Dataset Information

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.

ABSTRACT: A recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objective of this study was to apply the MFPI approach to investigate interactions between four continuous patient baseline variables and higher versus lower PEEP on clinical outcomes.Pooled data from three randomised trials in intensive care identified by a systematic review.2299 patients with acute lung injury requiring mechanical ventilation.Higher (N=1136) versus lower PEEP (N=1163) ventilation strategy.Prespecified outcomes included mortality, time to death and time-to-unassisted breathing. We examined the following continuous baseline characteristics as potential effect modifiers using MFPI: PaO2/FiO2 (arterial partial oxygen pressure/ fraction of inspired oxygen), oxygenation index, respiratory system compliance (tidal volume/(inspiratory plateau pressure-PEEP)) and body mass index (BMI).We found that for patients with PaO2/FiO2 below 150?mm?Hg, but above 100?mm?Hg or an oxygenation index above 12 (moderate ARDS), higher PEEP reduces hospital mortality, but the beneficial effect appears to level off for patients with very severe ARDS. Patients with mild ARDS (PaO2/FiO2 above 200?mm?Hg or an oxygenation index below 10) do not seem to benefit from higher PEEP and might even be harmed. For patients with a respiratory system compliance above 40?mL/cm?H2O or patients with a BMI above 35?kg/m(2), we found a trend towards reduced mortality with higher PEEP, but there is very weak statistical confidence in these findings.MFPI analyses suggest a nonlinear effect modification of higher PEEP ventilation by PaO2/FiO2 and oxygenation index with reduced mortality for some patients suffering from moderate ARDS.CRD42012003129.

SUBMITTER: Kasenda B

PROVIDER: S-EPMC5020750 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.

Kasenda Benjamin B Sauerbrei Willi W Royston Patrick P Mercat Alain A Slutsky Arthur S AS Cook Deborah D Guyatt Gordon H GH Brochard Laurent L Richard Jean-Christophe M JC Stewart Thomas E TE Meade Maureen M Briel Matthias M

BMJ open 20160908 9

<h4>Objectives</h4>A recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objecti ...[more]

PMID: 27609843

Similar Datasets

Project description:BackgroundMortality in patients with acute respiratory distress syndrome (ARDS) remains high. These patients require mechanical ventilation strategies that include high positive end-expiratory pressure (PEEP). It remains controversial whether high PEEP can improve outcomes for ARDS patients, especially patients who show improvement in oxygenation in response to PEEP. In this meta-analysis, we aimed to evaluate the effects of high PEEP on ARDS patients.MethodsWe electronically searched randomized controlled trials (RCTs) reported in the MEDLINE, CENTRAL, EMBASE, CINAHL and Web of Science databases from January 1990 to December 2017. Meta-analyses of the effects of PEEP on survival in adults with ARDS were conducted using the methods recommended by the Cochrane Collaboration.ResultsA total of 3612 patients from nine randomized controlled trials (RCTs) were included. There were 1794 and 1818 patients in the high and low PEEP groups, respectively. Hospital mortality showed no significant difference between the high and low PEEP groups (RR?=?0.92; 95% CI, 0.79 to 1.07; P?=?0.26). Similar results were found for 28-d mortality (RR?=?0.88; 95% CI, 0.72 to 1.07; P?=?0.19) and ICU mortality (RR?=?0.83; 95% CI, 0.65 to 1.07; P?=?0.15). The risk of clinically objectified barotrauma was not significantly different between the high and low PEEP groups (RR?=?1.24; 95% CI, 0.74 to 2.09, P?=?0.41). In the subgroup of ARDS patients who responded to increased PEEP by improved oxygenation (from 6 RCTs), high PEEP significantly reduced hospital mortality (RR?=?0.83; 95% CI 0.69 to 0.98; P?=?0.03), ICU mortality (RR?=?0.74; 95% CI, 0.56 to 0.98; P?=?0.04),but the 28-d mortality was not decreased(RR?=?0.83; 95% CI, 0.67 to 1.01; P?=?0.07). For ARDS patients in the low PEEP group who received a PEEP level lower than 10 cmH2O (from 6 RCTs), ICU mortality was lower in the high PEEP group than the low PEEP group (RR?=?0.65; 95% CI, 0.45 to 0.94; P?=?0.02).ConclusionsFor ARDS patients who responded to increased PEEP by improved oxygenation, high PEEP could reduce hospital mortality, ICU mortality and 28-d mortality. High PEEP does not increase the risk of clinically objectified barotrauma.

Project description:BackgroundEfficacy and safety of different hemoglobin thresholds for transfusion of red blood cells (RBCs) in adults with an acute respiratory distress syndrome (ARDS) are unknown. We therefore assessed the effect of two transfusion thresholds on short-term outcome in patients with ARDS.MethodsPatients who received transfusions of RBCs were identified from a cohort of 1044 ARDS patients. After propensity score matching, patients transfused at a hemoglobin concentration of 8 g/dl or less (lower-threshold) were compared to patients transfused at a hemoglobin concentration of 10 g/dl or less (higher-threshold). The primary endpoint was 28-day mortality. Secondary endpoints included ECMO-free, ventilator-free, sedation-free, and organ dysfunction-free composites.Measurements and main resultsOne hundred ninety-two patients were eligible for analysis of the matched cohort. Patients in the lower-threshold group had similar baseline characteristics and hemoglobin levels at ARDS onset but received fewer RBC units and had lower hemoglobin levels compared with the higher-threshold group during the course on the ICU (9.1 [IQR, 8.7-9.7] vs. 10.4 [10-11] g/dl, P < 0.001). There was no difference in 28-day mortality between the lower-threshold group compared with the higher-threshold group (hazard ratio, 0.94 [95%-CI, 0.59-1.48], P = 0.78). Within 28 days, 36.5% (95%-CI, 27.0-46.9) of the patients in the lower-threshold group compared with 39.5% (29.9-50.1) of the patients in the higher-threshold group had died. While there were no differences in ECMO-free, sedation-free, and organ dysfunction-free composites, the chance for successful weaning from mechanical ventilation within 28 days after ARDS onset was lower in the lower-threshold group (subdistribution hazard ratio, 0.36 [95%-CI, 0.15-0.86], P = 0.02).ConclusionsTransfusion at a hemoglobin concentration of 8 g/dl, as compared with a hemoglobin concentration of 10 g/dl, was not associated with an increase in 28-day mortality in adults with ARDS. However, a transfusion at a hemoglobin concentration of 8 g/dl was associated with a lower chance for successful weaning from the ventilator during the first 28 days after ARDS onset.Trial registrationClinicalTrials.gov NCT03871166.

Project description:BackgroundIn mechanically ventilated patients with acute respiratory distress syndrome (ARDS), electrical impedance tomography (EIT) provides information on alveolar cycling and overdistension as well as assessment of recruitability at the bedside. We developed a protocol for individualization of positive end-expiratory pressure (PEEP) and tidal volume (VT) utilizing EIT-derived information on recruitability, overdistension and alveolar cycling. The aim of this study was to assess whether the EIT-based protocol allows individualization of ventilator settings without causing lung overdistension, and to evaluate its effects on respiratory system compliance, oxygenation and alveolar cycling.Methods20 patients with ARDS were included. Initially, patients were ventilated according to the recommendations of the ARDS Network with a VT of 6 ml per kg predicted body weight and PEEP adjusted according to the lower PEEP/FiO2 table. Subsequently, ventilator settings were adjusted according to the EIT-based protocol once every 30 min for a duration of 4 h. To assess global overdistension, we determined whether lung stress and strain remained below 27 mbar and 2.0, respectively.ResultsProspective optimization of mechanical ventilation with EIT led to higher PEEP levels (16.5 [14-18] mbar vs. 10 [8-10] mbar before optimization; p = 0.0001) and similar VT (5.7 ± 0.92 ml/kg vs. 5.8 ± 0.47 ml/kg before optimization; p = 0.96). Global lung stress remained below 27 mbar in all patients and global strain below 2.0 in 19 out of 20 patients. Compliance remained similar, while oxygenation was significantly improved and alveolar cycling was reduced after EIT-based optimization.ConclusionsAdjustment of PEEP and VT using the EIT-based protocol led to individualization of ventilator settings with improved oxygenation and reduced alveolar cycling without promoting global overdistension. Trial registrationThis study was registered at clinicaltrials.gov (NCT02703012) on March 9, 2016 before including the first patient.

Dataset Information

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.

Publications

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets