Positive End-expiratory Pressure Strategy Research Articles

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

Acute respiratory distress syndrome (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 (ALVEOLI and ART) that compared different PEEP strategies. We classified patients into one of two subphenotypes as previously described. 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 1559 ARDS patients. Compared to lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in subphenotype A patients in ALVEOLI (OR, 1.61 [95% CrI 0.90 to 2.94]) and ART (OR 1.73 [ 95% CrI 1.01 to 2.98]), with a probability of harm from higher PEEP in this subphenotype of 94.3% and 97.7% in ALVEOLI and ART, respectively. Higher PEEP was not associated with mortality in subphenotype B patients in each trial (OR, 0.95 [95% CrI, 0.51 to 1.73]) and (OR, 1.00 [95% CrI 0.63 to 1.55]); probability of benefit of 56.4% and 50.7% in ALVEOLI and ART, respectively. These effects were not modified by PaO2/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.

Impact of a positive end-expiratory pressure strategy on oxygenation, respiratory compliance, and hemodynamics during laparoscopic surgery in non-obese patients: a systematic review and meta-analysis of randomized controlled trials

BackgroundHigher positive end-expiratory pressure (PEEP) during laparoscopic surgery may increase oxygenation and respiratory compliance. This meta-analysis aimed to compare the impact of different intraoperative PEEP strategies on arterial oxygenation, compliance, and hemodynamics during laparoscopic surgery in non-obese patients.MethodsWe searched RCTs in PubMed, Cochrane Library, Web of Science, and Google Scholar from January 2012 to April 2022 comparing the different intraoperative PEEP (Low PEEP (LPEEP): 0–4 mbar; Moderate PEEP (MPEEP): 5–8 mbar; high PEEP (HPEEP): >8 mbar; individualized PEEP - iPEEP) on arterial oxygenation, respiratory compliance (Cdyn), mean arterial pressure (MAP), and heart rate (HR). We calculated mean differences (MD) with 95% confidence intervals (CI), and predictive intervals (PI) using random-effects models. The Cochrane Bias Risk Assessment Tool was applied.Results21 RCTs (n = 1554) met the inclusion criteria. HPEEP vs. LPEEP increased PaO2 (+ 29.38 [16.20; 42.56] mmHg, p < 0.0001) or PaO2/FiO2 (+ 36.7 [+ 2.23; +71.70] mmHg, p = 0.04). HPEEP vs. MPEEP increased PaO2 (+ 22.00 [+ 1.11; +42.88] mmHg, p = 0.04) or PaO2/FiO2 (+ 42.7 [+ 2.74; +82.67] mmHg, p = 0.04). iPEEP vs. MPEEP increased PaO2/FiO2 (+ 115.2 [+ 87.21; +143.20] mmHg, p < 0.001). MPEEP vs. LPEP, and HPEEP vs. MPEEP increased PaO2 or PaO2/FiO2 significantly with different heterogeneity. HPEEP vs. LPEEP increased Cdyn (+ 7.87 [+ 1.49; +14.25] ml/mbar, p = 0.02). MPEEP vs. LPEEP, and HPEEP vs. MPEEP did not impact Cdyn (p = 0.14 and 0.38, respectively). iPEEP vs. LPEEP decreased driving pressure (-4.13 [-2.63; -5.63] mbar, p < 0.001). No significant differences in MAP or HR were found between any subgroups.ConclusionHPEEP and iPEEP during PNP in non-obese patients could promote oxygenation and increase Cdyn without clinically significant changes in MAP and HR. MPEEP could be insufficient to increase respiratory compliance and improve oxygenation. LPEEP may lead to decreased respiratory compliance and worsened oxygenation.Prospero registrationCRD42022362379; registered October 09, 2022.

Meta-Analysis of Higher PEEP Strategies' Effects on Mortality Rates and Inflammatory Mediators in Patients with ARDS: A Perspective Review on Patients with Severe COVID-19-Associated ARDS

&lt;strong&gt;Background: &lt;/strong&gt;Different strategies of positive end-expiratory pressure (PEEP) in mechanical ventilation are crucial for patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). PEEP acts as a “double-edged sword” for ARDS patients. PEEP could recover pulmonary atelectasis but can induce alveolar hyperinflation.&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This review aimed to evaluate the effect of higher PEEP in patients with severe COVID-19-associated ARDS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;This meta-analysis included randomized controlled trial (RCT) studies to assess the mortality rates, barotrauma events, and inflammatory mediators modulation due to higher PEEP strategies. The pooled effect of the mortality rates and barotrauma events were presented as risk ratios (RR) with 95% confidence of interval (CI) using random-effects model (REM) or fixed-effects model (FEM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified twelve RCTs comparing higher versus lower PEEP in ARDS patients. There was unsignificant result in overall mortality rates group [RR=0.94,95%CI(85,1.03),p=0.21] but not in mortality after positive response of oxygenation group [RR=0.88,95%CI(0.81,0.95),p=0.002] in higher PEEP group. In terms of patients without positive response of oxygenation, higher PEEP group had significantly higher mortality rates [RR=1.07,95%CI(1.00,1.15),p=0.06]. Higher PEEP significantly reduced the mortality rates in ARDS patients with PaO&lt;sub&gt;2&lt;/sub&gt;/FiO&lt;sub&gt;2&lt;/sub&gt;&amp;lt;150 mmHg [RR=0.867,95%CI(0.74,1.00),p=0.04] instead of patients with moderate ARDS (PaO&lt;sub&gt;2&lt;/sub&gt;/FiO&lt;sub&gt;2 &lt;/sub&gt;≥150 mmHg) [RR=1.12, 95%CI(0.85,1.47), p=0.44]. There were no differences in overall barotrauma events [RR=1.03,95%CI(0.78,1.36),p=0.85] between higher and lower PEEP group. The use of higher and lower PEEP also contribute to the modulation of inflammatory mediators including TNF-α, IL-6, IL-1RA, and IL-8.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Higher PEEP could reduce the mortality of patients with ARDS who responded to the oxygenation. Higher PEEP does not increase the risk of overall barotrauma events. Higher PEEP can modulate the inflammatory mediators.&lt;/p&gt;

Recruitment-to-inflation ratio assessed through sequential end-expiratory lung volume measurement in acute respiratory distress syndrome.

Positive end-expiratory pressure (PEEP) benefits in acute respiratory distress syndrome (ARDS) are driven by lung dynamic strain reduction: this depends on the variable extent of alveolar recruitment. The recruitment-to-inflation (R/I) ratio estimates recruitability across a 10-cmH2O PEEP range through a simplified maneuver. Whether recruitability is uniform or not across this range is unknown. The hypotheses of this study are that R/I represents an accurate estimate of PEEP-induced changes in dynamic strain, but may show a non-uniform behaviour across the conventionally tested PEEP range (15-5 cmH2O). Twenty patients with moderate-to-severe COVID-19 ARDS underwent a decremental PEEP trial (PEEP 15-13-10-8-5 cmH2O). Respiratory mechanics and end-expiratory lung volume by nitrogen dilution were measured the end of each step. Gas exchange, recruited volume, R/I, changes in dynamic, static and total strain were computed between 15 and 5 cmH2O (global R/I) and within narrower PEEP ranges (granular R/I). Between 15 and 5 cmH2O, median [Interquartile range] global R/I was 1.27 [0.40-1.69] and displayed a linear correlation with PEEP-induced dynamic strain reduction (r=-0.94, p<0.001). Intra-individual R/I variability within the narrower ranges was high (85% [70-109]). The relationship between granular R/I and PEEP was mathematically described by a non-linear, quadratic equation (r 2=0.96). Granular R/I across the narrower PEEP ranges had itself a linear correlation with PEEP-induced reduction in dynamic strain (r=-0.89, p<0.001). Both global and granular R/I well estimate PEEP-induced changes in lung dynamic strain. However, the effect of 10-cmH2O of PEEP on lung strain may be non-uniform. Granular R/I assessment within narrower PEEP ranges guided by end-expiratory lung volume measurement may aid more precise PEEP selection, especially when R/I obtained with the simplified maneuver between PEEP 15 and 5 cmH2O yields intermediate values, that are difficult to interpret for a proper choice between a high vs. low PEEP strategy.

Inflating Pressure and Not Expiratory Pressure Initiates Lung Injury at Birth in Preterm Lambs.

Rationale: Inflation is essential for aeration at birth, but current inflating pressure settings are without an evidence base. Objectives: To determine the role of inflating pressure (ΔP), and relationship with positive end-expiratory pressure (PEEP), in initiating early lung injury pathways in the preterm lamb lung. Methods: 124-127d steroid exposed preterm lambs (n=45) were randomly allocated (8-10/gp) to 15 min of respiratory support with placental circulation and 20 or 30 cmH2O ΔP, with an initial high PEEP (maximum 20 cmH2O) recruitment manoeuvre known to facilitate aeration (dynamic PEEP), and compared to dynamic PEEP with no ΔP or 30 cmH2O ΔP and low (4 cmH2O) PEEP. Lung mechanics and aeration were measured throughout. after an additional 30 min of apnoeic placental support, lung tissue and bronchoalveolar fluid were analysed for regional lung injury, including proteomics. Results: 30 cmH2O ΔP and dynamic PEEP resulted in quicker aeration, better compliance, but higher tidal volumes (often >8 ml/kg, all p<0.0001; mixed effects) and injury. ΔP 20 cmH2O with dynamic PEEP resulted in the same lung mechanics and aeration, but less energy transmission (tidal mechanical power), as ΔP 30 cmH2O with low PEEP.. Dynamic PEEP without any tidal inflations resulted in the least lung injury. Use of any tidal inflating pressures altered metabolic, coagulation and complemented protein pathways within the lung. Conclusions: Inflating pressure is essential for the preterm lung at birth, but also the primary mediator of lung injury. Greater focus is needed on strategies that identify safest application of pressure in the delivery room.

Individualized Positive End-expiratory Pressure Titration Strategies in Superobese Patients Undergoing Laparoscopic Surgery: Prospective and Nonrandomized Crossover Study.

Superobesity and laparoscopic surgery promote negative end-expiratory transpulmonary pressure that causes atelectasis formation and impaired respiratory mechanics. The authors hypothesized that end-expiratory transpulmonary pressure differs between fixed and individualized positive end-expiratory pressure (PEEP) strategies and mediates their effects on respiratory mechanics, end-expiratory lung volume, gas exchange, and hemodynamic parameters in superobese patients. In this prospective, nonrandomized crossover study including 40 superobese patients (body mass index 57.3 ± 6.4 kg/m2) undergoing laparoscopic bariatric surgery, PEEP was set according to (1) a fixed level of 8 cm H2O (PEEPEmpirical), (2) the highest respiratory system compliance (PEEPCompliance), or (3) an end-expiratory transpulmonary pressure targeting 0 cm H2O (PEEPTranspul) at different surgical positioning. The primary endpoint was end-expiratory transpulmonary pressure at different surgical positioning; secondary endpoints were respiratory mechanics, end-expiratory lung volume, gas exchange, and hemodynamic parameters. Individualized PEEPCompliance compared to fixed PEEPEmpirical resulted in higher PEEP (supine, 17.2 ± 2.4 vs. 8.0 ± 0.0 cm H2O; supine with pneumoperitoneum, 21.5 ± 2.5 vs. 8.0 ± 0.0 cm H2O; and beach chair with pneumoperitoneum; 15.8 ± 2.5 vs. 8.0 ± 0.0 cm H2O; P < 0.001 each) and less negative end-expiratory transpulmonary pressure (supine, -2.9 ± 2.0 vs. -10.6 ± 2.6 cm H2O; supine with pneumoperitoneum, -2.9 ± 2.0 vs. -14.1 ± 3.7 cm H2O; and beach chair with pneumoperitoneum, -2.8 ± 2.2 vs. -9.2 ± 3.7 cm H2O; P < 0.001 each). Titrated PEEP, end-expiratory transpulmonary pressure, and lung volume were lower with PEEPCompliance compared to PEEPTranspul (P < 0.001 each). Respiratory system and transpulmonary driving pressure and mechanical power normalized to respiratory system compliance were reduced using PEEPCompliance compared to PEEPTranspul. In superobese patients undergoing laparoscopic surgery, individualized PEEPCompliance may provide a feasible compromise regarding end-expiratory transpulmonary pressures compared to PEEPEmpirical and PEEPTranspul, because PEEPCompliance with slightly negative end-expiratory transpulmonary pressures improved respiratory mechanics, lung volumes, and oxygenation while preserving cardiac output.

One-Lung Ventilation and Postoperative Pulmonary Complications After Major Lung Resection Surgery. A Multicenter Randomized Controlled Trial

The effect of one-lung ventilation (OLV) strategy based on low tidal volume (TV), application of positive end-expiratory pressure (PEEP), and alveolar recruitment maneuvers (ARM) to reduce postoperative acute respiratory distress syndrome (ARDS) and pulmonary complications (PPCs) compared with higher TV without PEEP and ARM strategy in adult patients undergoing lobectomy or pneumonectomy has not been well established. Multicenter, randomized, single-blind, controlled trial. Sixteen Italian hospitals. A total of 880 patients undergoing elective major lung resection. Patients were randomized to receive lower tidal volume (LTV group: 4 mL/kg predicted body weight, PEEP of 5 cmH2O, and ARMs) or higher tidal volume (HTL group: 6 mL/kg predicted body weight, no PEEP, and no ARMs). After OLV, until extubation, both groups were ventilated using a tidal volume of 8 mL/kg and a PEEP value of 5 cmH2O. The primary outcome was the incidence of in-hospital ARDS. Secondary outcomes were the in-hospital rate of PPCs, major cardiovascular events, unplanned intensive care unit (ICU) admission, in-hospital mortality, ICU length of stay, and in-hospital length of stay. ARDS occurred in 3 of 438 patients (0.7%, 95% CI 0.1-2.0) and in 1 of 442 patients (0.2%, 95% CI 0-1.4) in the LTV and HTV group, respectively (Risk ratio: 3.03 95% CI 0.32-29, p=0.372). Pulmonary complications occurred in 125 of 438 patients (28.5%, 95% CI 24.5-32.9) and in 136 of 442 patients (30.8%, 95% CI 26.6-35.2) in the LTV and HTV group, respectively (risk ratio: 0.93, 95% CI 0.76-1.14, p=0.507). The incidence of major complications, in-hospital mortality, and unplanned ICU admission, ICU and in-hospital length of stay were comparable in both groups. In conclusion, among adult patients undergoing elective lung resection, an OLV with lower tidal volume, PEEP 5 cmH2O, and ARMs and a higher tidal volume strategy resulted in low ARDS incidence and comparable postoperative complications, in-hospital length of stay, and mortality.

Optimal positive end-expiratory pressure reduces right ventricular dysfunction in COVID-19 patients on venovenous extracorporeal membrane oxygenation: A retrospective single-center study

While mechanical ventilation practices on venovenous extracorporeal membrane oxygenation (VV ECMO) are variable, most institutions utilize a lung rest strategy utilizing relatively low positive end-expiratory pressure (PEEP). The effect of PEEP titration using esophageal manometry during VV ECMO on pulmonary and cardiac function is unknown. This was a retrospective study of 69 patients initiated on VV ECMO between March 2020 through November 2021. Patients underwent standard PEEP (typically 10 cm H2O) or optimal PEEP (PEEP titrated to an end-expiratory transpulmonary pressure 0–3 cm H2O) throughout the ECMO run. The optimal PEEP strategy had higher levels of applied PEEP (17.9 vs. 10.8 cm H2O on day 2 of ECMO), decreased incidence of hemodynamically significant RV dysfunction (4.55% vs. 44.0%, p = 0.0001), and higher survival to decannulation (72.7% vs. 44.0%, p = 0.022). Survival to discharge did not reach statistical significance (61.4% vs. 44.0%, p = 0.211). In univariate logistic regression analysis, optimal PEEP was associated with less hemodynamically significant RV dysfunction with an odds ratio (OR) of 0.06 (95% confidence interval [CI] = 0.01–0.27, p = 0.0008) and increased survival to decannulation with an OR of 3.39 (95% CI 1.23–9.79), p = 0.02), though other confounding factors may have contributed.

Efficacy of maintaining low-tidal volume mechanical ventilation as compared to resting lung strategy during coronary artery bypass graft cardiopulmonary bypass surgery: A post-hoc analysis of the MECANO trial

Study objectiveTo compare a low-tidal-volume with positive end-expiratory pressure strategy (VENT strategy) to a resting-lung-strategy (i.e., no-ventilation (noV) strategy) during cardiopulmonary bypass for coronary artery bypass graft surgery on the incidence of postoperative pulmonary complications. DesignPost-hoc analysis of the MECANO trial which was a prospective single-center, blind, randomized, parallel-group controlled trial. SettingTertiary care cardiac surgery center. PatientsPatients who underwent isolated on-pump coronary bypass surgery were randomized either to VENT or noV group. InterventionDuring the cardiopulmonary bypass phase of the cardiac surgery procedure, mechanical ventilation in the VENT group consisted of a tidal volume of 3 mL/kg, a respiratory rate of 5 per minute and a positive end-expiratory pressure of 5 cmH2O. Patients in the noV group received no ventilation during this phase. MeasurementsPrimary composite outcome combining death, early respiratory failure, ventilation support beyond day 2 and reintubation. Main resultsIn this post-hoc analysis, we retained 725 patients who underwent isolated CABG surgery, from the 1501 patients included in the original study. There were 352 in the VENT group and 373 patients in the noV group. Post-hoc comparison yielded no differences in baseline characteristics between these two groups. The primary outcome occurred less frequently in the VENT group than in the noV group, with 44 (12.5%) and 76 (20.4%) respectively (odds-ratio (OR) = 0.56 (0.37–0.84), p = 0.004). There were fewer early respiratory dysfunctions and prolonged respiratory support in the VENT group (respectively, OR = 0.34 (0.12–0.96) p = 0.033 and OR = 0.51 (0.27–0.94) p = 0.029). Complications related to mechanical ventilation were similar in the two groups. ConclusionsIn this post-hoc analysis, maintaining low-tidal ventilation compared to a resting-lung strategy was associated with fewer pulmonary postoperative complications in patients who underwent isolated CABG procedures.

Dynamic positive end-expiratory pressure strategies using time and pressure recruitment at birth reduce early expression of lung injury in preterm lambs.

Positive end-expiratory pressure (PEEP) is critical to the preterm lung at birth, but the optimal PEEP level remains uncertain. The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs. Steroid-exposed preterm lambs (124-127 days gestation; n = 65) were randomly assigned from birth to either 1) positive pressure ventilation (PPV) at 8 cmH2O PEEP or 3-min dynamic stepwise PEEP strategy (DynPEEP), with either 2) 20 cmH2O maximum PEEP (10 PEEP second steps) or 3) 14 cmH2O maximum PEEP (20-s steps), all followed by standardized PPV for 90 min. Lung mechanics, gas exchange, regional ventilation and aeration (electrical impedance tomography), and histological and molecular measures of lung injury were compared between groups. Dynamic compliance was greatest using a maximum 20 cmH2O (DynPEEP). There were no differences in gas exchange, end-expiratory volume, and ventilator requirements. Regional ventilation became more uniform with time following all PEEP strategies. For all groups, gene expression of markers of early lung injury was greater in the gravity nondependent lung, and inversely related to the magnitude of PEEP, being lowest in the 20 cmH2O DynPEEP group overall. PEEP levels had no impact on lung injury in the dependent lung. Transient high maximum PEEP levels using dynamic PEEP strategies may confer more lung protection at birth.

Aeration strategy at birth does not impact carotid haemodynamics in preterm lambs

BackgroundThe impact of different respiratory strategies at birth on the preterm lung is well understood; however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on carotid blood flow, carotid artery oxygen content and carotid oxygen delivery.Methods124–127-day gestation apnoeic intubated preterm lambs studied as part of a larger programme primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmH2O (No-RM; n = 12), sustained inflation (SI; n = 15) or dynamic PEEP strategy (DynPEEP; maximum PEEP 14 or 20 cmH2O, n = 41) at birth, followed by 90 min of standardised ventilation. Haemodynamic data were continuously recorded, with intermittent arterial blood gas analysis.ResultsOverall carotid blood flow measures were comparable between strategies. Except for mean carotid blood flow that was significantly lower for the SI group compared to the No-RM and DynPEEP groups over the first 3 min (p < 0.0001, mixed effects model). Carotid oxygen content and oxygen delivery were similar between strategies. Maximum PEEP level did not alter cerebral haemodynamic measures.ConclusionsAlthough there were some short-term variations in cerebral haemodynamics between different PEEP strategies and SI, these were not sustained.ImpactDifferent pressure strategies to facilitate lung aeration at birth in preterm infants have been proposed. There is minimal information on the effect of lung recruitment on cerebral haemodynamics.This is the first study that compares the effect of sustained lung inflation and dynamic and static positive end-expiratory pressure on cerebral haemodynamics.We found that the different ventilation strategies did not alter carotid blood flow, carotid oxygen content or carotid oxygen delivery.This preclinical study provides some reassurance that respiratory strategies designed to focus on lung aeration at birth may not impact cerebral haemodynamics in preterm neonates.

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial

Effects of different positive end-expiratory pressure titration strategies during prone positioning in patients with acute respiratory distress syndrome: a prospective interventional study

BackgroundProne positioning in combination with the application of low tidal volume and adequate positive end-expiratory pressure (PEEP) improves survival in patients with moderate to severe acute respiratory distress syndrome (ARDS). However, the effects of PEEP on end-expiratory transpulmonary pressure (Ptpexp) during prone positioning require clarification. For this purpose, the effects of three different PEEP titration strategies on Ptpexp, respiratory mechanics, mechanical power, gas exchange, and hemodynamics were evaluated comparing supine and prone positioning.MethodsIn forty consecutive patients with moderate to severe ARDS protective ventilation with PEEP titrated according to three different titration strategies was evaluated during supine and prone positioning: (A) ARDS Network recommendations (PEEPARDSNetwork), (B) the lowest static elastance of the respiratory system (PEEPEstat,RS), and (C) targeting a positive Ptpexp (PEEPPtpexp). The primary endpoint was to analyze whether Ptpexp differed significantly according to PEEP titration strategy during supine and prone positioning.ResultsPtpexp increased progressively with prone positioning compared with supine positioning as well as with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork (positioning effect p < 0.001, PEEP strategy effect p < 0.001). PEEP was lower during prone positioning with PEEPEstat,RS and PEEPPtpexp (positioning effect p < 0.001, PEEP strategy effect p < 0.001). During supine positioning, mechanical power increased progressively with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork, and prone positioning attenuated this effect (positioning effect p < 0.001, PEEP strategy effect p < 0.001). Prone compared with supine positioning significantly improved oxygenation (positioning effect p < 0.001, PEEP strategy effect p < 0.001) while hemodynamics remained stable in both positions.ConclusionsProne positioning increased transpulmonary pressures while improving oxygenation and hemodynamics in patients with moderate to severe ARDS when PEEP was titrated according to the ARDS Network lower PEEP table. This PEEP titration strategy minimized parameters associated with ventilator-induced lung injury induction, such as transpulmonary driving pressure and mechanical power. We propose that a lower PEEP strategy (PEEPARDSNetwork) in combination with prone positioning may be part of a lung protective ventilation strategy in patients with moderate to severe ARDS.Trial registrationGerman Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017449

Effects of dynamic individualized PEEP guided by driving pressure in laparoscopic surgery on postoperative atelectasis in elderly patients: a prospective randomized controlled trial

BackgroundDriving pressure (ΔP = Plateau pressure-PEEP) is highly correlated with postoperative pulmonary complications (PPCs) and appears to be a promising indicator for optimizing ventilator settings. We hypothesized that dynamic, individualized positive end-expiratory pressure (PEEP) guided by ΔP could reduce postoperative atelectasis and improve intraoperative oxygenation, respiratory mechanics, and reduce the incidence of PPCs on elderly patients undergoing laparoscopic surgery.MethodsFifty-one elderly patients who were subject to laparoscopic surgery participated in this randomized trial. In the PEEP titration group (DV group), the PEEP titration was decremented to the lowest ΔP and repeated every 1 h. Additional procedures were also performed when performing predefined events that may be associated with lung collapse. In the constant PEEP group (PV group), a PEEP of 6 cmH2O was used throughout the surgery. Moreover, zero PEEP was applied during the entire procedure in the conventional ventilation group (CV group). The primary objective of this study was lung ultrasound score noted at the end of surgery and 15 min after admission to the post-anesthesia care unit (PACU) at 12 lung areas bilaterally. The secondary endpoints were perioperative oxygenation function, expiratory mechanics, and the incidence of the PPCs.ResultsThe lung ultrasound scores of the DV group were significantly lower than those in the PV group and CV group (P < 0.05), whereas there was no significant difference between the PV group and CV group (P > 0.05). The lung static compliance (Cstat) and ΔP at all the intraoperative time points in the DV group were significantly better compared to the PV group and the CV group (p < 0.05).ConclusionsIntraoperative titrated PEEP reduced postoperative lung atelectasis and improved respiratory mechanics in elderly patients undergoing laparoscopic surgery. Meanwhile, standard PEEP strategy is not superior to conventional ventilation in reducing postoperative pulmonary atelectasis in laparoscopic surgery.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. US National Institutes of Health and European Society of Intensive Care Medicine.

The Association Between Etiologies and Mortality in Acute Respiratory Distress Syndrome: A Multicenter Observational Cohort Study.

Background: Lung-protective ventilation (LPV) strategies have been beneficial in patients with acute respiratory distress syndrome (ARDS). As a vital part of LPV, positive end-expiratory pressure (PEEP) can enhance oxygenation. However, randomized clinical trials of different PEEP strategies seem to show no advantages in clinical outcomes in patients with ARDS. A potential reason is that diverse etiologies and phenotypes in patients with ARDS may account for different PEEP responses, resulting in variations in mortality. We consider hospital mortality to be associated with a more specific classification of ARDS, such as sepsis induced or not, and pulmonary or extrapulmonary one. Our study aimed to compare clinical outcomes in various patients with ARDS by etiologies using the China Critical Care Sepsis Trial (CCCST) database. This was a retrospective analysis of a prospective cohort of 2,138 patients with ARDS in the CCCST database. According to ARDS induced by sepsis or not and medical history, patients were stratified into different four groups. Differences among groups were assessed in hospital mortality, ventilation-free days, and other clinical features.Results: A total of 2,138 patients with ARDS were identified in the database, including 647 patients with sepsis-induced pulmonary ARDS (30.3%), 396 patients with sepsis-induced extrapulmonary ARDS (18.5%), 536 patients with non-sepsis pulmonary ARDS (25.1%), and 559 patients with non-sepsis extrapulmonary ARDS (26.1%). The pulmonary ARDS group had higher mortality compared with the extrapulmonary group (45.9 vs. 23.0%, p < 0.01), longer intensive care unit (ICU) and hospital stays (9 vs. 6 days, p < 0.01, 20 vs. 18 days, p = 0.01, respectively), and fewer ventilation-free days (5 vs. 9 days) in the presence of sepsis. However, the mortality in ARDS without sepsis was inverted compared with extrapulmonary ARDS (pulmonary 23.5% vs. extrapulmonary 29.2%, p = 0.04). After adjusting for the Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores and other clinical features, the sepsis-induced pulmonary condition was still a risk factor for death in patients with ARDS (hazard ratio 0.66, 95% CI, 0.54–0.82, p < 0.01) compared with sepsis-induced extrapulmonary ARDS and other subphenotypes.Conclusions: In the presence of sepsis, hospital mortality in pulmonary ARDS is higher compared with extrapulmonary ARDS; however, mortality is inverted in ARDS without sepsis. Sepsis-induced pulmonary ARDS should attract more attention from ICU physicians and be cautiously treated.Trial registration: ChiCTR-ECH-13003934. Registered August 3, 2013, http://www.chictr.org.cn.

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome.

Background: Different positive end-expiratory pressure (PEEP) strategies are available for subjects with coronavirus disease 2019 (COVID-19)–induced acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. We aimed to evaluate three conventional PEEP strategies on their effects on respiratory mechanics, gas exchanges, and hemodynamics.Methods: This is a prospective, physiologic, multicenter study conducted in China. We recruited 20 intubated subjects with ARDS and confirmed COVID-19. We first set PEEP by the ARDSnet low PEEP–fraction of inspired oxygen (FIO2) table. After a recruitment maneuver, PEEP was set at 15, 10, and 5 cm H2O for 10 min, respectively. Among these three PEEP levels, best-compliance PEEP was the one providing the highest respiratory system compliance; best-oxygenation PEEP was the one providing the highest PaO2 (partial pressure of arterial oxygen)/FIO2.Results: At each PEEP level, we assessed respiratory mechanics, arterial blood gas, and hemodynamics. Among three PEEP levels, plateau pressure, driving pressure, mechanical power, and blood pressure improved with lower PEEP. The ARDSnet low PEEP–FIO2 table and the best-oxygenation strategies provided higher PEEP than the best-compliance strategy (11 ± 6 cm H2O vs. 11 ± 3 cm H2O vs. 6 ± 2 cm H2O, p = 0.001), leading to higher plateau pressure, driving pressure, and mechanical power. The three PEEP strategies were not significantly different in gas exchange. The subgroup analysis showed that three PEEP strategies generated different effects in subjects with moderate or severe ARDS (n = 12) but not in subjects with mild ARDS (n = 8).Conclusions: In our cohort with COVID-19–induced ARDS, the ARDSnet low PEEP/FIO2 table and the best-oxygenation strategies led to higher PEEP and potentially higher risk of ventilator-induced lung injury than the best-compliance strategy.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04359251.

Association of early positive end-expiratory pressure settings with ventilator-free days in patients with coronavirus disease 2019 acute respiratory distress syndrome: A secondary analysis of the Practice of VENTilation in COVID-19 study.

BACKGROUNDThere is uncertainty about how much positive end-expiratory pressure (PEEP) should be used in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).OBJECTIVETo investigate whether a higher PEEP strategy is superior to a lower PEEP strategy regarding the number of ventilator-free days (VFDs).DESIGNMulticentre observational study conducted from 1 March to 1 June 2020.SETTING AND PATIENTSTwenty-two ICUs in The Netherlands and 933 invasively ventilated COVID-19 ARDS patients.INTERVENTIONSPatients were categorised retrospectively as having received invasive ventilation with higher (n=259) or lower PEEP (n=674), based on the high and low PEEP/FiO2 tables of the ARDS Network, and using ventilator settings and parameters in the first hour of invasive ventilation, and every 8 h thereafter at fixed time points during the first four calendar days. We also used propensity score matching to control for observed confounding factors that might influence outcomes.MAIN OUTCOMES AND MEASURESThe primary outcome was the number of VFDs. Secondary outcomes included distant organ failures including acute kidney injury (AKI) and use of renal replacement therapy (RRT), and mortality.RESULTSIn the unmatched cohort, the higher PEEP strategy had no association with the median [IQR] number of VFDs (2.0 [0.0 to 15.0] vs. 0.0 [0.0 to 16.0] days). The median (95% confidence interval) difference was 0.21 (−3.34 to 3.78) days, P = 0.905. In the matched cohort, the higher PEEP group had an association with a lower median number of VFDs (0.0 [0.0 to 14.0] vs. 6.0 [0.0 to 17.0] days) a median difference of −4.65 (−8.92 to −0.39) days, P = 0.032. The higher PEEP strategy had associations with higher incidence of AKI (in the matched cohort) and more use of RRT (in the unmatched and matched cohorts). The higher PEEP strategy had no association with mortality.CONCLUSIONIn COVID-19 ARDS, use of higher PEEP may be associated with a lower number of VFDs, and may increase the incidence of AKI and need for RRT.TRIAL REGISTRATIONPractice of VENTilation in COVID-19 is registered at ClinicalTrials.gov, NCT04346342.

Invasive and noninvasive ventilation strategies for acute respiratory failure in children with coronavirus disease 2019.

Severe Acute Respiratory Syndrome Coronavirus 2 presents as symptomatic coronavirus disease 2019 (COVID-19) disease in susceptible patients. Severe pediatric COVID-19 disease is rare, limiting potential data accumulation on associated respiratory failure in children. Pediatric intensivists and pulmonologists managing COVID-19 patients look to adult guidelines and pediatric-specific consensus statements to guide management. The purpose of this article is to review the current literature and recommended strategies for the escalation of noninvasive and invasive respiratory support for acute respiratory failure associated with COVID-19 disease in children. There are no prospective studies comparing COVID-19 treatment strategies in children. Adult and pediatric ventilation management interim guidance is based on evidence-based guidelines in non-COVID acute respiratory distress syndrome, with considerations of (1) noninvasive positive pressure ventilation versus high-flow nasal cannula and (2) high versus lower positive end expiratory pressure strategies related to lung compliance and potential lung recruitability. Management of acute respiratory failure from COVID-19 requires individualized titration of noninvasive and invasive ventilation modalities with consideration of preserved or compromised pulmonary compliance. Research regarding best practices in the management of pediatric severe COVID-19 with respiratory failure is lacking and is acutely needed as the pandemic surges and vaccination of the pediatric population will be delayed compared to adults.