An updated study-level meta-analysis of randomised controlled trials on proning in ARDS and acute lung injury

International audienceINTRODUCTION: In patients with acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), recent randomised controlled trials (RCTs) showed a consistent trend of mortality reduction with prone ventilation. We updated a meta-analysis on this topic. METHODS: RCTs that compared ventilation of adult patients with ALI/ARDS in prone versus supine position were included in this study-level meta-analysis. Analysis was made by a random-effects model. The effect size on intensive care unit (ICU) mortality was computed in the overall included studies and in two subgroups of studies: those that included all ALI or hypoxemic patients, and those that restricted inclusion to only ARDS patients. A relationship between studies' effect size and daily prone duration was sought with meta-regression. We also computed the effects of prone positioning on major adverse airway complications. RESULTS: Seven RCTs (including 1,675 adult patients, of whom 862 were ventilated in the prone position) were included. The four most recent trials included only ARDS patients, and also applied the longest proning durations and used lung-protective ventilation. The effects of prone positioning differed according to the type of study. Overall, prone ventilation did not reduce ICU mortality (odds ratio = 0.91, 95% confidence interval = 0.75 to 1.2; P = 0.39), but it significantly reduced the ICU mortality in the four recent studies that enrolled only patients with ARDS (odds ratio = 0.71; 95% confidence interval = 0.5 to 0.99; P = 0.048; number needed to treat = 11). Meta-regression on all studies disclosed only a trend to explain effect variation by prone duration (P = 0.06). Prone positioning was not associated with a statistical increase in major airway complications. CONCLUSIONS: Long duration of ventilation in prone position significantly reduces ICU mortality when only ARDS patients are considered

Mechanical influences on fluid leakage past the tracheal tube cuff in a benchtop model

Purpose: High-volume low-pressure (HVLP) cuffs on endotracheal tubes do not fully protect the lower airway from leakage of potentially contaminated secretions down the longitudinal folds within the cuff. Here, our purpose was to evaluate potential effects of positive end-expiratory pressure (PEEP), inspiratory effort intensity, and tube characteristics on fluid leakage past the cuff. Methods: This benchtop study at a research laboratory used a tracheal tube inserted into an artificial Plexiglas trachea connected to a ventilator and lung model. Methylene blue was deposited above the tube cuff to simulate subglottic secretions. Five PEEP levels (0, 5, 10, 15, and 20cmH2O) were tested with volume-controlled ventilation and three simulated inspiratory effort levels with pressure-support ventilation. Several cuff materials and tube sizes were tested. Results: The leakage occurrence rate ranged from 91% with zero PEEP to 8% with 15 and 20cmH2O PEEP and was indirectly proportional to the PEEP level with significant correlation (R 2=0.39, p<0.001), an effect not explained by higher peak inspiratory pressure. Low, moderate, and high inspiratory effort intensities were associated with 38%, 46%, and 75% leakage rates, respectively (p=0.024). Leakage flow was considerably less with polyurethane than with polyvinylchloride tubes (mean 0.5 versus 31.8ml/h). Leakage increased with larger tube diameters. Conclusion: This benchtop study shows that PEEP and a polyurethane cuff prevent leakage past the endotracheal tube cuff, whereas greater inspiratory effort and larger tube diameters for given tracheal size induce or worsen leakag

Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study

International audienceABSTRACT: INTRODUCTION: Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question. METHODS: We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug. RESULTS: Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 67891011121314 vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug. CONCLUSIONS: Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Noninvasive ventilation with helium–oxygen mixture in hypercapnic COPD exacerbation: aggregate meta-analysis of randomized controlled trials

Abstract When used as a driving gas during NIV in hypercapnic COPD exacerbation, a helium–oxygen (He/O2) mixture reduces the work of breathing and gas trapping. The potential for He/O2 to reduce the rate of NIV failure leading to intubation and invasive mechanical ventilation has been evaluated in several RCTs. The goal of this meta-analysis is to assess the effect of NIV driven by He/O2 compared to air/O2 on patient-centered outcomes in hypercapnic COPD exacerbation. Relevant RCTs were searched using standard procedures. The main endpoint was the rate of NIV failure. The effect size was computed by a fixed-effect model, and estimated as odds ratio (OR) with 95% confidence interval (CI). Additional endpoints were ICU mortality, NIV-related side effects, and the length and costs of ICU stay. Three RCTs fulfilled the selection criteria and enrolled a total of 772 patients (386 patients received He/O2 and 386 received air/O2). Pooled analysis showed no difference in the rate of NIV failure when using He/O2 mixture compared to air/O2: 17 vs 19.7%, respectively; OR 0.84, 95% CI 0.58–1.22; p = 0.36; I 2 for heterogeneity = 0%, and no publication bias. ICU mortality was also not different: OR 0.8, 95% CI 0.45–1.4; p = 0.43; I 2 = 5%. However, He/O2 was associated with less NIV-related adverse events (OR 0.56, 95% CI 0.4–0.8, p = 0.001), and a shorter length of ICU stay (difference in means = −1.07 day, 95% CI −2.14 to −0.004, p = 0.049). Total hospital costs entailed by hospital stay and NIV gas were not different: difference in means = −279$, 95% CI −2052–1493, p = 0.76. Compared to air/O2, He/O2 does not reduce the rate of NIV failure in hypercapnic COPD exacerbation. It is, however, associated with a lower incidence of NIV-related adverse events and a shortening of ICU length of stay with no increase in hospital costs