Dataset Information

Myocardial Function during Ventilation with Lower versus Higher Positive End-Expiratory Pressure in Patients without ARDS.

ABSTRACT: The aim of this study was to investigate whether lower PEEP (positive end-expiratory pressure) had beneficial effects on myocardial function among intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) compared to higher PEEP. In this pre-planned substudy of a randomized controlled trial (RELAx), comparing lower to higher PEEP, 44 patients underwent transthoracic echocardiography. The exclusion criteria were known poor left ventricular function and severe shock requiring high dosages of norepinephrine. To create contrast, we also excluded patients who received PEEP between 2 cmH2O and 7 cmH2O in the two randomization arms of the study. The primary outcome was the right ventricular myocardial performance index (MPI), a measure of systolic and diastolic function. The secondary outcomes included systolic and diastolic function parameters. A total of 20 patients were ventilated with lower PEEP (mean ± SD, 0 ± 1 cmH2O), and 24 patients, with higher PEEP (8 ± 1 cmH2O) (mean difference, -8 cmH2O; 95% CI: -8.1 to -7.9 cmH2O; p = 0.01). The tidal volume size was low in both groups (median (IQR), 7.2 (6.3 to 8.1) versus 7.0 (5.3 to 9.1) ml/kg PBW; p = 0.97). The median right ventricular MPI was 0.32 (IQR, 0.26 to 0.39) in the lower-PEEP group versus 0.38 (0.32 to 0.41) in the higher-PEEP group; the median difference was -0.03; 95% CI: -0.11 to 0.03; p = 0.33. The other systolic and diastolic parameters were similar. In patients without ARDS ventilated with a low tidal volume, a lower PEEP had no beneficial effects on the right ventricular MPI.

SUBMITTER: Algera AG

PROVIDER: S-EPMC9104897 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Myocardial Function during Ventilation with Lower versus Higher Positive End-Expiratory Pressure in Patients without ARDS.

Algera Anna Geke AG Pierrakos Charalampos C Botta Michela M Zimatore Claudio C Pisani Luigi L Tuinman Pieter-Roel PR Bos Lieuwe D J LDJ Lagrand Wim K WK Gama de Abreu Marcello M Pelosi Paolo P Serpa Neto Ary A Schultz Marcus J MJ Cherpanath Thomas G V TGV Paulus Frederique F

Journal of clinical medicine 20220421 9

The aim of this study was to investigate whether lower PEEP (positive end-expiratory pressure) had beneficial effects on myocardial function among intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) compared to higher PEEP. In this pre-planned substudy of a randomized controlled trial (RELAx), comparing lower to higher PEEP, 44 patients underwent transthoracic echocardiography. The exclusion criteria were known poor left ventricular function and severe shock req ...[more]

PMID: 35566435

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Project description:ImportanceIt is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS).ObjectiveTo determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days.Design, setting, and participantsNoninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020.InterventionsParticipants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493).Main outcomes and measuresThe primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 28 of -10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation.ResultsAmong 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) and 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio, 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes.Conclusions and relevanceAmong patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS.Trial registrationClinicalTrials.gov Identifier: NCT03167580.

Project description:BackgroundIn ARDS patients, changes in respiratory mechanical properties and ventilatory settings can cause incomplete lung deflation at end-expiration. Both can promote dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP). The aim of this study was to investigate, in a large population of ARDS patients, the presence of intrinsic PEEP, possible associated factors (patients' characteristics and ventilator settings), and the effects of two different external PEEP levels on the intrinsic PEEP.MethodsWe made a secondary analysis of published data. Patients were ventilated with a tidal volume of 6-8 mL/kg of predicted body weight, sedated, and paralyzed. After a recruitment maneuver, a PEEP trial was run at 5 and 15 cmH2O, and partitioned mechanics measurements were collected after 20 min of stabilization. Lung computed tomography scans were taken at 5 and 45 cmH2O. Patients were classified into two groups according to whether or not they had intrinsic PEEP at the end of an expiratory pause.ResultsWe enrolled 217 sedated, paralyzed patients: 87 (40%) had intrinsic PEEP with a median of 1.1 [1.0-2.3] cmH2O at 5 cmH2O of PEEP. The intrinsic PEEP significantly decreased with higher PEEP (1.1 [1.0-2.3] vs 0.6 [0.0-1.0] cmH2O; p < 0.001). The applied tidal volume was significantly lower (480 [430-540] vs 520 [445-600] mL at 5 cmH2O of PEEP; 480 [430-540] vs 510 [430-590] mL at 15 cmH2O) in patients with intrinsic PEEP, while the respiratory rate was significantly higher (18 [15-20] vs 15 [13-19] bpm at 5 cmH2O of PEEP; 18 [15-20] vs 15 [13-19] bpm at 15 cmH2O). At both PEEP levels, the total airway resistance and compliance of the respiratory system were not different in patients with and without intrinsic PEEP. The total lung gas volume and lung recruitability were also not different between patients with and without intrinsic PEEP (respectively 961 [701-1535] vs 973 [659-1433] mL and 15 [0-32] % vs 22 [0-36] %).ConclusionsIn sedated, paralyzed ARDS patients without a known obstructive disease, the amount of intrinsic PEEP during lung-protective ventilation is negligible and does not influence respiratory mechanical properties.

Project description:BackgroundEvidence for benefit of high positive end-expiratory pressure (PEEP) is largely lacking for invasively ventilated, critically ill patients with uninjured lungs. We hypothesize that ventilation with low PEEP is noninferior to ventilation with high PEEP with regard to the number of ventilator-free days and being alive at day 28 in this population. METHODS/DESIGN: The "REstricted versus Liberal positive end-expiratory pressure in patients without ARDS" trial (RELAx) is a national, multicenter, randomized controlled, noninferiority trial in adult intensive care unit (ICU) patients with uninjured lungs who are expected not to be extubated within 24 h. RELAx will run in 13 ICUs in the Netherlands to enroll 980 patients under invasive ventilation. In all patients, low tidal volumes are used. Patients assigned to ventilation with low PEEP will receive the lowest possible PEEP between 0 and 5 cm H2O, while patients assigned to ventilation with high PEEP will receive PEEP of 8 cm H2O. The primary endpoint is the number of ventilator-free days and being alive at day 28, a composite endpoint for liberation from the ventilator and mortality until day 28, with a noninferiority margin for a difference between groups of 0.5 days. Secondary endpoints are length of stay (LOS), mortality, and occurrence of pulmonary complications, including severe hypoxemia, major atelectasis, need for rescue therapies, pneumonia, pneumothorax, and development of acute respiratory distress syndrome (ARDS). Hemodynamic support and sedation needs will be collected and compared.DiscussionRELAx will be the first sufficiently sized randomized controlled trial in invasively ventilated, critically ill patients with uninjured lungs using a clinically relevant and objective endpoint to determine whether invasive, low-tidal-volume ventilation with low PEEP is noninferior to ventilation with high PEEP.Trial registrationClinicalTrials.gov , ID: NCT03167580 . Registered on 23 May 2017.

Project description:IntroductionMechanical ventilation with high positive end-expiratory pressure (PEEP) has been used in patients with acute respiratory distress syndrome (ARDS) and intra-abdominal hypertension (IAH), but the role of PEEP in minimizing lung injury remains controversial. We hypothesized that in the presence of acute lung injury (ALI) with IAH: 1) higher PEEP levels improve pulmonary morphofunction and minimize lung injury; and 2) the biological effects of higher PEEP are more effective in extrapulmonary (exp) than pulmonary (p) ALI.MethodsIn 48 adult male Wistar rats, ALIp and ALIexp were induced by Escherichia coli lipopolysaccharide intratracheally and intraperitoneally, respectively. After 24 hours, animals were anesthetized and mechanically ventilated (tidal volume of 6 mL/kg). IAH (15 mmHg) was induced and rats randomly assigned to PEEP of 5 (PEEP5), 7 (PEEP7) or 10 (PEEP10) cmH2O for 1 hour.ResultsIn both ALIp and ALIexp, higher PEEP levels improved oxygenation. PEEP10 increased alveolar hyperinflation and epithelial cell damage compared to PEEP5, independent of ALI etiology. In ALIp, PEEP7 and PEEP10 increased lung elastance compared to PEEP5 (4.3 ± 0.7 and 4.3 ± 0.9 versus 3.1 ± 0.3 cmH2O/mL, respectively, P <0.01), without changes in alveolar collapse, interleukin-6, caspase-3, type III procollagen, receptor for advanced glycation end-products, and vascular cell adhesion molecule-1 expressions. Moreover, PEEP10 increased diaphragmatic injury compared to PEEP5. In ALIexp, PEEP7 decreased lung elastance and alveolar collapse compared to PEEP5 (2.3 ± 0.5 versus 3.6 ± 0.7 cmH2O/mL, P <0.02, and 27.2 (24.7 to 36.8) versus 44.2 (39.7 to 56.9)%, P <0.05, respectively), while PEEP7 and PEEP10 increased interleukin-6 and type III procollagen expressions, as well as type II epithelial cell damage compared to PEEP5.ConclusionsIn the current models of ALI with IAH, in contrast to our primary hypothesis, higher PEEP is more effective in ALIp than ALIexp as demonstrated by the activation of biological markers. Therefore, higher PEEP should be used cautiously in the presence of IAH and ALI, mainly in ALIexp.

Project description:BackgroundARDS 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.Research questionAre there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS?Study design and methodsWe evaluated data from two prior ARDS trials (Higher vs Lower 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.ResultsWe 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.InterpretationWe 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.

Project description:PurposeThere is significant variability in the application of positive end-expiratory pressure (PEEP) in patients undergoing invasive mechanical ventilation. There are numerous studies assessing methods of determining optimal PEEP, but many methods, patient populations, and study settings lack high-quality evidence. Guidelines make no recommendations about the use of a specific method because of equipoise and lack of high-quality evidence. We conducted a scoping review to determine which methods of determining optimal PEEP have been studied and what gaps exist in the literature.SourceWe searched five databases for primary research reports studying methods of determining optimal PEEP among adults undergoing invasive mechanical ventilation. Data abstracted consisted of the titration method, setting, study design, population, and outcomes.Principle findingsTwo hundred and seventy-one studies with 17,205 patients met the inclusion criteria, including 73 randomized controlled trials (RCTs) with 10,733 patients. We identified 22 methods. Eleven were studied with an RCT. Studies enrolled participants within an intensive care unit (ICU) (216/271, 80%) or operating room (55/271, 20%). Most ICU studies enrolled patients with acute respiratory distress syndrome (162/216, 75%). The three most studied methods were compliance (73 studies, 29 RCTs), imaging-based methods (65 studies, 11 RCTs), and use of PEEP-FIO2 tables (52 studies, 20 RCTs). Among ICU RCTs, the most common primary outcomes were mortality or oxygenation. Few RCTs assessed feasibility of different methods (n = 3). The strengths and limitations of each method are discussed.ConclusionNumerous methods of determining optimal PEEP have been evaluated; however, notable gaps remain in the evidence supporting their use. These include specific populations (normal lungs, patients weaning from mechanical ventilation) and using alternate outcomes (ventilator-free days and feasibility) and they present significant opportunities for future study.Study registrationOpen Science Framework ( https://osf.io/atzqc ); first posted, 19 July 2022.

Dataset Information

Myocardial Function during Ventilation with Lower versus Higher Positive End-Expiratory Pressure in Patients without ARDS.

Publications

Myocardial Function during Ventilation with Lower versus Higher Positive End-Expiratory Pressure in Patients without ARDS.

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