Intraoperative Protective Mechanical Ventilation For Prevention of Postoperative Pulmonary Complications

Review Article
David S. Warner, M.D., Editor
Intraoperative Protective Mechanical Ventilation for

Prevention of Postoperative Pulmonary Complications
A Comprehensive Review of the Role of Tidal Volume, Positive
End-expiratory Pressure, and Lung Recruitment Maneuvers
Andreas Güldner, M.D., Thomas Kiss, M.D., Ary Serpa Neto, M.D., M.Sc., Ph.D.,
Sabrine N. T. Hemmes, M.D., Jaume Canet, M.D., Ph.D., Peter M. Spieth, M.D.,
Patricia R. M. Rocco, M.D., Ph.D., Marcus J. Schultz, M.D., Ph.D., Paolo Pelosi, M.D., F.E.R.S.,
Marcelo Gama de Abreu, M.D., M.Sc., Ph.D., D.E.S.A.
This article has been selected for the Anesthesiology CME Program. Learning objectives
and disclosure and ordering information can be found in the CME section at the front
of this issue.
ABSTRACT
Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after
major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postopera-
tive pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occur-
rence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the
noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory
pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation
based on evidence from recent randomized controlled trials. (Anesthesiology 2015; 123:692-713)
P OSTOPERATIVE pulmonary complications (PPCs)

can have an important impact on the morbidity and
mortality of patients who need major surgery.1 Approxi-
(PEEP), and recruitment maneuvers prevents PPCs com-
pared with mechanical ventilation with high tidal volumes
and low levels of PEEP without recruitment maneuvers.3–6
mately 5% of patients undergoing general surgery will In the current article, we review the definition of and
develop a PPC, and one of the five patients who developed methods to predict PPCs, the pathophysiology of ventilator-
a PPC will die within 30 days of surgery.1 Furthermore, the induced lung injury (VILI) with emphasis on the noninjured
number of PPCs is strongly associated with postoperative lung, and ventilation strategies to minimize PPCs. To identify
length of stay and short-term and long-term mortality.1,2 the most recent evidence from the literature on randomized
There is growing evidence that intraoperative lung- controlled trials (RCTs) addressing intraoperative mechani-
protective mechanical ventilation using low tidal volumes, cal ventilation and nonclinical as well as clinical postopera-
with or without high levels of positive end-expiratory pressure tive outcome measures, we conducted a MEDLINE review
This article is featured in “This Month in Anesthesiology,” page 1A. Corresponding article on page 501. Figures 1, 3, and 7 were enhanced
by Annemarie B. Johnson, C.M.I., Medical Illustrator, Vivo Visuals, Winston-Salem, North Carolina. The first three authors contributed equally
to this article.
Submitted for publication September 4, 2014. Accepted for publication January 31, 2015. From the Department of Anesthesiology and
Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus at the Technische Universität Dresden,
Dresden, Germany (A.G., T.K., P.M.S., M.G.d.A.); Program of Post-Graduation, Research and Innovation; Faculdade de Medicina do ABC
(FMABC), and Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil (A.S.N.); Department of Intensive
Care Medicine and the Laboratory for Experimental Intensive Care and Anesthesiology, Academic Medical Center at the University of
Amsterdam, Amsterdam, The Netherlands (S.N.T.H., M.J.S.); Department of Anesthesiology and Postoperative Care Unit, Hospital Universitari
Germans Trias i Pujol, Badalona, Barcelona, Spain ( J.C.); Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics,
Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (P.R.M.R.); and IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) AOU
(Azienda Ospedaliera Universitaria) San Martino IST (Istituto Tumori) Hospital, Department of Surgical Sciences and Integrated Diagnostics,
University of Genoa, Genoa, Italy (P.P.). All authors are members of the Protective Ventilation Network (PROVEnet, www.provenet.eu).
Copyright © 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2015; 123:692–713
Anesthesiology, V 123 • No 3 692 September 2015
Copyright © 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
EDUCATION
Table 1. Risk Factors for Postoperative Pulmonary Complications
Patient Characteristics Preoperative Testing Surgery Anesthetic Management
Age Low albumin Open thoracic surgery General anesthesia

Male sex Low Spo2 (≤95%) Cardiac surgery High respiratory driving pressure
(≥13 cm H2O)
ASA class ≥3 Anemia (Hb <10 g/dl) Open upper abdominal surgery High inspiratory oxygen fraction
Previous respiratory infection Major vascular surgery High volume of crystalloid admin-
istration
Functional dependency Neurosurgery Erythrocyte transfusion
Congestive heart failure Urology Residual neuromuscular blockade
COPD Duration of surgery >2 h Nasogastric tube use
Smoking Emergent surgery
Renal failure
Gastroesophageal reflux disease
Weight loss
Respiratory driving pressure is defined as inspiratory plateau airway pressure minus positive end-expiratory pressure.
ASA = American Society of Anesthesiologists; COPD = chronic obstructive pulmonary disease; Hb = hemoglobin concentration; Spo2 = oxygen saturation
as measured by pulse oximetry.
using the following search terms: “lower tidal volume” OR associated with the development of PPCs must be identified.
“low tidal volume” OR “protective ventilation” OR “recruit- In 2006, the American College of Physicians published a sys-
ment maneuvers” OR “PEEP” OR “positive end expiratory tematic review of the literature listing a number of risk factors
pressure.” Retrieved articles, and cross-referenced studies for PPCs according to their respective levels of evidence.13 In
from those articles, were screened for pertinent information. recent years, that list has been expanded to include other fac-
tors found to increase the risk of PPCs. Table 1 depicts the
Definition and Prediction of PPCs risk factors associated with PPCs according to the current
literature. Approximately 50% of the risk factors for PPCs
Summary of Current Definitions are attributable to the patient’s health conditions, whereas
Postoperative pulmonary complications are usually pre- the other 50% are related to the surgical procedure and the
sented as a composite, which then includes possible fatal anesthetic management itself.1
and nonfatal respiratory events of new onset occurring in Based on risk factors, different scores have been devel-
the postoperative period. Currently, there is no agreement oped that have the potential to predict the occurrence of
about which of these events should be considered as PPC, PPCs,6,14–16 as shown in table 2. However, their applicability
for example, respiratory failure, lung injury, pneumonia, may be limited because they were derived from restricted
prolonged or unplanned mechanical ventilation or intuba- settings,16 retrospective databases,15 or only validated for
tion, hypoxemia, atelectasis, bronchospasm, pleural effu- specific PPCs.6,14 The Assess Respiratory RIsk in Surgical
sion, pneumothorax, ventilatory depression, and aspiration Patients in CATalonia (ARISCAT) study was conducted
pneumonitis.7,8 From a clinical standpoint, it is worthwhile in a general surgical population of Catalonia, Spain.1 After
to present PPCs as a composite because any of these events a multivariate analysis, a score based on seven risk factors
alone or their associations has a significant impact on the was developed and underwent internal validation, showing
postoperative outcome,1 using different definitions. How- a clinically relevant predictive capability (c-statistic, 0.90).
ever, it is clear that these events can have different patho- Recently, the ARISCAT score was externally validated in a
physiologic mechanisms. For this reason, some studies have large European surgical sample (the Prospective Evaluation
focused on single events, mainly respiratory failure9 and of a RIsk Score for Postoperative Pulmonary COmPlications
pneumonia.10 in Europe study).2 Although differences in the performance
Postoperative pulmonary complications, to be considered of the ARISCAT score have been observed between Euro-
as such, must be related to anesthesia and/or surgery. Fur- pean geographic areas, the score was able to discriminate
thermore, the time frame must be well defined. Usually, an three levels of PPCs risk (low, intermediate, and high). Thus,
event is only considered as PPC if it develops within 5 to 7 at present, the ARISCAT score may represent the most valu-
days after surgery.8,11 able tool for predicting PPCs across different countries and
surgical populations.
Prediction of PPCs
Prediction of PPCs, or any of the single postoperative respi- Putative Mechanisms of VILI
ratory events that is part of that composite, can be useful to The coexistence of closed, recruitable, and already overdis-
plan perioperative strategies aiming at their prevention and tended alveolar regions makes the lung vulnerable to det-
also to reduce health system costs.12 First, the risk factors rimental effects of mechanical stress and strain induced by
Anesthesiology 2015; 123:692-713 693 Güldner et al.
Table 2. Scores for Prediction of PPCs
References Quality of
Published Study Design Patient Population Patients, No. Score Acronym Scoring System Cutoff Prediction
Prediction of general PPCs

Canet et al. 1 Prospective, Adult patients 2,464 over- ARISCAT Age: 51–80 3 Level/point/rate of Derivation cohort:
multicenter, undergoing non- all; 1,624 >80 16 PPC: low/<26/1.6%; AUC: 0.89
obser- obstetric surgi- derivation; Spo2%: 91–95 8 medium/26–44/13.3%;
vational cal procedures 837 valida- high/≥45/42.1% (validation
cohort under general, tion; 3 patients <90 24 subsample)
study neuraxial, or with missing Respiratory infection dur- 17
regional anes- data for two ing last month
thesia parameters Preoperative anemia (Hb 11
relevant for the <10 g/dl)
score (Spo2 Surgical incision
+ respiratory Peripheral 1 PPC: respiratory infection, Validation cohort:
infection dur- respiratory failure, pleural AUC: 0.84
Upper abdominal 15
ing last month) effusion, atelectasis, pneu-
Intrathoracic 24
mothorax, bronchospasm,
Duration of surgery, h ≤2 1 aspiration pneumonitis
>2–3 16
>3 23
Emergency procedure 8
Mazo et al.2 Prospective, Adult patients 5,099 ARISCAT See above Level/point/predicted/ AUC: 0.80
(validation of multicenter, undergoing non- observed rate of PPC:
ARISCAT score obser- obstetric surgi- low/<26/0.87%/3.39%;
from the study vational cal procedures medium/26–
by Canet et cohort under general, 44/7.82%/12.96;
al.1 in a larger, study neuraxial, or high/≥45/
international, plexus block 38.13%/38.01%
multicenter anesthesia
cohort)
(Continued)
Mechanical Ventilation and Postoperative Pulmonary Complications
Table 2. Continued
EDUCATION
Prediction of selected PPCs

Johnson et al.14 Prospective, Adult patients 90,055 deriva- Respiratory fail- Type of surgery Level/point/predicted/ Derivation cohort:
(reevaluated multicenter, undergoing tion; 89,948 ure Risk Index Integumentary 1 observed probability of AUC: 0.856
in a broader obser- major general validation Respiratory and hemic 3 PRF: low/<8/0.2%/0.08%;
cohort from the vational or vascular medium/8–12/1.0%/0.84%;
Heart 2
study by Aro- cohort procedures per- high/>12/6.6%/6.75%
zullah et al.9) study formed under Aneurysm 2
general, spinal, Mouth, palate 7
or epidural Stomach, intestines 2
anesthesia Endocrine 2
Predisposing factors
Male sex 1
Age 40–65 2
Age >65 2
ASA class 3 3
ASA class 4–5 5
Work RVU 10–17 2
Work RVU >17 4
Emergency 2
Sepsis 2
History of severe COPD 2
Ascites 2 PRF: mechanical ventilation Validation cohort:
Dyspnea 1 for >48 h or unplanned AUC: 0.863
Impaired sensorium 1 reintubation
>2 alcoholic drinks/d in 2 wk 1
Bleeding disorders 1
Weight loss >10% 1
Acute renal failure 2
Congestive heart failure 1
Smoker 1
Stroke 1
Wound class other than clean 1
Preoperative albumin <3.5 1
Creatinine >1.5 2
Preoperative bilirubin >1.0 1
White blood count 1
<2.5/>10
Preoperative serum 2
sodium >145
Platelet count <150 1
SGOT >40 1
Hematocrit <38 1

(Continued)
Table 2. Continued
Brueckmann Retrospective, Cases with a surgi- 33,769 overall; Score for ASA score ≥3 3 Score values/probability of Derivation cohort:
et al.15 single- cal procedure if 16,885 deriva- Prediction of reintubation: 0/0.12%; AUC: 0.81
center, the adult patient tion; 16,884 Postoperative Emergency procedure 3 1–3/0.45%; 4–6/1.64%; Validation cohort:
obser- was intubated validation Respiratory High-risk service 2 7–11/5.86% (validation AUC: 0.81
vational at the beginning Complications subsample)
cohort and extubated Congestive heart failure 2
study at the end of the Chronic pulmonary 1
procedure disease
Prediction of ALI/ARDS
Gajic et al.6 (simi- Prospective, Adult patients with 5,584 overall; Lung Injury Predisposing conditions >4; cutoff for development Combined: AUC:
lar to the study multicenter, one or more 2,500 deriva- Prediction Shock 2 of ALI/ARDS 0.80; sensitivity:
by Trillo-Alva- obser- ALI risk fac- tion; 3,084 Score Aspiration 2 0.69; specificity:
rez et al.17 but vational tors, including validation 0.78
used a larger, cohort sepsis, shock, Sepsis 1
multicenter study pancreatitis, Pneumonia 1.5
cohort) pneumonia, High-risk surgery
aspiration, high- Orthopedic spine 1
risk trauma, Acute abdomen 2
or high-risk
Cardiac 2.5
surgery
Aortic vascular 3.5
If emergency surgery +1.5
High-risk trauma
Traumatic brain injury 2
Smoke inhalation 2
Near drowning 2
Lung contusion 1.5
Multiple fractures 1.5
Risk modifiers
Alcohol abuse 1
Obesity (BMI >30) 1
Hypoalbuminemia 1
Chemotherapy 1
Fio2 >0.35 (>4 l/min) 2
Tachypnea (RR >30) 1.5
Spo2 <95% 1
Acidosis (pH <7.35) 1.5
Diabetes mellitus −1, if
septic
(Continued)
EDUCATION
mechanical ventilation.19,20 The physical forces in some
under the curve; BMI = body mass index; COPD = chronic obstructive pulmonary disease; Fio2 = fraction of inspired oxygen; Hb = hemoglobin; PPC = postoperative pulmonary complication; PRF = postoperative
respiratory failure; RR = respiratory rate; RVU = relative value units (a measure of surgical complexity); SGOT = serum glutamic-oxaloacetic transaminase; Spo2 = oxygen saturation as measured by pulse oximetry.
ALI = acute lung injury; ARDS = acute respiratory distress syndrome; ARISCAT = Assess Respiratory RIsk in Surgical Patients in CATalonia; ASA = American Society of Anesthesiologists classification; AUC = area
Specificity: 0.75
alveolar regions may exceed the elastic properties of the lungs
AUC: 0.84; Sen-
sitivity: 0.82;
Prediction
Quality of
although gross measurements of airway pressures or lung

mechanics as usually monitored under anesthesia still suggest
mechanical ventilation is in a “safe” zone.21,22 Several mecha-
nisms have been postulated to describe the development of
VILI.23 Increased airway pressure (barotrauma) or the appli-
cation of high tidal volumes (volutrauma) may cause damage
≥19; cutoff for development
or disruption of alveolar epithelial cells, by generating trans-

pulmonary pressures (stress) that exceed the elastic properties
of the lung parenchyma above its resting volume (strain).24,25
Cutoff
It has been demonstrated that the duration of mechani-

cal stress defined as the stress versus time product affects
of ARDS
the development of pulmonary inflammatory response.26

Although high stress versus time product increased the gene
expression of biological markers associated with inflamma-
tion and alveolar epithelial cell injury and low stress versus
11
10
10
20
14
13
7
time product increased the molecular markers of endothelial

cell damage, balanced stress versus time product as defined by
Scoring System
High-risk cardiac surgery
an inspiratory to expiratory time ratio of 1:1 was associated

High-risk aortic vascular
Admission source other
Physiologic markers of
Respiratory rate 20–29

Baseline health status
with attenuated lung damage.26 Especially in the presence

Respiratory rate ≥30
Emergency surgery
Surgical procedure
of atelectasis, mechanical ventilation may cause damage by

repetitive collapse and reopening of alveolar units, a phenom-
than home 9
acute illness
Spo2 <95%
enon known as atelectrauma.27 All three mechanisms, namely

Fio2 >35%
surgery
Cirrhosis
barotrauma, volutrauma, and atelectrauma, may affect alveo-

Sepsis
lar as well as vascular epithelial and endothelial cells28,29 and

promote extracellular matrix fragmentation.30,31
The extracellular matrix of the lung parenchyma seems
Score Acronym
Injury Predic-
Surgical Lung
to be particularly sensitive to stress from mechanical ventila-

tion, as illustrated in figure 1. Initially, the proteoglycans on
tion 2
the endothelial side and between the endothelial and epi-

thelial lines undergo damage dependent on tidal volume,30
as well as breathing pattern.31 The mechanical fragmenta-
tion of the extracellular matrix promotes interstitial edema
Patients, No.
1,562
and activation of metalloproteinases, further damaging

the extracellular matrix itself. In a second step, fragments
of the extracellular matrix can promote the activation of
inflammatory mediators.32,33 Furthermore, the damage of
the extracellular matrix induced by mechanical ventilation
Study Design Patient Population
aspiration, high-
gery and under-

going a surgical
presenting with
risk trauma, or
sepsis, shock,
tors, including
high-risk sur-
might be exacerbated by fluid load,34 which is not uncom-

pancreatitis,
one or more
ALI risk fac-
pneumonia,
Adult patients
procedure
mon during general anesthesia. However, fluid overload

seems to minimize the inflammatory response, likely by
dilution of extracellular matrix fragments or changes in
their structure, thereby down-regulating the local inflam-
analysis of a
prospective,
matory response.34 This suggests that (1) injurious mechani-

multicenter
cal ventilation makes the lung more susceptible to further

Kor et al.16 (similar Secondary
cohort
cohort; second- study
insults; and (2) in previously healthy lungs, VILI can be

induced without early increase in inflammatory mediators.
At the cellular level, physical stimuli are transformed into
Table 2. Continued
Kor et al.18, but

to the study by
chemical signals, for example, proinflammatory and antiin-

ary analysis of
used a larger,
the study by
Gajic et al. )
6
multicenter
flammatory mediators by means of direct cell injury or indi-

rect activation of cellular signaling pathways. This process
References
Published
is known as “mechanotransduction.”35 Some mediators may

promote local effects such as proapoptotic or profibrotic
actions, whereas others act as homing molecules recruiting
Fig. 1. Alterations of the extracellular matrix in lungs during mechanical ventilation and fluid administration. CS-PG = chondroi-
tin sulfate proteoglycans; HS-PG = heparan sulphate proteoglycans; ICs = inflammatory cells; IMs = inflammatory mediators;
MMPs = metalloproteases; MV = mechanical ventilation; Pi = interstitial pressure; W/D = wet/dry ratio.
local and remote immune cell populations (e.g., neutro- development of interstitial and alveolar edema, which sub-
phils and macrophages).36 These local effects as well as their sequently causes surfactant dysfunction, and impairs lungs
immunological consequences are summarized by the term elastic and resistive properties.49 Dysfunction of the surfac-
“biotrauma.”37 tant system makes the lung susceptible to alveolar collapse
Besides the extracellular matrix, both the endothelial and contributing to deterioration of lung mechanics and impair-
the epithelial compartments of the alveolar–capillary unit ing pulmonary host defense.50
are affected by stress and strain originating from mechani- Although most evidence of gross structural alterations of
cal ventilation. In the endothelium, high stress can lead to endothelium and epithelium induced by mechanical ventila-
direct cell breaks, resulting in capillary stress failure.38,39 Fur- tion originates from in vitro investigations of cultured cells or
thermore, mechanical stress as well as inflammatory stimuli in vivo investigations in acute lung injury models,51 ventila-
(i.e., tumor necrosis factor-α) may trigger contractions of tion applying clinically relevant settings in noninjured lungs
the cytoskeleton,40 resulting in disruption of adherence can affect the alveolar–capillary barrier function, especially
junctions,41 which increase the endothelial permeability and in the presence of independent inflammatory triggers, mak-
contribute to edema formation. Similar to the pulmonary ing mechanical ventilation a powerful hit in the presence of
endothelium, mechanical stress and strain increase the per- systemic inflammation.29
meability of the alveolar epithelium,42 a phenomenon found Due to the disturbed integrity of the alveolar–capillary
during ventilation at high43 as well as low44 lung volumes. In barrier function and consecutive systemic translocation of
addition, low lung volume ventilation can lead to repetitive pathogens or inflammatory mediators, VILI may lead to a
collapse and reopening of lung, affecting the epithelium of systemic inflammatory response affecting not only the lungs
small airways, yielding plasma membrane disruption,45 and but the distal organs as well.52
epithelial necrosis and sloughing.46 Lung inhomogeneity, for example, due to atelectasis
Alveolar fluid clearance is essential to maintain intraalve- formation, is a major contributing factor to the develop-
olar fluid homeostasis, which is usually compromised during ment of VILI. However, most experimental evidence is
VILI. Whereas ventilation with high tidal volumes directly derived from the acute lung injury models. Although their
decreases Na+/K+-adenosine triphosphatase activity,47 venti- basic pathogenetic mechanisms may be similar, the mag-
lation at low lung volumes may indirectly impair fluid clear- nitude and time course of atelectasis formation in acute
ance due to hypoxia following increased alveolar collapse.48 lung injury may be very different from those of atelecta-
Impairment of barrier function of the endothelium sis occurring during anesthesia and relatively short-term
and epithelium, as well as of fluid clearance, leads to the intraoperative mechanical ventilation. Resorption of
EDUCATION
alveolar gas53,54 and compression of lung structures55–58 ventilator settings were able to induce VILI in the absence of
may lead to atelectasis during short-term mechanical ven- a previous pulmonary insult in mice.63 Of note, the delete-
tilation in noninjured lungs, whereby the former might rious effects of mechanical ventilation in noninjured lungs
play a more important role. are partly dependent on its duration.64 However, an experi-
In a porcine model of experimental pneumonia, both mental study demonstrated that large tidal volumes had only
exogenous surfactant administration and ventilation accord- minor if any deleterious effects on lungs, despite prolonged
ing to the open lung approach attenuated bacterial growth mechanical ventilation.25 Possibly, this is explained by the
and systemic translocation by minimizing alveolar collapse lack of a previous inflammatory insult, as for example, sur-
and atelectasis formation.59 In a similar model of experimen- gery. In fact, systemic inflammation may prime the lungs to
tal pneumonia in mechanically ventilated piglets, bacterial injury by mechanical ventilation.65
translocation was lowest with individually tailored PEEP
levels, whereas low and high PEEP promoted bacterial Mechanical Ventilation Strategies to Protect
translocation.60 Lungs during Surgery
In isolated nonperfused mouse lungs, both an “open lung
approach” (tidal volume 6 ml/kg, recruitment maneuvers, Atelectasis and Intraoperative Mechanical Ventilation
and PEEP of 14 to 16 cm H2O) and a “lung rest strategy” Atelectasis develops in as much as 90% of patients undergo-
(tidal volume of 6 ml/kg, PEEP of 8 to 10 cm H2O, and no ing general anesthesia66 and can persist to different degrees
recruitment maneuvers) were associated with reduced pul- after surgery, also surrounding pleura effusion, as illustrated
monary inflammatory response and improved respiratory in figure 2. The area of nonaerated lung tissue near to the
mechanics compared with injurious mechanical ventila- diaphragm varies depending on the surgical procedure and
tion (tidal volume of 20 ml/kg and PEEP of 0 cm H2O).61 patient characteristics but has been estimated in the range of
Interestingly, the “lung rest strategy” was associated with less 3 to 6%67–69 to 20 to 25%66 and even higher if calculated as
apoptosis but more ultrastructural cell damage, most likely amount of tissue.
due to increased activation of mitogen-activated protein Different mechanisms have been postulated to favor atel-
kinase pathways as compared with the “open lung strategy.”61 ectasis formation during anesthesia, including (1) collapse of
In healthy mice, mechanical ventilation with a tidal vol- small airways,70–72 (2) compression of lung structures,55–58
ume of 8 ml/kg and PEEP of 4 cm H2O induced a revers- (3) absorption of intraalveolar gas content,53,54 and
ible increase in plasma and lung tissue cytokines as well as (4) impairment of lung surfactant function.73 Mechanical
increased leukocyte influx, but the integrity of the lung tissue ventilation strategies for general anesthesia have been impor-
was preserved.62 In another investigation, even least-injurious tantly influenced by the progressive decrease in oxygenation
Fig. 2. Magnetic resonance imaging scans of lungs of three patients before and on the first day after open abdominal surgery.
Images were obtained throughout spontaneous breathing and represent an average of total lung volume (TLV) during the breath
cycles. (A) Minor atelectasis, (B) major atelectasis, (C) pleural effusion. Segmentation of lungs, atelectasis (red lines) and pleura
effusion (blue lines), in magnetic resonance imaging scans was performed manually. Values were calculated for whole lungs. Note
that the amounts of atelectasis and pleura effusion, two common postoperative pulmonary complications, are relatively low after
surgery. L = left side of chest; N/A = arbitrary gray scale; PostOP = postoperative; PreOP = preoperative; R = right side of chest.
and compliance.74 Tidal volumes up to 15 ml/kg of predicted

body weight were advocated to increase the end-expiratory
lung volume (EELV) and counteract atelectasis in the intra-
operative period.74 Provided there is no contraindication,
PEEP and lung recruitment maneuvers may also contribute
to revert or prevent the loss of EELV and closure of small
airways during anesthesia.
Tidal Volumes for Intraoperative Protective Ventilation

Driven by clinical and experimental studies, tidal volumes
during mechanical ventilation have been importantly
reduced in patients suffering from the acute respiratory dis-
tress syndrome (ARDS) to limit lung overdistension.75 Influ-
enced by this practice in intensive care unit patients, a similar
trend was observed in the operation room. As reported by
different investigators,76,77 average tidal volumes in the range
of 6 to 9 ml/kg of predicted body weight have gained broad
acceptance for noninjured lungs, in spite of experimental25,78
and clinical79–81 data suggesting that higher values are not
associated with increased lung damage or inflammation.
Furthermore, anesthesiologists have consistently reduced
tidal volumes also during one-lung ventilation. Whereas val-
ues as high as 10 ml/kg have been used in the past, experi-
mental,82,83 and clinical84–87 studies have suggested that
Fig. 3. Effects of high and low tidal volumes (VT) at end-
tidal volumes of approximately 4 to 5 ml/kg may be more
inspiration and end-expiration with low and high positive
appropriate for lung protection, while still allowing adequate end-expiratory pressure (PEEP) during general anesthe-
gas exchange. Furthermore, a small RCT showed that atel- sia. Atelectatic lung regions (red), overinflated lung regions
ectasis did not increase significantly with low tidal volume (blue), normally aerated lung regions (white). During ventila-
without PEEP from induction of anesthesia until the end of tion with low VT and low PEEP, higher amounts of atelectasis
surgery.67 This is also supported by the fact that mechanical are present at end-expiration and end-inspiration with mini-
ventilation with low tidal volume and PEEP did not result in mal areas of overinflation; during ventilation with high VT and
low PEEP, less atelectasis is present at end-expiration and
a progressive deterioration of the respiratory system compli-
end-inspiration, with increased areas of overinflation at end-
ance and gas exchange during open abdominal surgery in a inspiration. Furthermore, a higher amount of tissue collapsing
larger RCT.88 It must be kept in mind that “set” and “actual” and decollapsing during breathing is present. During ventila-
(i.e., delivered) tidal volumes can differ substantially89 and tion with low VT and higher PEEP, less atelectasis is present.
that settings should be adjusted judiciously. However, higher overinflation occurs at end-inspiration and
end-expiration, with minimal collapse and reopening during
breathing cycling.
PEEP for Intraoperative Protective Ventilation
Clinical studies have shown that a PEEP of 10 cm H2O is
required to reduce or eliminate atelectasis,69,90,91 improve Although controversial, an alternative approach for PEEP
compliance without increasing dead space,92,93 and main- during general anesthesia is the so-called “intraoperative per-
tain EELV during general anesthesia in both nonobese and missive atelectasis,” when PEEP is kept relatively low and
obese patients.94 Another study in normal subjects showed recruitment maneuvers are waived. This concept aims at
that PEEP of 10 cm H2O increased lung volume but did reducing the static stress in lungs, which is closely related
not improve the respiratory function compared with PEEP to the mean airway pressure, assuming that collapsed lung
of 0 cm H2O.56 Certainly, the level of PEEP should be cho- tissue is protected against injury from mechanical ventila-
sen according to the patient’s particular characteristics, the tion (fig. 3). Intraoperative permissive atelectasis may be lim-
particularities of the surgical approach, and patient position- ited by deterioration in oxygenation, which could require
ing. Several targets have been proposed for a more individ- higher inspiratory oxygen fractions. Also, shear stress may
ual titration of PEEP during general anesthesia, including occur at the interface between collapsed and open tissue,20
the following: (1) oxygenation,95 also combined with dead likely resulting in lung damage and inflammation, even in
space92 or EELV,93 (2) mechanical properties of the respira- presence of low global stress.99 Theoretically, intraoperative
tory system,96 and (3) distribution of ventilation using elec- low PEEP could increase the incidence and the amount of
tric impedance tomography.97,98 However, none of these has atelectasis even in the postoperative period, resulting in fur-
been shown to improve patient outcome. ther PPCs. A recent large retrospective study investigating
EDUCATION
the association between intraoperative mechanical ventilator

settings and outcomes suggested that the use of “minimal”
PEEP (2.2 to 5 cm H2O) combined with low tidal volumes
(6 to 8 ml/kg) is associated with increased risk of 30-day
mortality.79 However, a large international multicenter
RCT challenged the concept that “minimal” PEEP com-
bined with low tidal volumes in the intraoperative period is
harmful.88 Also in elderly patients undergoing major open
abdominal surgery, a strategy consisting of low tidal volume,
PEEP 12 cm H2O, and recruitment maneuvers increased the
Pao2 intraoperatively compared with a strategy with high
tidal volume without PEEP, but this effect was not main-
tained in the postoperative period.100 Even without recruit-
ment maneuvers, PEEP improved oxygenation during upper
abdominal surgery compared with zero end-expiratory pres-
sure, but again such effects were limited to the intraoperative
period and did not prevent postoperative complications.101
Lung Recruitment Maneuvers for Intraoperative Protective

Ventilation
Positive end-expiratory pressure is most effective for pre-
serving respiratory function if preceded by a recruitment
maneuver, which must overcome the opening pressures of
up to 40 cm H2O in nonobese102 and 40 to 50 cm H2O in
obese patients,103 in the absence of lung injury. Recruit-
ment maneuvers can be performed in different ways using
the anesthesia ventilator, as illustrated in figure 4. Most
commonly, such maneuvers are performed by “bag squeez-
ing” using the airway pressure-limiting valve of the anes-
thesia machine (fig. 4A). However, recruitment maneuvers
are better controlled if performed during tidal ventilation,
for example, using a stepwise increase of PEEP, tidal vol-
Fig. 4. Illustrative fluctuation of airway pressure during three
umes, or a combination of these (fig. 4B). Provided there types of lung recruitment maneuvers for intraoperative me-
are no contraindications, the inspiratory plateau pres- chanical ventilation (red lines). (A) “Bag squeezing” using the
sure as high as 40 cm H2O is more likely to result in full airway pressure-limiting valve of the anesthesia machine. The
recruitment.104 airway pressure is difficult to control, possibly resulting in over-
In anesthesia devices that allow pressure-controlled pressure, with the risk of barotrauma, or values lower than the
closing pressure of small airways when controlled mechanical
ventilation, recruitment maneuvers can be conducted with
ventilation is resumed, with consequent lung derecruitment.
a constant driving pressure of 15 to 20 cm H2O and by (B) “Stepwise increase of tidal volume” during volume-controlled
increasing PEEP up to 20 cm H2O in steps of 5 cm H2O ventilation. Positive end-expiratory pressure (PEEP) is set at
(30 to 60 s per step). After three to five breaths at a PEEP 12 cm H2O, the respiratory frequency at 6 to 8 breaths/min, and
level that allows achieving the target inspiratory pressure, tidal volume increased from 8 ml/kg in steps of 4 ml/kg until the
PEEP and tidal volume are adjusted to the respective target opening pressure (e.g., 30 to 40 cm H2O) is achieved.
desired levels (fig. 4C). After three to five breaths at that pressure, the PEEP is kept
at 12 cm H2O, tidal volume reduced to 6 to 8 ml/kg, and the
respiratory frequency adjusted to normocapnia. (C) Stepwise
Recent Evidence for Intraoperative increase of PEEP at a constant driving pressure of 15 to 20 cm
Protective Ventilation H2O in pressure-controlled ventilation. The PEEP is increased in
steps of 5 cm H2O (30 to 60 s per step) up to 20 cm H2O. After
Randomized Controlled Trials Using Nonclinical Primary three to five breaths at a PEEP level that allows achieving the
Outcomes target inspiratory pressure, PEEP and tidal volume are adjusted
The literature search identified 11 RCTs that compared a to the respective desired levels.
protective ventilation strategy with a nonprotective ven-
tilation strategy during general anesthesia for surgery with abdominal surgery,80,100,109 or spinal surgery,110 as depicted
regard to nonclinical primary outcome in patients under- in table 3. In eight RCTs, the protective ventilation strategy
going thoracic surgery,80,84,85,105,106 cardiac surgery,95,107,108 consisted of both lower tidal volumes and higher levels of
Table 3. Randomized Controlled Trials Using Nonclinical Primary Outcomes
Reference Patient Population/ Nonclinical Primary Secondary

Published Study Design Number Intervention Group(s) Control Group Outcomes Outcomes
Thoracic surgery
Wrigge et al.80 Prospective, Adult patients undergoing PV: VT: 6 ml/kg; PEEP: CV: VT: 12–15 ml/kg; Inflammatory mediators in Gas exchange: no differ-
single-center, major thoracic surgery, 10 cm H2O; Paw limit: ZEEP: Paw limit: 35 cm plasma: no differences ences between groups
randomized con- n = 34 (2 excluded) 35 cm H2O during TLV H2O during TLV and between groups for
trolled trial and OLV (n = 15) OLV (n = 17) TNFα, IL-1, IL-6, IL-8,
IL-10, IL-12
Schilling et al.84 Prospective, Adult patients undergoing PV: VT: 5 ml/kg during CV: VT: 10 ml/kg during Inflammatory mediators in Pao2/Fio2: no differences
single-center, elective open thoracic TLV and OLV; PEEP: TLV and OLV; PEEP: BAL: TNFα and sICAM between groups;
randomized con- surgery (n = 32) 3 cm H2O, TLV; PEEP: 3 cm H2O, TLV; PEEP: lower during PV; no Paco2: higher during
trolled trial 0–2 cm H2O, OLV; Paw 0–2 cm H2O, OLV; Paw differences between PV
limit: 30 cm H2O (n = limit: 30 cm H2O (n = 16) groups for cell count,
16) PMN elastase, total
protein, albumin, IL-8,
and IL-10
Michelet et al.85 Prospective, Adult patients undergoing PV: VT: 9 ml/kg, TLV; VT: CV: VT: 9 ml/kg, TLV and Inflammatory mediators Pao2/Fio2 and Paco2:
single-center, planned esophagec- 5 ml/kg OLV; PEEP: OLV; ZEEP: TLV and in plasma: IL-1β, IL-6, higher during PV;
randomized con- tomy (n = 52) 5 cm H2O, TLV and OLV (n = 26) IL-8 lower during PV; EVLWI: lower during
trolled trial OLV (n = 26) no differences between PV; time to extubation:
groups for TNFα shorter during PV
Lin et al.105 Prospective, Adult patients undergoing PV: VT: 10 ml/kg, TLV; VT: CV: VT: 10 ml/kg, TLV and Inflammatory mediators Ppeak, Pplat, and Raw: lower
single-center, esophagectomy 5–6 ml/kg OLV; PEEP: OLV; ZEEP: TLV and in plasma: IL-6, IL-8, during PV
randomized (n = 40) 3–5 cm H2O, OLV (n OLV (n = 20) lower during PV
controlled trial = 20)
Unzueta et al.106 Prospective, Adult patients undergoing PV: VT: 8 ml/kg, TLV; VT: CV: VT: 8 ml/kg, TLV; VT: Dead space: Pao2/Fio2: higher during
single-center, elective open 6 ml/kg OLV; PEEP: 6 ml/kg OLV; PEEP: lower during PV PV; Paco2: lower
randomized thoracotomy 8 cm H2O, TLV and 8 cm H2O, TLV and OLV; during PV
controlled trial (n = 40) OLV; RM with stepwise no RM before start of
PEEP/Paw increase until OLV (n = 20)
20/40 cm H2O before
start of OLV (n = 20)
Cardiac surgery
Koner et al.107 Prospective, Adult patients undergo- (1) PV: VT: 6 ml/kg; PEEP: (3) CV + ZEEP: VT: 10 ml/ Inflammatory mediators in Pplat: lower during PV
single-center, ing elective on-pump 5 cm H2O (n = 15) kg; PEEP: 0 cm H2O plasma: no differences compared with both CV
randomized con- coronary artery bypass (2) CV + PEEP: V : 10 ml/ (n = 15) between groups for groups; shunt fraction:
T
trolled trial grafting surgery (n = 44) kg; PEEP: 5 cm H2O (n TNFα and IL-6 lower during PV com-
= 14) pared with both CV +
ZEEP; Pao2/Fio2: higher
during ventilation with
PEEP, (1) + (2)
Zupancich Prospective, Adult patients undergo- PV: VT: 8 ml/kg; PEEP: CV: VT: 10–12 ml/kg; Inflammatory mediators in Paco2: higher during PV
et al.108 single-center, ing elective on-pump 10 cm H2O (n = 20) PEEP: 2–3 cm H2O plasma and BAL: IL-6,
randomized con- coronary artery bypass (n = 20) IL-8, lower during PV
trolled trial grafting surgery (n = 40) in both
(Continued)
Table 3. Continued
EDUCATION
Reference Patient Population/ Nonclinical Primary Secondary

Published Study Design Number Intervention Group(s) Control Group Outcomes Outcomes
Reis Miranda Prospective, single- Adult patients undergo- (1) Late open lung: VT: (3) VT: 6–8 ml/kg; PEEP: Inflammatory mediators in Evidence of perioperative
et al.95 center, rand- ing elective on-pump 4–6 ml/kg; PEEP: 10 cm 5 cm H2O (n = 22) plasma: IL-8 decreased myocardial infarction
omized controlled coronary artery bypass H2O starting at post- after CPB in both open (CK-MB and ECG): no
trial grafting or valve sur- operative ICU arrival (n lung groups; IL-10 differences between
gery (n = 62) = 18) decreased faster after groups
(2) (1) Early open lung: VT: CPB in early open lung
4–6 ml/kg; PEEP: 10 cm group
H2O starting after intu-
bation (n = 22)
Abdominal surgery
Wrigge et al.80 Prospective, single- Adult patients undergo- PV: VT: 6 ml/kg; PEEP: CV: VT: 12–15 ml/kg; Inflammatory mediators in Pao2/Fio2: no differences
center, rand- ing major abdominal 10 cm H2O; Paw limit ZEEP: Paw limit: 35 cm plasma: no differences between groups;
omized controlled surgery (n = 30) 35 cm H2O (n = 15) H2O (n = 15) between groups for Paco2: higher during
trial TNFα, IL-1, IL-6, IL-8, PV
IL-10, and IL-12
Wolthuis et al.109 Prospective, single- Adult patients undergoing PV: VT: 6 ml/kg; PEEP: CV: VT: 10–12 ml/kg Inflammatory mediators in Paco2: higher during PV;
center, rand- a surgical procedure in 10 cm H2O (n = 24) ZEEP: n = 22 plasma and BAL: lower PPCs: no differences
omized controlled general anesthesia ≥5 h myeloperoxidase and between groups
trial (n = 46) nucleosome level in
BAL during PV
Weingarten Prospective, single- Adult patients aged PV: VT: 6 ml/kg; PEEP: CV: VT: 10 ml/kg; Inflammatory mediators in Pao2/Fio2 + Paco2: higher
et al.100 center, rand- > 65 yr undergoing 12 cm H2O RM with ZEEP: no RM plasma: no differences during PV; compliance
omized controlled major open abdominal stepwise PEEP (n = 20) between groups higher and resistance
trial surgery under general increase until 15 cm lower during PV
anesthesia (n = 40) H2O (n = 20)
Spinal surgery
Memtsoudis Prospective, single- Adult patients undergoing PV: VT: 6 ml/kg; PEEP: CV: VT: 12 ml/kg; Inflammatory mediators in Paco2: higher during PV
et al.110 center, rand- elective lumbar decom- 8 cm H2O (n = 13) ZEEP: n = 13 plasma: no differences
omized controlled pression and fusion in between groups
trial prone position under
general anesthesia (n
= 26)
BAL = bronchoalveolar lavage; CK-MB = muscle-brain type creatine kinase; CPB = cardiopulmonary bypass; CV = conventional ventilation; ECG = electrocardiogram; EVLWI =extravascular lung water index;
Fio2 = inspired fraction of oxygen; ICAM = intercellular adhesion molecule; ICU = intensive care unit; IL = interleukin; OLV = one-lung ventilation; Paco2 = partial pressure of arterial carbon dioxide; Pao2 = partial
pressure of arterial oxygen; Pao2/Fio2 = ratio of partial pressure of arterial oxygen to inspired fraction of oxygen; Paw = airway pressure; PEEP = positive end-expiratory pressure; PMN = polymorphonuclear leuko-
cyte; PPCs = postoperative pulmonary complications; Ppeak = peak pressure; Pplat = plateau pressure; PV = protective ventilation; Raw = airway resistance; RM = recruitment maneuver; sICAM = soluble intercellular
adhesion molecule; TLV = two-lung ventilation; TNFα = tumor necrosis factor-α; VT = tidal volume; ZEEP = zero end-expiratory pressure.
PEEP80,85,100,105,107–110; in two RCTs, it consisted of either H2O PEEP with recruitment maneuvers) versus nonprotec-
lower tidal volume,84 a higher level of PEEP.95 In one RCT, tive ventilation (tidal volume 9 ml/kg and zero end-expiratory
lung recruitment maneuvers were used during the protective pressure) in 56 patients scheduled for open abdominal surgery
ventilation strategy.106 lasting more than 2 h. The modified “Clinical Pulmonary
The effects on inflammatory responses are slightly contra- Infection Score” was lower in patients receiving protective
dictory. Although four RCTs showed no difference in local ventilation. These patients also had fewer chest radiograph
levels of inflammatory mediators between patients on pro- abnormalities and higher arterial oxygenation compared with
tective and those on nonprotective ventilation,80,100,107,110 six patients receiving nonprotective ventilation.
RCTs84,85,95,105,108,109 showed that protective strategies were Finally, in an international multicenter trial conducted
associated with lower levels of inflammatory mediators. in Europe and the United States (PROtective Ventilation
using HIgh vs. LOw PEEP [PROVHILO]),88 the PROtec-
Randomized Controlled Trials Using Clinical Primary tive VEntilation Network investigators compared PEEP of
Outcomes 12 cm H2O combined with recruitment maneuvers versus
In total, eight RCTs were identified that compared a pro- PEEP of 2 cm H2O without recruitment maneuvers in 900
tective ventilation strategy with a nonprotective ventilation nonobese patients at high risk for PPCs planned for open
strategy during surgery with regard to a clinical primary out- abdominal surgery under ventilation at tidal volumes of
comes in patients planned for abdominal surgery,88,111–113 8 ml/kg. The incidence of PPCs was not different between
thoracic surgery,87,114 cardiac surgery,115 or spinal surgery,116 patients receiving protective ventilation and patients receiv-
as shown in table 4. In four RCTs, the protective strategy ing nonprotective ventilation.
consisted of both lower tidal volumes and higher levels of
PEEP,112–114,116 and in the four remaining RCTs, it con- Challenges of Studies Using Bundles
sisted of either lower tidal volumes87,111,115 or higher levels As shown in preceding subsections Randomized Con-
of PEEP.88 trolled Trials Using Nonclinical Primary Outcomes
Four trials reported on PPCs in the first postoperative and Randomized Controlled Trials Using Clinical Pri-
days, including bronchitis, hypoxemia, and atelectasis,116 mary Outcomes, most RCTs addressing intraoperative
pneumonia, need for invasive or noninvasive ventilation for mechanical ventilation compared bundles of interventions
acute respiratory failure,112 a modified “Clinical Pulmonary consisting of tidal volumes and levels of PEEP, usually
Infection Score,” and chest radiograph abnormalities,113 and accompanied by a lung recruitment maneuver.112–114,116
hypoxemia, bronchospasm, suspected pulmonary infection, Notably, recruitment maneuvers differed between the tri-
pulmonary infiltrate, aspiration pneumonitis, development als. In the Italian single-center RCT,113 investigators used
of ARDS, atelectasis, pleural effusion, pulmonary edema, incremental titration of tidal volumes until a plateau pres-
and pneumothorax.88 sure of 30 cm H2O, directly after induction of anesthesia,
In a Chinese single-center RCT,116 investigators com- after any disconnection from the ventilator and immedi-
pared protective ventilation (tidal volume 6 ml/kg and 10 cm ately before extubation, similar as in PROVHILO.88 In
H2O PEEP) versus nonprotective (tidal volume 10 to 12 ml/ Intraoperative PROtective Ventilation trial,112 recruitment
kg and 0 cm H2O PEEP) in 60 elderly patients with Ameri- was performed with a continuous positive airway pressure
can Society of Anesthesiologists class II and III scheduled for of 30 cm H2O for 30 s every 30 min, also known as sus-
spinal surgery. Patients receiving protective ventilation had tained inflation, after tracheal intubation. Finally, in the
less PPCs. Chinese single-center RCT,116 the recruitment maneuvers
In a French multicenter trial (Intraoperative PROtec- followed a similar approach, but to plateau pressures of
tive VEntilation),112 protective ventilation (tidal volume 6 up to 35 cm H2O, and they were performed every 15 min.
to 8 ml/kg and PEEP 6 to 8 cm H2O) was compared with It is difficult, if not impossible, to conclude from these
nonprotective ventilation (tidal volume 10 to 12 ml/kg and trials what caused the benefit, tidal volume reduction or
0 cm H2O PEEP) in 400 nonobese patients at intermediate increase of PEEP or both, and to determine the role of
to high risk of pulmonary complications after planned major recruitment maneuvers. Moreover, to what extent the
abdominal surgery. The primary outcome (postoperative recruitment maneuver has succeeded in reopening lung
pulmonary and extrapulmonary complications) occurred has not been analyzed in the different studies.
less often in patients receiving “protective” ventilation. Such The results of the PROVHILO trial, however, suggest that
complications have been ascribed to the release of inflam- low tidal volumes rather than PEEP combined with lung
matory mediators by the lungs into the systemic circulation, recruitment maneuvers are responsible for lung protection in
affecting the lungs,117 as well as peripheral organs.52 These the intraoperative period. This interpretation is also supported
patients also had a shorter length of hospital stay, but mor- by an analysis of different studies on the odds ratios of lower
tality was unaffected. tidal volumes,87,111,115 higher levels of PEEP,88 their combina-
An Italian single-center trial113 investigated the effective- tion,112–114,116 regarding the development of PPCs (fig. 5), as
ness of protective ventilation (tidal volume 7 ml/kg and 10 cm well as a recent individual patient data meta-analysis.131
Table 4. Randomized Controlled Trials Using Clinical Primary Outcomes
Reference Patient Clinical Secondary

Published Study Design Population/Number Intervention Control Group Primary Outcomes Outcomes
EDUCATION
Thoracic surgery
Maslow et al.114 Prospective, single- Adult patients undergoing PV: VT: 5 ml/kg, TLV and CV: VT: 10 ml/kg, TLV Rate of atelectasis: lower Paco2 and alveolar dead
center, randomized elective pulmonary resec- OLV; PEEP: 5 cm H2O, and OLV; ZEEP: TLV with CV; length of space: higher during
controlled trial tion (n = 34) TLV and OLV (n = 17) and OLV (n = 17) hospital stay: no differ- PV; Cdyn: higher
ences between groups during CV
Shen et al.87 Prospective, single- Adult patients undergoing PV: VT: 8 ml/kg TLV; VT: CV: VT: 8 ml/kg, TLV; PPCs: lower rate with PV; Pao2/Fio2 and Paco2:
center, randomized elective thoracoscopic 5 ml/kg OLV; PEEP: 5 cm VT: 8 ml/kg OLV; mortality: no difference higher during PV;
controlled trial esophagectomy (n = 101) H2O, TLV and OLV (n = ZEEP: TLV and OLV between groups inflammatory media-
53) (n = 48) tors in BAL: lower
IL-1β, IL-6, and IL-8
Cardiac surgery
Sundar et al.115 Prospective, single- Adult patients undergoing PV: VT: 6 ml/kg; PEEP/ CV: VT: 10 ml/kg; Rate of reintubation: Gas exchange: no differ-
center, randomized elective cardiac surgery Fio2: according to ARDS PEEP/Fio2: accord- lower with PV; number ence between groups
controlled trial (n = 149) Network table (n = 75) ing to ARDS Net- of patients requiring
work table (n = 74) ventilation 6 h postop-
eratively: lower with PV
Abdominal surgery
Treschan et al.111 Prospective, single- Adult patients undergoing PV: VT: 6 ml/kg; PEEP: 5 cm CV: VT: 12 ml/kg; Rate of atelectasis: lower Pao2/Fio2: higher during
center, randomized elective upper abdominal H2O (n = 50) PEEP: 5 cm H2O with CV CV; Cdyn and Raw:
controlled trial surgery lasting ≥3 h under (n = 51) higher during CV; Pao2
combined general and epi- at postoperative day
dural anesthesia (n = 101) 5: higher with CV
Futier et al.112 Prospective randomized Adults patients at inter- PV: VT: 6–8 ml/kg; PEEP: CV: VT: 10–12 ml/kg; Composite primary Reduced rate of atelec-
controlled multicenter mediate to high risk of 6–8 cm H2O (n = 200) ZEEP (n = 200) outcome of major tasis, pneumonia,
study pulmonary complications pulmonary or extrapul- need for ventilation
undergoing major abdomi- monary complications: within 7 days and sep-
nal surgery (n = 400) lower with PV sis with PV. Reduced
length of hospital stay
with PV
Severgnini Prospective, single- Adult patients undergoing PV: VT: 7 ml/kg; PEEP: CV: VT: 9 ml/kg; Pulmonary function tests: Modified Clinical Pulmo-
et al.113 center, randomized elective open abdominal 10 cm H2O (n = 28) ZEEP (n = 27) improved with PV nary Infection Score:
controlled trial surgery ≥2 h lower with PV; Pao2
n = 56 (1 excluded) at postoperative days
1, 3, and 5: higher
with PV. Rate of chest
radiograph abnormali-
ties: lower with PV.
Length of hospital
stay: no difference
between groups
(Continued)
Certainly, these conclusions are only valid for the studied
ARDS = acute respiratory distress syndrome; BAL = bronchoalveolar lavage; Cdyn = dynamic compliance of the respiratory system; CV = conventional ventilation; Fio2 = inspired fraction of oxygen; IL = interleu-
kin; OLV = one-lung ventilation; Paco2 = partial pressure of arterial carbon dioxide; Pao2 = partial pressure of arterial oxygen; Pao2/Fio2 = ratio of partial pressure of arterial oxygen to inspired fraction of oxygen;
PEEP = positive end-expiratory pressure; PPCs = postoperative pulmonary complications; PROVE = PROtective VEntilation; PV = protective ventilation; Raw = airway resistance; RM = recruitment maneuver; TLV
and length of hospital
amount of vasoactive
population, that is, nonobese patients at risk of PPCs under-
during PV. Mortality

Rate of intraoperative
drugs given: higher
desaturation: lower
stay: no difference
during PV. Rate of
going elective abdominal surgery. Other patient populations
hypotension and
between groups
Secondary
Outcomes
Pao2/Fio2, higher
could still benefit from higher levels of PEEP and recruit-
ment maneuvers.
during PV
Challenges of Composite Outcome Measures
Composite outcome measures offer the benefit of an increased
event rate, which is helpful to ensure adequate statistical power
ence between groups
of a trial.8 It is reasonable to combine related outcomes that rep-

Rate of PPCs: no differ-
Primary Outcomes
resent different aspects of a single underlying pathophysiologic

process, such as PPCs for VILI. There are, though, two major
Clinical
lower with PV
Rate of PPCs,
limitations regarding the use of composite outcomes. First, the

component variables can differ importantly in terms of severity
and frequency. Second, differences in the frequency of compo-
nent variables in a composite outcome may be masked.
PEEP: 0–2 cm H2O
Drawbacks of Protective Ventilation

CV: VT: 10–12 ml/kg;
Control Group
The term “protective” in the context of mechanical ventila-

ZEEP (n = 30)
CV: VT: 8 ml/kg;
tion implies a decrease in the major components of VILI,

(n = 449)
namely atelectrauma, volutrauma, and biotrauma. However,

a strategy that is protective to lungs may also cause harm
to other organ systems. The potential for harm caused by
protective ventilation was reported in PROVHILO trial,88
in which patients receiving higher PEEP and lung recruit-
VT after induction and
10 cm H2O; RM every

stepwise increase of
ment maneuvers developed intraoperative hypotension more

12 cm H2O; RM with
PV: VT: 8 ml/kg; PEEP:
PV: VT: 6 ml/kg; PEEP:

before extubation
Intervention
frequently and needed more vasoactive drugs. These findings

15 min (n = 30)
are at least in part in line with the finding that protective

ventilation was associated with a higher incidence of intra-
(n = 445)
operative hypotension in the French trial.112
Standard of Care versus Unusual Settings: Were the

Control Groups of Recent Trials Representative of Clinical
undergoing major abdomi-
pulmonary complications
Practice?
Adult patients undergoing
mediate to high risk of
Population/Number
Adults patients at inter-
In RCTs addressing intraoperative protective mechanical

nal surgery (n = 900)
spine fusion (n = 60)
= two-lung ventilation; VT = tidal volume; ZEEP = zero end-expiratory pressure.
ventilation, the strategy used to treat control groups can

Patient
play an important role when drawing conclusions for daily

practice of general anesthesia. Meta-analyses suggest that
lower tidal volumes are protective not only during long-term
ventilation in critically ill patients118,119 but also short-term
ventilation during general anesthesia for surgery.119 Accord-
ingly, anesthesiologists have been using tidal volumes of
approximately 8 to 9 ml/kg on average, and seldom higher
center, randomized
Prospective, interna-
tional, multicenter,
Prospective, single-
randomized con-
Study Design
than 10 ml/kg,76 as also illustrated in figure 6A. In contrast

controlled trial
to this practice, the tidal volumes used in the control groups

trolled trial
of recent RCTs were as high as 9113 to 12 ml/kg,112 except

to PROVHILO88 (fig. 6B), which used a tidal volume of
7 ml/kg both in the intervention and in the control group.
Similarly, levels of PEEP in the control arms of three of four
Table 4. Continued
recent RCTs112,113,116 on protective mechanical ventilation

PROVE Network
Investigators
were much lower than the standard of care at the moment

Spinal surgery
Ge et al.116
the respective studies were designed (fig. 6, C and D). Taken

201488
Reference
Published
together, these facts suggest that, among the most impor-

tant recent RCTs on intraoperative protective mechani-
cal ventilation, only the PROVHILO trial used a control
EDUCATION
Fig. 5. Odds ratios for postoperative pulmonary complications of “protective” versus “nonprotective” ventilation in trials com-
paring different tidal volumes,87,111,115 different tidal volumes and positive end-expiratory pressure (PEEP),112–114,116 and different
levels of PEEP.88 df = degrees of freedom; M-H = Mantel-Haenszel.
group that reproduced the standard of anesthesia care at the PEEP (≤2 cm H2O) because higher PEEP combined with
time it was conducted. Accordingly, the PROVHILO trial recruitment maneuvers does not confer further protection
addressed a major question regarding mechanical ventila- against PPCs and can deteriorate the hemodynamics. If
tion during anesthesia, namely whether the combination of hypoxemia develops and provided that other causes have
high PEEP with recruitment maneuvers confers protection been excluded (e.g., hypotension, hypoventilation, and
against PPCs. In this study, high PEEP was not individual- pulmonary embolism), the Fio2 should be increased first,
ized, but based on previous findings from computed tomog- followed by increase of PEEP, and recruitment maneuvers
raphy69,90,91 and physiological studies.92,94 based on stepwise increase of tidal volume during regular
mechanical ventilation, according to the rescue algorithm
Intraoperative Mechanical Ventilation described in the PROVHILO trial,88 provided no contra-
According to the Utmost Recent Evidence indication is present. In patients with ARDS126 undergo-
ing open abdominal surgery, intraoperative mechanical
A number of reviews and commentaries have suggested
ventilation should be guided by the ARDS network pro-
that intraoperative mechanical ventilation for surgery
tocol,127 whereby higher PEEP values128 may be useful in
should consist of low tidal volumes (6 to 8 ml/kg), mod-
more severe ARDS.129 If the target Pao2 (55 to 80 mmHg)
erate levels of PEEP (6 to 8 cm H2O), and periodic lung
or Spo2 (88 to 95%) cannot be achieved, a maximal lung
recruitment maneuvers (e.g., every 30 min).5,123–125 How-
recruitment maneuver with a decremental PEEP trial can
ever, previous reviews and recommendations have been
be considered.130
based on bundles, which do not permit to infer on the
contribution of individual measures. Furthermore, the
results of the largest RCT in this field (PROVHILO) Future Perspectives
could not be taken into account. Also, a recommenda- Despite the increasing number of highly qualitative RCTs
tion regarding the use of positive pressure ventilation dur- on intraoperative mechanical ventilation, a number of issues
ing induction and emergence of anesthesia, as proposed remain unaddressed. Although meta-analyses strongly sug-
recently,124 is not supported by outcome data. Currently, gest that low tidal volumes during intraoperative mechani-
the only recommendations that can be given for clinical cal ventilation protect against postoperative pulmonary
practice are summarized in figure 7. In nonobese patients events, no single RCT has been able to prove this claim.
without ARDS126 undergoing open abdominal surgery, Because meta-analyses in this field frequently include the
mechanical ventilation should be performed with low tidal studies that tested intervention bundles, for example, low
volumes (approximately 6 to 8 ml/kg) combined with low tidal volume and high PEEP with recruitment maneuvers
Fig. 6. Settings of tidal volume (VT) (A) and positive end-expiratory pressure (PEEP) (C) according to observational studies of
mechanical ventilation in the operation room (in Canada,120 France,121 and the United States3,76,77,122); settings of VT (B) and
PEEP (D) in “nonprotective” ventilation (red) and “protective” ventilation (blue) groups in four recent randomized controlled trials
(Severgnini et al.,113 Intraoperative PROtective VEntilation trial [IMPROVE],112 Ge et al.,116 and PROtective Ventilation using HIgh
vs. LOw PEEP [PROVHILO]88). PBW = predicted body weight.
versus high tidal volumes without PEEP, the estimation of postoperative atelectasis, the most frequent of the differ-
the effects of single measures, for example, low tidal volume ent PPCs, influences the development of pulmonary infec-
or PEEP, is prone to criticism. Therefore, RCTs are most tions and severe respiratory failure and affects other relevant
relevant for clinical practice if they test single interven- outcome measures, including hospital length of stay and
tions, and if control groups reproduce current standards. mortality. In addition, further studies should shed light on
Whereas direct testing of the hypothesis that intraoperative the potential contributions of ventilatory strategies during
low tidal volumes protect against PPCs is still lacking, ethi- induction and emergence of anesthesia, as well as in the
cal issues preclude such a trial. postoperative period (e.g., noninvasive ventilation). Accord-
Despite convincing evidence that PEEP and recruitment ingly, the potential of perioperative nonventilatory measures
maneuvers do not confer further protection and may even (e.g., muscle paralysis, use of short-acting neuromuscular-
impair hemodynamics during a ventilatory strategy based blocking agents, and monitoring and reversal of muscle
on low tidal volumes in open abdominal surgery, we do not paralysis, early mobilization, and respiratory therapy) for
know whether patients with obesity or undergoing one- reducing PPCs should be investigated. Such studies are nec-
lung anesthesia procedures may benefit from those inter- essary to support future guidelines on the practice of peri-
ventions. Also, we cannot rule out the possibility that an operative mechanical ventilation and adjunctive measures
individual PEEP titration targeted on lung function could in a broad spectrum of patients as well as surgical interven-
yield different results. Furthermore, it remains unclear how tions, both open and laparoscopic.
EDUCATION
Acknowledgments
The authors are indebted to Anja Braune, M.Sc., and
Lorenzo Ball, M.D., from the Pulmonary Engineering Group,
Department of Anesthesiology and Intensive Care Medicine,
University Hospital Dresden, Technische Universität Dres-
den, Dresden, Germany, for segmentation and calculations
of atelectasis and pleura effusion volumes in magnetic reso-
nance imaging scans.
Support was provided solely from institutional and/or
departmental sources.
Competing Interests
The authors declare no competing interests.
Correspondence
Address correspondence to Dr. Gama de Abreu: Pulmo-
nary Engineering Group, Department of Anesthesiology
and Intensive Care Medicine, University Hospital Dresden,
Technische Universität Dresden, Fetscherstrasse 74, 01307
Fig. 7. Proposed settings of protective mechanical ventilation
Dresden, Germany. mgabreu@uniklinikum-dresden.de.
This article may be accessed for personal use at no charge
in nonobese patients during open abdominal surgery accord-
through the Journal Web site, www.anesthesiology.org.
ing to the concept of intraoperative permissive atelectasis.
ARDS = acute respiratory distress syndrome; Fio2 = inspi-
ratory oxygen fraction of oxygen; Pao2 = partial pressure of References
arterial oxygen; PBW = predicted body weight; PEEP = posi- 1. Canet J, Gallart L, Gomar C, Paluzie G, Vallès J, Castillo J,
tive end-expiratory pressure; Petco2 = end-tidal pressure of Sabaté S, Mazo V, Briones Z, Sanchis J; ARISCAT Group:
carbon dioxide; Pplat = inspiratory airway plateau pressure; Prediction of postoperative pulmonary complications in
a population-based surgical cohort. Anesthesiology 2010;
RR = respiratory rate; Spo2 = peripheral oxygen saturation;
113:1338–50
VT = tidal volume.
2. Mazo V, Sabaté S, Canet J, Gallart L, Gama de Abreu M, Belda
J, Langeron O, Hoeft A, Pelosi P: Prospective external valida-
tion of a predictive score for postoperative pulmonary com-
Conclusions plications. Anesthesiology 2014; 121:219–31
The potential of intraoperative lung-protective mechanical 3. Fernández-Pérez ER, Sprung J, Afessa B, Warner DO, Vachon
CM, Schroeder DR, Brown DR, Hubmayr RD, Gajic O:
ventilation to reduce the incidence of PPCs is well estab- Intraoperative ventilator settings and acute lung injury after
lished. RCTs have suggested that low tidal volumes, high elective surgery: A nested case control study. Thorax 2009;
64:121–7
PEEP, and recruitment maneuvers may be protective intra-
4. Hemmes SN, Serpa Neto A, Schultz MJ: Intraoperative ven-
operatively, but the precise role of each single intervention tilatory strategies to prevent postoperative pulmonary com-
has been less clearly defined. A meta-analysis taking the plications: A meta-analysis. Curr Opin Anaesthesiol 2013;
utmost recent clinical data shows that the use of low tidal 26:126–33
5. Futier E, Constantin JM, Jaber S: Protective lung ventilation
volumes, rather than PEEP, recruitment maneuvers, or a in operating room: A systematic review. Minerva Anestesiol
combination of these two, is the most important deter- 2014; 80:726–35
minant of protection in intraoperative mechanical venti- 6. Gajic O, Dabbagh O, Park PK, Adesanya A, Chang SY, Hou P,
lation. In nonobese patients without ARDS undergoing Anderson H III, Hoth JJ, Mikkelsen ME, Gentile NT, Gong MN,
Talmor D, Bajwa E, Watkins TR, Festic E, Yilmaz M, Iscimen
open abdominal surgery, mechanical ventilation should R, Kaufman DA, Esper AM, Sadikot R, Douglas I, Sevransky
be performed with low tidal volumes (approximately 6 J, Malinchoc M; U.S. Critical Illness and Injury Trials Group:
Lung Injury Prevention Study Investigators (USCIITG-LIPS):
to 8 ml/kg) combined with low PEEP because the use of Early identification of patients at risk of acute lung injury:
higher PEEP combined with recruitment maneuvers does Evaluation of lung injury prediction score in a multicenter
not confer further protection against PPCs and can deteri- cohort study. Am J Respir Crit Care Med 2011; 183:462–70
orate the hemodynamics. If hypoxemia develops, and pro- 7. Canet J, Gallart L: Predicting postoperative pulmonary com-
plications in the general population. Curr Opin Anaesthesiol
vided that other causes have been excluded, for example, 2013; 26:107–15
hypotension, hypoventilation, and pulmonary embolism, 8. Jammer I, Wickboldt N, Sander M, Smith A, Schultz MJ, Pelosi
the Fio2 should be increased first, followed by increase P, Leva B, Rhodes A, Hoeft A, Walder B, Chew MS, Pearse RM;
European Society of Anaesthesiology (ESA) and the European
of PEEP, and recruitment maneuvers based on stepwise Society of Intensive Care Medicine (ESICM): Standards for
increase of tidal volume during regular mechanical ventila- definitions and use of outcome measures for clinical effec-
tion. Further studies are warranted to guide intraoperative tiveness research in perioperative medicine: European
Perioperative Clinical Outcome (EPCO) definitions: A state-
mechanical ventilation in a broader spectrum of patients ment from the ESA-ESICM joint taskforce on perioperative
and surgical interventions. outcome measures. Eur J Anaesthesiol 2015; 32:88–105
9. Arozullah AM, Daley J, Henderson WG, Khuri SF: Multifactorial ventilation: Any safe threshold? Am J Respir Crit Care Med
risk index for predicting postoperative respiratory failure in 2011; 183:1354–62
men after major noncardiac surgery. The National Veterans 26. Spieth PM, Silva PL, Garcia CS, Ornellas DS, Samary CS, Moraes
Administration Surgical Quality Improvement Program. Ann L, Bentes M, Morales MM, Kasper M, Güldner A, Huhle R, Koch
Surg 2000; 232:242–53 T, Pelosi P, de Abreu MG, Rocco PR: Modulation of stress versus
10. Arozullah AM, Khuri SF, Henderson WG, Daley J; Participants time product during mechanical ventilation influences inflam-
in the National Veterans Affairs Surgical Quality Improvement mation as well as alveolar epithelial and endothelial response
Program: Development and validation of a multifactorial risk in rats. Anesthesiology 2015; 122:106–16
index for predicting postoperative pneumonia after major 27. Davidovich N, DiPaolo BC, Lawrence GG, Chhour P, Yehya
noncardiac surgery. Ann Intern Med 2001; 135:847–57 N, Margulies SS: Cyclic stretch-induced oxidative stress
11. Canet J, Gallart L: Postoperative respiratory failure:
increases pulmonary alveolar epithelial permeability. Am J
Pathogenesis, prediction, and prevention. Curr Opin Crit Respir Cell Mol Biol 2013; 49:156–64
Care 2014; 20:56–62 28. Hussein O, Walters B, Stroetz R, Valencia P, McCall D,

12. Sabaté S, Mazo V, Canet J: Predicting postoperative pulmo- Hubmayr RD: Biophysical determinants of alveolar epithe-
nary complications: Implications for outcomes and costs. lial plasma membrane wounding associated with mechani-
Curr Opin Anaesthesiol 2014; 27:201–9 cal ventilation. Am J Physiol Lung Cell Mol Physiol 2013;
13. Smetana GW, Lawrence VA, Cornell JE; American College of 305:L478–84
Physicians: Preoperative pulmonary risk stratification for non- 29. Suki B, Hubmayr R: Epithelial and endothelial damage

cardiothoracic surgery: Systematic review for the American induced by mechanical ventilation modes. Curr Opin Crit
College of Physicians. Ann Intern Med 2006; 144:581–95 Care 2014; 20:17–24
14. Johnson RG, Arozullah AM, Neumayer L, Henderson WG,
30. Moriondo A, Pelosi P, Passi A, Viola M, Marcozzi

Hosokawa P, Khuri SF: Multivariable predictors of postop- C, Severgnini P, Ottani V, Quaranta M, Negrini D:
erative respiratory failure after general and vascular surgery: Proteoglycan fragmentation and respiratory mechanics
Results from the patient safety in surgery study. J Am Coll in mechanically ventilated healthy rats. J Appl Physiol
Surg 2007; 204:1188–98 (1985) 2007; 103:747–56
15. Brueckmann B, Villa-Uribe JL, Bateman BT, Grosse-Sundrup 31. Moriondo A, Marcozzi C, Bianchin F, Passi A, Boschetti F,
M, Hess DR, Schlett CL, Eikermann M: Development and vali- Lattanzio S, Severgnini P, Pelosi P, Negrini D: Impact of respi-
dation of a score for prediction of postoperative respiratory ratory pattern on lung mechanics and interstitial proteogly-
complications. Anesthesiology 2013; 118:1276–85 cans in spontaneously breathing anaesthetized healthy rats.
16. Kor DJ, Lingineni RK, Gajic O, Park PK, Blum JM, Hou PC, Acta Physiol (Oxf) 2011; 203:331–41
Hoth JJ, Anderson HL III, Bajwa EK, Bartz RR, Adesanya A, 32. Pelosi P, Rocco PR: Effects of mechanical ventilation on the
Festic E, Gong MN, Carter RE, Talmor DS: Predicting risk extracellular matrix. Intensive Care Med 2008; 34:631–9
of postoperative lung injury in high-risk surgical patients: A 33. Negrini D, Passi A, Moriondo A: The role of proteoglycans in
multicenter cohort study. Anesthesiology 2014; 120:1168–81 pulmonary edema development. Intensive Care Med 2008;
17. Trillo-Alvarez C, Cartin-Ceba R, Kor DJ, Kojicic M, Kashyap 34:610–8
R, Thakur S, Thakur L, Herasevich V, Malinchoc M, Gajic O: 34. Moriondo A, Marcozzi C, Bianchin F, Reguzzoni M, Severgnini
Acute lung injury prediction score: Derivation and validation P, Protasoni M, Raspanti M, Passi A, Pelosi P, Negrini D:
in a population-based sample. Eur Respir J 2011; 37:604–9 Impact of mechanical ventilation and fluid load on pulmo-
18. Kor DJ, Warner DO, Alsara A, Fernández-Pérez ER, Malinchoc nary glycosaminoglycans. Respir Physiol Neurobiol 2012;
M, Kashyap R, Li G, Gajic O: Derivation and diagnos- 181:308–20
tic accuracy of the surgical lung injury prediction model. 35. Spieth PM, Bluth T, Gama De Abreu M, Bacelis A, Goetz AE,
Anesthesiology 2011; 115:117–28 Kiefmann R: Mechanotransduction in the lungs. Minerva
19. Higuita-Castro N, Mihai C, Hansford DJ, Ghadiali SN:
Anestesiol 2014; 80:933–41
Influence of airway wall compliance on epithelial cell injury 36. Rocco PR, Dos Santos C, Pelosi P: Pathophysiology of ven-
and adhesion during interfacial flows. J Appl Physiol (1985) tilator-associated lung injury. Curr Opin Anaesthesiol 2012;
2014; 117:1231–42 25:123–30
20. Mead J, Takishima T, Leith D: Stress distribution in lungs: 37. Uhlig S: Ventilation-induced lung injury and mechanotrans-
A model of pulmonary elasticity. J Appl Physiol 1970; duction: Stretching it too far? Am J Physiol Lung Cell Mol
28:596–608 Physiol 2002; 282:L892–6
21. Needham DM, Colantuoni E, Mendez-Tellez PA, Dinglas VD, 38. Parker JC, Hernandez LA, Longenecker GL, Peevy K, Johnson
Sevransky JE, Dennison Himmelfarb CR, Desai SV, Shanholtz W: Lung edema caused by high peak inspiratory pressures in
C, Brower RG, Pronovost PJ: Lung protective mechanical dogs. Role of increased microvascular filtration pressure and
ventilation and two year survival in patients with acute lung permeability. Am Rev Respir Dis 1990; 142:321–8
injury: Prospective cohort study. BMJ 2012; 344:e2124 39. West JB, Tsukimoto K, Mathieu-Costello O, Prediletto R:

22. Hager DN, Krishnan JA, Hayden DL, Brower RG; ARDS
Stress failure in pulmonary capillaries. J Appl Physiol (1985)
Clinical Trials Network: Tidal volume reduction in patients 1991; 70:1731–42
with acute lung injury when plateau pressures are not high. 40. Tinsley JH, De Lanerolle P, Wilson E, Ma W, Yuan SY: Myosin
Am J Respir Crit Care Med 2005; 172:1241–5 light chain kinase transference induces myosin light chain
23. Tremblay LN, Slutsky AS: Ventilator-induced lung injury:
activation and endothelial hyperpermeability. Am J Physiol
From the bench to the bedside. Intensive Care Med 2006; Cell Physiol 2000; 279:C1285–9
32:24–33 41. Del Maschio A, Zanetti A, Corada M, Rival Y, Ruco L,

24. Chiumello D, Carlesso E, Cadringher P, Caironi P, Valenza F, Lampugnani MG, Dejana E: Polymorphonuclear leukocyte
Polli F, Tallarini F, Cozzi P, Cressoni M, Colombo A, Marini JJ, adhesion triggers the disorganization of endothelial cell-to-
Gattinoni L: Lung stress and strain during mechanical venti- cell adherens junctions. J Cell Biol 1996; 135:497–510
lation for acute respiratory distress syndrome. Am J Respir 42. Cavanaugh KJ Jr, Oswari J, Margulies SS: Role of stretch

Crit Care Med 2008; 178:346–55 on tight junction structure in alveolar epithelial cells. Am J
25. Protti A, Cressoni M, Santini A, Langer T, Mietto C, Febres Respir Cell Mol Biol 2001; 25:584–91
D, Chierichetti M, Coppola S, Conte G, Gatti S, Leopardi O, 43. Egan EA: Lung inflation, lung solute permeability, and alveo-
Masson S, Lombardi L, Lazzerini M, Rampoldi E, Cadringher lar edema. J Appl Physiol Respir Environ Exerc Physiol 1982;
P, Gattinoni L: Lung stress and strain during mechanical 53:121–5
EDUCATION
44. Albert RK, Lakshminarayan S, Hildebrandt J, Kirk W, Butler 62. Vaneker M, Halbertsma FJ, van Egmond J, Netea MG, Dijkman
J: Increased surface tension favors pulmonary edema forma- HB, Snijdelaar DG, Joosten LA, van der Hoeven JG, Scheffer
tion in anesthetized dogs’ lungs. J Clin Invest 1979; 63:1015–8 GJ: Mechanical ventilation in healthy mice induces reversible
45. Pecchiari M, Monaco A, Koutsoukou A, D’Angelo E: Plasma pulmonary and systemic cytokine elevation with preserved
membrane disruptions with different modes of injurious alveolar integrity: An in vivo model using clinical relevant
mechanical ventilation in normal rat lungs. Crit Care Med ventilation settings. Anesthesiology 2007; 107:419–26
2012; 40:869–75 63. Wolthuis EK, Vlaar AP, Choi G, Roelofs JJ, Juffermans NP,
46. D’Angelo E, Koutsoukou A, Della Valle P, Gentile G, Pecchiari Schultz MJ: Mechanical ventilation using non-injurious ven-
M: Cytokine release, small airway injury, and parenchymal tilation settings causes lung injury in the absence of pre-
damage during mechanical ventilation in normal open-chest existing lung injury in healthy mice. Crit Care 2009; 13:R1
rats. J Appl Physiol (1985) 2008; 104:41–9 64. Hegeman MA, Hemmes SN, Kuipers MT, Bos LD, Jongsma
47. Lecuona E, Saldías F, Comellas A, Ridge K, Guerrero C,
G, Roelofs JJ, van der Sluijs KF, Juffermans NP, Vroom MB,
Sznajder JI: Ventilator-associated lung injury decreases lung Schultz MJ: The extent of ventilator-induced lung injury in
ability to clear edema in rats. Am J Respir Crit Care Med mice partly depends on duration of mechanical ventilation.
1999; 159:603–9 Crit Care Res Pract 2013; 2013:435236
48. Planès C, Escoubet B, Blot-Chabaud M, Friedlander G,
65. Wellman TJ, Winkler T, Costa EL, Musch G, Harris RS, Zheng
Farman N, Clerici C: Hypoxia downregulates expression and H, Venegas JG, Vidal Melo MF: Effect of local tidal lung strain
activity of epithelial sodium channels in rat alveolar epithe- on inflammation in normal and lipopolysaccharide-exposed
lial cells. Am J Respir Cell Mol Biol 1997; 17:508–18 sheep. Crit Care Med 2014; 42:e491–500
49. Bhattacharya J, Matthay MA: Regulation and repair of the 66. Lundquist H, Hedenstierna G, Strandberg A, Tokics L, Brismar
B: CT-assessment of dependent lung densities in man during
alveolar-capillary barrier in acute lung injury. Annu Rev
general anaesthesia. Acta Radiol 1995; 36:626–32
Physiol 2013; 75:593–615
67. Cai H, Gong H, Zhang L, Wang Y, Tian Y: Effect of low tidal
50. Rugonyi S, Biswas SC, Hall SB: The biophysical function

volume ventilation on atelectasis in patients during general
of pulmonary surfactant. Respir Physiol Neurobiol 2008;
anesthesia: A computed tomographic scan. J Clin Anesth
163:244–55
2007; 19:125–9
51. Vlahakis NE, Hubmayr RD: Cellular stress failure in ventilator-
68. Rusca M, Proietti S, Schnyder P, Frascarolo P, Hedenstierna G,
injured lungs. Am J Respir Crit Care Med 2005; 171:1328–42
Spahn DR, Magnusson L: Prevention of atelectasis formation
52. Imai Y, Parodo J, Kajikawa O, de Perrot M, Fischer S, Edwards during induction of general anesthesia. Anesth Analg 2003;
V, Cutz E, Liu M, Keshavjee S, Martin TR, Marshall JC, Ranieri 97:1835–9
VM, Slutsky AS: Injurious mechanical ventilation and end-
69. Neumann P, Rothen HU, Berglund JE, Valtysson J, Magnusson
organ epithelial cell apoptosis and organ dysfunction in an A, Hedenstierna G: Positive end-expiratory pressure prevents
experimental model of acute respiratory distress syndrome. atelectasis during general anaesthesia even in the presence
JAMA 2003; 289:2104–12 of a high inspired oxygen concentration. Acta Anaesthesiol
53. Rothen HU, Sporre B, Engberg G, Wegenius G, Högman M, Scand 1999; 43:295–301
Hedenstierna G: Influence of gas composition on recurrence 70. Milic-Emili J, Torchio R, D’Angelo E: Closing volume: A reap-
of atelectasis after a reexpansion maneuver during general praisal (1967–2007). Eur J Appl Physiol 2007; 99:567–83
anesthesia. Anesthesiology 1995; 82:832–42
71. Juno J, Marsh HM, Knopp TJ, Rehder K: Closing capacity

54. Joyce CJ, Williams AB: Kinetics of absorption atelectasis dur- in awake and anesthetized-paralyzed man. J Appl Physiol
ing anesthesia: A mathematical model. J Appl Physiol (1985) Respir Environ Exerc Physiol 1978; 44:238–44
1999; 86:1116–25
72. Bergman NA, Tien YK: Contribution of the closure of pul-
55. D’Angelo E: Factors affecting the distribution of transpulmo- monary units to impaired oxygenation during anesthesia.
nary pressure in animals and in man. Bull Eur Physiopathol Anesthesiology 1983; 59:395–401
Respir 1984; 20:415–22
73. Stanley TH, Zikria BA, Sullivan SF: The surface tension of
56. Pelosi P, Ravagnan I, Giurati G, Panigada M, Bottino N,
tracheobronchial secretions during general anesthesia.
Tredici S, Eccher G, Gattinoni L: Positive end-expiratory pres- Anesthesiology 1972; 37:445–9
sure improves respiratory function in obese but not in nor-
74. Bendixen HH, Hedley-Whyte J, Laver MB: Impaired oxy-

mal subjects during anesthesia and paralysis. Anesthesiology
genation in surgical patients during general anesthesia with
1999; 91:1221–31
controlled ventilation. A concept of atelectasis. N Engl J Med
57. Albert RK, Hubmayr RD: The prone position eliminates com- 1963; 269:991–6
pression of the lungs by the heart. Am J Respir Crit Care Med 75. Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Peñuelas
2000; 161:1660–5 O, Abraira V, Raymondos K, Rios F, Nin N, Apezteguía C,
58. Pelosi P, Goldner M, McKibben A, Adams A, Eccher G, Caironi Violi DA, Thille AW, Brochard L, González M, Villagomez AJ,
P, Losappio S, Gattinoni L, Marini JJ: Recruitment and dere- Hurtado J, Davies AR, Du B, Maggiore SM, Pelosi P, Soto L,
cruitment during acute respiratory failure: An experimental Tomicic V, D’Empaire G, Matamis D, Abroug F, Moreno RP,
study. Am J Respir Crit Care Med 2001; 164:122–30 Soares MA, Arabi Y, Sandi F, Jibaja M, Amin P, Koh Y, Kuiper
59. van Kaam AH, Lachmann RA, Herting E, De Jaegere A, van MA, Bülow HH, Zeggwagh AA, Anzueto A: Evolution of mor-
Iwaarden F, Noorduyn LA, Kok JH, Haitsma JJ, Lachmann B: tality over time in patients receiving mechanical ventilation.
Reducing atelectasis attenuates bacterial growth and trans- Am J Respir Crit Care Med 2013; 188:220–30
location in experimental pneumonia. Am J Respir Crit Care 76. Hess DR, Kondili D, Burns E, Bittner EA, Schmidt UH: A

Med 2004; 169:1046–53 5-year observational study of lung-protective ventilation in
60. Lachmann RA, van Kaam AH, Haitsma JJ, Lachmann B: High the operating room: A single-center experience. J Crit Care
positive end-expiratory pressure levels promote bacterial 2013; 28:533.e9–15
translocation in experimental pneumonia. Intensive Care 77. Levin MA, McCormick PJ, Lin HM, Hosseinian L, Fischer GW:
Med 2007; 33:1800–4 Low intraoperative tidal volume ventilation with minimal
61. Fanelli V, Mascia L, Puntorieri V, Assenzio B, Elia V, Fornaro PEEP is associated with increased mortality. Br J Anaesth
G, Martin EL, Bosco M, Delsedime L, Fiore T, Grasso S, 2014; 113:97–108
Ranieri VM: Pulmonary atelectasis during low stretch ventila- 78. Hong CM, Xu DZ, Lu Q, Cheng Y, Pisarenko V, Doucet D,
tion: “Open lung” versus “lung rest” strategy. Crit Care Med Brown M, Aisner S, Zhang C, Deitch EA, Delphin E: Low
2009; 37:1046–53 tidal volume and high positive end-expiratory pressure
mechanical ventilation results in increased inflammation and 94. Futier E, Constantin JM, Petit A, Jung B, Kwiatkowski F,
ventilator-associated lung injury in normal lungs. Anesth Duclos M, Jaber S, Bazin JE: Positive end-expiratory pres-
Analg 2010; 110:1652–60 sure improves end-expiratory lung volume but not oxy-
79. Wrigge H, Zinserling J, Stüber F, von Spiegel T, Hering R, genation after induction of anaesthesia. Eur J Anaesthesiol
Wetegrove S, Hoeft A, Putensen C: Effects of mechanical ven- 2010; 27:508–13
tilation on release of cytokines into systemic circulation in 95. Reis Miranda D, Gommers D, Struijs A, Dekker R, Mekel J,
patients with normal pulmonary function. Anesthesiology Feelders R, Lachmann B, Bogers AJ: Ventilation according to
2000; 93:1413–7 the open lung concept attenuates pulmonary inflammatory
80. Wrigge H, Uhlig U, Zinserling J, Behrends-Callsen E,
response in cardiac surgery. Eur J Cardiothorac Surg 2005;
Ottersbach G, Fischer M, Uhlig S, Putensen C: The effects 28:889–95
of different ventilatory settings on pulmonary and systemic 96. Cinnella G, Grasso S, Spadaro S, Rauseo M, Mirabella L,
inflammatory responses during major surgery. Anesth Analg Salatto P, De Capraris A, Nappi L, Greco P, Dambrosio M:
2004; 98:775–81 Effects of recruitment maneuver and positive end-expira-
81. Wrigge H, Uhlig U, Baumgarten G, Menzenbach J, Zinserling J, tory pressure on respiratory mechanics and transpulmo-
Ernst M, Drömann D, Welz A, Uhlig S, Putensen C: Mechanical nary pressure during laparoscopic surgery. Anesthesiology
ventilation strategies and inflammatory responses to cardiac 2013; 118:114–22
surgery: A prospective randomized clinical trial. Intensive 97. Karsten J, Luepschen H, Grossherr M, Bruch HP, Leonhardt
Care Med 2005; 31:1379–87 S, Gehring H, Meier T: Effect of PEEP on regional venti-
82. Gama de Abreu M, Heintz M, Heller AR, Sezchenyi RCM,
lation during laparoscopic surgery monitored by electri-
Albrecht DM, Koch T: One-lung ventilation with high tidal vol- cal impedance tomography. Acta Anaesthesiol Scand 2011;
umes and zero positive end-expiratory pressure is injurious in 55:878–86
the isolated rabbit lung model. Anesth Analg 2003; 96:220–8 98. Zhao Z, Guttmann J, Möller K: Adaptive SLICE method: An
83. Kozian A, Schilling T, Schütze H, Senturk M, Hachenberg T, enhanced method to determine nonlinear dynamic respira-
Hedenstierna G: Ventilatory protective strategies during tho- tory system mechanics. Physiol Meas 2012; 33:51–64
racic surgery: Effects of alveolar recruitment maneuver and 99. Gattinoni L, Carlesso E, Caironi P: Stress and strain within
low-tidal volume ventilation on lung density distribution. the lung. Curr Opin Crit Care 2012; 18:42–7
Anesthesiology 2011; 114:1025–35 100. Weingarten TN, Whalen FX, Warner DO, Gajic O, Schears
84. Schilling T, Kozian A, Huth C, Bühling F, Kretzschmar M,
GJ, Snyder MR, Schroeder DR, Sprung J: Comparison of two
Welte T, Hachenberg T: The pulmonary immune effects of ventilatory strategies in elderly patients undergoing major
mechanical ventilation in patients undergoing thoracic sur- abdominal surgery. Br J Anaesth 2010; 104:16–22
gery. Anesth Analg 2005; 101:957–65 101. Wetterslev J, Hansen EG, Roikjaer O, Kanstrup IL, Heslet
85. Michelet P, D’Journo XB, Roch A, Doddoli C, Marin V, Papazian L: Optimizing peroperative compliance with PEEP during
L, Decamps I, Bregeon F, Thomas P, Auffray JP: Protective venti- upper abdominal surgery: Effects on perioperative oxygen-
lation influences systemic inflammation after esophagectomy: A ation and complications in patients without preoperative
randomized controlled study. Anesthesiology 2006; 105:911–9 cardiopulmonary dysfunction. Eur J Anaesthesiol 2001;
86. Licker M, Diaper J, Villiger Y, Spiliopoulos A, Licker V, Robert 18:358–65
J, Tschopp JM: Impact of intraoperative lung-protective inter- 102. Rothen HU, Neumann P, Berglund JE, Valtysson J,

ventions in patients undergoing lung cancer surgery. Crit Magnusson A, Hedenstierna G: Dynamics of re-expansion
Care 2009; 13:R41 of atelectasis during general anaesthesia. Br J Anaesth 1999;
87. Shen Y, Zhong M, Wu W, Wang H, Feng M, Tan L, Wang Q: 82:551–6
The impact of tidal volume on pulmonary complications 103. Tusman G, Groisman I, Fiolo FE, Scandurra A, Arca JM,

following minimally invasive esophagectomy: A random- Krumrick G, Bohm SH, Sipmann FS: Noninvasive moni-
ized and controlled study. J Thorac Cardiovasc Surg 2013; toring of lung recruitment maneuvers in morbidly obese
146:1267–73; discussion 1273–4 patients: The role of pulse oximetry and volumetric capnog-
88. Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ: High versus raphy. Anesth Analg 2014; 118:137–44
low positive end-expiratory pressure during general anaesthe- 104. Rothen HU, Sporre B, Engberg G, Wegenius G, Hedenstierna
sia for open abdominal surgery (PROVHILO trial): A multicen- G: Re-expansion of atelectasis during general anaesthesia:
tre randomised controlled trial. Lancet 2014; 384:495–503 A computed tomography study. Br J Anaesth 1993;
89. Scott DH, Drummond GB: III. Tidal volume measurement: 71:788–95
OK for science, but too difficult for a workstation standard? 105. Lin WQ, Lu XY, Cao LH, Wen LL, Bai XH, Zhong ZJ: [Effects
Br J Anaesth 2013; 110:891–5 of the lung protective ventilatory strategy on proinflamma-
90. Brismar B, Hedenstierna G, Lundquist H, Strandberg A,
tory cytokine release during one-lung ventilation]. Ai Zheng
Svensson L, Tokics L: Pulmonary densities during anesthe- 2008; 27:870–3
sia with muscular relaxation—A proposal of atelectasis. 106. Unzueta C, Tusman G, Suarez-Sipmann F, Böhm S, Moral V:
Anesthesiology 1985; 62:422–8 Alveolar recruitment improves ventilation during thoracic
91. Reinius H, Jonsson L, Gustafsson S, Sundbom M, Duvernoy surgery: A randomized controlled trial. Br J Anaesth 2012;
O, Pelosi P, Hedenstierna G, Fredén F: Prevention of atelecta- 108:517–24
sis in morbidly obese patients during general anesthesia and 107. Koner O, Celebi S, Balci H, Cetin G, Karaoglu K, Cakar N:
paralysis: A computerized tomography study. Anesthesiology Effects of protective and conventional mechanical ventila-
2009; 111:979–87 tion on pulmonary function and systemic cytokine release
92. Maisch S, Reissmann H, Fuellekrug B, Weismann D,
after cardiopulmonary bypass. Intensive Care Med 2004;
Rutkowski T, Tusman G, Bohm SH: Compliance and dead 30:620–6
space fraction indicate an optimal level of positive end-expi- 108. Zupancich E, Paparella D, Turani F, Munch C, Rossi A,

ratory pressure after recruitment in anesthetized patients. Massaccesi S, Ranieri VM: Mechanical ventilation affects
Anesth Analg 2008; 106:175–81 inflammatory mediators in patients undergoing cardiopul-
93. Satoh D, Kurosawa S, Kirino W, Wagatsuma T, Ejima Y,
monary bypass for cardiac surgery: A randomized clinical
Yoshida A, Toyama H, Nagaya K: Impact of changes of posi- trial. J Thorac Cardiovasc Surg 2005; 130:378–83
tive end-expiratory pressure on functional residual capacity 109. Wolthuis EK, Choi G, Dessing MC, Bresser P, Lutter R,

at low tidal volume ventilation during general anesthesia. J Dzoljic M, van der Poll T, Vroom MB, Hollmann M, Schultz
Anesth 2012; 26:664–9 MJ: Mechanical ventilation with lower tidal volumes and
EDUCATION
positive end-expiratory pressure prevents pulmonary 121. Jaber S, Coisel Y, Chanques G, Futier E, Constantin JM,

inflammation in patients without preexisting lung injury. Michelet P, Beaussier M, Lefrant JY, Allaouchiche B,
Anesthesiology 2008; 108:46–54 Capdevila X, Marret E: A multicentre observational study
110. Memtsoudis SG, Bombardieri AM, Ma Y, Girardi FP: The
of intra-operative ventilatory management during general
effect of low versus high tidal volume ventilation on inflam- anaesthesia: Tidal volumes and relation to body weight.
matory markers in healthy individuals undergoing posterior Anaesthesia 2012; 67:999–1008
spine fusion in the prone position: A randomized controlled 122. Chaiwat O, Vavilala MS, Philip S, Malakouti A, Neff MJ,

trial. J Clin Anesth 2012; 24:263–9 Deem S, Treggiari MM, Wang J, Lang JD: Intraoperative
111. Treschan TA, Kaisers W, Schaefer MS, Bastin B, Schmalz
adherence to a low tidal volume ventilation strategy in criti-
U, Wania V, Eisenberger CF, Saleh A, Weiss M, Schmitz cally ill patients with preexisting acute lung injury. J Crit
A, Kienbaum P, Sessler DI, Pannen B, Beiderlinden M: Care 2011; 26:144–51
Ventilation with low tidal volumes during upper abdominal 123. Goldenberg NM, Steinberg BE, Lee WL, Wijeysundera DN,
surgery does not improve postoperative lung function. Br J Kavanagh BP: Lung-protective ventilation in the operating
Anaesth 2012; 109:263–71 room: Time to implement? Anesthesiology 2014; 121:184–8
112. Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, 124. Futier E, Marret E, Jaber S: Perioperative positive pressure
Neuschwander A, Marret E, Beaussier M, Gutton C, Lefrant ventilation: An integrated approach to improve pulmonary
JY, Allaouchiche B, Verzilli D, Leone M, De Jong A, Bazin JE, care. Anesthesiology 2014; 121:400–8
Pereira B, Jaber S; IMPROVE Study Group: A trial of intraop- 125. Coppola S, Froio S, Chiumello D: Protective lung ventilation
erative low-tidal-volume ventilation in abdominal surgery. during general anesthesia: Is there any evidence? Crit Care
N Engl J Med 2013; 369:428–37 2014; 18:210
113. Severgnini P, Selmo G, Lanza C, Chiesa A, Frigerio A,
126. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND,
Bacuzzi A, Dionigi G, Novario R, Gregoretti C, Gama de Caldwell E, Fan E, Camporota L, Slutsky AS: Acute respira-
Abreu M, Schultz MJ, Jaber S, Futier E, Chiaranda M, Pelosi tory distress syndrome: The Berlin Definition. JAMA 2012;
P: Protective mechanical ventilation during general anes- 307:2526–33
thesia for open abdominal surgery improves postoperative
127.
The Acute Respiratory Distress Syndrome Network:
pulmonary function. Anesthesiology 2013; 118:1307–21
Ventilation with lower tidal volumes as compared with tradi-
114. Maslow AD, Stafford TS, Davignon KR, Ng T: A randomized tional tidal volumes for acute lung injury and the acute respi-
comparison of different ventilator strategies during thora- ratory distress syndrome. N Engl J Med 2000; 342:1301–8
cotomy for pulmonary resection. J Thorac Cardiovasc Surg
2013; 146:38–44 128. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris
A, Ancukiewicz M, Schoenfeld D, Thompson BT; National
115. Sundar S, Novack V, Jervis K, Bender SP, Lerner A, Panzica Heart, Lung, and Blood Institute ARDS Clinical Trials
P, Mahmood F, Malhotra A, Talmor D: Influence of low tidal Network: Higher versus lower positive end-expiratory pres-
volume ventilation on time to extubation in cardiac surgical sures in patients with the acute respiratory distress syn-
patients. Anesthesiology 2011; 114:1102–10 drome. N Engl J Med 2004; 351:327–36
116. Ge Y, Yuan L, Jiang X, Wang X, Xu R, Ma W: [Effect of lung 129. Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD,
protection mechanical ventilation on respiratory function in Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L,
the elderly undergoing spinal fusion]. Zhong Nan Da Xue Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G:
Xue Bao Yi Xue Ban 2013; 38:81–5 Higher vs lower positive end-expiratory pressure in patients
117. Bouadma L, Dreyfuss D, Ricard JD, Martet G, Saumon G: with acute lung injury and acute respiratory distress syndrome:
Mechanical ventilation and hemorrhagic shock-resuscita- Systematic review and meta-analysis. JAMA 2010; 303:865–73
tion interact to increase inflammatory cytokine release in 130. Borges JB, Okamoto VN, Matos GF, Caramez MP, Arantes
rats. Crit Care Med 2007; 35:2601–6 PR, Barros F, Souza CE, Victorino JA, Kacmarek RM, Barbas
118. Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi CS, Carvalho CR, Amato MB: Reversibility of lung collapse
P: Meta-analysis: Ventilation strategies and outcomes of the and hypoxemia in early acute respiratory distress syn-
acute respiratory distress syndrome and acute lung injury. drome. Am J Respir Crit Care Med 2006; 174:268–78
Ann Intern Med 2009; 151:566–76 131. Serpa Neto A, Hemmes SN, Barbas CS, Beiderlinden M,

119. Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Espósito Biehl M, Binnekade JM, Canet J, Fernandez-Bustamante A,
DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ: Futier E, Gajic O, Hedenstierna G, Hollmann MW, Jaber S,
Association between use of lung-protective ventilation with Kozian A, Licker M, Lin WQ, Maslow AD, Memtsoudis SG, Reis
lower tidal volumes and clinical outcomes among patients Miranda D, Moine P, Ng T, Putensen C, Ranieri M, Scavonetto
without acute respiratory distress syndrome: A meta-analy- F, Schilling T, Schmid W, Selmo G, Severgnini P, Sprung J,
sis. JAMA 2012; 308:1651–9 Sundar S, Talmor D, Treschan T, Unzueta C, Weingarten TN,
120. Lellouche F, Dionne S, Simard S, Bussières J, Dagenais
Wolthuis EK, Wrigge H, Gama de Abreu M, Pelosi P, Schultz
F: High tidal volumes in mechanically ventilated patients MJ, Sprung J: Protective versus conventional ventilation for
increase organ dysfunction after cardiac surgery. surgery: A systematic review and individual patient data
Anesthesiology 2012; 116:1072–82 meta-analysis. Anesthesiology 2015 [Epub ahead of print]

Intraoperative Protective Mechanical Ventilation For Prevention of Postoperative Pulmonary Complications

Uploaded by

Copyright:

Available Formats

You might also like

Intraoperative Protective Mechanical Ventilation For Prevention of Postoperative Pulmonary Complications

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Intraoperative Protective Mechanical Ventilation For Prevention of Postoperative Pulmonary Complications

Uploaded by

Copyright:

Available Formats

Review Article

David S. Warner, M.D., Editor

Intraoperative Protective Mechanical Ventilation for

P OSTOPERATIVE pulmonary complications (PPCs)

Anesthesiology, V 123 • No 3 692 September 2015

Table 1. Risk Factors for Postoperative Pulmonary Complications

Patient Characteristics Preoperative Testing Surgery Anesthetic Management

Age Low albumin Open thoracic surgery General anesthesia

Anesthesiology 2015; 123:692-713 693 Güldner et al.

Prediction of general PPCs

Anesthesiology 2015; 123:692-713 694 Güldner et al.

Prediction of selected PPCs

Anesthesiology 2015; 123:692-713 695 Güldner et al.

Anesthesiology 2015; 123:692-713 696 Güldner et al.

mechanical ventilation.19,20 The physical forces in some

although gross measurements of airway pressures or lung

or disruption of alveolar epithelial cells, by generating trans-

It has been demonstrated that the duration of mechani-

the development of pulmonary inflammatory response.26

time product increased the molecular markers of endothelial

High-risk cardiac surgery

an inspiratory to expiratory time ratio of 1:1 was associated

Admission source other

Respiratory rate 20–29

with attenuated lung damage.26 Especially in the presence

of atelectasis, mechanical ventilation may cause damage by

enon known as atelectrauma.27 All three mechanisms, namely

barotrauma, volutrauma, and atelectrauma, may affect alveo-

lar as well as vascular epithelial and endothelial cells28,29 and

to be particularly sensitive to stress from mechanical ventila-

the endothelial side and between the endothelial and epi-

and activation of metalloproteinases, further damaging

gery and under-

might be exacerbated by fluid load,34 which is not uncom-

mon during general anesthesia. However, fluid overload

matory response.34 This suggests that (1) injurious mechani-

cal ventilation makes the lung more susceptible to further

insults; and (2) in previously healthy lungs, VILI can be

Kor et al.18, but

chemical signals, for example, proinflammatory and antiin-

flammatory mediators by means of direct cell injury or indi-

is known as “mechanotransduction.”35 Some mediators may

Anesthesiology 2015; 123:692-713 697 Güldner et al.

Anesthesiology 2015; 123:692-713 698 Güldner et al.

Anesthesiology 2015; 123:692-713 699 Güldner et al.

and compliance.74 Tidal volumes up to 15 ml/kg of predicted

Tidal Volumes for Intraoperative Protective Ventilation

Anesthesiology 2015; 123:692-713 700 Güldner et al.

the association between intraoperative mechanical ventilator

Lung Recruitment Maneuvers for Intraoperative Protective

Anesthesiology 2015; 123:692-713 701 Güldner et al.

Reference Patient Population/ Nonclinical Primary Secondary

Anesthesiology 2015; 123:692-713 702 Güldner et al.

Reference Patient Population/ Nonclinical Primary Secondary

Anesthesiology 2015; 123:692-713 703 Güldner et al.

Anesthesiology 2015; 123:692-713 704 Güldner et al.

Reference Patient Clinical Secondary

Anesthesiology 2015; 123:692-713 705 Güldner et al.

= two-lung ventilation; VT = tidal volume; ZEEP = zero end-expiratory pressure.