Low Positive End-expiratory Pressure Research Articles

Driving pressure during general anesthesia for minimally invasive abdominal surgery (GENERATOR)—study protocol of a randomized clinical trial

BackgroundIntraoperative driving pressure (ΔP) has an independent association with the development of postoperative pulmonary complications (PPCs) in patients receiving ventilation during general anesthesia for major surgery. Ventilation with high intraoperative positive end–expiratory pressure (PEEP) with recruitment maneuvers (RMs) that result in a low ΔP has the potential to prevent PPCs. This trial tests the hypothesis that compared to standard low PEEP without RMs, an individualized high PEEP strategy, titrated to the lowest ΔP, with RMs prevents PPCs in patients receiving intraoperative protective ventilation during anesthesia for minimally invasive abdominal surgery.Methods“DrivinG prEssure duriNg gEneRal AnesThesia fOr minimally invasive abdominal suRgery (GENERATOR)” is an international, multicenter, two–group, patient and outcome–assessor blinded randomized clinical trial. In total, 1806 adult patients scheduled for minimally invasive abdominal surgery and with an increased risk of PPCs based on (i) the ARISCAT risk score for PPCs (≥ 26 points) and/or (ii) a combination of age > 40 years and scheduled surgery lasting > 2 h and planned to receive an intra–arterial catheter for blood pressure monitoring during the surgery will be included. Patients are assigned to either an intraoperative ventilation strategy with individualized high PEEP, titrated to the lowest ΔP, with RMs or one with a standard low PEEP of 5 cm H2O without RMs. The primary outcome is a collapsed composite endpoint of PPCs until postoperative day 5.DiscussionGENERATOR will be the first adequately powered randomized clinical trial to compare the effects of individualized high PEEP with RMs versus standard low PEEP without RMs on the occurrence of PPCs after minimally invasive abdominal surgery. The results of the GENERATOR trial will support anesthesiologists in their decisions regarding PEEP settings during minimally invasive abdominal surgery.Trial registrationGENERATOR is registered at ClinicalTrials.gov (study identifier: NCT06101511) on 26 October 2023.

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.

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. 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. 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. 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.

Heterogeneous impact of Sighs on mortality in patients with acute hypoxemic respiratory failure: insights from the PROTECTION study.

Sigh breaths may impact outcomes in acute hypoxemic respiratory failure (AHRF) during assisted mechanical ventilation. We investigated whether sigh breaths may impact mortality in predefined subgroups of patients enrolled in the PROTECTION multicenter clinical trial according to: 1.the physiological response in oxygenation to Sigh (responders versus non-responders) and 2.the set levels of positive end-expiratory pressure (PEEP) (High vs. Low-PEEP). If mortality differed between Sigh and No Sigh, we explored physiological daily differences at 7-days. Patients were randomized to pressure support ventilation (PSV) with Sigh (Sigh group) versus PSV with no sigh (No Sigh group). (1) Sighs were not associated with differences in 28-day mortality in responders to baseline sigh-test. Contrarily-in non-responders-56 patients were randomized to Sigh (55%) and 28-day mortality was lower with sighs (17%vs.36%, log-rank p = 0.031). (2) In patients with PEEP > 8cmH2O no difference in mortality was observed with sighs. With Low-PEEP, 54 patients were randomized to Sigh (48%). Mortality at 28-day was reduced in patients randomised to sighs (13%vs.31%, log-rank p = 0.021). These findings were robust to multivariable adjustments. Tidal volume, respiratory rate and ventilatory ratio decreased with Sigh as compared with No Sigh at 7-days. Ventilatory ratio was associated with mortality and successful extubation in both non-responders and Low-PEEP. Addition of Sigh to PSV could reduce mortality in AHRF non-responder to Sigh and exposed to Low-PEEP. Results in non-responders were not expected. Findings in the low PEEP group may indicate that insufficient PEEP was used or that Low PEEP may be used with Sigh. Sigh may reduce mortality by decreasing physiologic dead space and ventilation intensity and/or optimizing ventilation/perfusion mismatch. ClinicalTrials.gov; Identifier: NCT03201263.

Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI).

Rationale: Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. Objectives: To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. Methods: In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency, and acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. Measurements and Main Results: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.79; P = 0.025). Mortality was 28.9% and 15.1% (RR, 1.91; 95% CI, 1.06-3.42; P = 0.02), ventilator dependency was 42.3% and 27.9% (RR, 1.52; 95% CI, 1.01-2.28; P = 0.039), and incidence of ARDS was 30.8% and 22.1% (RR, 1.39; 95% CI, 0.85-2.27; P = 0.179), respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. Conclusions: In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with www.clinicaltrials.gov (NCT01690819).

Effect of perioperative sigh ventilation on postoperative hypoxemia and pulmonary complications after on-pump cardiac surgery (E-SIGHT): study protocol for a randomized controlled trial

BackgroundPostoperative hypoxemia and pulmonary complications remain a frequent event after on-pump cardiac surgery and mostly characterized by pulmonary atelectasis. Surfactant dysfunction or hyposecretion happens prior to atelectasis formation, and sigh represents the strongest stimulus for surfactant secretion. The role of sigh breaths added to conventional lung protective ventilation in reducing postoperative hypoxemia and pulmonary complications among cardiac surgery is unknown.MethodsThe perioperative sigh ventilation in cardiac surgery (E-SIGHT) trial is a single-center, two-arm, randomized controlled trial. In total, 192 patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) and aortic cross-clamp will be randomized into one of the two treatment arms. In the experimental group, besides conventional lung protective ventilation, sigh volumes producing plateau pressures of 35 cmH2O (or 40 cmH2O for patients with body mass index > 35 kg/m2) delivered once every 6 min from intubation to extubation. In the control group, conventional lung protective ventilation without preplanned recruitment maneuvers is used. Lung protective ventilation (LPV) consists of low tidal volumes (6–8 mL/kg of predicted body weight) and positive end-expiratory pressure (PEEP) setting according to low PEEP/FiO2 table for acute respiratory distress syndrome (ARDS). The primary endpoint is time-weighted average SpO2/FiO2 ratio during the initial post-extubation hour. Main secondary endpoint is the severity of postoperative pulmonary complications (PPCs) computed by postoperative day 7.DiscussionThe E-SIGHT trial will be the first randomized controlled trial to evaluate the impact of perioperative sigh ventilation on the postoperative outcomes after on-pump cardiac surgery. The trial will introduce and assess a novel perioperative ventilation approach to mitigate the risk of postoperative hypoxemia and PPCs in patients undergoing cardiac surgery. Also provide the basis for a future larger trial aiming at verifying the impact of sigh ventilation on postoperative pulmonary complications.Trial registrationClinicalTrials.gov NCT06248320. Registered on January 30, 2024. Last updated February 26, 2024.

Positive end-expiratory pressure and postoperative pulmonary complications in laparoscopic bariatric surgery: systematic review and meta-analysis

BackgroundThis study compares the effect of positive end-expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in patients with obesity undergoing laparoscopic bariatric surgery (LBS) under general anesthesia with mechanical ventilation.MethodsA comprehensive search was conducted in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Internet, Wanfang database, and Google Scholar for studies published up to July 29, 2023, without time or language restrictions. The search terms included “PEEP,” “laparoscopic,” and “bariatric surgery.” Randomized controlled trials comparing different levels of PEEP or PEEP with zero-PEEP (ZEEP) in patients with obesity undergoing LBS were included. The primary outcome was a composite of PPCs, and the secondary outcomes were intraoperative oxygenation, respiratory compliance, and mean arterial pressure (MAP). A fixed-effect or random-effect model was selected for meta-analysis based on the heterogeneity of the included studies.ResultsThirteen randomized controlled trials with a total of 708 participants were included for analysis. No statistically significant difference in PPCs was found between the PEEP and ZEEP groups (risk ratio = 0.27, 95% CI: 0.05–1.60; p = 0.15). However, high PEEP ≥ 10 cm H2O significantly decreased PPCs compared with low PEEP < 10 cm H2O (risk ratio = 0.20, 95% CI: 0.05–0.89; p = 0.03). The included studies showed no significant heterogeneity (I2 = 20% & 0%). Compared with ZEEP, PEEP significantly increased intraoperative oxygenation and respiratory compliance (WMD = 74.97 mm Hg, 95% CI: 41.74-108.21; p < 0.001 & WMD = 9.40 ml cm H2O− 1, 95% CI: 0.65–18.16; p = 0.04). High PEEP significantly improved intraoperative oxygenation and respiratory compliance during pneumoperitoneum compared with low PEEP (WMD = 66.81 mm Hg, 95% CI: 25.85-107.78; p = 0.001 & WMD = 8.03 ml cm H2O− 1, 95% CI: 4.70-11.36; p < 0.001). Importantly, PEEP did not impair hemodynamic status in LBS.ConclusionsIn patients with obesity undergoing LBS, high PEEP ≥ 10 cm H2O could decrease PPCs compared with low PEEP < 10 cm H2O, while there was a similar incidence of PPCs between PEEP (8–10 cm H2O) and the ZEEP group. The application of PEEP in ventilation strategies increased intraoperative oxygenation and respiratory compliance without affecting intraoperative MAP. A PEEP of at least 10 cm H2O is recommended to reduce PPCs in patients with obesity undergoing LBS.Registration numberCRD42023391178 in PROSPERO.

Optimizing Positive End-Expiratory Pressure Based on Intra-Abdominal Pressure in Patients with Acute Respiratory Failure.

Positive end-expiratory pressure (PEEP) is a crucial component of mechanical ventilation to improve oxygenation in critically ill patients with respiratory failure. The interaction between abdominal and thoracic compartment pressures is known well. Especially in intra-abdominal hypertension, lower PEEP may cause atelectotrauma by repetitive opening and closing of alveoli. In this study, it was aimed to investigate the effect of PEEP adjustment according to the intra-abdominal pressure (IAP) on oxygenation and clarify possible harms. Patients older than 18 were mechanically ventilated due to hypoxemic respiratory failure and had normal IAP (<15 mmHg) included in the study. Patients with severe cardiovascular dysfunction were excluded. The following PEEP levels were applied: PEEPzero of 0 cmH2O, PEEPIAP/2 = 50% of IAP, and PEEPIAP = 100% of IAP. After a 30-minute equilibration period, arterial blood gases and mean arterial pressures were measured. One hundred thirty-eight patients (mean age 66.5 ± 15.9, 56.5% male) enrolled on the study. The mean IAP was 9.8 ± 3.4. Seventy-nine percent of the patients' PaO2/FiO2 ratio was under 300 mmHg. Figure 1 shows the change in PaO2/FiO2 ratio, PaCO2, PPlato, and MAP of the patients according to the PEEP levels. Overall increases were detected in the PaO2/FiO2 ratio (P < 0.001) and Pplato (P < 0.001), while PaCO2 and MAP did not change after increasing PEEP gradually. Pairwise analyses revealed differences in PaO2/FiO2 between PEEPzero (186.4 [85.7-265.8]) and PEEPIAP/2 (207.7 [101.7-292.9]) (t = -0.77, P < 0.001), between baseline and PEEPIAP (236.1 [121.4-351.0]) (t = -1.7, P < 0.001), and between PEEPIAP/2 and PEEPIAP (t = -1.0, P < 0.001). Plato pressures were in the safe range (<30 cmH2O) at all three PEEP levels (PEEPzero = 12 [10-15], PEEPIAP/2 = 15 [13-18], PEEPIAP = 17 [14-22]). In patients with acute hypoxemic respiratory failure and mechanically ventilated, PEEP adjustment according to the IAB improves oxygenation, especially in the settings of the limited source where other PEEP titration methods are absent.

The impact of positive end-expiratory pressure on right ventricular function in patients with moderate-to-severe ARDS: a prospective paired-design study.

To determine the effects of varying positive end-expiratory pressures (PEEPs) on right ventricular function, hemodynamics, oxygenation, and the incidence of acute cor pulmonale (ACP) in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). This prospective paired-design study involved patients with moderate-to-severe ARDS in the ICU. Participants received lung-protective ventilation and hemodynamic monitoring. During the study, mechanical ventilation was administered with PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, while maintaining an end-inspiratory plateau pressure ≤ 30 cmH2O. Various assessments, including transthoracic echocardiography, cardiac output measurement, and blood gas analysis, were conducted at baseline and after 1 h of ventilation at each PEEP. Subsequently, variations in ventilation oxygenation, echocardiographic parameters, and hemodynamic indicators under different PEEPs were analyzed to explore the potential effects of PEEP on right ventricular function and hemodynamics, as well as the incidence of ACP. A total of 317 ARDS patients were screened. Among them, 104 met the diagnostic criteria for moderate-to-severe ARDS, and 52 completed the study. The baseline PEEP of these 52 participants, acquired before commencement, was 11.5 ± 1.7 cmH2O, and the incidence of ACP was 25.0% (13/52). Intensive care unit mortality, overall hospital mortality, and 28-day mortality rates were 19.2% (10/52), 21.2% (11/52), and 32.7% (17/52), respectively. During the study, ACP incidences at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O were 17.3% (9/52), 21.2% (11/52), and 38.5% (20/52), respectively. Meanwhile, the PaO2/FiO2 ratio improved with increasing PEEP, reaching 162.0 (140.9, 174.0), 171.0 (144.0, 182.0), and 176.5 (151.0, 196) mmHg at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, respectively. In addition, higher PEEPs were associated with a slight increase in PaCO2, showing statistically significant differences compared to moderate and low PEEPs. Compared to a PEEP of 5 cmH2O or 10 cmH2O, right ventricular function exhibited substantial changes at 15 cmH2O PEEP, manifested as increased pulmonary artery systolic pressure, enlarged right ventricular end-diastolic area, and decreased tricuspid annular plane systolic excursion, all with significant differences. Conversely, variations in left ventricular end-diastolic area and ejection fraction were not statistically significant. In terms of hemodynamics, increasing PEEP resulted in a decline in cardiac index (CI), with statistically significant differences between different PEEPs. Specifically, compared to the value at a PEEP of 5 cmH2O, the CI at a PEEP of 15 cmH2O decreased by 14.3% (2.63 [2.20, 2.95] vs. 3.07 [2.69, 3.67], p < 0.001). The decline in the stroke volume index with PEEP was more obvious (22.1 [18.4, 27.1] vs. 27.0 [24.2, 33.0], p < 0.001), reaching 18.1%. Additionally, both end-diastolic volume index and extravascular lung water index decreased significantly with increasing PEEP, while the pulmonary vascular permeability index remained unaffected. Different PEEPs can affect the incidence of ACP in patients with moderate-to-severe ARDS. High PEEP improves oxygenation and reduces extravascular lung water without significantly affecting the pulmonary vascular permeability index and left ventricular systolic function. Nevertheless, it can cause right ventricular dilation, as well as substantial declines in right ventricular systolic function and CI, thereby causing ACP.

The Effect of Positive End-Expiratory Pressure on Pulmonary Vascular Resistance Depends on Lung Recruitability in Patients with Acute Respiratory Distress Syndrome.

Rationale: A U-shaped relationship should exist between lung volume and pulmonary vascular resistance (PVR), with minimal PVR at FRC. Thus, positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) should increase PVR if it induces significant lung distension compared with recruitment. However, this has never been proved in patients. Objectives: To study the effects of PEEP on PVR according to lung recruitability, evaluated by the recruitment-to-inflation (R/I) ratio. Methods: In patients with ARDS, we measured hemodynamic (pulmonary artery catheter), echocardiographic, and ventilatory variables (including esophageal pressure) at both low PEEP and higher PEEP by 10 cm H2O. Preload responsiveness was assessed by the passive leg-raising test at high PEEP. Measurements and Main Results: We enrolled 23 patients, including 10 low recruiters (R/I <0.5) and 13 high recruiters (R/I ⩾0.5). Raising PEEP from 4 (2-5) to 14 (12-15) cm H2O increased PVR in low recruiters (from 160 [120-297] to 243 [166-380] dyn·s/cm5; P < 0.01), whereas PVR was unchanged in high recruiters (from 224 [185-289] to 235 [168-300] dyn·s/cm5; P = 0.55). Right-to-left ventricular end-diastolic area ratio simultaneously increased in low recruiters (from 0.54 [0.50-0.59] to 0.64 [0.56-0.70]; P < 0.01) while remaining stable in high recruiters (from 0.70 [0.65-0.79] to 0.68 [0.58-0.80]; P = 0.48). Raising PEEP decreased cardiac index only in preload responsive patients. Conclusions: PEEP increases PVR only when it induces significant lung distension compared with recruitment according to the R/I ratio. Tailoring PEEP on this recruitability index should mitigate its hemodynamic effects.

Comparison of the ability of short time low PEEP challenge and mini fluid challenge to predict fluid responsiveness in patients undergoing open pancreaticoduodenectomy: an observational cohort study.

The mini-fluid challenge (MFC), which assesses the change in stroke volume index (SVI) following the administration of 100 mL of crystalloids, and the short-time low positive end-expiratory pressure (PEEP) challenge (SLPC), which evaluates the temporary reduction in SVI due to a PEEP increment, are two functional hemodynamic tests used to predict fluid responsiveness in the operating room. However, SLPC has not been assessed in patients undergoing abdominal surgery, and there is no study comparing these two methods during laparotomy. Therefore, we aimed to compare the SLPC and MFC in patients undergoing open pancreaticoduodenectomy. All patients received a standard hemodynamic management. The study protocol evaluated the percentage change in SVI following the application of an additional 5 cmH2O PEEP (SVIΔ%-SLPC) and the infusion of 100 mL crystalloid (SVIΔ%-MFC). Challenges that resulted in an increase of more than 15% in SVI after the 500 ml of fluid loading were classified as positive challenges (PC). Areas under the receiver operating characteristics curves (ROC AUCs) were used for the comparison of the methods. Thirty-three patients completed the study with 94 challenges. Fifty-five (58.5%) of them were PCs. The ROC AUC of SVIΔ%-MFC was observed to be significantly higher than that of SVIΔ%-SLPC (0.97 vs. 0.64, p < 0.001). The best cut-off value for SVIΔ%-MFC was 5.6%. If we had stopped the bolus fluid administration when SVIΔ%-MFC ≤ 5% was observed (lower limit of the gray zone), we would have postponed the fluid loading in 35 (89.7%) of 39 negative challenges. The amount of fluid deferred would have corresponded to up to 40% of the total fluid given. SVIΔ%-MFC predicts fluid responsiveness with high diagnostic performance and is better than SVIΔ%-SLPC in patients undergoing open pancreatoduodenectomy. Additionally, the use of SVIΔ%-MFC has the potential to defer up to 40% of the total fluid given. gov: NCT05419570.

Differential Effect of Positive End-Expiratory Pressure Strategies in Patients With ARDS: A Bayesian Analysis of Clinical Subphenotypes

ARDS is a heterogeneous condition with two subphenotypes identified by different methodologies. Our group similarly identified two ARDS subphenotypes using nine routinely available clinical variables. However, whether these are associated with differential response to treatment has yet to be explored. Are there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS? We evaluated data from two prior ARDS trials (Higher vsLower Positive End-Expiratory Pressures in Patients With the ARDS [ALVEOLI] and the Alveolar Recruitment in ARDS Trial [ART]) that compared different PEEP strategies. We classified patients into one of two subphenotypes as described previously. We assessed the differential effect of PEEP with a Bayesian hierarchical logistic model for the primary outcome of 28-day mortality. We analyzed data from 1,559 patients with ARDS. Compared with lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in patients with subphenotype A disease in the ALVEOLI study (OR, 1.61; 95%credible interval [CrI], 0.90-2.94) and ART (OR, 1.73; 95%CrI, 1.01-2.98), with a probability of harm resulting from higher PEEP in this subphenotype of 94.3%and 97.7%in the ALVEOLI and ART studies, respectively. Higher PEEP was not associated with mortality in patients with subphenotype B disease in each trial (OR, 0.95 [95%CrI, 0.51-1.73] and 1.00 [95%CrI, 0.63-1.55], respectively), with probability of benefit of 56.4%and 50.7%in the ALVEOLI and ART studies, respectively. These effects were not modified by Pao2 to Fio2 ratio, driving pressure, or the severity of illness for the cohorts. We found evidence of differential response to PEEP strategies across two ARDS subphenotypes, suggesting possible harm with a higher PEEP strategy in one subphenotype. These observations may assist with predictive enrichment in future clinical trials.

Effect of the alveolar recruitment maneuver during laparoscopic colorectal surgery on postoperative pulmonary complications: A randomized controlled trial.

Intraoperative lung-protective ventilation, including low tidal volume and positive end-expiratory pressure, reduces postoperative pulmonary complications. However, the effect and specific alveolar recruitment maneuver method are controversial. We investigated whether the intraoperative intermittent recruitment maneuver further reduced postoperative pulmonary complications while using a lung-protective ventilation strategy. Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to the recruitment or control groups. Intraoperative ventilation was adjusted to maintain a tidal volume of 6-8 mL kg-1 and positive end-expiratory pressure of 5 cmH2O in both groups. The alveolar recruitment maneuver was applied at three time points (at the start and end of the pneumoperitoneum, and immediately before extubation) by maintaining a continuous pressure of 30 cmH2O for 30 s in the recruitment group. Clinical and radiological evidence of postoperative pulmonary complications was investigated within 7 days postoperatively. A total of 125 patients were included in the analysis. The overall incidence of postoperative pulmonary complications was not significantly different between the recruitment and control groups (28.1% vs. 31.1%, P = 0.711), while the mean ± standard deviation intraoperative peak inspiratory pressure was significantly lower in the recruitment group (10.7 ± 3.2 vs. 13.5 ± 3.0 cmH2O at the time of CO2 gas-out, P < 0.001; 9.8 ± 2.3 vs. 12.5 ± 3.0 cmH2O at the time of recovery, P < 0.001). The alveolar recruitment maneuver with a pressure of 30 cmH2O for 30 s did not further reduce postoperative pulmonary complications when a low tidal volume and 5 cmH2O positive end-expiratory pressure were applied to patients undergoing laparoscopic colorectal surgery and was not associated with any significant adverse events. However, the alveolar recruitment maneuver significantly reduced intraoperative peak inspiratory pressure. Further study is needed to validate the beneficial effect of the alveolar recruitment maneuver in patients at increased risk of postoperative pulmonary complications. Trial registration: Clinicaltrials.gov (NCT03681236).

Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial

BackgroundAcute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on “focal” or “non-focal” lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish “focal” from “non-focal” lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation.MethodsThe Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as “focal” or “non-focal”. Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for “non-focal” ARDS and lower PEEP and prone positioning for “focal” ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated.DiscussionPEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach.Trial registrationThe PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Low-volume ventilation of preinjured lungs degrades lung function via stress concentration and progressive alveolar collapse.

Mechanical ventilation can cause ventilation-induced lung injury (VILI). The concept of stress concentrations suggests that surfactant dysfunction-induced microatelectases might impose injurious stresses on adjacent, open alveoli and function as germinal centers for injury propagation. The aim of the present study was to quantify the histopathological pattern of VILI progression and to test the hypothesis that injury progresses at the interface between microatelectases and ventilated lung parenchyma during low-positive end-expiratory pressure (PEEP) ventilation. Bleomycin was used to induce lung injury with microatelectases in rats. Lungs were then mechanically ventilated for up to 6 h at PEEP = 1 cmH2O and compared with bleomycin-treated group ventilated protectively with PEEP = 5 cmH2O to minimize microatelectases. Lung mechanics were measured during ventilation. Afterward, lungs were fixed at end-inspiration or end-expiration for design-based stereology. Before VILI, bleomycin challenge reduced the number of open alveoli [N(alvair,par)] by 29%. No differences between end-inspiration and end-expiration were observed. Collapsed alveoli clustered in areas with a radius of up to 56 µm. After PEEP = 5 cmH2O ventilation for 6 h, N(alvair,par) remained stable while PEEP = 1 cmH2O ventilation led to an additional loss of aerated alveoli by 26%, mainly due to collapse, with a small fraction partly edema filled. Alveolar loss strongly correlated to worsening of tissue elastance, quasistatic compliance, and inspiratory capacity. The radius of areas of collapsed alveoli increased to 94 µm, suggesting growth of the microatelectases. These data provide evidence that alveoli become unstable in neighborhood of microatelectases, which most likely occurs due to stress concentration-induced local vascular leak and surfactant dysfunction.NEW & NOTEWORTHY Low-volume mechanical ventilation in the presence of high surface tension-induced microatelectases leads to the degradation of lung mechanical function via the progressive loss of alveoli. Microatelectases grow at the interfaces of collapsed and open alveoli. Here, stress concentrations might cause injury and alveolar instability. Accumulation of small amounts of alveolar edema can be found in a fraction of partly collapsed alveoli but, in this model, alveolar flooding is not a major driver for degradation of lung mechanics.

Positive end-expiratory pressure and the incidence of postoperative pulmonary complications in patients undergoing general anaesthesia.

To evaluate the effect of intraoperative positive end-expiratory pressure and driving pressure on the development of postoperative pulmonary complications. The prospective study included 83 patients undergoing abdominal surgery and receiving general anaesthesia. Patients were divided into two groups: with low intraoperative positive end-expiratory pressure (0-2cm H2O) and with high intraoperative positive end-expiratory pressure (8-10cm H2O). The primary endpoint is the development of postoperative pulmonary complications during follow-up. The incidence of postoperative pulmonary complications in the group of low intraoperative positive end-expiratory pressure was 9.8%, while in the group of high positive end-expiratory pressure was 7.1% (p = 0.6), demonstrating that high positive end-expiratory pressure used during general anaesthesia does not affect the frequency of complications (odds ratio = 0.71, p = 0.6). In the multivariate analysis that controls for all confounders, driving pressure resulted in a significant and independent risk factor for complications. High intraoperative positive end-expiratory pressure does not affect the frequency of postoperative pulmonary complications. The increase in driving pressure is a risk factor for complications. Positive end-expiratory pressure is easily implemented, and its use does not result in significant economic costs.

Exploring alveolar recruitability using positive end-expiratory pressure in mice overexpressing TGF-β1: a structure–function analysis

Pre-injured lungs are prone to injury progression in response to mechanical ventilation. Heterogeneous ventilation due to (micro)atelectases imparts injurious strains on open alveoli (known as volutrauma). Hence, recruitment of (micro)atelectases by positive end-expiratory pressure (PEEP) is necessary to interrupt this vicious circle of injury but needs to be balanced against acinar overdistension. In this study, the lung-protective potential of alveolar recruitment was investigated and balanced against overdistension in pre-injured lungs. Mice, treated with empty vector (AdCl) or adenoviral active TGF-β1 (AdTGF-β1) were subjected to lung mechanical measurements during descending PEEP ventilation from 12 to 0 cmH2O. At each PEEP level, recruitability tests consisting of two recruitment maneuvers followed by repetitive forced oscillation perturbations to determine tissue elastance (H) and damping (G) were performed. Finally, lungs were fixed by vascular perfusion at end-expiratory airway opening pressures (Pao) of 20, 10, 5 and 2 cmH2O after a recruitment maneuver, and processed for design-based stereology to quantify derecruitment and distension. H and G were significantly elevated in AdTGF-β1 compared to AdCl across PEEP levels. H was minimized at PEEP = 5–8 cmH2O and increased at lower and higher PEEP in both groups. These findings correlated with increasing septal wall folding (= derecruitment) and reduced density of alveolar number and surface area (= distension), respectively. In AdTGF-β1 exposed mice, 27% of alveoli remained derecruited at Pao = 20 cmH2O. A further decrease in Pao down to 2 cmH2O showed derecruitment of an additional 1.1 million alveoli (48%), which was linked with an increase in alveolar size heterogeneity at Pao = 2–5 cmH2O. In AdCl, decreased Pao resulted in septal folding with virtually no alveolar collapse. In essence, in healthy mice alveoli do not derecruit at low PEEP ventilation. The potential of alveolar recruitability in AdTGF-β1 exposed mice is high. H is optimized at PEEP 5–8 cmH2O. Lower PEEP folds and larger PEEP stretches septa which results in higher H and is more pronounced in AdTGF-β1 than in AdCl. The increased alveolar size heterogeneity at Pao = 5 cmH2O argues for the use of PEEP = 8 cmH2O for lung protective mechanical ventilation in this animal model.

Effects of prone positioning on lung mechanical power components in patients with acute respiratory distress syndrome: a physiologic study

BackgroundProne positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV).MethodsThis prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters.ResultsLung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9–10.6] versus 11.0 [6.6–14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1–5.0] versus 5.3 [3.3–7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP.ConclusionsIn patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery.Trial registration: German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449

Maintaining moderate versus lower PEEP after cardiac surgery: a propensity-scored matched analysis

BackgroundSetting positive end-expiratory pressure (PEEP) at around 5 cm H2O in the early postoperative period seems a common practice for most patients. It remains unclear if the routine application of higher levels of PEEP confers any meaningful clinical benefit for cardiac surgical patients. The aim of this study was to compare moderate versus conventional lower PEEP on patient-centered outcomes in the intensive care unit (ICU).MethodsThis is a single-center retrospective study involving patients receiving cardiac surgery from June 2022 to May 2023. Propensity-score matching (PSM) was used to balance the baseline differences. Primary outcomes were the duration of mechanical ventilation and ICU length of stay. Secondary outcomes included PaO2/FiO2 ratio at 24 h and the need for prone positioning during ICU stay.ResultsA total of 334 patients were included in the study, 102 (31%) of them received moderate PEEP (≥ 7 cm H2O) for the major time in the early postoperative period (12 h). After PSM, 79 pairs of patients were matched with balanced baseline data. The results showed that there was marginal difference in the distribution of mechanical ventilation duration (p = 0.05) and the Moderate PEEP group had a higher extubation rate at the day of T-piece trial (65 [82.3%] vs 52 [65.8%], p = 0.029). Applying moderate PEEP was also associated with better oxygenation. No differences were found regarding ICU length of stay and patients requiring prone positioning between groups.ConclusionIn selective cardiac surgical patients, using moderate PEEP compared with conventional lower PEEP in the early postoperative period correlated to better oxygenation, which may have potential for earlier liberation of mechanical ventilation.

Recruitment-to-inflation ratio for bedside PEEP selection in acute respiratory distress syndrome.

In acute respiratory distress syndrome, the role of positive end-expiratory pressure (PEEP) to prevent ventilator-induced lung injury is controversial. Randomized trials comparing higher versus lower PEEP strategies failed to demonstrate a clinical benefit. This may depend on the inter-individually variable potential for lung recruitment (i.e. recruitability), which would warrant PEEP individualization to balance alveolar recruitment and the unavoidable baby lung overinflation produced by high pressure. Many techniques have been used to assess recruitability, including lung imaging, multiple pressure-volume curves and lung volume measurement. The Recruitment-to-Inflation ratio (R/I) has been recently proposed to bedside assess recruitability without additional equipment. R/I assessment is a simplified technique based on the multiple pressure-volume curve concept: it is measured by monitoring respiratory mechanics and exhaled tidal volume during a 10-cmH<inf>2</inf>O one-breath derecruitment maneuver after a short high-PEEP test. R/I scales recruited volume to respiratory system compliance, and normalizes recruitment to a proxy of actual lung size. With modest R/I (<0.3-0.4), setting low PEEP (5-8 cmH<inf>2</inf>O) may be advisable; with R/I>0.6-0.7, high PEEP (≥15 cmH<inf>2</inf>O) can be considered, provided that airway and/or transpulmonary plateau pressure do not exceed safety limits. In case of intermediate R/I (≈0.5), a more granular assessment of recruitability may be needed. This could be accomplished with advanced monitoring tools, like sequential lung volume measurement with granular R/I assessment or electrical impedance tomography monitoring during a decremental PEEP trial. In this review, we discuss R/I rationale, applications and limits, providing insights on its clinical use for PEEP selection in moderate-to-severe acute respiratory distress syndrome.

Influence of Fractional Inspired Oxygen Tension on Lung Perfusion Distribution, Regional Ventilation, and Lung Volume during Mechanical Ventilation of Supine Healthy Swine.

Lower fractional inspired oxygen tension (Fio2) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2 (0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis. In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2 in three combinations: high PEEP with low Fio2 (Fio2 = 0.4), zero PEEP (PEEP0) with low Fio2 (Fio2 = 0.4), and PEEP0 with high Fio2 (Fio2 = 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2 = 0.21) and low aerated (Fio2 = 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography. During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2 in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007). PEEP0 with low Fio2, compared with high Fio2, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2 = 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.