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Positive End-Expiratory Pressure During Anesthesia for Prevention of Postoperative Pulmonary Complications: A Meta-analysis With Trial Sequential Analysis of Randomized Controlled Trials

Zhang, Pengcheng MD*; Wu, Lingmin MD*; Shi, Xuan MD; Zhou, Huanping MD, PhD; Liu, Meiyun MD; Chen, Yuanli MD, PhD; Lv, Xin MD, PhD*,†

Author Information
doi: 10.1213/ANE.0000000000004421

Abstract

KEY POINTS

  • Question: Does intraoperative positive end-expiratory pressure (PEEP) prevent postoperative pulmonary complications?
  • Findings: A meta-analysis revealed that intraoperative PEEP reduces postoperative pulmonary complications, but the result was too unreliable.
  • Meaning: The effect of intraoperative PEEP in postoperative pulmonary complications remains unclear.

Approximately 313 million patients worldwide undergo major operations every year under general anesthesia with mechanical ventilation.1 However, existing data suggest that mechanical ventilation may induce or aggravate lung injury.2 Some studies have shown that some patients undergoing surgery with general anesthesia are at a moderate to high risk for postoperative pulmonary complications,3,4 which adversely affect hospital length of stay, clinical outcomes, and health care resource utilization.5 Prevention of these complications can not only help solve these problems but also accelerate postoperative recovery.

Lung-protective ventilation (LPV), a ventilation strategy involving low tidal volume (VT) and positive end-expiratory pressure (PEEP), reduces mortality and improves clinical outcomes in patients with acute respiratory distress syndrome (ARDS).6,7 During anesthesia and surgery, low VTs predispose to atelectasis,8,9 which may be accompanied with hypoxemia, pneumonia, and lung injury.10,11 Although low VT is an important component of an LPV strategy for surgical patients, PEEP may also be necessary to achieve the outcome benefit. PEEP, or positive intrapulmonary pressure during end-expiration, addresses atelectasis by increasing functional residual capacity (FRC). Whereas some studies find that LPV without PEEP may not prevent pulmonary complications,12 others13,14 suggest that intraoperative LPV with PEEP can reduce postoperative pulmonary complications and improve lung function. We, therefore, performed a meta-analysis with trial sequential analysis (TSA) of randomized controlled trials (RCTs) to compare the effect of PEEP versus zero PEEP (ZEEP) with atelectasis as the primary outcome. We hypothesized that when compared with no PEEP (ZEEP), PEEP is associated with decreased risk of atelectasis morbidity in patients undergoing surgery with general anesthesia. In addition, we assessed the effect of intraoperative PEEP with respect to secondary outcomes, postoperative pulmonary atelectasis, pneumonia, respiratory insufficiency, cardiac complications, mortality, and respiratory failure.

METHODS

The systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA; Cochrane Handbook for Systematic Reviews of Interventions)15 and reported based on PRISMA guidelines.16 This meta-analysis has no protocol.

Search Strategy and Study Selection

Studies were searched through the following databases: PubMed, Cochrane library, and Embase from the inception to August 2018, using the keywords “Positive End-expiratory Pressure” and “anesthesia.” We included randomized trials with no restrictions on language or airway instrumentation method (laryngeal masks or endotracheal tubes). We reran the searches on October 10, 2018 and checked previous reviews and references of the retrieved articles to identify other eligible studies. (Details of the search strategy are shown in Supplemental Digital Content, Appendix 1, https://links.lww.com/AA/C930.)

Trials in compliance with the following criteria were included: (1) Population: adult patients undergoing any surgical procedure with general anesthesia, who did not have ARDS at the onset of mechanical ventilation; patients were also required to have had PEEP or ZEEP either from or immediately postinduction and had to have PEEP continued throughout the duration of mechanical ventilation; (2) Intervention: patients who received PEEP of any quantity greater than zero throughout the duration of general anesthesia and with no restrictions on ventilatory setting (include VT, plateau airway pressure, inspired fraction of oxygen, inspiratory/expiratory ratio, mode of ventilation, respiratory rate, duration of mechanical ventilation, etc); (3) Comparison: the intervention group was compared with a control group. Participants who had ZEEP throughout the duration of general anesthesia constituted the control group; (4) Outcomes: postoperative pulmonary complications mainly including postoperative atelectasis, postoperative pulmonary atelectasis score, pneumonia, respiratory insufficiency, cardiac complications, mortality, and respiratory failure; and (5) Design: RCTs. Patients who received both PEEP and ZEEP crossover studies were excluded.

Data Extraction and Outcome Measures

Two researchers independently extracted the data from each study. Collected information included the following: first author, year of publication, number of patients, demographic characteristics, surgical procedure, VTs, use of PEEP, use of recruitment maneuvers in lung-protective and conventional ventilation groups, ventilatory settings, and reported outcomes. The extracted data were entered into a data recording form. For some data were obtained from published meta-analyses,17,18 we also reviewed the original articles to determine whether the trials were accurate and met our inclusion criteria. We would also contact the corresponding authors whenever needed to obtain additional data. The primary outcome measures were postoperative pulmonary atelectasis (as defined in the trials). The secondary outcomes for postoperative pulmonary complications included atelectasis score, pneumonia (as defined in the trials), respiratory insufficiency, cardiac complications, mortality (any death during the follow-up period), and respiratory failure.

Assessment for Risk of Bias and Grading the Quality of Evidence

Two investigators independently assessed the risk of bias using the Cochrane Collaboration’s tool.19 We reviewed each trial and assigned a value of high, low, or unclear risk of bias to the following criteria: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. Trials with high (or low) risk of bias for any one or more key domains were considered as at high (or low) risk of bias. Otherwise, they were considered as unclear risk of bias.19

The trials were evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)20 and graded as low, very low quality, high quality, or moderate quality based on the risk of bias, inconsistency, indirectness, imprecision, and publication bias. Summary tables were constructed using the GRADE Profiler (version 3.6, GRADEpro; McMaster University, Hamilton, Ontario, Canada; http://gradepro.org/).

Statistical Analysis

We performed meta-analysis to estimate relative risks (RRs) for dichotomous outcomes and the standardized mean difference (SMD) for continuous outcomes by 95% confidence interval (CI) using the Mantel–Haenszel method. A random-effects model was used to account for heterogeneity. If zero events were reported for PEEP or ZEEP group, a value of 0.5 was added to both groups for each such study, and trials with zero events in both groups were not included in the meta-analysis when RRs were calculated.15

Heterogeneity across studies was reported with the I2 statistic. An I2 statistic of 25%–50% was considered to represent low heterogeneity, I2 statistic of 50%–75% was considered to have moderate heterogeneity, and those with an I2 statistic of >75% were considered to have high heterogeneity. I2 >50% indicates significant heterogeneity.21 Publication bias was evaluated by using the Begg and Egger tests.22,23 All statistical analyses were performed using RevMan 5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark), and a 2-sided P value of <.05 was considered statistically significant. In addition, we also conducted subgroup analyses for dichotomous outcomes according to risk of bias (low versus unclear or high risk), surgical setting (abdominal surgery versus nonabdominal surgery), and PEEP gradient (≤5 vs >5 cm H2O).

Trial Sequential Analysis

When a meta-analysis includes a small number of studies or the sample size is not large enough, random error resulting from sparse data and repetitive testing of accumulating data increases the risk of type I error.24,25 The resulting evidence is insufficient for clinical decision making. In a single RCT, interim analyses increase the risk of type I error. To avoid this possibility, monitoring boundaries can be identified to decide whether a single RCT could be terminated early. Similarly, trial sequential monitoring boundaries (TSMBs) can be applied to meta-analysis; this method for meta-analysis corrects for the increased risk of type I errors, is called “TSA,” and can determine whether the evidence in the meta-analysis is reliable and conclusive. We performed TSA for our dichotomous outcomes. We calculated the required sample size (ie, information size [IS]) required to be able to determine whether the evidence in our meta-analysis is reliable and conclusive based on the observed data and the TSMBs (using an α-spending function).26 When the overall sample size in the study reaches the required IS (RIS), or the cumulative Z-value curve passes through the sequential monitoring boundary of the test or enters the invalid region, the statistical test results of meta-analysis are likely to be stable and no further testing is needed. If the Z-value curve does not cross any boundaries and has not yet reached the required sample size, there is insufficient evidence to reach a conclusion. For dichotomous outcomes, we have set effect measure “RR” and model as “Random-effects (DerSimonian-Laird [DL])” in TSA software (Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark; http://www.ctu.dk/tsa). D2 (diversity) was defined as heterogeneity correction.

The diversity-adjusted IS and O’Brien-Fleming α-spending boundaries were calculated using 2-sided 5% type I error and 20% type 2 error rate (80% power), and the control event proportions calculated from the average incidence in all included studies or low risk of bias studies, and an RR reduction of 20% in dichotomous outcomes, and we estimated RIS based on D2 as 50%. We used software TSA version 0.9 beta for these analyses.27

RESULTS

Study Selection and Characteristics

A detailed illustration of the study selection process and results is shown in Figure 1. Our initial search identified 1340 studies (110 from PubMed, 432 from Embase, and 798 from Cochrane library). After removing 379 duplicate studies, we evaluated the abstracts of 961 studies. Through screening the titles and abstracts, we excluded 922 studies because they did not meet the inclusion criteria. Subsequently, we read the full text of each potentially eligible study for inclusion and excluded 26 articles. Finally, 14 RCTs13,28–40 including a total of 1238 patients were included in the meta-analysis.

F1
Figure 1.:
Literature search and screening process. RCT indicates randomized controlled trial.
Table. - Characteristics of the Included Trials and Participants
Study No. Patients Setting PEEP Group ZEEP Group Outcomes Primary Outcomes
VT, mL/kg PEEP, cm H2O RMS VT, mL/kg PEEP, cm H2O RMS Atelectasis Atelectasis Score Pneumonia Respiratory Insufficiency Respiratory Failure Cardiac Complications Mortality
Azab et al28 30 Laparoscopic cholecystectomies NS 5 No NS 0 No No Yes No No No No No Postoperative atelectasis
Choi et al29 40 Surgical procedure of ≥5 h 6 10 No 12 0 No No No Yes No No No Yes Alveolar hemostatic balance
Pang et al30 24 Laparoscopic cholecystectomies 10 5 Yes 10 0 No No No No No No Yes No Arterial oxygenation
Talab et al32 66 Bariatric surgery 8–10 5, 10 No 8–10 0 No Yes Yes No No No No No Pulmonary atelectasis
Tusman et al33 30 Not specified 7–9 5, 15 No 7–9 0 No No No No No No No Yes Arterial oxygenation
Wetterslev et al35 38 Upper abdominal surgery 8–10 5, 8, 10 No 8–10 0 No No No Yes Yes Yes Yes Yes Arterial oxygenation
Severgnini et al31 55 Open abdominal surgery 7 10 Yes 9 0 Yes No No No No No No No Modified clinical pulmonary infection score
Weingarten et al34 40 Open abdominal surgery 6 12 Yes 10 0 No No No No No No No Yes Intraoperative Pao 2/Fio 2 ratio
Futier et al13 400 Abdominal surgery 6–8 6–8 Yes 10–12 0 No Yes No Yes Yes No No Yes Major pulmonary and extrapulmonary complications
Park et al38 40 Laparoscopic hepatobiliary surgery 6 5 No 10 0 Yes Yes No Yes Yes No No No Postoperative pulmonary complications
Edmark et al37 30 Eye surgery or day-case orthopedic surgery 6 6 No 6 0 Yes No No No No No No No Postoperative atelectasis
Marret et al36 343 Thoracic surgery 5 5–8 No 10 0 No Yes No Yes No Yes Yes Yes Major pulmonary and nonpulmonary complications or death
Soh et al39 78 Spinal surgery 6 6 Yes 10 0 No Yes No Yes No No No No Postoperative FVC and FEV1 values on POD 3
Östberg et al40 24 Nonabdominal surgery 7 7–9 No 7 0 Yes No No No No No No No Atelectasis area
Abbreviations: FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; NS, not specified; PEEP, positive end-expiratory pressure; POD 3, postoperative day 3; RMS, Recruitment maneuver Strategy; VT, Tidal volume; ZEEP, zero positive end-expiratory pressure.

The Table reports the main characteristics of the included RCTs. Demographic characteristics of the patients and ventilatory settings are summarized in Supplemental Digital Content, Table 1, https://links.lww.com/AA/C930. The 14 studies were published between 1999 and 2018. Population sizes for individual studies ranged from 24 to 400, and the total population was 1238 patients, with 643 in the PEEP group and 595 in the control group. Two studies used a multicenter design.13,36 Nine studies included patients with abdominal surgery,13,28–32,34,35,38 1 included patients with lung cancer surgery,36 1 included patients with eye or day-case orthopedic surgery,37 1 included patients with surgery unspecified,33 1 spinal surgery,38 and 1 nonabdominal surgery.39

Risk of Bias and Grade of Evidence

Figure 2 shows the risk of bias for each study. Six trials were judged as low risk of bias,13,35,36,38–40 and the remaining 8 were judged as overall high risk of bias. An adequate randomized sequence was generated in 7 trials,13,31,35,36,38–40 and 8 trials13,31,35–40 reported appropriate allocation concealment.

F2
Figure 2.:
Assessment for risk of bias. + = low risk, – = high risk, and ? = uncertain risk.

We found that GRADE Working Group grades of evidence for outcomes were moderate for postoperative atelectasis, moderate for postoperative pneumonia, and low for overall postoperative mortality (Supplemental Digital Content, Table 2, https://links.lww.com/AA/C930).

Primary Outcomes

Atelectasis.

F3
Figure 3.:
Effect of PEEP on preventing atelectasis. A, Forest plot of meta-analysis of the effects of PEEP versus ZEEP on atelectasis. B, Trial sequential analysis of 2 trials comparing PEEP with ZEEP for atelectasis: α = .05 (2-sided) and β = .20 (power, 80%), an anticipated relative risk reduction of 20%, and an event proportion of 17% in the control arm. CI indicates confidence interval; df, degrees of freedom; M-H, Mantel–Haenszel; PEEP, positive end-expiratory pressure; ZEEP, zero positive end-expiratory pressure.

Nine trials13,28,31,32,36–40 reported atelectasis as the postoperative outcome; 2 trials28,31 measured this outcome using computerized tomography (CT) scan or chest radiography and reported atelectasis score as the outcome; and 2 studies37,40 reported the area of atelectasis as the outcome. These studies did not contribute to the pooled analysis. Five trials13,32,36,38,39 reported atelectasis morbidity as the outcome. Using PEEP during mechanical ventilation significantly reduced atelectasis morbidity in the random-effects model (RR, 0.51; 95% CI, 0.35–0.76), with heterogeneity (I2 = 27%). TSA results showed that a diversity-adjusted RIS of 7040 patients was calculated and the TSA-adjusted CI was 0.10–2.55 with a cumulative Z-value curve that crossed the traditional boundary but not the TSMB, indicating that false-positive results may have been obtained. Therefore, further trials are required to verify these results and new findings may change the existing conclusions (Figure 3).

Secondary Outcomes

We found that intraoperative PEEP may decrease the risk of postoperative pneumonia13,29,35,36,38,39 (RR, 0.48; 95% CI, 0.27–0.84). However, TSA results suggested that the number of randomly assigned patients was much smaller than our calculated optimal IS (16,390 patients) and TSA-adjusted CI was 0.05–4.86 with the sequential monitoring boundary not crossed, indicating that the cumulative evidence is unreliable and inconclusive (Figure 4). No significant differences were observed between the 2 groups in mortality13,29,33–36 (RR, 1.78; 95% CI, 0.55–5.70). Due to inadequate data, we did not use TSA for mortality (Figure 5).

F4
Figure 4.:
Effect of PEEP on preventing pneumonia. A, Forest plot of meta-analysis of the effects of PEEP versus ZEEP on pneumonia. B, Trial sequential analysis of 2 trials comparing PEEP with ZEEP for pneumonia: α = .05 (2-sided) and β = .20 (power, 80%), an anticipated relative risk reduction of 20%, and an event proportion of 8% in the control arm. CI indicates confidence interval; df, degrees of freedom; IV, intravenous; PEEP, positive end-expiratory pressure; SD, standard deviation; ZEEP, zero positive end-expiratory pressure.
F5
Figure 5.:
Forest plot of meta-analysis of the effects of PEEP versus ZEEP on mortality. CI indicates confidence interval; df, degrees of freedom; M-H, Mantel–Haenszel; PEEP, positive end-expiratory pressure; ZEEP, zero positive end-expiratory pressure.

Two studies reported postoperative respiratory failure35,36 as an outcome. The event rate was 0/21 vs 3/19 in PEEP versus ZEEP group in Wetterslev et al35 and 11/172 vs 19/171 in PEEP versus ZEEP group in Marret et al.36 Three studies reported cardiac complications33,35,36 (the event rate was zero in both groups in Tusman et al33 and 0/21 vs 1/19 in PEEP versus ZEEP group in Wetterslev et al35 and 1/172 vs 1/171 in PEEP versus ZEEP group in Marret et al36). Three studies reported respiratory insufficiency.13,35,38 The event rate was zero in both groups in Park et al38 and 11/200 (PEEP) versus 36/200 (ZEEP) in Futier et al13 and 0/21 (PEEP) versus 3/19 (ZEEP) in Wetterslev et al.35 Two studies reported an atelectasis score,28 32 (0.8 ± 0.77 [15 participants, PEEP] versus 3 ± 0.93 [15 participants, ZEEP] in Azab et al,28 and 2.85 ± 0.96 [44 participants, PEEP] versus 3.65 ± 0.75 [22 participants, ZEEP] in Talab et al32; mean ± standard deviation [SD]). Due to the small sample size and low event frequency in those studies, the results are considered fragile and, therefore, we did not conduct a pooled analysis.

Subgroup Analyses

Supplemental Digital Content, Table 3, https://links.lww.com/AA/C930, summarizes findings for the effect of PEEP versus ZEEP on dichotomous outcomes of atelectasis, pneumonia and mortality stratified by risk of bias, surgical setting, and PEEP gradient. The effect of PEEP versus ZEEP on postoperative pulmonary complications did not vary as a function of intraoperative PEEP gradient (>5 vs ≤5 cm H2O), interaction P = .79 for atelectasis and P = .80 for pneumonia. The PEEP effect varied by surgical setting for pneumonia (P = .04), but not for other outcomes. There were no significant interactions between the effect of PEEP and risk of bias.

Publication Bias

We assessed publication bias. But because the incidence of events in the present study was relatively low, the main final conclusion was based on the data from 4 studies. This low power of inclusion may limit the interpretability of the findings.

DISCUSSION

Main Findings

This is a systematic review and meta-analysis of 14 RCTs to evaluate the benefits and risks of intraoperative PEEP for postoperative pulmonary complications in all adult patients undergoing surgery. Our traditional meta-analysis showed that intraoperative PEEP can reduce the morbidity of postoperative atelectasis and pneumonia, but the more robust powerful TSA analysis suggests that we may have obtained false-positive results and more studies are needed to answer the research question. In addition, we observed no effects of PEEP versus ZEEP ventilation on postoperative mortality.

Strengths and Concerns/Limitations

Strengths of our study include the explicit eligibility criteria, a comprehensive search built on a prior review, reproducible duplicate assessment of eligibility, and risk of bias. We rated the certainty (or confidence) of evidence using the GRADE approach, highlighting the moderate certainty evidence for the impact of PEEP versus ZEEP on atelectasis and pneumonia, and the low certainty for mortality. Meanwhile, we also followed PRISMA statement and the recommendations of the Cochrane Collaboration, although we had no registered protocol. Finally, we further applied TSA to evaluate the overall risk of random error to increase the reliability of the meta-analyses results.

This study also has some limitations. First, the frequency of event rates in this systematic review was smaller than the optimal IS required. Our TSA analysis also got the same conclusion that a false-positive result may have been obtained. Second, the intervention group in some trials received low VT and PEEP, while the control group received high VT and ZEEP; therefore, it was difficult to know whether the lung-protection effect was from the low VT, PEEP, or both. Although many studies suggested low VT could reduce the incidence of lung injury (ventilator associated lung injury [VALI]),41 a study of thoracic surgery12 maintained that low VT was unable to prevent postoperative respiratory complications without adequate PEEP. Similarly, a meta-analysis42,43 also believed that the use of intraoperative low tidal volume (LTV) ventilation in patients with general anesthesia could not completely reduce the incidence of postoperative pulmonary complications.

Third, the analysis results of protective ventilation are confounded by nonuniform application of recruitment maneuvers strategy, the use of which has a growing evidence base to support. Maneuvers consist of stepwise increase in VT to plateau pressures of 30 cm H2O, applying a continuous positive airway pressure of 30 cm H2O for 30 seconds or using sustained inspiratory pressure of 40 cm H2O for 30 seconds applied. This strategy is theorized to reduce incidence of atelectasis. A systematic review42,43 confirmed reduction of postoperative pulmonary complications and improve patient outcomes with use of alveolar recruitment maneuvers, but further studies are warranted in this area.

Fourth, a large registry-based analysis44 reported a dose–response association between intraoperative inspiratory oxygen fraction (Fio2) and incidence of pulmonary complications and with 30-day mortality. But, a recent studies believed that intraoperative hyperoxia did not change the risk for postoperative pulmonary complications.45,46 Similarly, a meta-analysis by Hovaguimian et al47 also reported no difference in the incidence of postoperative atelectasis and partial arterial oxygen pressure to Fio2 (Pao2/Fio2) ratio in patients receiving high or normal intraoperative Fio2. Although many studies included in our study did not specified Fio2, we also believe that there is no significant correlation between Fio2 and postoperative pulmonary complications.

Fifth, plateau pressures are one of the causes of lung injury; acute respiratory distress syndrome clinical trials network (ARDSnet) study48 shows that control platform pressure <30 cm H2O may be related to reduced mortality. Certainly, compared with regional anesthesia, general anesthesia with endotracheal intubation is the main mechanism of ventilator-associated pneumonia caused by bacteria into the lower respiratory tract and increased mortality and morbidity.49 A duration of surgery and anesthesia were also risk factors for postoperative pulmonary complications, and 2 studies50,51 confirmed that a duration of surgical procedures >2 hours is independently associated with postoperative pulmonary complications (PPC) development. Importantly, the risk of postoperative pulmonary complications varies with different surgical procedures.4,52 Among the 14 trials, the inspiratory/expiratory ratio and primary outcome differed. However, due to the above limitations in the included studies, this makes analysis of pooled data challenging. Therefore, we would attempt to further stratify our own data to establish the isolated effects of PEEP and different ventilatory settings or different surgery settings. Unfortunately, such analyses in this case would be far from make conclusions. Finally, limited data on the predefined secondary outcomes made it impossible to perform meta-analyses on all outcomes of interest for this review, and the subgroup analyses planned were not possible.

Relation to Previous Work

To the best of our knowledge, most previous meta-analyses mainly focused on the effect of low VT ventilation on postoperative outcomes. Only 2 previous Cochrane reviews compared PEEP and ZEEP for mechanical ventilation in patients undergoing surgery. But a recent study by Barbosa et al17 included 10 RCTs14,28–35 for analysis, involving a total of 432 participants. They found that the use of PEEP during anesthesia decreased postoperative atelectasis morbidity, but because the sample size is small, the incidence of events is relatively low. Finally, no conclusion was reached. In this meta-analysis, we included 2 low-biased, high-quality, multicenter studies13,36 with the primary outcome to analyze the risk of postoperative atelectasis. It was found that the use of PEEP during anesthesia may decrease postoperative atelectasis and pneumonia morbidity compared with ZEEP, but because the number of included cases was relatively small, the low incidence of events made the results seem unreliable.

PEEP has been widely used during mechanical ventilation for years, especially in patients with ARDS in the intensive care setting.6,7 The results of previous RCTs and observational studies are similar to the findings of our meta-analysis. Two large multicenter prospective studies also found that perioperative use of PEEP was associated with beneficial clinical outcomes. An earlier study53 reported that individualized PEEP could not only optimize intraoperative mechanical ventilation and reduce postoperative atelectasis, but also improve intraoperative oxygenation and driving pressure and minimize the adverse effects. We used TSA to calculate a diversity-adjusted RIS for meta-analysis. TSA suggested that evidence of the effect from current meta-analyses was insufficient and potentially spurious. Importantly, TSA analysis showed that Z-line did not increase steadily with the increase of research. This indicates that the application of PEEP may not be effective in preventing postoperative pulmonary complications. Thus, more research is needed to get more reliable and convincing results.

Future Perspectives

Further studies should focus on the following points: first, the collapse and reexpansion of the alveoli (to some extent, there is potential for lung injury) should be monitored in some proinflammatory and anti-inflammatory factors in the blood. In addition, the protective lung ventilation strategy is composed of low VT, PEEP, and pulmonary recruitment. PEEP is only a part of it; we need to further study their interactions. Finally, there may be differences in LPV strategies among different populations, and the setting of PEEP needs to be individualized.

CONCLUSIONS

In anesthetized adults undergoing surgery, intraoperative PEEP may decrease the risk of postoperative atelectasis and pneumonia and mortality, but our use of methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the current evidence for postoperative pulmonary complications is insufficient and inconclusive. More studies are needed to provide data better applicable to clinical practice.

ACKNOWLEDGMENTS

The authors wish to express their sincere gratitude to all the researchers of the research team, for supplying their valuable knowledge about the systematic review and meta-analyses methods.

DISCLOSURES

Name: Pengcheng Zhang, MD.

Contribution: This author helped design and conduct the study; collect, analyze, and interpret the data; write and revise the manuscript; and approve the final manuscript.

Name: Lingmin Wu, MD.

Contribution: This author helped collect the data, write and revise the manuscript, and approve the final manuscript.

Name: Xuan Shi, MD.

Contribution: This author helped collect the data, write and revise the manuscript, and approve the final manuscript.

Name: Huanping Zhou, MD, PhD.

Contribution: This author helped collect the data, write and revise the manuscript, and approve the final manuscript.

Name: Meiyun Liu, MD.

Contribution: This author helped analyze and interpret the data, write and revise the manuscript, and approve the final manuscript.

Name: Yuanli Chen, MD, PhD.

Contribution: This author helped analyze and interpret the data, write and revise the manuscript, and approve the final manuscript.

Name: Xin Lv, MD, PhD.

Contribution: This author helped design and conduct the study; collect, analyze, and interpret the data; write and revise the manuscript; and approve the final manuscript.

This manuscript was handled by: Avery Tung, MD, FCCM.

FOOTNOTES

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