 (3 /8 22 9) 0.0 (2 /7 49 7) 0.1 (1 /7 14 ) 0.0 (3 /6 62 9) 0.0 (0 /1 60 0) 0.0 (2 /6 08 9) 0.0 (1 /2 14 0) Fu nctio na l s ta tu s N on de pe nde nt 93 .0 (7 66 2/8 23 7) 93 .2 (6 99 4/7 50 3) 91 .3 (6 54 /7 16 ) 92 .3 (6 12 2/6 63 3) 96 .0 (1 54 0/1 60 4) 94 .8 (5 77 8/6 09 4) 87 .9 (1 88 4/2 14 3) P ar tially de pe nde nt 5.9 (4 83 /8 23 7) 5.7 (4 28 /7 50 3) 7.3 (5 2/7 16 ) 6.5 (4 29 /6 63 3) 3.4 (5 4/1 60 4) 4.2 (2 58 /6 09 4) 10 .5 (2 25 /2 14 3) T ot ally de pe nde nt 1.1 (9 2/8 23 7) 1.1 (8 1/7 50 3) 1.4 (1 0/7 16 ) 1.2 (8 2/6 63 3) 0.6 (1 0/1 60 4) 1.0 (5 8/6 09 4) 1.6 (3 4/2 14 3) Blood t ra ns fusion (< 2 4h pr eope ra tiv ely ) 0.6 (5 2/8 24 1) 0.7 (4 9/7 50 7) 0.4 (3 /7 16 ) 0.7 (4 7/6 63 6) 0.3 (5 /1 60 5) 0.1 (8 /6 09 7) 2.1 (4 4/2 14 4) AR ISCA T sc or e $ 15 .0 (3 .0 – 26 .0 ) 15 .0 (3 .0 – 26 .0 ) 16 .0 (3 .0 – 27 .0 ) 11 .0 (3 .0 – 23 .0 ) 18 .0 (1 5.0 – 3 1.0 ) 3.0 (0 .0 – 1 6.0 ) 34 .0 (3 0.0 – 4 1.0 ) < 2 6 74 .0 (6 09 7/8 24 1) 74 .5 (5 59 4/7 50 7) 68 .6 (4 91 /7 16 ) 76 .6 (5 08 4/6 63 6) 63 .1 (1 01 3/1 60 5) 10 0.0 (6 09 7/6 09 7) ---26 – 44 21 .8 (1 79 3/8 24 1) 21 .3 (1 59 6/7 50 7) 26 .7 (1 91 /7 16 ) 19 .3 (1 28 1/6 63 6) 31 .9 (5 12 /1 60 5) ---83 .6 (1 79 3/2 14 4) > 4 4 4.3 (3 51 /8 24 1) 4.2 (3 17 /7 50 7) 4.7 (3 4/7 16 ) 4.1 (2 71 /6 63 6) 5.0 (8 0/1 60 5) ---16 .4 (3 51 /2 14 4) Pr eope ra tiv e SpO 2 (% ) 98 .0 (9 6.0 – 9 9.0 ) 98 .0 (9 6.0 – 9 9.0 ) 97 .0 (9 5.0 – 9 8.0 ) 98 .0 (9 6.0 – 9 9.0 ) 98 .0 (9 6.0 – 9 9.0 ) 98 .0 (9 7.0 – 9 9.0 ) 97 .0 (9 5.0 – 9 8.0 ) ≥ 9 6 83 .6 (6 11 2/7 31 1) 84 .5 (5 62 5/6 65 7) 74 .4 (4 76 /6 40 ) 82 .8 (4 86 0/5 87 1) 86 .9 (1 25 2/1 44 0) 89 .9 (4 85 0/5 39 7) 65 .9 (1 26 2/1 91 4) 91 –9 5 15 .2 (1 11 4/7 31 1) 14 .4 (9 60 /6 65 7) 23 .6 (1 51 /6 40 ) 15 .9 (9 36 /5 87 1) 12 .4 (1 78 /1 44 0) 10 .1 (5 47 /5 39 7) 29 .6 (5 67 /1 91 4) ≤ 90 1.2 (8 5/7 31 1) 1.1 (7 2/6 65 7) 2.0 (1 3/6 40 ) 1.3 (7 5/5 87 1) 0.7 (1 0/1 44 0) 0.0 (0 /5 39 7) 4.4 (8 5/1 91 4) Ha em og lobin – g /dL* 13 .8 (1 2.6 – 1 4.9 ) 13 .8 (1 2.6 – 1 4.9 ) 13 .8 (1 2.8 – 1 4.9 ) 13 .8 (1 2.6 – 1 4.9 ) 13 .7 (1 2.8 – 1 4.6 ) 13 .9 (1 2.9 – 1 5.0 ) 13 .3 (1 1.6 – 1 4.5 ) Pr eope ra tiv e a na em ia (Hb ≤ 1 0 g /dl) 3.4 (2 38 /6 92 9) 3.5 (2 24 /6 33 2) 2.2 (1 3/5 80 ) 3.7 (2 06 /5 54 2) 2.3 (3 2/1 38 7) 1.0 (5 0/4 92 7) 9.4 (1 88 /2 00 2)

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Va ria bl e Al l p atien ts BM I < 3 5 BM I ≥ 3 5 N on la pa ro sc op ic La pa ro sc op ic AR IS CA T < 2 6 AR IS CA T ≥ 2 6 M ale se x 45 .0 (3 71 1/8 24 1) 46 .4 (4 02 0/7 50 7) 30 .4 (2 18 /7 16 ) 47 .6 (3 15 7/6 63 6) 34 .5 (5 54 /1 60 5) 43 .7 (2 66 4/6 09 7) 48 .8 (1 04 7/2 14 4) Ag e (y ea rs) 54 .0 (4 0.0 – 6 6.0 ) 54 .0 (4 0.0 – 6 6.0 ) 54 .0 (4 3.0 – 6 3.0 ) 54 .0 (4 1.0 – 6 7.0 ) 50 .0 (3 7.0 – 6 3.0 ) 50 .0 (3 7.0 – 6 3.0 ) 63 .0 (5 1.0 – 7 2.0 ) ≤ 5 0 44 .1 (3 63 5/8 23 9) 44 .2 (3 32 1/7 50 6) 43 .1 (3 08 /7 15 ) 42 .3 (2 80 6/6 63 4) 51 .7 (8 29 /1 60 5) 51 .5 (3 13 7/6 09 6) 23 .2 (4 98 /2 14 3) 51 – 8 0 52 .2 (4 30 4/8 23 9) 52 .0 (3 90 3/7 50 6) 55 .0 (3 93 /7 15 ) 53 .8 (3 57 1/6 63 4) 45 .7 (7 33 /1 60 5) 46 .7 (2 84 9/6 09 6) 67 .9 (1 45 5/2 14 3) > 8 0 3.6 (3 00 /8 23 9) 3.8 (2 82 /7 50 6) 2.0 (1 4/7 15 ) 3.9 (2 57 /6 63 4) 2.7 (4 3/1 60 5) 1.8 (1 10 /6 09 6) 8.9 (1 90 /2 14 3) BM I (k g/m 2) 26 .2 (2 3.4 – 3 0.0 ) 25 .8 (2 3.0 – 2 8.8 ) 38 .3 (3 6.2 – 4 1.4 ) 26 .1 (2 3.3 – 2 9.7 ) 26 .9 (2 3.5 – 3 1.2 ) 26 .1 (2 3.2 – 2 9.7 ) 26 .8 (2 3.7 – 3 0.5 ) Unde rw eig ht (< 1 8.5 ) 2.4 (1 94 /8 22 3) 2.6 (1 94 /7 50 7) ---2.3 (1 51 /6 62 3) 2.7 (4 3/1 60 0) 2.3 (1 38 /6 08 5) 2.6 (5 6/2 13 8) No obe sit y (1 8.5 – 2 4.9 ) 37 .1 (3 05 1/8 22 3) 40 .6 (3 05 1/7 50 7) ---37 .8 (2 50 6/6 62 3) 34 .1 (5 45 /1 60 0) 38 .6 (2 34 7/6 08 5) 32 .9 (7 04 /2 13 8) Ov er w eig ht (≥ 2 5.0 - 29 .9 ) 35 .5 (2 91 7/8 22 3) 38 .9 (2 91 7/7 50 7) ---36 .2 (2 40 0/6 62 3) 32 .3 (5 17 /1 60 0) 35 .1 (2 13 3/6 08 5) 36 .7 (7 84 /2 13 8) Obe sit y Cla ss 1 (3 0.0 to 3 4.9 ) 16 .3 (1 34 5/8 22 3) 17 .9 (1 34 5/7 50 7) ---16 .0 (1 06 1/6 62 3) 17 .8 (2 84 /1 60 0) 16 .0 (9 76 /6 08 5) 17 .3 (3 69 /2 13 8) Obe sit y Cla ss 2 (3 5.0 to 3 9.9 ) 5.7 (4 64 /8 22 3) ---64 .8 (4 64 /7 16 ) 5.3 (3 51 /6 62 3) 7.1 (1 13 /1 60 0) 5.4 (3 29 /6 08 5) 6.3 (1 35 /2 13 8) M or bid obe sit y (≥ 4 0) 3.1 (2 52 /8 22 3) ---35 .2 (2 52 /7 16 ) 2.3 (1 54 /6 62 3) 6.1 (9 8/1 60 0) 2.7 (1 62 /6 08 5) 4.2 (9 0/2 13 8) AS A p hy sic al st at us cl as sific atio n sy st em A SA 1 29 .5 (2 42 6/8 22 9) 31 .5 (2 36 0/7 49 7) 8.7 (6 2/7 14 ) 29 .0 (1 92 1/6 62 9) 31 .6 (5 05 /1 60 0) 35 .8 (2 17 7/6 08 9) 11 .6 (2 49 /2 14 0) A SA 2 49 .2 (4 05 1/8 22 9) 48 .5 (3 63 5/7 49 7) 57 .6 (4 11 /7 14 ) 48 .5 (3 21 4/6 62 9) 52 .3 (8 37 /1 60 0) 49 .6 (3 01 9/6 08 9) 48 .2 (1 03 2/2 14 0) A SA 3 19 .6 (1 61 5/8 22 9) 18 .5 (1 38 4/7 49 7) 31 .5 (2 25 /7 14 ) 20 .5 (1 36 2/6 62 9) 15 .8 (2 53 /1 60 0) 13 .9 (8 44 /6 08 9) 36 .0 (7 71 /2 14 0) A SA 4 1.6 (1 34 /8 22 9) 1.5 (1 16 /7 49 7) 2.1 (1 5/7 14 ) 1.9 (1 29 /6 62 9) 0.3 (5 /1 60 0) 0.8 (4 7/6 08 9) 4.1 (8 7/2 14 0) A SA 5 0.0 (3 /8 22 9) 0.0 (2 /7 49 7) 0.1 (1 /7 14 ) 0.0 (3 /6 62 9) 0.0 (0 /1 60 0) 0.0 (2 /6 08 9) 0.0 (1 /2 14 0) Fu nctio na l s ta tu s N on de pe nde nt 93 .0 (7 66 2/8 23 7) 93 .2 (6 99 4/7 50 3) 91 .3 (6 54 /7 16 ) 92 .3 (6 12 2/6 63 3) 96 .0 (1 54 0/1 60 4) 94 .8 (5 77 8/6 09 4) 87 .9 (1 88 4/2 14 3) P ar tially de pe nde nt 5.9 (4 83 /8 23 7) 5.7 (4 28 /7 50 3) 7.3 (5 2/7 16 ) 6.5 (4 29 /6 63 3) 3.4 (5 4/1 60 4) 4.2 (2 58 /6 09 4) 10 .5 (2 25 /2 14 3) T ot ally de pe nde nt 1.1 (9 2/8 23 7) 1.1 (8 1/7 50 3) 1.4 (1 0/7 16 ) 1.2 (8 2/6 63 3) 0.6 (1 0/1 60 4) 1.0 (5 8/6 09 4) 1.6 (3 4/2 14 3) Blood t ra ns fusion (< 2 4h pr eope ra tiv ely ) 0.6 (5 2/8 24 1) 0.7 (4 9/7 50 7) 0.4 (3 /7 16 ) 0.7 (4 7/6 63 6) 0.3 (5 /1 60 5) 0.1 (8 /6 09 7) 2.1 (4 4/2 14 4) AR ISCA T sc or e $ 15 .0 (3 .0 – 26 .0 ) 15 .0 (3 .0 – 26 .0 ) 16 .0 (3 .0 – 27 .0 ) 11 .0 (3 .0 – 23 .0 ) 18 .0 (1 5.0 – 3 1.0 ) 3.0 (0 .0 – 1 6.0 ) 34 .0 (3 0.0 – 4 1.0 ) < 2 6 74 .0 (6 09 7/8 24 1) 74 .5 (5 59 4/7 50 7) 68 .6 (4 91 /7 16 ) 76 .6 (5 08 4/6 63 6) 63 .1 (1 01 3/1 60 5) 10 0.0 (6 09 7/6 09 7) ---26 – 44 21 .8 (1 79 3/8 24 1) 21 .3 (1 59 6/7 50 7) 26 .7 (1 91 /7 16 ) 19 .3 (1 28 1/6 63 6) 31 .9 (5 12 /1 60 5) ---83 .6 (1 79 3/2 14 4) > 4 4 4.3 (3 51 /8 24 1) 4.2 (3 17 /7 50 7) 4.7 (3 4/7 16 ) 4.1 (2 71 /6 63 6) 5.0 (8 0/1 60 5) ---16 .4 (3 51 /2 14 4) Pr eope ra tiv e SpO 2 (% ) 98 .0 (9 6.0 – 9 9.0 ) 98 .0 (9 6.0 – 9 9.0 ) 97 .0 (9 5.0 – 9 8.0 ) 98 .0 (9 6.0 – 9 9.0 ) 98 .0 (9 6.0 – 9 9.0 ) 98 .0 (9 7.0 – 9 9.0 ) 97 .0 (9 5.0 – 9 8.0 ) ≥ 9 6 83 .6 (6 11 2/7 31 1) 84 .5 (5 62 5/6 65 7) 74 .4 (4 76 /6 40 ) 82 .8 (4 86 0/5 87 1) 86 .9 (1 25 2/1 44 0) 89 .9 (4 85 0/5 39 7) 65 .9 (1 26 2/1 91 4) 91 –9 5 15 .2 (1 11 4/7 31 1) 14 .4 (9 60 /6 65 7) 23 .6 (1 51 /6 40 ) 15 .9 (9 36 /5 87 1) 12 .4 (1 78 /1 44 0) 10 .1 (5 47 /5 39 7) 29 .6 (5 67 /1 91 4) ≤ 90 1.2 (8 5/7 31 1) 1.1 (7 2/6 65 7) 2.0 (1 3/6 40 ) 1.3 (7 5/5 87 1) 0.7 (1 0/1 44 0) 0.0 (0 /5 39 7) 4.4 (8 5/1 91 4) Ha em og lobin – g /dL* 13 .8 (1 2.6 – 1 4.9 ) 13 .8 (1 2.6 – 1 4.9 ) 13 .8 (1 2.8 – 1 4.9 ) 13 .8 (1 2.6 – 1 4.9 ) 13 .7 (1 2.8 – 1 4.6 ) 13 .9 (1 2.9 – 1 5.0 ) 13 .3 (1 1.6 – 1 4.5 ) Pr eope ra tiv e a na em ia (Hb ≤ 1 0 g /dl) 3.4 (2 38 /6 92 9) 3.5 (2 24 /6 33 2) 2.2 (1 3/5 80 ) 3.7 (2 06 /5 54 2) 2.3 (3 2/1 38 7) 1.0 (5 0/4 92 7) 9.4 (1 88 /2 00 2)

92 Va ria bl e Al l p atien ts BM I < 3 5 BM I ≥ 3 5 N on la pa ro sc op ic La pa ro sc op ic AR IS CA T < 2 6 AR IS CA T ≥ 2 6 Ch ro ni c c o-mo rb id ity - a patie nt c an hav e mor e t han one co-mor bidit y M et as ta tic ca nc er 4.1 (3 40 /8 24 1) 4.3 (3 24 /7 50 7) 2.2 (1 6/7 16 ) 4.4 (2 94 /6 63 6) 2.9 (4 6/1 60 5) 1.8 (1 11 /6 09 7) 10 .7 (2 29 /2 14 4) Chr onic k idne y dy sfunc tion 3.2 (2 60 /8 24 1) 3.2 (2 43 /7 50 7) 2.2 (1 6/7 16 ) 3.5 (2 31 /6 63 6) 1.8 (2 9/1 60 5) 2.0 (1 23 /6 09 7) 6.4 (1 37 /2 14 4) COP D 6.1 (5 02 /8 24 1) 6.0 (4 50 /7 50 7) 7.3 (5 2/7 16 ) 6.2 (4 13 /6 63 6) 5.5 (8 9/1 60 5) 4.8 (2 92 /6 09 7) 9.8 (2 10 /2 14 4) He ar t f ailur e 5.8 (4 82 /8 24 1) 5.8 (4 33 /7 50 7) 6.6 (4 7/7 16 ) 6.1 (4 04 /6 63 6) 4.9 (7 8/1 60 5) 4.7 (2 89 /6 09 7) 9.0 (1 93 /2 14 4) Ob st ruc tiv e sle ep apnoe a 2.2 (1 81 /8 24 1) 1.2 (9 2/7 50 7) 12 .4 (8 9/7 16 ) 2.0 (1 35 /6 63 6) 2.9 (4 6/1 60 5) 2.0 (1 23 /6 09 7) 2.7 (5 8/2 14 4) Ne ur om usc ula r dise ase ** 1.0 (8 0/8 24 1) 1.0 (7 3/7 50 7) 1.0 (7 /7 16 ) 1.1 (7 2/6 63 6) 0.5 (8 /1 60 5) 1.0 (6 1/6 09 7) 0.9 (1 9/2 14 4) Liv er dy sfunc tion 1.0 (7 9/8 24 1) 1.0 (7 4/7 50 7) 0.7 (5 /7 16 ) 1.1 (7 0/6 63 6) 0.6 (9 /1 60 5) 0.7 (4 4/6 09 7) 1.6 (3 5/2 14 4) Su rgi ca l p ro ced ur e - a patie nt can hav e m or e t han one type of sur gic al pr oc edur e Lo w er g as tr o-in te stina l 10 .5 (8 68 /8 24 1) 10 .9 (8 15 /7 50 7) 6.8 (4 9/7 16 ) 9.4 (6 21 /6 63 6) 15 .4 (2 47 /1 60 5) 6.3 (3 86 /6 09 7) 22 .5 (4 82 /2 14 4) Uppe r G I, he pa to-bilia ry , pa nc re as 13 .8 (1 13 8/8 24 1) 12 .8 (9 59 /7 50 7) 24 .7 (1 77 /7 16 ) 6.5 (4 31 /6 63 6) 44 .0 (7 06 /1 60 5) 10 .6 (6 49 /6 09 7) 22 .8 (4 89 /2 14 4) Va sc ula r sur ge ry § 3.1 (2 57 /8 24 1) 3.2 (2 40 /7 50 7) 2.4 (1 7/7 16 ) 3.9 (2 57 /6 63 6) 0.0 (0 /1 60 5) 2.9 (1 75 /6 09 7) 3.8 (8 2/2 14 4) Aor tic sur ge ry 0.7 (5 9/8 24 1) 0.7 (5 4/7 50 7) 0.7 (5 /7 16 ) 0.9 (5 9/6 63 6) 0.0 (0 /1 60 5) 0.3 (1 7/6 09 7) 2.0 (4 2/2 14 4) Ne ur osur ge ry , he ad & ne ck 20 .2 (1 66 6/8 24 1) 20 .7 (1 55 3/7 50 7) 15 .4 (1 10 /7 16 ) 25 .0 (1 66 1/6 63 6) 0.3 (5 /1 60 5) 23 .9 (1 45 5/6 09 7) 9.8 (2 11 /2 14 4) Ur olog ica l a nd k idne y 8.9 (7 32 /8 24 1) 9.1 (6 80 /7 50 7) 7.1 (5 1/7 16 ) 9.0 (5 99 /6 63 6) 8.3 (1 33 /1 60 5) 6.9 (4 22 /6 09 7) 14 .5 (3 10 /2 14 4) Gy na ec olog ica l 11 .7 (9 63 /8 24 1) 11 .6 (8 69 /7 50 7) 12 .7 (9 1/7 16 ) 8.1 (5 37 /6 63 6) 26 .5 (4 26 /1 60 5) 10 .9 (6 65 /6 09 7) 13 .9 (2 98 /2 14 4) Endoc rine sur ge ry 2.0 (1 64 /8 24 1) 2.0 (1 47 /7 50 7) 2.4 (1 7/7 16 ) 2.3 (1 53 /6 63 6) 0.7 (1 1/1 60 5) 2.3 (1 41 /6 09 7) 1.1 (2 3/2 14 4) Tr anspla nt 0.4 (3 2/8 24 1) 0.4 (3 2/7 50 7) 0.0 (0 //7 16 ) 0.5 (3 0/6 63 6) 0.1 (2 /1 60 5) 0.1 (5 /6 09 7) 1.3 (2 7/2 14 4) Plas tic , c ut ane ous, br ea st 1 0.8 (8 91 /8 24 1) 10 .9 (8 20 /7 50 7) 9.9 (7 1/7 16 ) 13 .3 (8 80 /6 63 6) 0.7 (1 1/1 60 5) 13 .3 (8 10 /6 09 7) 3.8 (8 1/2 14 4) Bone , join t, t ra um a, spine 16 .2 (1 33 7/8 24 1) 16 .3 (1 22 0/7 50 7) 15 .6 (1 12 /7 16 ) 19 .8 (1 31 6/6 63 6) 1.3 (2 1/1 60 5) 18 .7 (1 14 1/6 09 7) 9.1 (1 96 /2 14 4) Ot he r pr oc edur e 6.1 (5 00 /8 24 1) 6.2 (4 64 /7 50 7) 5.0 (3 6/7 16 ) 6.7 (4 42 /6 63 6) 3.6 (5 8/1 60 5) 7.2 (4 36 /6 09 7) 3.0 (6 4/2 14 4) Su rgi ca l t ech ni qu e - a patie nt can hav e m or e t han one type of sur gic al pr oc edur e Ope n a bdom ina l sur ge ry 17 .4 (1 43 4/8 24 1) 17 .5 (1 31 0/7 50 7) 16 .9 (1 21 /7 16 ) 21 .4 (1 42 0/6 63 6) ---7.0 (4 24 /6 09 7) 47 .1 (1 01 0/2 14 4) Lapa rosc opic sur ge ry 17 .9 (1 47 8/8 24 1) 17 .0 (1 27 7/7 50 7) 27 .4 (1 96 /7 16 ) ---93 .0 (1 49 3/1 60 5) 15 .6 (9 53 /6 09 7) 24 .5 (5 25 /2 14 4) Lapa rosc opic a ssis te d sur ge ry 1.8 (1 45 /8 24 1) 1.7 (1 27 /7 50 7) 2.5 (1 8/7 16 ) ---9.0 (1 44 /1 60 5) 1.0 (6 2/6 09 7) 3.9 (8 3/2 14 4) Pe riphe ra l sur ge ry 18 .7 (1 54 0/8 24 1) 18 .6 (1 40 0/7 50 7) 18 .7 (1 34 /7 16 ) 23 .2 (1 53 8/6 63 6) 0.1 (2 /1 60 5) 22 .2 (1 35 1/6 09 7) 8.8 (1 89 /2 14 4) Ot he r 44 .9 (3 70 2/8 24 1) 45 .9 (3 44 7/7 50 7) 35 .1 (2 51 /7 16 ) 55 .7 (3 69 8/6 63 6) 0.2 (4 /1 60 5) 54 .5 (3 32 0/6 09 7) 17 .8 (3 82 /2 14 4) Ur gen cy o f s ur ger y # Ele ctiv e 90 .8 (7 48 6/8 24 0) 90 .7 (6 80 9/7 50 6) 93 .2 (6 67 /7 16 ) 91 .1 (6 04 7/6 63 5) 89 .7 (1 43 9/1 60 5) 92 .3 (5 62 9/6 09 6) 86 .6 (1 85 7/2 14 4) U rg en t 7.2 (5 95 /8 24 0) 7.3 (5 45 /7 50 6) 5.9 (4 2/7 16 ) 7.0 (4 66 /6 63 5) 8.0 (1 29 /1 60 5) 6.4 (3 93 /6 09 6) 9.4 (2 02 /2 14 4) Em er ge nc y 1.9 (1 59 /8 24 0) 2.0 (1 52 /7 50 6) 1.0 (7 /7 16 ) 1.8 (1 22 /6 63 5) 2.3 (3 7/1 60 5) 1.2 (7 4/6 09 6) 4.0 (8 5/2 14 4)

Ch apt er 5 93 Va ria bl e Al l p atien ts BM I < 3 5 BM I ≥ 3 5 N on la pa ro sc op ic La pa ro sc op ic AR IS CA T < 2 6 AR IS CA T ≥ 2 6 Ch ro ni c c o-mo rb id ity - a patie nt c an hav e mor e t han one co-mor bidit y M et as ta tic ca nc er 4.1 (3 40 /8 24 1) 4.3 (3 24 /7 50 7) 2.2 (1 6/7 16 ) 4.4 (2 94 /6 63 6) 2.9 (4 6/1 60 5) 1.8 (1 11 /6 09 7) 10 .7 (2 29 /2 14 4) Chr onic k idne y dy sfunc tion 3.2 (2 60 /8 24 1) 3.2 (2 43 /7 50 7) 2.2 (1 6/7 16 ) 3.5 (2 31 /6 63 6) 1.8 (2 9/1 60 5) 2.0 (1 23 /6 09 7) 6.4 (1 37 /2 14 4) COP D 6.1 (5 02 /8 24 1) 6.0 (4 50 /7 50 7) 7.3 (5 2/7 16 ) 6.2 (4 13 /6 63 6) 5.5 (8 9/1 60 5) 4.8 (2 92 /6 09 7) 9.8 (2 10 /2 14 4) He ar t f ailur e 5.8 (4 82 /8 24 1) 5.8 (4 33 /7 50 7) 6.6 (4 7/7 16 ) 6.1 (4 04 /6 63 6) 4.9 (7 8/1 60 5) 4.7 (2 89 /6 09 7) 9.0 (1 93 /2 14 4) Ob st ruc tiv e sle ep apnoe a 2.2 (1 81 /8 24 1) 1.2 (9 2/7 50 7) 12 .4 (8 9/7 16 ) 2.0 (1 35 /6 63 6) 2.9 (4 6/1 60 5) 2.0 (1 23 /6 09 7) 2.7 (5 8/2 14 4) Ne ur om usc ula r dise ase ** 1.0 (8 0/8 24 1) 1.0 (7 3/7 50 7) 1.0 (7 /7 16 ) 1.1 (7 2/6 63 6) 0.5 (8 /1 60 5) 1.0 (6 1/6 09 7) 0.9 (1 9/2 14 4) Liv er dy sfunc tion 1.0 (7 9/8 24 1) 1.0 (7 4/7 50 7) 0.7 (5 /7 16 ) 1.1 (7 0/6 63 6) 0.6 (9 /1 60 5) 0.7 (4 4/6 09 7) 1.6 (3 5/2 14 4) Su rgi ca l p ro ced ur e - a patie nt can hav e m or e t han one type of sur gic al pr oc edur e Lo w er g as tr o-in te stina l 10 .5 (8 68 /8 24 1) 10 .9 (8 15 /7 50 7) 6.8 (4 9/7 16 ) 9.4 (6 21 /6 63 6) 15 .4 (2 47 /1 60 5) 6.3 (3 86 /6 09 7) 22 .5 (4 82 /2 14 4) Uppe r G I, he pa to-bilia ry , pa nc re as 13 .8 (1 13 8/8 24 1) 12 .8 (9 59 /7 50 7) 24 .7 (1 77 /7 16 ) 6.5 (4 31 /6 63 6) 44 .0 (7 06 /1 60 5) 10 .6 (6 49 /6 09 7) 22 .8 (4 89 /2 14 4) Va sc ula r sur ge ry § 3.1 (2 57 /8 24 1) 3.2 (2 40 /7 50 7) 2.4 (1 7/7 16 ) 3.9 (2 57 /6 63 6) 0.0 (0 /1 60 5) 2.9 (1 75 /6 09 7) 3.8 (8 2/2 14 4) Aor tic sur ge ry 0.7 (5 9/8 24 1) 0.7 (5 4/7 50 7) 0.7 (5 /7 16 ) 0.9 (5 9/6 63 6) 0.0 (0 /1 60 5) 0.3 (1 7/6 09 7) 2.0 (4 2/2 14 4) Ne ur osur ge ry , he ad & ne ck 20 .2 (1 66 6/8 24 1) 20 .7 (1 55 3/7 50 7) 15 .4 (1 10 /7 16 ) 25 .0 (1 66 1/6 63 6) 0.3 (5 /1 60 5) 23 .9 (1 45 5/6 09 7) 9.8 (2 11 /2 14 4) Ur olog ica l a nd k idne y 8.9 (7 32 /8 24 1) 9.1 (6 80 /7 50 7) 7.1 (5 1/7 16 ) 9.0 (5 99 /6 63 6) 8.3 (1 33 /1 60 5) 6.9 (4 22 /6 09 7) 14 .5 (3 10 /2 14 4) Gy na ec olog ica l 11 .7 (9 63 /8 24 1) 11 .6 (8 69 /7 50 7) 12 .7 (9 1/7 16 ) 8.1 (5 37 /6 63 6) 26 .5 (4 26 /1 60 5) 10 .9 (6 65 /6 09 7) 13 .9 (2 98 /2 14 4) Endoc rine sur ge ry 2.0 (1 64 /8 24 1) 2.0 (1 47 /7 50 7) 2.4 (1 7/7 16 ) 2.3 (1 53 /6 63 6) 0.7 (1 1/1 60 5) 2.3 (1 41 /6 09 7) 1.1 (2 3/2 14 4) Tr anspla nt 0.4 (3 2/8 24 1) 0.4 (3 2/7 50 7) 0.0 (0 //7 16 ) 0.5 (3 0/6 63 6) 0.1 (2 /1 60 5) 0.1 (5 /6 09 7) 1.3 (2 7/2 14 4) Plas tic , c ut ane ous, br ea st 1 0.8 (8 91 /8 24 1) 10 .9 (8 20 /7 50 7) 9.9 (7 1/7 16 ) 13 .3 (8 80 /6 63 6) 0.7 (1 1/1 60 5) 13 .3 (8 10 /6 09 7) 3.8 (8 1/2 14 4) Bone , join t, t ra um a, spine 16 .2 (1 33 7/8 24 1) 16 .3 (1 22 0/7 50 7) 15 .6 (1 12 /7 16 ) 19 .8 (1 31 6/6 63 6) 1.3 (2 1/1 60 5) 18 .7 (1 14 1/6 09 7) 9.1 (1 96 /2 14 4) Ot he r pr oc edur e 6.1 (5 00 /8 24 1) 6.2 (4 64 /7 50 7) 5.0 (3 6/7 16 ) 6.7 (4 42 /6 63 6) 3.6 (5 8/1 60 5) 7.2 (4 36 /6 09 7) 3.0 (6 4/2 14 4) Su rgi ca l t ech ni qu e - a patie nt can hav e m or e t han one type of sur gic al pr oc edur e Ope n a bdom ina l sur ge ry 17 .4 (1 43 4/8 24 1) 17 .5 (1 31 0/7 50 7) 16 .9 (1 21 /7 16 ) 21 .4 (1 42 0/6 63 6) ---7.0 (4 24 /6 09 7) 47 .1 (1 01 0/2 14 4) Lapa rosc opic sur ge ry 17 .9 (1 47 8/8 24 1) 17 .0 (1 27 7/7 50 7) 27 .4 (1 96 /7 16 ) ---93 .0 (1 49 3/1 60 5) 15 .6 (9 53 /6 09 7) 24 .5 (5 25 /2 14 4) Lapa rosc opic a ssis te d sur ge ry 1.8 (1 45 /8 24 1) 1.7 (1 27 /7 50 7) 2.5 (1 8/7 16 ) ---9.0 (1 44 /1 60 5) 1.0 (6 2/6 09 7) 3.9 (8 3/2 14 4) Pe riphe ra l sur ge ry 18 .7 (1 54 0/8 24 1) 18 .6 (1 40 0/7 50 7) 18 .7 (1 34 /7 16 ) 23 .2 (1 53 8/6 63 6) 0.1 (2 /1 60 5) 22 .2 (1 35 1/6 09 7) 8.8 (1 89 /2 14 4) Ot he r 44 .9 (3 70 2/8 24 1) 45 .9 (3 44 7/7 50 7) 35 .1 (2 51 /7 16 ) 55 .7 (3 69 8/6 63 6) 0.2 (4 /1 60 5) 54 .5 (3 32 0/6 09 7) 17 .8 (3 82 /2 14 4) Ur gen cy o f s ur ger y # Ele ctiv e 90 .8 (7 48 6/8 24 0) 90 .7 (6 80 9/7 50 6) 93 .2 (6 67 /7 16 ) 91 .1 (6 04 7/6 63 5) 89 .7 (1 43 9/1 60 5) 92 .3 (5 62 9/6 09 6) 86 .6 (1 85 7/2 14 4) U rg en t 7.2 (5 95 /8 24 0) 7.3 (5 45 /7 50 6) 5.9 (4 2/7 16 ) 7.0 (4 66 /6 63 5) 8.0 (1 29 /1 60 5) 6.4 (3 93 /6 09 6) 9.4 (2 02 /2 14 4) Em er ge nc y 1.9 (1 59 /8 24 0) 2.0 (1 52 /7 50 6) 1.0 (7 /7 16 ) 1.8 (1 22 /6 63 5) 2.3 (3 7/1 60 5) 1.2 (7 4/6 09 6) 4.0 (8 5/2 14 4)

94 Va ria bl e Al l p atien ts BM I < 3 5 BM I ≥ 3 5 N on la pa ro sc op ic La pa ro sc op ic AR IS CA T < 2 6 AR IS CA T ≥ 2 6 Pl an ned d ur atio n of s ur ger y ≤ 2 hour s 69 .5 (5 72 4/8 23 3) 69 .9 (5 24 2/7 49 9) 65 .6 (4 70 /7 16 ) 68 .3 (4 52 5/6 62 8) 74 .7 (1 19 9/1 60 5) 87 .0 (5 29 6/6 08 9) 20 .0 (4 28 /2 14 4) > 2 – 3 hour s 19 .2 (1 58 4/8 23 3) 18 .8 (1 41 0/7 49 9) 23 .6 (1 69 /7 16 ) 20 .0 (1 32 6/6 62 8) 16 .1 (2 58 /1 60 5) 10 .8 (6 55 /6 08 9) 43 .3 (9 29 /2 14 4) > 3 hour s 11 .2 (9 25 /8 23 3) 11 .3 (8 47 /7 49 9) 10 .8 (7 7/7 16 ) 11 .7 (7 77 /6 62 8) 9.2 (1 48 /1 60 5) 2.3 (1 38 /6 08 9) 36 .7 (7 87 /2 14 4) Dur ation of sur ge ry (m in)† 73 .0 (4 1.0 – 1 25 .0 ) 71 .0 (4 0.0 – 1 25 .0 ) 80 .0 (5 0.0 – 1 30 .0 ) 75 .0 (4 0.0 – 1 26 .0 ) 68 .0 (4 5.0 – 1 18 .0 ) 60 .0 (3 5.0 – 9 3.0 ) 14 6.5 (9 4.0 – 21 0.0 ) Dur ation of a na es the sia (m in)†† 10 4.0 (6 7.0 – 16 5.5 ) 10 1.0 (6 5.0 – 16 3.0 ) 11 3.0 (7 5.0 – 17 1.0 ) 10 5.0 (6 7.0 – 16 5.0 ) 96 .0 (6 9.0 – 1 55 .0 ) 87 .0 (6 0.0 – 1 25 .0 ) 19 0.0 (1 25 .0 – 26 0.0 ) Da ta is pr ese nt ed as: m edian (Q R) or pr opor tion (n/N ); BM I: Body Mass Inde x; A SA : A m er ic an Soc ie ty of Ane sthe siolog y; $ AR SICA T sc or e < 26 pr edic ts a lo w risk for pos tope ra tiv e pulmonar y complic ations (PP Cs); AR SICA T sc or e ≥ 26 pr edicts an in te rme dia te to high risk for PP Cs; SpO2: P eriphe ral O xy ge n Sa tur ation; *Labor at or y value s: hae moglobin w as colle ct ed w he n av aila ble fr om c olle ction w ithin routine c ar e; C OP D: Chr onic Ob st ruc tiv e Pulm ona ry Dise ase ; * *N eur om usc ula r dise ase a ffe cting the re spir at or y sy st em ; §V asc ula r sur ge ry is car otid enda rt er ec tom y, a or tic sur ge ry a nd pe riphe ra l v asc ula r t ak en tog et he r; #U rg enc y of sur ge ry : e le ctiv e: sur ge ry tha t is sc he dule d in adv anc e be ca use it doe s not in volv e a m edic al em er ge nc y, ur ge nt : sur ge ry re quir ed w ithin < 48 hour s, e m er ge nc y: non-e le ctiv e sur ge ry pe rf or m ed w he n the pa tie nt ’s lif e or w ell-be ing is in dir ec t je opar dy ; †Dur ation of sur ge ry is the time be tw een skin incisi on and cl osur e of the incision. ††Dur ation of anaes thesi a is the time be tw een st art induction and ex tuba tion or dischar ge fr om oper ation room if mechanic al ve ntila tion r em aine d

Ch apt er 5 95

Discussion

The main findings of the LAS VEGAS study were that: 1) median tidal volume (V

T

) was 500.0

(454.2 – 550.5) mL or 8.1 (7.2 – 9.1) mL/kg PBW, PEEP level was 4.0 (0.0 – 5.0) cm H

2

O and

recruitment manoeuvres were rarely performed; 2) PPCs occurred frequently within 3 days after

surgery and were associated with longer length of hospital stay and mortality; 3) increasing

levels of PEEP but not V

T

size was independently associated with PPCs.

LAS VEGAS is the largest investigation of the association between intraoperative ventilation

strategies and PPCs conducted to date. We investigated both preoperative patient–related and

procedure–related risk factors combined with intraoperative complications that were identified

in previous investigations.

1,16–19,23

_{The prospective design of the study not only improved the}

completeness of the data collection, but also avoided any effect of time. The international

character makes it representative for many countries.

The most frequently chosen V

T

and respiratory rate represent the default settings on many

anaesthesia ventilators, suggesting a lack of individualization. However, V

T

size was lower than

in previous publications on intraoperative ventilation,

24–26

_{implying that V}

T

size has decreased,

at least in the countries that participated in this investigation. Our findings further suggest that

there is uncertainty on what PEEP level to use during surgery (0 or 5 cm H

2

O), but that PEEP

levels higher than 5 cm H

2

O are almost never used, even not in patients with a high BMI, or

with high risk for PPCs.

27,28

In our cohort, PPCs occurred at a higher rate than previously reported.

1,19

_{The most frequent}

pulmonary complication was need for oxygen excluding supplementation given as standard of

care or continuation of preoperative therapy. When this PPC is not considered, the incidence of

PPCs was 1.9%. Patients who developed PPCs had a longer stay in hospital and higher mortality.

The most frequent intraoperative complication in all groups was hypotension and need for

vasoactive drugs, followed by desaturation, mainly in patients with a BMI ≥ 35 kg/m

2

_{and an}

ARISCAT score ≥ 26. This observation might reflect attempts to reverse alveolar collapse and

atelectasis and their hemodynamic side effects.

The results of the multivariable model seem to be in contrast with results from previous

investigations. While several randomized controlled trials showed that the use of low V

T

is

associated with improved outcome of intensive care unit patients,

3

_{and a recent metaanalysis}

suggested that V

T

is the major factor responsible for lung protection during intraoperative

ventilation,

11

_{the present analysis shows that the occurrence of PPCs is not associated with V}

T

size. Also, differently from the results of three recently published randomized controlled trials,

8-10

we found that use of level of PEEP ≥ 7 cmH

2

O is associated with an increased incidence of PPCs.

Both in obese and in high risk patients, increasing PEEP was also independently associated

with development of PPCs. There are two possible explanations for these discrepancies. First,

in patients included in the present cohort, V

T

size was remarkably lower than in previous

investigations in the intensive care unit,

6,7

_{and in the operation room.}

3,11,30

_{Indeed, variations}

in V

T

were much smaller, and V

T

was seldom > 10 ml/kg PBW. Consequently, an association

96

Table 2. Intraoperative ventilation characteristics

Variable All patients BMI < 35 BMI ≥ 35 p value* Non-laparoscopic Laparoscopic p value* ARISCAT < 26 ARISCAT ≥ 26 p value*

Ventilation mode Volume Control 69.8 (5683/8147) 70.1 (5204/7421) 65.9 (467/709) 0.041 69.0 (4525/6558) 72.9 (1158/1589) 0.005 68.9 (4154/6026) 72.1 (1529/2121) < 0.0001 Pressure Control 17.0 (1383/8147) 16.8 (1250/7421) 18.3 (130/709) 17.3 (1132/6558) 15.8 (251/1589) 17.9 (1081/6026) 14.2 (302/2121) Pressure Support or Spontaneous 5.9 (482/8147) 5.8 (431/7421) 7.1 (50/709) 6.3 (412/6558) 4.4 (70/1589) 6.2 (373/6026) 5.2 (109/2121) Other$ _{7.4 (599/8147) 7.2 (536/7421) 8.7 (62/709) 7.5 (489/6558) 6.9 (110/1589) 6.9 (418/6026) 8.5 (181/2121)} Tidal volumes – mL 500.0 (454.2 – 550.5) 500.0 (450.0 – 550.0) 527.7 (487.1 – 600.0) < 0.0001 500.0 (452.0 – 550.0) 500.0 (460.0 – 552.7) 0.247 500.0 (452.5 – 550.0) 500.0 (456.0 – 559.9) 0.155 Tidal volumes – mL/kg PBW 8.1 (7.2 – 9.1) 8.0 (7.2 – 9.0) 9.2 (8.0 – 10.5) < 0.0001 8.1 (7.2 – 9.0) 8.4 (7.5 – 9.4) < 0.0001 8.1 (7.2 – 9.1) 8.2 (7.4 – 9.2) 0.0001 Tidal volumes – mL/kg ABW 6.7 (5.8 – 7.6) 6.8 (6.0 – 7.7) 5.0 (4.4 – 5.6) < 0.0001 6.7 (5.9 – 7.6) 6.7 (5.7 – 7.6) 0.110 6.7 (5.8 – 7.7) 6.7 (5.8 – 7.5) 0.171 PEEP – cm H2O 4.0 (0.0 – 5.0) 4.0 (0.0 – 5.0) 5.0 (2.0 – 5.0) < 0.0001 3.5 (0.0 – 5.0) 4.0 (1.5 – 5.0) < 0.0001 3.0 (0.0 – 5.0) 5.0 (2.0 – 5.0) < 0.0001 Respiratory rate – breaths/min 12.0 (12.0 – 13.0) 12.0 (12.0 – 13.0) 12.0 (12.0 – 14.0) < 0.0001 12.0 (11.5 – 13.0) 12.0 (12.0 – 14.0) < 0.0001 12.0 (12.0 – 13.0) 12.0 (12.0 – 13.0) 0.027 Minute ventilation – mL/ min 6049 (5400 – 6960) 6000 (5400 – 6881) 6750 (6000 – 7560) < 0.0001 6000 (5400 – 6864) 6453 (5722 – 7200) < 0.0001 6000 (5400 – 6900) 6160 (5500 – 7020) 0.002 Ppeak – cm H2O 17.5 (15.0 – 21.0) 17.0 (15.0 – 20.0) 23.0 (20.0 – _26.0) < 0.0001 17.0 (14.5 – 20.0) 19.5 (16.5 – 23.5) < 0.0001 17.0 (14.5 – 20.0) 19.0 (16.0 – 22.0) < 0.0001 Cdyn.calc. – mL/cm H2O 35.3 (28.6 – 43.0) 35.7 (2.93 – 43.6) 28.9 (23.7 – 35.1) < 0.0001 36.1 (29.4 – 44.1) 31.2 (25.5 – 38.4) < 0.0001 35.7 (29.1 – 43.7) 33.8 (27.3 – 41.2) < 0.0001 Cq.stat. – mL/cm H2O 41.8 (34.0 – 51.5) 42.8 (34.8 – 52.3) 33.9 (28.2 – 42.0) < 0.0001 43.3 (35.3 – 52.5) 36.5 (29.5 – 46.1) < 0.0001 42.6 (34.6 – 52.2) 40.0 (32.3 – 50.0) < 0.0001 Recruitment manoeuvre performed 9.5 (779/82141) 8.7 (653/7507) 17.6 (126/716) < 0.0001 8.3 (550/6636) 14.3 (229/1605) < 0.0001 7.9 (484/6097) 13.8 (295/2144) < 0.0001 FiO2 0.51 (0.45 – 0.70) 0.50 (0.45 – 0.70) 0.55 (0.50 – _0.72) < 0.0001 0.50 (0.45 – 0.70) 0.54 (0.48 – 0.70) 0.002 0.54 (0.46 – 0.72) 0.50 (0.45 – 0.60) < 0.0001 < 0.40 7.0 (577/8241) 7.3 (549/7507) 3.8 (27/716) < 0.0001 7.3 (484/6636) 5.8 (93/1605) 0.014 6.5 (398/6097) 8.3 (179/2144) < 0.0001 >= 0.40 – < 0.60 52.9 (4358/8241) 53.0 (3977/7507) 52.0 (372/716) 53.2 (3531/6636) 51.5 (827/1605) 49.5 (3017/6097) 62.5 (1341/2144) >= 0.60 – < 0.80 29.9 (2460/8241) 29.8 (2238/7507) 30.2 (216/716) 29.6 (1966/6636) 30.8 (494/1605) 32.4 (1974/6097) 22.7 (486/2144) ≥ 0.80 10.3 (846/8241) 9.9 (743/7507) 14.1 (101/716) 9.9 (655/6636) 11.9 (191/1605) 11.6 (708/6097) 6.4 (138/2144) SpO2 – % 99.0 (98.0 – 100.0) 99.0 (98.0 – 100.0) 98.0 (97.0 – _99.0) < 0.0001 99.0 (98.0 – 100.0) 99.0 (98.0 – 100.0) < 0.0001 99.0 (98.0 – 100.0) 99.0 (98.0 – _100.0) 0.122 ≥ 96 97.5 (8036/8240) 98.0 (7353/7506) 93.2 (667/716) < 0.0001 97.5 (6472/6635) 97.4 (1564/1605) 0.765 97.8 (5961/6097) 96.8 (2075/2143) 0.016 > 90 – < 96 2.4 (195/8240) 1.9 (145/7506) 6.7 (48/716) 2.3 (155/6635) 2.5 (40/1605) 2.1 (128/6097) 3.1 (67/2143) ≤ 90 0.1 (9/8240) 0.1 (8/7506) 0.1 (1/716) 0.1 (8/6635) 0.1 (1/1605) 0.1 (8/6097) 0.0 (1/2143) etCO2 – mmHg 33.7 (31.0 – 36.5) 33.7 (31.0 – 36.4) 35.0 (32.0 – _38.0) < 0.0001 33.7 (31.0 – 36.0) 34.5 (32.0 – 37.5) < 0.0001 34.0 (31.0 – 36.7) 33.4 (30.5 – 36.0) < 0.0001

Data is presented as median (QR) or proportion % (n/N); *Chi-square for categorical variables and Mann-Whitney for continuous variables; $_{Other (e.g. high frequency oscillatory ventilation, jet ventilation, synchronized intermittent mandatory ventilation}

(SIMV); PBW: predicted body weight, calculated as: 50 + 0.91 x (centimetres of height – 152.4) for males and 45.5 + 0.91 x (centimetres of height – 152.4) for females; ABW: actual body weight; PEEP: positive end-expiratory pressure; Cdyn.calc.: calculated dynamic respiratory compliance: Cdyn = tidal volume / (peak pressure minus PEEP); Cq.stat.: static respiratory compliance; FiO2: fraction inspired oxygen; SpO2: peripheral oxygen saturation; etCO2: expiratory carbon dioxide

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Table 2. Intraoperative ventilation characteristics

Variable All patients BMI < 35 BMI ≥ 35 p value* Non-laparoscopic Laparoscopic p value* ARISCAT < 26 ARISCAT ≥ 26 p value*

Ventilation mode Volume Control 69.8 (5683/8147) 70.1 (5204/7421) 65.9 (467/709) 0.041 69.0 (4525/6558) 72.9 (1158/1589) 0.005 68.9 (4154/6026) 72.1 (1529/2121) < 0.0001 Pressure Control 17.0 (1383/8147) 16.8 (1250/7421) 18.3 (130/709) 17.3 (1132/6558) 15.8 (251/1589) 17.9 (1081/6026) 14.2 (302/2121) Pressure Support or Spontaneous 5.9 (482/8147) 5.8 (431/7421) 7.1 (50/709) 6.3 (412/6558) 4.4 (70/1589) 6.2 (373/6026) 5.2 (109/2121) Other$ _{7.4 (599/8147) 7.2 (536/7421) 8.7 (62/709) 7.5 (489/6558) 6.9 (110/1589) 6.9 (418/6026) 8.5 (181/2121)} Tidal volumes – mL 500.0 (454.2 – 550.5) 500.0 (450.0 – 550.0) 527.7 (487.1 – 600.0) < 0.0001 500.0 (452.0 – 550.0) 500.0 (460.0 – 552.7) 0.247 500.0 (452.5 – 550.0) 500.0 (456.0 – 559.9) 0.155 Tidal volumes – mL/kg PBW 8.1 (7.2 – 9.1) 8.0 (7.2 – 9.0) 9.2 (8.0 – 10.5) < 0.0001 8.1 (7.2 – 9.0) 8.4 (7.5 – 9.4) < 0.0001 8.1 (7.2 – 9.1) 8.2 (7.4 – 9.2) 0.0001 Tidal volumes – mL/kg ABW 6.7 (5.8 – 7.6) 6.8 (6.0 – 7.7) 5.0 (4.4 – 5.6) < 0.0001 6.7 (5.9 – 7.6) 6.7 (5.7 – 7.6) 0.110 6.7 (5.8 – 7.7) 6.7 (5.8 – 7.5) 0.171 PEEP – cm H2O 4.0 (0.0 – 5.0) 4.0 (0.0 – 5.0) 5.0 (2.0 – 5.0) < 0.0001 3.5 (0.0 – 5.0) 4.0 (1.5 – 5.0) < 0.0001 3.0 (0.0 – 5.0) 5.0 (2.0 – 5.0) < 0.0001 Respiratory rate – breaths/min 12.0 (12.0 – 13.0) 12.0 (12.0 – 13.0) 12.0 (12.0 – 14.0) < 0.0001 12.0 (11.5 – 13.0) 12.0 (12.0 – 14.0) < 0.0001 12.0 (12.0 – 13.0) 12.0 (12.0 – 13.0) 0.027 Minute ventilation – mL/ min 6049 (5400 – 6960) 6000 (5400 – 6881) 6750 (6000 – 7560) < 0.0001 6000 (5400 – 6864) 6453 (5722 – 7200) < 0.0001 6000 (5400 – 6900) 6160 (5500 – 7020) 0.002 Ppeak – cm H2O 17.5 (15.0 – 21.0) 17.0 (15.0 – 20.0) 23.0 (20.0 – _26.0) < 0.0001 17.0 (14.5 – 20.0) 19.5 (16.5 – 23.5) < 0.0001 17.0 (14.5 – 20.0) 19.0 (16.0 – 22.0) < 0.0001 Cdyn.calc. – mL/cm H2O 35.3 (28.6 – 43.0) 35.7 (2.93 – 43.6) 28.9 (23.7 – 35.1) < 0.0001 36.1 (29.4 – 44.1) 31.2 (25.5 – 38.4) < 0.0001 35.7 (29.1 – 43.7) 33.8 (27.3 – 41.2) < 0.0001 Cq.stat. – mL/cm H2O 41.8 (34.0 – 51.5) 42.8 (34.8 – 52.3) 33.9 (28.2 – 42.0) < 0.0001 43.3 (35.3 – 52.5) 36.5 (29.5 – 46.1) < 0.0001 42.6 (34.6 – 52.2) 40.0 (32.3 – 50.0) < 0.0001 Recruitment manoeuvre performed 9.5 (779/82141) 8.7 (653/7507) 17.6 (126/716) < 0.0001 8.3 (550/6636) 14.3 (229/1605) < 0.0001 7.9 (484/6097) 13.8 (295/2144) < 0.0001 FiO2 0.51 (0.45 – 0.70) 0.50 (0.45 – 0.70) 0.55 (0.50 – _0.72) < 0.0001 0.50 (0.45 – 0.70) 0.54 (0.48 – 0.70) 0.002 0.54 (0.46 – 0.72) 0.50 (0.45 – 0.60) < 0.0001 < 0.40 7.0 (577/8241) 7.3 (549/7507) 3.8 (27/716) < 0.0001 7.3 (484/6636) 5.8 (93/1605) 0.014 6.5 (398/6097) 8.3 (179/2144) < 0.0001 >= 0.40 – < 0.60 52.9 (4358/8241) 53.0 (3977/7507) 52.0 (372/716) 53.2 (3531/6636) 51.5 (827/1605) 49.5 (3017/6097) 62.5 (1341/2144) >= 0.60 – < 0.80 29.9 (2460/8241) 29.8 (2238/7507) 30.2 (216/716) 29.6 (1966/6636) 30.8 (494/1605) 32.4 (1974/6097) 22.7 (486/2144) ≥ 0.80 10.3 (846/8241) 9.9 (743/7507) 14.1 (101/716) 9.9 (655/6636) 11.9 (191/1605) 11.6 (708/6097) 6.4 (138/2144) SpO2 – % 99.0 (98.0 – 100.0) 99.0 (98.0 – 100.0) 98.0 (97.0 – _99.0) < 0.0001 99.0 (98.0 – 100.0) 99.0 (98.0 – 100.0) < 0.0001 99.0 (98.0 – 100.0) 99.0 (98.0 – _100.0) 0.122 ≥ 96 97.5 (8036/8240) 98.0 (7353/7506) 93.2 (667/716) < 0.0001 97.5 (6472/6635) 97.4 (1564/1605) 0.765 97.8 (5961/6097) 96.8 (2075/2143) 0.016 > 90 – < 96 2.4 (195/8240) 1.9 (145/7506) 6.7 (48/716) 2.3 (155/6635) 2.5 (40/1605) 2.1 (128/6097) 3.1 (67/2143) ≤ 90 0.1 (9/8240) 0.1 (8/7506) 0.1 (1/716) 0.1 (8/6635) 0.1 (1/1605) 0.1 (8/6097) 0.0 (1/2143) etCO2 – mmHg 33.7 (31.0 – 36.5) 33.7 (31.0 – 36.4) 35.0 (32.0 – _38.0) < 0.0001 33.7 (31.0 – 36.0) 34.5 (32.0 – 37.5) < 0.0001 34.0 (31.0 – 36.7) 33.4 (30.5 – 36.0) < 0.0001

Data is presented as median (QR) or proportion % (n/N); *Chi-square for categorical variables and Mann-Whitney for continuous variables; $_{Other (e.g. high frequency oscillatory ventilation, jet ventilation, synchronized intermittent mandatory ventilation}

(SIMV); PBW: predicted body weight, calculated as: 50 + 0.91 x (centimetres of height – 152.4) for males and 45.5 + 0.91 x (centimetres of height – 152.4) for females; ABW: actual body weight; PEEP: positive end-expiratory pressure; Cdyn.calc.: calculated dynamic respiratory compliance: Cdyn = tidal volume / (peak pressure minus PEEP); Cq.stat.: static respiratory compliance; FiO2: fraction inspired oxygen; SpO2: peripheral oxygen saturation; etCO2: expiratory carbon dioxide

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Table 3. Intraoperative complications

Variable All patients BMI < 35 BMI ≥ 35 p value* Non _laparoscopic Laparoscopic p-value* ARISCAT < 26 ARISCAT ≥ 26 p value*

Any de–saturation 4.0 (331/8227) 3.4 (252/7496) 10.8 (77/714) < 0.0001 4.1 _(274/6627) 3.6 (57/1600) 0.295 3.3 (202/6092) 6.0 (129/2135) < 0.0001 Unplanned recruitment manoeuvre 3.4 (282/8222) 3.0 (225/7492) 7.9 (56/713) < 0.0001 3.2 (214/6624) 4.3 (68/1598) 0.043 2.5 (151/6087) 6.1 (131/2135) < 0.0001 Ventilatory pressure reduction 2.8 (234/8216) 2.3 (172/7485) 8.4 (60/714) < 0.0001 2.0 (132/6621) 6.4 (102/1595) < 0.0001 2.1 (127/6087) 5.0 (107/2129) < 0.0001 Expiratory flow limitation 0.5 (43/8180) 0.5 (34/7456) 1.3 (9/707) 0.004 0.4 (27/6590) 1.0 (16/1590) 0.003 0.4 (23/6063) 0.9 (20/2117) 0.0001 Hypotension 27.4 (2251/8229) 27.3 (2046/7498) 27.9 (199/714) 0.738 29.1 _(1929/6629) 20.1 (322/1600) < 0.0001 23.5 (1433/6092) 38.3 (818/2137) < 0.0001 Vaso-active drugs 23.6 (1938/8229) 23.4 (1754/7498) 24.9 (178/714) 0.354 25.1 _(1664/6629) 17.1 (274/1600) < 0.0001 18.7 (1139/6092) 37.4 (799/2137) < 0.0001 New arrhythmias 0.6 (48/8223) 0.6 (44/7492) 0.4 (3/714) 0.571 0.6 (41/6625) 0.4 (7/1598) 0.394 0.3 (18/6088) 1.4 (30/2135) < 0.0001 All complications presented as proportion % (n/N); *Chi-square for categorical variables; Definitions intraoperative

complications: Any de–saturation: defined as occurrence of SpO2 < 92%; Unplanned recruitment manoeuvre: ventilation

strategies aimed to restore lung aeration; ventilation pressure reduction: ventilation strategies aimed to lower peak and/or plateau pressures; Expiratory flow limitation: defined as expiratory flow higher than zero at end-expiration as suggested by visual analysis of the flow curve; Hypotension: defined as SAP < 90mmHg for 3 min or longer; Need for vaso-active drugs: any vaso-active drug given to correct hypotension; New onset arrhythmias: defined as new onset of atrial fibrillation, sustained ventricular tachycardia, supraventricular tachycardia, and ventricular fibrillation

Table 4. Postoperative outcome measures

Variable All patients BMI < 35 BMI ≥ 35 p value* Non-Laparoscopic Laparoscopic p value* ARISCAT < 26 ARISCAT ≥ 26 p value*

Total PPCs# _{861 / 8241 (10.4) 756 / 7507 (10.1) 101 / 716 (14.1) < 0.0001 705 / 6636 (10.6) 156 / 1605 (9.7) 0.277 410 / 6097 (6.7) 451 / 2144 (21.0) < 0.0001}

Need for O2 therapy$ 700 / 8241 (8.5) 611 / 7507 (8.1) 86 / 716 (12) < 0.0001 567 / 6636 (8.6) 133 / 1605 (8.3) 0.721 339 / 6097 (5.6) 361 / 2144 (16.8) < 0.0001

Respiratory failure 138 / 8241 (1.7) 113 / 7507 (1.5) 25 / 716 (3.5) < 0.0001 115 / 6636 (1.7) 23 / 1605 (1.4) 0.399 55 / 6097 (0.9) 83 / 2144 (3.9) < 0.0001 Mechanical ventilation 89 / 8241 (1.1) 80 / 7507 (1.1) 9 / 716 (1.3) 0.635 78 / 6636 (1.2) 11 / 1605 (0.7) 0.088 34 / 6097 (0.6) 55 / 2144 (2.6) < 0.0001 ARDS 9 / 8241 (0.1) 7 / 7507 (0.1) 2 / 716 (0.3) 0.150 9 / 6636 (0.1) 0 / 1605 (0) 0.139 1 / 6097 (0) 8 / 2144 (0.4) < 0.0001 Pneumonia 35 / 8241 (0.4) 29 / 7507 (0.4) 5 / 716 (0.7) 0.213 31 / 6636 (0.5) 4 / 1605 (0.2) 0.227 9 / 6097 (0.1) 26 / 2144 (1.2) < 0.0001 Pneumothorax 12 / 8241 (0.1) 12 / 7507 (0.2) 0 / 716 (0) 0.284 12 / 6636 (0.2) 0 / 1605 (0) 0.088 8 / 6097 (0.1) 4 / 2144 (0.2) 0.564 Hospital LOS 1 (0 – 4) 1 (0 – 4) 1 (0 – 4) 0.404 1 (0 – 4) 1 (0 – 3) < 0.0001 1 (0 – 3) 4 (1 – 5) < 0.0001 In-hospital mortality 42 / 7594 (0.5) 37 / 6917 (0.5) 4 / 661 (0.6) 0.813 40 / 6113 (0.7) 2 / 1481 (0.1) 0.015 5 / 5613 (0.1) 37 / 1981 (1.9) < 0.0001 Hospital-free days** 26 (23 – 27) 26 (23 – 27) 26 (23 – 27) 0.460 26 (23 – 27) 26 (24 – 27) < 0.0001 26 (24 – 27) 23 (21 – 26) < 0.0001 All data is presented as proportion, % (n/N) or median (QR); *Comparison of differences within a subgroup is performed

by using the t-test for continuous variables; BMI: body mass index in kg/m2_{; ARISCAT: Assess Respiratory Risk in Surgical}

Patients in Catalonia (score); PPCs: Postoperative pulmonary complications; ARDS: the acute respiratory distress syndrome; LOS: length of hospital stay; PPCs: on day 1 to 5 were scored YES as soon as the event occurred on either ward or intensive care unit; #_{Total PPCs: one patient could present with multiple PPCs, but was scored only once (YES or NO principle);} $_Need

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Table 3. Intraoperative complications

Variable All patients BMI < 35 BMI ≥ 35 p value* Non _laparoscopic Laparoscopic p-value* ARISCAT < 26 ARISCAT ≥ 26 p value*

Any de–saturation 4.0 (331/8227) 3.4 (252/7496) 10.8 (77/714) < 0.0001 4.1 _(274/6627) 3.6 (57/1600) 0.295 3.3 (202/6092) 6.0 (129/2135) < 0.0001 Unplanned recruitment manoeuvre 3.4 (282/8222) 3.0 (225/7492) 7.9 (56/713) < 0.0001 3.2 (214/6624) 4.3 (68/1598) 0.043 2.5 (151/6087) 6.1 (131/2135) < 0.0001 Ventilatory pressure reduction 2.8 (234/8216) 2.3 (172/7485) 8.4 (60/714) < 0.0001 2.0 (132/6621) 6.4 (102/1595) < 0.0001 2.1 (127/6087) 5.0 (107/2129) < 0.0001 Expiratory flow limitation 0.5 (43/8180) 0.5 (34/7456) 1.3 (9/707) 0.004 0.4 (27/6590) 1.0 (16/1590) 0.003 0.4 (23/6063) 0.9 (20/2117) 0.0001 Hypotension 27.4 (2251/8229) 27.3 (2046/7498) 27.9 (199/714) 0.738 29.1 _(1929/6629) 20.1 (322/1600) < 0.0001 23.5 (1433/6092) 38.3 (818/2137) < 0.0001 Vaso-active drugs 23.6 (1938/8229) 23.4 (1754/7498) 24.9 (178/714) 0.354 25.1 _(1664/6629) 17.1 (274/1600) < 0.0001 18.7 (1139/6092) 37.4 (799/2137) < 0.0001 New arrhythmias 0.6 (48/8223) 0.6 (44/7492) 0.4 (3/714) 0.571 0.6 (41/6625) 0.4 (7/1598) 0.394 0.3 (18/6088) 1.4 (30/2135) < 0.0001 All complications presented as proportion % (n/N); *Chi-square for categorical variables; Definitions intraoperative

complications: Any de–saturation: defined as occurrence of SpO2 < 92%; Unplanned recruitment manoeuvre: ventilation

strategies aimed to restore lung aeration; ventilation pressure reduction: ventilation strategies aimed to lower peak and/or plateau pressures; Expiratory flow limitation: defined as expiratory flow higher than zero at end-expiration as suggested by visual analysis of the flow curve; Hypotension: defined as SAP < 90mmHg for 3 min or longer; Need for vaso-active drugs: any vaso-active drug given to correct hypotension; New onset arrhythmias: defined as new onset of atrial fibrillation, sustained ventricular tachycardia, supraventricular tachycardia, and ventricular fibrillation

Table 4. Postoperative outcome measures

Variable All patients BMI < 35 BMI ≥ 35 p value* Non-Laparoscopic Laparoscopic p value* ARISCAT < 26 ARISCAT ≥ 26 p value*

Total PPCs# _{861 / 8241 (10.4) 756 / 7507 (10.1) 101 / 716 (14.1) < 0.0001 705 / 6636 (10.6) 156 / 1605 (9.7) 0.277 410 / 6097 (6.7) 451 / 2144 (21.0) < 0.0001}

Need for O2 therapy$ 700 / 8241 (8.5) 611 / 7507 (8.1) 86 / 716 (12) < 0.0001 567 / 6636 (8.6) 133 / 1605 (8.3) 0.721 339 / 6097 (5.6) 361 / 2144 (16.8) < 0.0001

Respiratory failure 138 / 8241 (1.7) 113 / 7507 (1.5) 25 / 716 (3.5) < 0.0001 115 / 6636 (1.7) 23 / 1605 (1.4) 0.399 55 / 6097 (0.9) 83 / 2144 (3.9) < 0.0001 Mechanical ventilation 89 / 8241 (1.1) 80 / 7507 (1.1) 9 / 716 (1.3) 0.635 78 / 6636 (1.2) 11 / 1605 (0.7) 0.088 34 / 6097 (0.6) 55 / 2144 (2.6) < 0.0001 ARDS 9 / 8241 (0.1) 7 / 7507 (0.1) 2 / 716 (0.3) 0.150 9 / 6636 (0.1) 0 / 1605 (0) 0.139 1 / 6097 (0) 8 / 2144 (0.4) < 0.0001 Pneumonia 35 / 8241 (0.4) 29 / 7507 (0.4) 5 / 716 (0.7) 0.213 31 / 6636 (0.5) 4 / 1605 (0.2) 0.227 9 / 6097 (0.1) 26 / 2144 (1.2) < 0.0001 Pneumothorax 12 / 8241 (0.1) 12 / 7507 (0.2) 0 / 716 (0) 0.284 12 / 6636 (0.2) 0 / 1605 (0) 0.088 8 / 6097 (0.1) 4 / 2144 (0.2) 0.564 Hospital LOS 1 (0 – 4) 1 (0 – 4) 1 (0 – 4) 0.404 1 (0 – 4) 1 (0 – 3) < 0.0001 1 (0 – 3) 4 (1 – 5) < 0.0001 In-hospital mortality 42 / 7594 (0.5) 37 / 6917 (0.5) 4 / 661 (0.6) 0.813 40 / 6113 (0.7) 2 / 1481 (0.1) 0.015 5 / 5613 (0.1) 37 / 1981 (1.9) < 0.0001 Hospital-free days** 26 (23 – 27) 26 (23 – 27) 26 (23 – 27) 0.460 26 (23 – 27) 26 (24 – 27) < 0.0001 26 (24 – 27) 23 (21 – 26) < 0.0001 All data is presented as proportion, % (n/N) or median (QR); *Comparison of differences within a subgroup is performed

by using the t-test for continuous variables; BMI: body mass index in kg/m2_{; ARISCAT: Assess Respiratory Risk in Surgical}

Patients in Catalonia (score); PPCs: Postoperative pulmonary complications; ARDS: the acute respiratory distress syndrome; LOS: length of hospital stay; PPCs: on day 1 to 5 were scored YES as soon as the event occurred on either ward or intensive care unit; #_{Total PPCs: one patient could present with multiple PPCs, but was scored only once (YES or NO principle);} $_Need