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Lung-protective perioperative mechanical ventilation
Hemmes, S.N.T.
Publication date
2015
Document Version
Final published version
Link to publication
Citation for published version (APA):
Hemmes, S. N. T. (2015). Lung-protective perioperative mechanical ventilation.
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Incidence of mortality and morbidity
related to postoperative lung injury in
patients who have undergone abdominal
or thoracic surgery: a systematic review
and metaanalysis
Serpa Neto A, Hemmes SNT, Barbas CS, Beiderlinden M, Fernandez-Bustamante A, Futier E, Hollmann MW, Jaber S, Kozian A, Licker M, Lin WQ, Moine P, Scavonetto F, Schilling T, Selmo G, Severgnini P, Sprung J, Treschan T, Unzueta C, Weingarten TN, Wolthuis EK, Wrigge H, Gama de Abreu M, Pelosi P, Schultz MJ for the PROVE Network investigators. Lancet Respiratory Medicine 2014; 2(12):1007-15
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Abstract
Background. Lung injury is one of the most serious complications following surgery.
Development of postoperative lung injury and its effect on outcome could depend on ventilator settings during the surgical procedure. We performed a systematic review and metaanalysis to estimate the incidence and determined the crude and attributable morbidity and in-hospital mortality of postoperative lung injury in published investigations of intra-operative ventilation for abdominal or thoracic surgery.
Methods. Observational studies and randomized controlled trials were identified by a systematic
search of MEDLINE, CINAHL, Web of Science, and CENTRAL and screened for inclusion into a metaanalysis. Key inclusion criteria were: adults; ventilation for general anesthesia for abdominal or thoracic surgery; use of protective versus conventional ventilation. Individual patient data were obtained from the corresponding authors. Attributable mortality was calculated subtracting the in-hospital mortality rate of patients who did not develop postoperative lung injury from those who developed postoperative lung injury in predefined patient groups.
Findings. Data from 12 investigations were included, comprising 3,365 patients. The total
incidence of postoperative lung injury in abdominal and thoracic surgery patients was similar (3.4 vs. 4.3%; p = 0.198). Patients who developed postoperative lung injury were older, had higher ASA scores, higher prevalence of sepsis or pneumonia, more frequently had received blood transfusions during surgery, and ventilation with higher tidal volumes and/or lower positive end-expiratory pressure levels. The occurrence of postoperative lung injury was associated with longer stay in intensive care unit and hospital (8 ± 13 vs. 1 ± 4 days; p < 0.001, and 21 ± 18 vs. 15 ± 14 days; p < 0.001, respectively), and increased in-hospital mortality (20.3 vs. 1.4%; p < 0.001). Overall attributable mortality of postoperative lung injury was 19% [95% confidence interval 18–19%), and differed between abdominal and thoracic surgery patients (12% vs. 27%, respectively; p < 0.001) but it was independent from intra-operative ventilator settings.
Interpretation. Development of postoperative lung injury was associated with increased in–
hospital mortality and by a longer ICU and hospital lengths of stay. Attributable mortality of postoperative lung injury is higher in thoracic than in abdominal surgery patients. Protective mechanical ventilation reduces the incidence of postoperative lung injury but seems to have no effect on attributable mortality of this condition.
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Introduction
More than 230 million major surgical procedures are undertaken worldwide each year.1 Postoperative
complications after major surgery increase resource use and are an important cause of death.1
Especially postoperative pulmonary complications, including postoperative lung injury, are suggested to have a strong impact on morbidity and mortality of patients who need major surgery.2-4 There is
growing evidence that so–called intra–operative lung–protective mechanical ventilation with low tidal volumes and with or without high levels of positive end–expiratory pressure (PEEP) prevents postoperative lung injury compared to conventional ventilation with the use of high tidal volume levels and low levels of PEEP.2-4 Recently, in a report of a large retrospective study that showed use
of low tidal volumes during general anesthesia for surgery to be associated with increased mortality, it was suggested that excess mortality could have been caused by the use of too low levels of PEEP.5
The exact impact of postoperative lung injury on morbidity and mortality is uncertain, and the outcome of postoperative lung injury could be different in patients who had abdominal surgery from those who underwent thoracic surgery. In addition, the impact of lung–protective ventilation on outcome of patients developing postoperative lung injury needs to be better defined.2-4 Indeed,
it seems possible that outcome of lung injury is different according to the strategy of intraoperative ventilation.
A better understanding of the incidence, morbidity and mortality of postoperative lung injury may help design future trials, and possibly improves the approach to this condition, therefore, we performed an individual patient data metaanalysis of studies and trials of intra–operative ventilation for abdominal and thoracic surgery, which offered the possibility to quantify crude and attributable mortality of postoperative lung injury and its relationship with the strategy of ventilation used during surgery. We compared patients after abdominal surgery with patients after thoracic surgery, and related the outcome to intra–operative ventilator settings. We hypothesized that crude and attributable mortality are different between abdominal and thoracic surgery. In addition we hypothesized outcome of postoperative lung injury to be dependent on intraoperative ventilation settings.
Methods
The full statistical analysis plan of this collaborative metaanalysis has been published before.6
Search strategy
Two authors performed a computerized blinded search of MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) up to April 2014. The sensitive search strategy combined the following Medical Subject Headings and Keywords ([protective ventilation OR lower tidal volume OR low tidal volume OR positive end–expiratory pressure OR positive end–expiratory pressure OR PEEP]). All reviewed articles and cross–referenced studies from retrieved articles were screened for pertinent information. We ran a computerized search of proceedings of annual meetings
226
from critical care and anaesthesiology societies to identify relevant studies published in abstract form only.
Selection of studies
Observational studies and randomized controlled trials comparing different tidal volume and PEEP settings during intraoperative ventilation for surgical general anesthesia identified by the search criteria and reporting outcomes of interest were screened for inclusion with no restrictions on language. Key inclusion criteria were: adults (i.e., age > 18 years); patients receiving ventilation for general anesthesia for abdominal or thoracic surgery; use of protective versus conventional ventilation. Studies or trials were excluded from this metaanalysis if they: included patients with pre–existing lung injury; or reported on patients receiving ventilation in a non–surgical setting (i.e., continued ventilation in the intensive care unit). The Jadad score was used to assess the quality of the randomized controlled trials and the GRACE checklist to observational studies. Collection of individual patient data
Corresponding authors of the identified eligible published studies were contacted via email with a letter detailing background and objectives of this metaanalysis, and a datasheet for input of individual patient data. The filled out data templates were sent back to the principal investigator and further communication was by email. Corresponding authors were also contacted on unpublished data, if present to enlarge the clinical data pool. The same two investigators who performed the electronic database search handled the individual patient data provided by the corresponding authors. Data was accepted in any kind of electronic format (SPSS, STATA, Word document, Excel document, and Access document) and only the coordinators of the collaboration have direct access to the data. Both authors performed data validation, checking the received data set for data entry mistakes and inconsistency. Differences were discussed and settled in consensus.
Definitions
For postoperative lung injury we used the definitions for acute lung injury and ARDS from the American–European Consensus criteria group (PaO2 / FiO2 < 300),7 since all studies were
conducted before the publication of the Berlin definition; follow–up was defined as the time between the day of the surgery and hospital discharge, or in–hospital death. The number of ICU and hospital–free days and alive by day 28 was defined as the mean number of days on which patients were outside the ICU or hospital and alive from day 1 to day 28. Protective ventilation was defined as ventilation using low tidal volume (defined as a tidal volume ≤ 8 ml/kg predicted body weight [PBW]) with or without high levels of PEEP (defined as PEEP ≥ 5 cmH2O) and with
or without recruitment manoeuvres. Conventional ventilation was defined as ventilation using high tidal volume (> 8 ml/kg PBW) with low levels of PEEP (< 5 cmH2O) and without recruitment
manoeuvres. The definition of protective and conventional ventilation was made based on several reports in the literature and according to the previously published protocol.2-4
Statistical analysis
Attributable morbidity was calculated by subtracting the in–hospital mortality rate of patients without postoperative lung injury from the in–hospital mortality of patients with postoperative lung injury. The incidence rate was calculated as number of cases person-years = ([number of
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cases / person-day] x [365 person-day / 1 person-year]). A random-effect model was used to pool the overall data.
Survival curves were constructed using the Kaplan–Meier methods and compared using the log–rank test. Time–to–event was defined as time from the day of surgery to the event. We used a Cox proportional–hazards regression model to examine simultaneously effects of multiple covariates on outcome, censoring a patient’s data at the time of death, hospital discharge, or after 30 days. The initial model included age, sex, body mass index, ASA (American Society of Anesthesiology score), smoking, and predisposing conditions [defined as shock, pneumonia, blood transfusion and/or sepsis]). Variables with p < 0.2 in the univariate analysis are included in the multivariate regression. The final model was developed by dropping each variable in turn from the model and conducting a likelihood-ratio test to compare the full and the nested models (stepwise backward approach). We used a significance level of 0.05 as the cut-off to exclude a variable from the model. In all models, the categorical variables were tested for trend with the absence of postoperative lung injury as reference and the proportional–hazards assumption was assessed. A test for interaction between pairs of variables in the final model was performed. Interaction between biological plausible variable was assessed. The effect of each variable in these models was assessed with the use of the Wald test and described by the HR with 95% CI. Subgroup analyses were performed to examine the effects of intra–operative ventilation (conventional vs. lung–protective ventilation), age (< 65 vs. ≥ 65 years), surgery (abdominal vs. thoracic) and severity of illness (ASA score < 3 or ≥ 3).
All analyses were conducted with SPSS v.20 (IBM Corporation, New York, USA) and R v.2.12.0 (R Foundation for Statistical Computing, Vienna, Austria). For all analyses two–sided p values < 0.05 were considered significant.
Results
Search results and collection of individual patient data
The search identified three observational studies and 21 randomized controlled trials comparing different tidal volume and/or PEEP settings in intra–operative ventilation during general anaesthesia for major surgery.8-31 We were not able to collect data from five randomized
controlled trials due to the following reasons: the corresponding author could not provide data of interest or had no longer access to the complete database (n = 3);20-22 or the corresponding
author could not be contacted (n = 2).23,24 Seven papers were excluded because assessed patients
under cardiac (n = 6)25-30 or orthopaedic surgery (n = 1).31 The total enrolment based on the
studies and trials for which individual patient data could be collected was 3,365 patients (table 1, Appendix figure 1, Appendix tables 2, Appendix table 3, and Appendix table 4).
Characteristics of patients who did or did not developed postoperative lung injury
Baseline characteristics and predisposing conditions differed between patients who did and those who did not develop postoperative lung injury (table 2). Patients who developed postoperative
228 Ta bl e 1 . Ch ar act eri stics o f i ncl ud ed st ud ies St ud y Yea r Co un tr y Des ign o f St ud y Ja da d Sc or e Su rg er y To ta l N umb er o f P atien ts Po st op L un g I nju ry Mo rt al ity Pr ot ect Co nv Pr ot ect Co nv Pr ot ect Co nv W rig ge e t al 7 20 04 Ge rm an y RC T 2 Abd / Tho* 29 (4 7% ) 33 (5 3% ) 0 (0 % ) 3 (9 % ) 0 (0 % ) 0 (0 % ) Sc hilling e t al 8 20 05 Ge rm an y RC T 2 Thor ac ic * 75 (6 8% ) 35 (3 2% ) 0 (0 % ) 0 (0 % ) 0 (0 % ) 0 (0 % ) W olt huis et al 9 20 08 Dut ch RC T 3 Abdom ina l 24 (5 2% ) 22 (4 8% ) 0 (0 % ) 2 (9 % ) 0 (0 % ) 0 (0 % ) Lin et al 10 20 08 China RC T 1 Thor ac ic * 50 (4 9% ) 52 (5 1% ) 1 (2 % ) 14 (2 7% ) 0 (0 % ) 1 (2 % ) Lic ke r e t al 11 20 09 Sw iss N on-R CT ---Thor ac ic * 55 8 (5 1% ) 53 3 (4 9% ) 15 (3 % ) 28 (5 % ) 13 (2 % ) 15 (3 % ) W eing ar te n et al 12 20 10 U SA RC T 3 Abdom ina l 20 (5 0% ) 20 (5 0% ) 0 (0 % ) 1 (5 % ) 1 (5 % ) 0 (0 % ) Fe rna nde z-Bus tam an te e t al 13 20 11 U SA N on-R CT ---Abdom ina l 15 4 (3 6% ) 27 5 (6 4% ) 7 (4 % ) 14 (5 % ) 3 (2 % ) 3 1(% ) Tr esc ha n e t al 14 20 12 Ge rm an y RC T 5 Abdom ina l 50 (4 9% ) 51 (5 1% ) 1 (2 % ) 0 (0 % ) 3 (6 % ) 5 (1 0% ) U nz ue ta e t al 15 20 12 Spa in RC T 2 Thor ac ic * 40 (1 00 % ) ---0 (0 % ) ---1 (2 % ) ---Se ve rg nini et al 16 20 13 Italy RC T 5 Abdom ina l 28 (5 1% ) 27 (4 9% ) 9 (3 2% ) 16 (5 9% ) 0 (0 % ) 0 (0 % ) Futie r e t al 17 20 13 Fr anc e RC T 5 Abdom ina l 20 0 (5 0% ) 20 0 (5 0% ) 1 (0 .5 % ) 8 (4 % ) 6 (3 % ) 7 (3 % ) He m m es et al 18 20 14 M ulti* * RC T 5 Abdom ina l 88 9 (1 00 % ) ---7 (0 .8 % ) ---14 (2 % ) ---Con v.: c on ve ntional: A bd: abdominal; Tho: thor acic; R CT : r andomiz ed con tr olle d tr ial; *: Thor acic pr oce dur es: Lobe ct om y (52%); P ne ume ct om y (20%); Small re se ctions, lik e par tial lobe ct om y, a ty pic al and w edg e r ese ctions (2 0% ); Esopha ge ct om y (3 % ); Ot he rs, lik e m edia stina l r ese ction a nd e xplor ativ e t hor ac ot om y (5 % ); **: Eur ope a nd U SA
Ch apt er 1 0 229
lung injury were older, presented higher ASA score, higher prevalence of sepsis or pneumonia, more frequently had received blood transfusion, and were ventilated with higher tidal volumes and/or lower PEEP levels (table 2). Baseline characteristics stratified according to the type of surgery are shown in the Appendix table 5 and Appendix table 6. Ventilatory parameters and duration of ventilation in patients ventilated with a protective or conventional strategy of ventilation are shown in Appendix table 7.
Incidence and timing of postoperative lung injury
The incidence of postoperative lung injury in the whole cohort was 3.9% (crude incidence 0.99 cases per person-year). The individual and pooled postoperative lung injury incidence rates are shown in Appendix figure 8. The incidence of postoperative lung injury was higher in patients older than 65 years (4.7 vs. 2.8%; p = 0.008), and in those ventilated with conventional ventilation (6.7 vs. 2.0%; p < 0.001), while it was similar after abdominal or thoracic surgery (3.4 vs. 4.3%; p
Table 2. Patient demographics
Variable Total(n = 3365) No PLI(n = 3150) PLI(n = 123) p value
Age, years 62.6 ± 12.7 62.5 ± 12.7 66.4 ± 11.6 0.001 Gender, male 2019 (60.0) 1941 (61.6) 78 (63.4) 0.834 ASA 2.4 ± 0.6 2.4 ± 0.6 2.6 ± 0.6 0.003 BMI, kg/m2 25.7 ± 4.8 25.7 ± 4.9 26.1 ± 4.8 0.323 Current smoker 1107 (32.9) 1058 (33.5) 49 (39.8) 0.122 Predisposing conditions Shock Pneumonia
Transfusion of blood products Sepsis 54 (1.6) 25 (0.7) 183 (5.4) 12 (0.3) 52 (1.6) 11 (0.3) 168 (5.3) 8 (0.2) 2 (1.6) 14 (11.3) 15 (12.1) 4 (3.2) 0.714 < 0.001 < 0.001 < 0.001 Ventilatory Parameters* Tidal volume, ml/kg PBW PEEP, cmH2O Respiratory rate, bpm FiO2, % 8.2 ± 1.9 4.4 ± 3.8 11.9 ± 2.7 44.9 ± 14.2 8.2 ± 1.8 4.3 ± 3.7 11.9 ± 2.7 41.4 ± 3.9 9.3 ± 2.1 2.9 ± 3.4 11.7 ± 2.2 40.5 ± 4.2 < 0.001 < 0.001 0.384 0.102 Oxygenation Parameters* pH PaO2 / FiO2 PaCO2 7.3 ± 0.1 320.0 ± 176.7 40.5 ± 6.5 7.3 ± 0.1 315.0 ± 180.3 40.7 ± 6.7 7.4 ± 0.0 302.4 ± 165.8 41.3 ± 3.8 0.002 0.681 0.708 ICU LOS, days 1.5 ± 4.8 1.1 ± 3.7 8.0 ± 12.4 < 0.001 Hospital LOS, days 15.1 ± 14.8 14.7 ± 14.3 20.9 ± 18.1 < 0.001
Mortality, % 70 (2.1) 45 (1.4) 25 (20.3) < 0.001
PLI: postoperative lung injury; BMI: body mass index; PBW: predicted body weight; BPM: breaths per minute; FiO2: inspired fraction of oxygen; ICU: intensive care unit; LOS: length of stay; PEEP: positive-end expiratory pressure *: in the middle of the surgery
230
= 0.198) (Table 3). The results stratified according to type of surgery are shown in the Appendix table 9 and Appendix table 10. The development of postoperative lung injury occurred within the first three days after surgery (mean of 2.9 ± 2.2 days; median and interquartile range of 2.0 [2.0 – 3.0] days); in 22% of cases postoperative lung injury developed after the first postoperative day (table 3 and figure 1).
Outcomes of postoperative lung injury
Outcome data for the study cohort are shown in table 3 and 4. Development of postoperative lung injury was associated with an increased in–hospital mortality (20.3 vs. 1.4% in patients with or without postoperative lung injury, respectively; p < 0.001) and by a longer ICU (8 ± 13 vs. 1 ± 4 days; p < 0.001) and hospital (21 ± 18 vs. 15 ± 14 days; p < 0.001) lengths of stay. The number of ICU–free days at day 28 and hospital–free days at day 28 were lower in patients who developed postoperative lung injury (21 ± 8 vs. 27 ± 2 days; p < 0.001; and 10 ± 7 vs. 15 ± 7 days; p < 0.001). When adjusted for age, severity of illness using ASA score, smoking, and predisposing conditions (sepsis, pneumonia, transfusion and/or shock), development of postoperative lung injury markedly increased the risk of in–hospital mortality (adjusted hazard ratio [HR], 9.58; 95% CI, 5.32 – 17.34) (figure 2 & 3, table 4 and Appendix figure 11). Patients who developed postoperative lung injury had a lower chance per day for ICU discharge, as represented by the adjusted HR of 0.45 (95% CI, 0.33 – 0.66) (table 4). The estimate of attributable mortality due to postoperative lung injury was 19% (95% CI, 18.0 – 19.1%).
In the group of patients who did develop postoperative lung injury, total duration of mechanical ventilation, ICU and hospital length of stay was similar between survivors and non–survivors
Figure 1. Timing of postoperative lung injury development during hospital stay
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(Appendix table 12). The mean time to death was 35.2 ± 63.4 days and the median was 18.0 (10.0 – 31.0) days. Patients ventilated with conventional strategy during surgery died earlier than those ventilated with protective strategy (17.8 ± 13.1 vs. 51.2 ± 84.3 days; p = 0.027).
Outcomes of postoperative lung injury in predefined subgroups
The attributable mortality of postoperative lung injury was lower in patients undergoing abdominal surgery (12.2% [95% CI, 12.0 – 12.6%]) compared to those undergoing thoracic surgery (26.5% [95% CI, 26.2 – 27.0%]) (p < 0.001). Development of postoperative lung injury was associated with a longer ICU and hospital lengths of stay, which was similar in abdominal and thoracic surgery patients (Appendix table 5 and Appendix table 6). When adjusted for age, severity of illness using ASA score, smoking, and predisposing conditions (sepsis, pneumonia, transfusion and/or shock), development of postoperative lung injury was lower in those receiving protective ventilation during surgery (adjusted HR, 0.31; 95% CI, 0.19 – 0.45). However, in– hospital mortality was independent of the ventilation strategy used in the operation room (adjusted HR, 0.71; 95% CI, 0.41 – 1.22). Attributable mortality of postoperative lung injury was similar in patients under protective ventilation (18.5% [95% CI, 17.8 – 19.2%]) compared to those under conventional ventilation (19.3% [95% CI, 19.0 – 19.7%]) (p = 0.359). Notably, patients who received conventional ventilation and developed postoperative lung injury died earlier compared to patients who received lung–protective ventilation and developed postoperative lung injury (18 ± 16 vs. 35 ± 53 days; p = 0.018). Characteristics of patients with postoperative lung injury stratified according to the type of ventilation used during surgery are shown in Appendix table
Figure 2. Kaplan–Meier estimates of the probability of overall survival
Data for the Kaplan–Meier estimates of the probability of overall survival in patients without postoperative lung injury (black solid line), and patients with postoperative lung injury (black dotted line). Data were censored at 30 days after surgery
232 Ta bl e 3 . I nci den ce o f p os to per ativ e l un g i nju ry a nd it s ch ar act eri stics in a ll gr ou ps o f p atien ts * N umb er o f P atien ts ICU L OS (d ay s) M ort al ity On se t o f PL I N o PL I PL I In ci den ce ** N o PL I PL I p va lu e N o PL I PL I p va lu e All pa tie nt s 31 50 (9 6.1 ) 12 3 (3 .9 ) 0.9 9 1.1 ± 3 .7 8.0 ± 1 2.4 < 0 .0 01 45 (1 .4 ) 25 (2 0.3 ) < 0 .0 01 2.9 ± 2 .2 Con ve ntiona l ve ntila tion 10 41 (9 3.3 ) 75 (6 .7 ) 1.7 1 1.0 ± 3 .0 9.2 ± 1 0.2 < 0 .0 01 17 (1 .4 ) 17 (2 0.7 ) < 0 .0 01 2.5 ± 1 .5 Pr ot ec tiv e ve ntila tion 17 62 (9 8.0 ) 37 (2 .0 ) 0.4 6 1.3 ± 4 .3 6.1 ± 1 6.2 < 0 .0 01 28 (1 .5 ) 8 (2 0.0 ) < 0 .0 01 3.9 ± 3 .3 Age < 6 5 y ear s ≥ 6 5 y ear s 15 04 (9 .2 ) 13 90 (9 5.3 ) 44 (2 .8 ) 68 (4 .7 ) 0.7 6 1.0 2 0.8 ± 2 .6 1.5 ± 4 .7 5.0 ± 6 .0 10 .5 ± 1 5.4 < 0 .0 01 < 0 .0 01 8 (0 .5 ) 37 (2 .5 ) 6 (1 2.8 ) 19 (2 5.3 ) < 0 .0 01 < 0 .0 01 2.5 ± 1 .2 3.2 ± 2 .6 AS A sc or e < 3 ≥ 3 13 91 (9 6.6 ) 11 06 (9 5.3 ) 49 (3 .4 ) 55 (4 .7 ) 0.8 1 1.1 4 1.0 ± 4 .0 1.8 ± 4 .4 4.2 ± 5 .3 9.0 ± 1 4.4 0.0 01 0.0 17 10 (0 .7 ) 25 (2 .3 ) 9 (1 7.0 ) 16 (2 9.1 ) < 0 .0 01 < 0 .0 01 2.5 ± 1 .2 3.4 ± 2 .9 Sur ge ry A bdom inal Thor ac ic 17 98 (9 6.6 ) 12 85 (9 5.7 ) 64 (3 .4 ) 58 (4 .3 ) 0.7 9 1.3 2 1.0 ± 4 .1 1.5 ± 0 .9 9.0 ± 1 4.5 5.9 ± 2 .1 < 0 .0 01 < 0 .0 01 32 (1 .8 ) 13 (1 .0 ) 9 (1 4.1 ) 16 (2 7.6 ) < 0 .0 01 < 0 .0 01 2.3 ± 0 .9 3.4 ± 2 .7 PLI : pos tope ra tiv e lung injur y; ICU : in te nsiv e c ar e unit ; L OS: le ng th of s ta y; Onse t of P LI is expr esse d in da ys * I n som e c ase s t he num be r of pa tie nt s a re not a dding up due to m issing v alue s ** Expr esse d a s c ase s pe r pe rson-ye ar
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13. There was no interaction between mortality and the design of the study (RCT versus No-RCT) in the overall cohort (p for interaction = 0.11), abdominal surgery (p for interaction = 0.23), or thoracic surgery (p for interaction = 0.78) (Appendix figure 14).
Based on the excluded studies where the data is available,21,23,24 the crude incidence of PLI was
6.6%, similar to that found in our study (p = 0.116). Also, protective ventilation was associated with lower incidence of PLI compared to conventional ventilation (5.3% vs. 13.1%; p = 0.031), similar to the findings of the present study. There was no interaction between mortality and PLI incidence and the excluded analysis (Appendix figure 15).
Discussion
This individual patient data metaanalysis shows that development of postoperative lung injury is associated with high attributable mortality. In addition, development of postoperative lung injury is associated with an important increase in resource use as reflected in longer ICU and hospital length of stay. The incidence of postoperative lung injury is similar in patients undergoing abdominal or thoracic surgery. However, the attributable mortality of this condition is higher in those submitted to thoracic procedures. Intraoperative protective ventilation is associated with lower incidence of postoperative lung injury compared to conventional ventilation in abdominal or thoracic surgery. However, if postoperative lung injury develops, intraoperative protective strategy of ventilation is not associated with reduced attributable mortality, at least suggesting that the benefits of this strategy of ventilation is mainly due the reduction in the incidence of postoperative lung injury.
Table 4. Outcome of patients with postoperative lung injury
Variable HR of Mortality (95% CI) HR of ICU Discharge (95% CI)
All patients 9.58 (5.32 – 17.34) 0.45 (0.33 – 0.66) Conventional ventilation 14.22 (5.91 – 34.26) 0.39 (0.25 – 0.58) Protective ventilation 6.07 (2.47 – 14.55) 0.71 (0.42 – 1.19) Age < 65 years ≥ 65 years 33.10 (8.32 – 131.39)7.32 (3.72 – 14.23) 0.52 (0.32 – 0.83)0.43 (0.26 – 0.68) ASA score < 3 ≥ 3 26.67 (9.44 – 75.22)6.05 (2.91 – 12.66) 0.55 (0.34 – 0.92)0.41 (0.26 – 0.60) Surgery Abdominal Thoracic 7.12 (2.67 – 19.08)10.46 (4.72 – 23.18) 0.47 (0.32 – 0.69)0.19 (0.08 – 0.40)
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Our analysis presents several strengths. First, we performed an individual patient data metaanalysis including a larger number of patients with a higher number of variables and well– documented risk factors compared to previous studies.1-4 Second, the primary and secondary
outcomes were clearly defined in the majority of the investigations and the definition of postoperative lung injury was done a priori. Third, we included the two most recent largest and well–performed randomized controlled trials in the field.18,19 Fourth, we analysed patients
undergoing abdominal and thoracic surgery and they are at high risk for development of postoperative lung injury.1 Finally, individual patient data metaanalysis including a higher number
of randomized controlled trials have some advantages compared to large observational studies. Since the number of major surgical procedures undertaken worldwide each year is high, the finding that postoperative lung injury is associated with such a bad outcome is important. Identification of mechanisms contributing to the development of this complication and finding of preventive measures is highly needed. The use of lower tidal volumes during intraoperative ventilation appears to be a clinically relevant and modifiable strategy.2,18 At the same time,
ventilation strategies that use high PEEP levels are associated with potentially dangerous side– effects, as reported in the last randomized controlled trial comparing high with low PEEP levels in patients under intraoperative ventilation with low tidal volume.19
The results of this metaanalysis are, at least in part in line with results from previous investigations. Studies suggest that in patients undergoing high risk elective surgery,2 the reported
incidence of postoperative lung injury was 3%, similar to what the present metaanalysis found.
Figure 3. Kaplan–Meier estimates of the probability of overall survival
Data for the Kaplan–Meier estimates of the probability of overall survival in: A) patients undergoing thoracic surgery without postoperative lung injury (black solid line), patients undergoing thoracic surgery with postoperative lung injury (black dotted line), patients undergoing abdominal surgery without postoperative lung injury (gray solid line), and patients undergoing abdominal surgery with postoperative lung injury (gray dotted line); and in B) patients undergoing protective ventilation without postoperative lung injury (black solid line), patients undergoing protective ventilation with postoperative lung injury (black dotted line), patients undergoing conventional ventilation without postoperative lung injury (gray solid line), and patients undergoing conventional ventilation with postoperative lung injury (gray dotted line). Data were censored at 30 days after surgery. Abd: abdominal; Tho: thoracic; LI: lung injury; Pro: protective; Conv: conventional
Ch apt er 1 0 235
That same investigation showed a similar increased length of hospital stay in patients who developed postoperative lung injury, and an increased in–hospital mortality of as high as 17%. Furthermore, in that study 60–day and one–year survival of patients with postoperative lung injury was lower than that of patients who did not develop this complication. Studies in other patient groups show similar findings.12,22 It is important to emphasize that incidence and outcomes
of postoperative lung injury might be different in different types of surgery3 and according to
definitions used.
The findings of this metaanalysis add to our knowledge on the outcome of postoperative lung injury, and the potential measures to prevent this important complication after major surgery, mainly the use of protective strategies of mechanical ventilation during surgery. This is of particular importance for those who apply intraoperative ventilation, since most of the time they follow on patients’ outcomes only the first postoperative day. Indeed, the metaanalysis shows that many patients do develop lung injury after major surgery beyond the first postoperative day. Second, development of postoperative lung injury was dependent on the intraoperative ventilation strategy, and thus should be seen as a potentially preventable complication. Finally, the attributable mortality of postoperative lung injury after intraoperative ventilation using conventional settings is similar to those after lung–protective ventilation, meaning that the benefits of intraoperative protective ventilation is mainly due the reduction of the incidence of postoperative lung injury. This finding might simply reflects the heterogeneous factors that cause death in this population well beyond just postoperative lung injury.
The finding that patients who received conventional intra–operative ventilation and developed postoperative lung injury died earlier than those who developed this complication after protective intraoperative ventilation, even though attributable mortality at the end of follow up was the same, is intriguing. One possible explanation is that patients who did not receive intraoperative lung–protective ventilation could have been ventilated with injurious ventilation after surgery, and maybe even after development of lung injury. Unfortunately, it was impossible to collect data on ventilator settings after surgery, therefore our reasoning, although plausible, remains speculative.
The observed incidence and outcome of postoperative lung injury might not be easily appreciated during daily clinical work among physicians, surgeons, and anaesthesiologists involved in the perioperative management. In fact, this is a large cohort evaluating the development and impact of postoperative lung injury in patients undergoing elective abdominal and thoracic procedures. The finding that postoperative lung injury develops after the first postoperative day is important, suggesting we need a more precise timing for monitoring and clinical management.
Some limitations should also be discussed. First, our analyses were restricted to studies of intraoperative protective ventilation and data on postoperative ventilation are not available. Second, not all investigators could provide individual patient data, and, therefore, data from seven studies were not included. However, the results of a classical metaanalysis are in agreement with those found in the present analysis.4 Third, there was no information on choices of treatment
after surgery, like postoperative ventilation, blood transfusion policies, fluid regimens, pain control, cardiac protection and others, and it could be anaesthetists that applied protective
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ventilation also provided other lung protective strategies after surgery. Therefore, we cannot answer the question of how much the in–hospital mortality is influenced by the adequacy of treatment. Also, we do not know the reason of death in each patient. Fourth, since there is no gold standard for the diagnosis of postoperative lung injury, misclassification of patients with this complication might have underestimated as well as overestimated the observed attributable morbidity. Fifth, we were not able to collect information regarding history of previous abdominal or thoracic surgery, which can influence the outcome. Sixth, these results should be analysed within the context of the included studies and one limitation is that we pooled data from studies with heterogeneous research methodologies and with significant quantitative heterogeneity. Seventh, the number of studies included is moderate and therefore the model may lack power to detect association and are unable to ascertain multiple potential sources of confounding. Eight, we did not include previous pulmonary alterations as co-variate in the model however, only 4.9% of the population analysed presented chronic obstructive pulmonary disease (COPD) or other chronic pulmonary disease. Ninth, it should be noted that minimal invasive techniques for thoracic surgery are increasingly used, and these techniques usually last shorter and are associated with a shorter length of stay. Since the studies included in the present analysis did not include these techniques, we cannot assess the outcomes and effects of protective ventilation during minimal invasive procedures. However, a recent study suggests that protective ventilation strategies benefits patients undergoing minimally invasive esophagectomy as well.32
Finally, although the type of intraoperative ventilation appears to play an important role in development of acute lung injury, other factors during postoperative management may plausibly be contributory, especially for patients who developed lung injury days after surgery (or cessation of mechanical ventilation).
In conclusion, based on an individual patient data from seven studies of intraoperative protective ventilation, development of postoperative lung injury is associated with high attributable mortality. The attributable mortality of postoperative lung injury is higher in patients undergoing thoracic compared to abdominal surgery. Intraoperative protective ventilation is associated with lower incidence of postoperative lung injury, but seems not to affect in–hospital mortality. Role of the funding source
The corresponding author had full access to all of the data and the final responsibility to submit for publication.
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Research in context
Systematic reviewWe searched MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) up to April 2014. The sensitive search strategy combined the following Medical Subject Headings and Keywords ([protective ventilation OR lower tidal volume OR low tidal volume OR positive end–expiratory pressure OR positive end expiratory pressure OR PEEP]). We restricted our analysis to studies in surgery. We assessed the quality of identified studies to ensure minimization of bias.
Interpretation
Development of postoperative lung injury is associated with high attributable mortality. The attributable mortality of postoperative lung injury is higher in patients undergoing thoracic compared to abdominal surgery. Intraoperative protective ventilation is associated with lower incidence of postoperative lung injury, but seems not to affect in–hospital mortality.
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Supplementary Appendix to: ‘Incidence of mortality and morbidities of postoperative lung injury in abdominal and thoracic surgery patients: A systematic review and metaanalysis
Ary Serpa Neto MD MSc, Sabrine NT Hemmes MD, Carmen SV Barbas MD PhD, Martin Beiderlinden MD, Michelle Biehl MD, Ana Fernandez-Bustamante MD PhD, Emmanuel Futier MD PhD, Ognjen Gajic MD PhD, Samir Jaber MD PhD, Alf Kozian MD PhD, Marc Licker MD, Wen-Qian Lin MD, Stavros G Memtsoudis MD PhD, Dinis Reis Miranda MD, Pierre Moine MD, Domenico Paparella MD, Marco Ranieri MD PhD, Federica Scavonetto MD, Thomas Schilling MD PhD DEEA, Gabriele Selmo MD, Paolo Severgnini MD, Juraj Sprung MD PhD, Sugantha Sundar MD, Daniel Talmor MD PhD, Tanja Treschan MD, Gerardo Tusman MD PhD, Maria Carmen Unzueta MD, Toby N Weingarten MD, Esther K Wolthuis MD PhD, Hermann Wrigge MD PhD, Marcelo Gama de Abreu MD PhD, Paolo Pelosi MD, Marcus J Schultz MD PhD
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eFigure 2. Individual and pooled incidence rate of postoperative lung injury
eFigure 3. In-hospital mortality in patients who developed or not postoperative lung injury in thoracic or abdominal surgery
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eFigure 4. Interaction between mortality and design of the study
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eTable 1. Characteristics of included studies
Study, year Allocation Concealment Baseline Similarity Early Stoppinga
Lost to
Follow-up Intention-to-Treat Analysis
Wrigge, 2004 Sealed envelopes Age: similarIllness severity:
similar (ASA) No 4.6% NS
Schilling, 2005 Random numbers Age: similar No No NS Wolthuis, 2008 Sealed envelopes Age: similarIllness severity:
similar (ASA) No No No
Lin, 2008 NS Age: similar No No NS
Licker, 2009 Not applicable
Age: similar Illness severity: favour higher VT
(ASA)
Not
applicable Not applicable Not applicable
Fernandez-Bustamante, 2011 Not applicable
Age: similar Illness severity: similar (ASA)
Not
applicable Not applicable Not applicable Weingarten, 2010 Schedule Age: similarIllness severity:
similar (ASA) No No NS
Treschan, 2012 Sealed envelopes Age: similarIllness severity:
similar (ASA) No No Yes
Unzueta, 2012 Random table Age: similarIllness severity:
similar (ASA) No No NS
Severgnini, 2013 Sealed envelopes Age: similarIllness severity:
similar (ASA) No 1.7% NS
Futier, 2013 Computer-Generated Age: similarIllness severity:
similar (PORI) No No Yes
Hemmes, 2014 Computer-Generated Age: similarIllness severity:
similar (ARISCAT) No No Yes
NS: not specified; VT: tidal volume; STSMS: society of thoracic surgeons mortality score; PORI: preoperative risk index a: Early termination for benefit or futility and the presence of an explicit a priori stopping rules
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eTable 2. Jadad scale
Studies Was the study described as
randomized?
Was the study described as double blind? Was there a description of withdrawals and dropouts? The method of randomization was described in the paper, and that method was appropriate. The method of blinding was described, and it was appropriate.
Wrigge, 2004 Yes No Yes No No
Schilling, 2005 Yes No Yes No No
Wolthuis, 2008 Yes No Yes Yes No
Lin, 2008 Yes No No No No
Weingarten, 2010 Yes No Yes Yes No
Treschan, 2012 Yes Yes Yes Yes Yes
Unzueta, 2012 Yes No Yes No No
Severgnini, 2013 Yes Yes Yes Yes Yes
Futier, 2013 Yes Yes Yes Yes Yes
Hemmes, 2014 Yes Yes Yes Yes Yes
eTable 3. GRACE checklist1
Studies
Adequate
Treatment Adequate Outcomes Objective Outcomes Valid Outcomes Similar Outcomes RecordedCovariates New Initiators Concurrent Comparators Covariates Accounted For Immortal Time Bias Sensitivity Analysis
D1 D2 D3 D4 D5 D6 M1 M2 M3 M4 M5
Licker, 2009 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Fernandez, 2011 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
1Dreyer NA, Velentgas P, Westrich K, Dubois R. The GRACE checklist for rating the quality of observational studies of
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eTable 4. Demographics of patients undergoing thoracic surgery
Variable Total(n = 1374) No PLI(n = 1285) PLI(n = 58) p value
Age, years 61.73 ± 11.85 61.57 ± 11.88 66.00 ± 10.35 0.005 Gender, male 872 (63.4) 837 (65.1) 35 (60.3) 0.482 ASA 2.45 ± 0.63 2.44 ± 0.63 2.72 ± 0.64 0.001 BMI, kg/m2 25.10 ± 4.43 25.10 ± 4.45 25.07 ± 4.36 0.956 Predisposing conditions Shock Pneumonia
Transfusion of blood products Sepsis 1 (0.0) 9 (0.6) 39 (2.8) 5 (0.3) 0 (0.0) 4 (0.3) 26 (2.0) 1 (0.0) 1 (1.7) 5 (8.6) 13 (22.4) 4 (6.8) 0.714 < 0.001 < 0.001 < 0.001 Ventilatory Parameters* Tidal volume, ml/kg PBW Respiratory rate, mpm FiO2, % 7.78 ± 2.05 12.90 ± 2.21 45.00 ± 16.61 7.64 ± 1.84 12.94 ± 2.21 45.17 ± 16.86 9.54 ± 2.53 11.81 ± 1.89 40.40 ± 5.07 < 0.001 0.001 0.064 Oxygenation Parameters* pH PaO2 / FiO2 PaCO2 7.26 ± 0.12 392.64 ± 118.45 41.17 ± 6.89 7.28 ± 0.10 398.87 ± 118.69 41.13 ± 7.05 7.13 ± 0.15 294.28 ± 55.22 41.86 ± 3.31 < 0.001 0.001 0.689 ICU LOS, days 1.88 ± 1.52 1.57 ± 0.90 5.93 ± 2.15 < 0.001 Hospital LOS, days 13.05 ± 6.47 12.71 ± 6.10 20.72 ± 9.14 < 0.001 In-Hospital Mortality, % 29 (2.1) 13 (1.0) 16 (27.5) < 0.001
PLI: postoperative lung injury; BMI: body mass index; PBW: predicted body weight; MPM: movements per minute; FiO2:
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eTable 5. Demographics of patients undergoing abdominal surgery
Variable Total(n = 1991) No PLI(n = 1798) PLI(n = 64) p value
Age, years 63.24 ± 13.25 63.20 ± 13.21 66.75 ± 12.66 0.035 Gender, male 1235 (62.0) 1191 (66.2) 44 (68.7) 0.433 ASA 2.32 ± 0.67 2.34 ± 0.67 2.43 ± 0.63 0.347 BMI, kg/m2 26.13 ± 5.02 26.11 ± 5.09 27.12 ± 5.00 0.122 Predisposing conditions Shock Pneumonia
Transfusion of blood products Sepsis 51 (2.5) 8 (0.4) 157 (7.8) 7 (0.3) 50 (2.7) 7 (0.3) 144 (8.0) 7 (0.3) 1 (1.5) 1 (1.5) 13 (20.3) 0 (0.0) 0.714 0.231 < 0.001 0.871 Ventilatory Parameters* Tidal volume, ml/kg PBW Respiratory rate, mpm FiO2, % 8.56 ± 1.80 11.00 ± 2.86 44.87 ± 9.64 8.53 ± 1.76 10.97 ± 2.83 45.34 ± 10.07 9.15 ± 1.72 11.62 ± 2.38 40.78 ± 2.70 0.006 0.093 0.011 Oxygenation Parameters* pH PaO2 / FiO2 PaCO2 7.35 ± 0.06 334.73 ± 220.76 38.62 ± 5.16 7.33 ± 0.05 365.58 ± 230.31 38.49 ± 3.79 7.43 ± 0.04 308.14 ± 214.2 32.42 ± 4.62 0.462 0.245 0.493 ICU LOS, days 1.41 ± 5.24 1.08 ± 4.10 9.00 ± 14.57 < 0.001 Hospital LOS, days 16.53 ± 18.45 16.17 ± 17.92 21.09 ± 23.58 0.035 In-Hospital Mortality, % 42 (2.1) 33 (1.8) 9 (14.1) < 0.001
PLI: postoperative lung injury; BMI: body mass index; PBW: predicted body weight; MPM: movements per minute; FiO2:
inspired fraction of oxygen; ICU: intensive care unit; LOS: length of stay; *: in the end of the surgery
eTable 6. Ventilatory parameters and duration of ventilation
Parameters
Total Abdominal Thoracic
Protective
(n = 1799) Conventional(n = 1116) p value Protective(n = 1155) Conventional(n = 707) p value Protective(n = 707) Conventional(n = 636) p-value
Tidal volume, ml/kg PBW 7.10 ± 1.15 9.95 ± 1.62 < 0.01 7.54 ± 0.93 10.40 ± 1.52 < 0.01 6.34 ± 1.09 9.46 ± 1.58 < 0.01
PEEP, cmH2O 5.41 ± 4.10 2.79 ± 2.68 < 0.01 6.44 ± 4.57 2.72 ± 3.29 < 0.01 3.61 ± 2.08 2.87 ± 1.77 < 0.01
Respiratory rate, bpm 12.91 ± 2.82 10.45 ± 1.77 < 0.01 11.76 ± 2.97 9.60 ± 1.97 < 0.01 14.38 ± 1.73 11.15 ± 1.21 < 0.01 Plateau pressure, cmH2O 16.52 ± 5.87 16.49 ± 4.03 0.912 19.12 ± 5.81 17.32 ± 6.53 < 0.01 13.63 ± 4.43 16.23 ± 2.75 < 0.01
Duration of ventilation, minutes 369.23 ± 758.59 408.53 ± 844.14 0.857 382.74 ± 788.87 487.21 ± 755.43 0.101 401.12 ± 672.21 498.21 ± 512.32 0.222
ICU length of stay, days 1.49 ± 5.24 1.51 ± 4.33 0.935 1.42 ± 5.92 1.40 ± 4.59 0.958 1.71 ± 0.99 2.13 ± 2.04 0.045
Hospital length of stay, days 15.77 ± 16.75 14.01 ± 14.97 0.231 15.99 ± 17.34 15.76 ± 13.76 0.121 12.01 ± 5.80 14.28 ± 6.98 < 0.01
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eTable 7. Incidence of postoperative lung injury and its characteristics in patients undergoing thoracic surgery
Postoperative Lung Injury No-Postoperative Lung Injury
Number of
Patients Onset (days) Mortality ICU LOS (days) Number of Patients Mortality ICU LOS (days)
All patients 58 (4.3) 3.4 ± 2.7 16 (27.6) 5.9 ± 2.1 1285 (95.7) 13 (1.0) 1.5 ± 0.9 Conventional ventilation 42 (6.7) 2.7 ± 1.7 12 (28.6) 6.0 ± 2.1 578 (93.3) 4 (0.7) 1.3 ± 0.7 Protective ventilation 16 (2.2) 5.5 ± 4.2 4 (25.0) 4.0 ± 4.5 707 (97.8) 9 (1.3) 1.6 ± 0.9 Age < 65 years ≥ 65 years 25 (3.3)33 (5.5) 2.6 ± 1.33.9 ± 3.3 6 (24.0)10 (30.3) 5.1 ± 1.16.8 ± 2.7 717 (96.7)566 (94.5) 1 (0.1)12 (2.1) 1.4 ± 0.81.7 ± 0.9 ASA score < 3 ≥ 3 22 (3.0)36 (5.8) 2.9 ± 1.43.6 ± 3.1 8 (36.4)8 (22.2) 5.5 ± 2.06.4 ± 2.3 694 (97.0)581 (94.2) 3 (0.4)10 (1.7) 1.4 ± 0.81.6 ± 0.9
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eTable 8. Incidence of postoperative lung injury and its characteristics in patients undergoing abdominal surgery
Postoperative Lung Injury No-Postoperative Lung Injury
Number of
Patients Onset (days) Mortality ICU LOS (days) Number of Patients Mortality ICU LOS (days)
All patients 64 (3.4) 2.3 ± 0.9 9 (14.1) 9.0 ± 14.5 1798 (96.6) 32 (1.8) 1.0 ± 4.1 Conventional ventilation 40 (6.0) 2.2 ± 1.0 5 (12.5) 11.1 ± 12.6 620 (94.0) 13 (2.1) 0.9 ± 3.2 Protective ventilation 24 (1.9) 2.4 ± 0.8 4 (16.7) 6.2 ± 16.7 1178 (98.1) 19 (1.6) 1.2 ± 4.9 Age < 65 years ≥ 65 years 22 (2.4)42 (4.3) 2.2 ± 0.92.3 ± 1.0 0 (0.0)9 (21.4) 4.9 ± 7.411.6 ± 17.3 884 (97.6)914 (95.7) 7 (0.8)25 (2.7) 0.6 ± 2.91.5 ± 5.1 ASA score < 3 ≥ 3 31 (3.7)24 (3.9) 2.2 ± 1.02.5 ± 0.5 1 (3.2)5 (20.8) 3.5 ± 6.510.0 ± 16.8 797 (96.3)577 (96.1) 7 (0.9)14 (2.4) 0.9 ± 4.71.8 ± 5.1
ICU: intensive care unit; LOS: length of stay
eTable 9. Characteristics of patients with postoperative lung injury
Variable Total(n = 123) Survivors(n = 98) Non-Survivors(n = 25) p value
Age, years 66.39 ± 11.58 65.14 ± 11.96 71.24 ± 8.52 0.018 Gender, male 78 (63.4) 61 (62.2) 17 (68.0) 0.635 ASA 2.58 ± 0.65 2.54 ± 0.63 2.72 ± 0.70 0.252 BMI, kg/m2 26.14 ± 4.79 26.24 ± 4.92 25.74 ± 4.36 0.643 Ventilatory Parameters* Tidal volume, ml/kg PBW PEEP, cmH2O Respiratory rate, mpm FiO2, % 9.34 ± 2.14 2.86 ± 3.43 11.71 ± 2.17 40.56 ± 4.21 9.33 ± 2.12 2.88 ± 3.60 11.40 ± 2.26 55.55 ± 22.36 9.36 ± 2.29 2.80 ± 2.70 10.66 ± 1.63 57.11 ± 25.02 0.943 0.911 0.450 0.845 Duration of ventilation, hours 30.35 ± 75.50 29.80 ± 78.95 34.13 ± 47.81 0.867 ICU LOS, days 8.17 ± 12.55 8.34 ± 13.23 7.00 ± 6.37 0.793 Hospital LOS, days 20.91 ± 18.08 20.33 ± 17.42 23.16 ± 20.66 0.489
BMI: body mass index; PBW: predicted body weight; MPM: movements per minute; FiO2: inspired fraction of oxygen;
Ch apt er 1 0 249 eT ab le 1 0. Ch ar act eri stics o f t he p atien ts wi th p os to per ativ e l un g i nju ry u nd er p ro tectiv e o r c on ven tio na l v en til atio n Va ria bl es Gen er al (n = 1 22 ) p-va lu e Th or aci c ( n = 5 8) p-va lu e Ab do mi na l ( n = 6 4) p-va lu e Pr ot ectiv e (n = 4 0) Co nv en tio na l (n = 8 2) Pr ot ectiv e (n = 1 6) Co nv en tio na l (n = 4 2) Pr ot ectiv e (n = 2 4) Co nv en tio na l (n = 4 0) Ag e, y ea rs 64 .3 ± 1 4.0 67 .4 ± 1 0.2 0.1 69 63 .2 ± 1 4.3 67 .0 ± 8 .4 0.2 15 65 .0 ± 1 4.0 67 .8 ± 1 1.9 0.4 07 Ge nde r, m ale 28 (7 0.0 ) 50 (6 1.0 ) 0.3 30 AS A 2.5 8 ± 0 .7 2.5 8 ± 0 .6 0.9 47 2.8 ± 0 .5 2.7 ± 0 .7 0.5 23 2.4 ± 0 .7 2.4 ± 0 .6 0.9 88 BM I, k g/m 2 25 .7 ± 5 .3 26 .3 ± 4 .5 0.4 96 25 .4 ± 5 .5 25 .0 ± 3 .9 0.7 52 26 .0 ± 5 .3 27 .9 ± 4 .7 0.1 44 Ve ntila tor y P ar am et er s * Tida l v olum e, m l/k g P BW P EEP , c m H2 O R espir at or y r at e, m pm FiO 2 , % 7.4 ± 1 .3 5.7 ± 3 .9 13 .1 ± 2 .4 40 .0 ± 4 .4 10 .3 ± 1 .8 1.5 ± 2 .1 10 .8 ± 1 .4 41 .0 ± 4 .1 < 0 .0 01 < 0 .0 01 < 0 .0 01 0.3 96 7.2 ± 1 .9 2.6 ± 1 .5 13 .5 ± 1 .6 38 .5 ± 4 .6 10 .4 ± 2 .1 1.3 ± 1 .6 10 .9 ± 1 .3 41 .4 ± 5 .0 < 0 .0 01 0.0 08 < 0 .0 01 0.0 68 7.5 ± 0 .6 7.8 ± 3 .6 12 .9 ± 2 .8 55 .6 ± 2 2.1 10 .2 ± 1 .3 1.6 ± 2 .5 10 .7 ± 1 .5 55 .8 ± 2 3.1 < 0 .0 01 < 0 .0 01 < 0 .0 01 0.9 68 O xy ge na tion P ar am et er s * pH a P aO2 / FiO 2 P aC O2 7.3 2 ± 0 .1 1 25 8.5 ± 1 03 .7 35 .5 ± 3 .5 7.1 4 ± 0 .1 6 31 7.0 ± 1 81 .1 42 .1 ± 3 .1 5 0.1 65 0.3 67 0.2 04 ---7.3 8 ± 0 .0 1 24 7.1 ± 1 04 .6 37 .1 ± 0 .2 7.4 5 ± 0 .0 3 34 5.7 ± 2 57 .1 30 .5 ± 4 .0 0.4 95 0.3 18 0.0 81 Dur ation of v en tila tion, hour s 28 .8 ± 7 0.3 31 .1 ± 7 8.4 0.9 04 ---29 .9 ± 7 1.6 40 .4 ± 8 9.5 0.6 26 ICU LOS, da ys 6.1 ± 1 6.2 9.2 ± 1 0.3 0.3 93 ---6.3 ± 1 6.7 11 .1 ± 1 2.6 0.2 96 Hospit al L OS, da ys 21 .2 ± 2 4.1 20 .8 ± 1 4.6 0.9 05 20 .1 ± 5 .4 21 .0 ± 1 0.2 0.7 37 22 .0 ± 3 1.3 20 .6 ± 1 8.2 0.8 20 In-H ospit al M or ta lit y, % 8 (2 0.0 ) 17 (2 0.7 ) 0.9 25 4 (2 5.0 ) 12 (2 8.6 ) 0.7 86 4 (1 6.7 ) 5 (1 2.5 ) 0.6 42 BM I: body m ass inde x; P BW : pr edic te d body w eig ht ; M PM : m ov em en ts pe r m inut e; FiO 2 : inspir ed fr ac tion of oxy ge n; ICU : in te nsiv e ca re unit ; L OS: le ng th of st ay ; P EEP : positiv e-e nd expir at or y pr essur e; * : in t he m iddle of t he sur ge ry
