scholarly journals Early neuromuscular blocking agents for adults with acute respiratory distress syndrome: a systematic review, meta-analysis and meta-regression

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e037737
Author(s):  
Shuai Shao ◽  
Hanyujie Kang ◽  
Zhaohui Tong

ObjectiveTo determine whether neuromuscular blocking agents (NMBAs) can decrease the mortality of patients with acute respiratory distress syndrome (ARDS) and improve their clinical outcomes.DesignSystematic review, meta-analysis and meta-regression.Data sourcesPubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov.MethodsRandomised controlled trials (RCTs) comparing the treatment effect of NMBAs with that of placebo (or traditional treatment) in patients with ARDS were carefully selected. The primary outcome was 90-day mortality. The secondary outcomes were 21–28 days mortality, NMBA-related complications (barotrauma, pneumothorax and intensive care unit (ICU)-acquired muscle weakness), days free of ventilation and days not in the ICU by day 28, Medical Research Council score, Acute Physiology and Chronic Health Evaluation II score and arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (at 48 hours and 72 hours). Random-effects meta-regression was used to explore models involving potential moderators. Trial sequential analysis was performed to estimate the cumulative effect on mortality across RCTs.ResultsNMBAs were not associated with reduced 90-day mortality (risk ratio (RR) 0.85; 95% CI 0.66 to 1.09; p=0.20). However, they decreased the 21–28 days mortality (RR 0.71; 95% CI 0.53 to 0.96; p=0.02) and the rates of pneumothorax (RR 0.46; 95% CI 0.28 to 0.77; p=0.003) and barotrauma (RR 0.56; 95% CI 0.37 to 0.86; p=0.008). In addition, NMBAs increased PaO2/FiO2 at 48 hours (mean difference (MD) 18.91; 95% CI 4.29 to 33.53; p=0.01) and 72 hours (MD 12.27; 95% CI 4.65 to 19.89; p=0.002). Meta-regression revealed an association between sample size (p=0.042) and short-term mortality. Publication year (p=0.050), sedation strategy (p=0.047) and sample size (p=0.046) were independently associated with PaO2/FiO2 at 48 hours.ConclusionsIn summary, the results suggested that use of NMBAs might reduce 21–28 days mortality, NMBA-related complications and oxygenation. However, NMBAs did not reduce the 90-day mortality of patients with ARDS, which contradicts a previous meta-analysis.PROSPERO registration numberCRD42019139440.

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Nehal Tarazan ◽  
◽  
Moayad Alshehri ◽  
Sameer Sharif ◽  
Zainab Al Duhailib ◽  
...  

Abstract Purpose Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS. Methods We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries (ClinicalTrials.gov, ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data. Results Seven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86–1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57–0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35–0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain. Conclusions Inconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review.


2020 ◽  
Author(s):  
Divyajot Sadana ◽  
Simrat Kaur ◽  
Kesavan Sankaramangalam ◽  
Kinjal Banerjee ◽  
Matthew Siuba ◽  
...  

Abstract Background: Acute respiratory distress syndrome (ARDS) is a common occurrence in an intensive care unit. The reported mortality in studies evaluating acute respiratory distress syndrome is highly variable. The adherence to ventilatory specific and adjunctive therapies is also highly variable. We investigated the mortality of ARDS since the 2009 H1N1 pandemic and examined the adherence to ventilatory specific and adjunctive therapies.Methods: We performed a systematic search in MEDLINE and EMBASE using a highly sensitive criterion from January 2009 to May 2019. We then ran a proportional meta-analysis for mortality and a meta-regression analysis using certain variables to address heterogeneity. Results: We screened 5361 citations, of which 85 fully met inclusion criteria. The weighted pooled mortality of all 85 studies published from 2009 to 2019 was 38% (95% CI 35,40). Mortality was higher in observational studies [40% (95% CI 37, 42)] compared to RCTs [35% (95% CI 30,39)], (p=0.04) Significant variability exists in literature of reported tidal volumes, positive end expiratory pressures, plateau pressures, and use adjunctive therapies. The tidal volumes in our systematic review ranged from 5.8 to 8.9 ml/kg with a mean of 7.2 ml/kg. PEEP ranged from 4.6 to 16.1 cm H2O at the time of enrollment with a mean of 10.2 cm H2O. Reported plateau pressures ranged from 21.0 to 35.1 cm H2O, with a mean of 25.6 cm H2O. Higher reported initial PaO2/FiO2 ratios were associated with decreased mortality. A trend towards decreased mortality was seen with lower reported tidal volumes in the included studies.Conclusions: Over the last decade, the mortality in ARDS has marginally improved and there exists significant heterogeneity in the utilization of low tidal volume strategies, application of PEEP and the adoption of adjunctive therapies in the management of these patients in published literature.


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