Individual and combined effects of chemical and mechanical power on postoperative pulmonary complications: a secondary analysis of the REPEAT study

Introduction: Intra-operative supplemental oxygen and mechanical ventilation expose the lungs to potentially injurious energy. This can be quantified as 'chemical power' and 'mechanical power', respectively. In this study, we sought to determine if intra-operative chemical and mechanical power, individually and/or in combination, are associated with postoperative pulmonary complications. Methods: Using an individual patient data analysis of three randomised clinical trials of intra-operative ventilation, we summarised intra-operative chemical and mechanical power using time-weighted averages. We evaluated the association between intra-operative chemical and mechanical power and a collapsed composite of postoperative pulmonary complications using multivariable logistic regression to estimate the odds ratios related to the effect of 1 J.min-1 increase in chemical or mechanical power with adjustment for demographic and intra-operative characteristics. We also included an interaction term to assess for potential synergistic effects of chemical and mechanical power on postoperative pulmonary complications. Results: Of 3837 patients recruited to three individual trials, 2492 with full datasets were included in the analysis. Intra-operative time-weighted average (SD) chemical power was 10.2 (3.9) J.min-1 and mechanical power was 10.5 (4.4) J.min-1. An increase of 1 J.min-1 in chemical power was associated with 8% higher odds of postoperative pulmonary complications (OR 1.08, 95%CI 1.05-1.10, p < 0.001), while the same increase in mechanical power raised odds by 5% (OR 1.05, 95%CI 1.02-1.08, p = 0.003). We did not find evidence of a significant interaction between chemical and mechanical power (p = 0.40), suggestive of an additive rather than synergistic effect on postoperative pulmonary complications. Discussion: Both chemical and mechanical power are independently associated with postoperative pulmonary complications. Further work is required to determine causality

High Positive End-expiratory Pressure (PEEP) with Recruitment Maneuvers versus Low PEEP during General Anesthesia for Surgery: A Bayesian Individual Patient Data Meta-analysis of Three Randomized Clinical Trials

Background: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. Our objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. Methods: Multilevel Bayesian logistic regression analysis on individual patient data from three randomized clinical trials carried out on surgical patients at Intermediate-to-High Risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. We studied the effect of high PEEP with recruitment maneuvers versus Low PEEP Ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect. Results: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio (OR) for High PEEP with recruitment maneuvers compared to Low PEEP was 0.85 (95% Credible Interval [CrI] 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (OR: 0.67 [0.50 to 0.87]) and those at high risk for PPCs (OR: 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results. Conclusion: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of PPC occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial (vol 321, pg 2292, 2019)

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Effect of intraoperative high Positive End-Expiratory Pressure (PEEP) with recruitment maneuvers vs low PEEP on postoperative pulmonary complications in obese patients : a randomized clinical trial

IMPORTANCE An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. OBJECTIVE To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. INTERVENTIONS Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. MAIN OUTCOMES AND MEASURES The primary outcomewas a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with SpO(2) 1 minute). RESULTS Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3%[95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P =.23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6%[95% CI, -11.1% to 6.1%]; P <.001). CONCLUSIONS AND RELEVANCE Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial.

IMPORTANCE An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain

Association of intraoperative end-tidal CO2 levels with postoperative outcomes: a patient-level analysis of two randomised clinical trials

Background: The relationship between intraoperative end-tidal CO2 (etCO2) levels and postoperative outcomes remains unclear. We conducted a post hoc analysis of two randomised trials in adults undergoing major surgery under general anaesthesia. Methods: We re-analysed individual participant data comparing high or low positive end-expiratory pressure with low tidal volume intraoperative ventilation using a merged database derived from two randomised trials in non-obese (PROVHILO: ISRCTN70332574) and obese (PROBESE: NCT02148692) patients. The exposure of interest was low etCO2 (<4.7 kPa) vs normal-high etCO2 (≥4.7 kPa). The primary outcome was postoperative pulmonary complications within 5 days. A time-weighted etCO2 analysis and propensity score matching were also performed to adjust for confounding. Results: Of 2793 participants, 891 (29.4%; 52% female) had low etCO2, compared with 1972/2793 (70.6%; 65% female) participants with normal-high etCO2. Compared with participants with normal-high etCO2, higher minute volumes (normalised to body weight) were delivered in participants with low etCO2. Postoperative pulmonary complications developed in 278/821 (34%) participants with low etCO2, compared with 462/1972 (23%) participants who had normal-high etCO2 (adjusted hazard ratio, 1.3; 95% confidence interval, 1.1–1.6; P<0.001). The time-weighted analysis showed an inverse linear relationship between the mean etCO2 and postoperative pulmonary complications, which was also confirmed by propensity matching. Conclusions: Low etCO2 occurs often during intraoperative ventilation and is associated with a higher rate of PPCs. The etCO2 level has an inverse dose-dependent relationship with postoperative pulmonary complications. Clinical trial registration: NCT05550181

High PEEP with recruitment maneuvers versus Low PEEP During General Anesthesia for Surgery -a Bayesian individual patient data meta-analysis of three randomized clinical trials

Background: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. Our objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. Methods: Multilevel Bayesian logistic regression analysis on individual patient data from three randomized clinical trials carried out on surgical patients at Intermediate-to-High Risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. We studied the effect of high PEEP with recruitment maneuvers versus Low PEEP Ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect. Results: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio (OR) for High PEEP with recruitment maneuvers compared to Low PEEP was 0.85 (95% Credible Interval [CrI] 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (OR: 0.67 [0.50 to 0.87]) and those at high risk for PPCs (OR: 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results. Conclusion: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of PPC occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy