Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials

Abstract

IntroductionRandomized trials investigating neuromuscular blocking agents in adult acute respiratory distress syndrome (ARDS) have been inconclusive about effects on mortality, which is very high in this population. Uncertainty also exists about the associated risk of ICU-acquired weakness.MethodsWe conducted a systematic review and meta-analysis. We searched the Cochrane (Central) database, MEDLINE, EMBASE, ACP Journal Club, and clinical trial registries for randomized trials investigating survival effects of neuromuscular blocking agents in adults with ARDS. Two independent reviewers abstracted data and assessed methodologic quality. Primary study investigators provided additional unpublished data.ResultsThree trials (431 patients; 20 centers; all from the same research group in France) met inclusion criteria for this review. All trials assessed 48-hour infusions of cisatracurium besylate. Short-term infusion of cisatracurium besylate was associated with lower hospital mortality (RR, 0.72; 95% CI, 0.58 to 0.91; P = 0.005; I2 = 0). This finding was robust on sensitivity analyses. Neuromuscular blockade was also associated with lower risk of barotrauma (RR, 0.43; 95% CI, 0.20 to 0.90; P = 0.02; I2 = 0), but had no effect on the duration of mechanical ventilation among survivors (MD, 0.25 days; 95% CI, 5.48 to 5.99; P = 0.93; I2 = 49%), or the risk of ICU-acquired weakness (RR, 1.08; 95% CI, 0.83 to 1.41; P = 0.57; I2 = 0). Primary studies lacked protracted measurements of weakness.ConclusionsShort-term infusion of cisatracurium besylate reduces hospital mortality and barotrauma and does not appear to increase ICU-acquired weakness for critically ill adults with ARDS.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…Although many of the patients in this trial appeared to meet sepsis criteria, it is not clear whether similar results would occur in sepsis patients or in patients ventilated with alternate modes. Pooled analysis including three trials that examined the role of NMBAs in ARDS, including the one above, showed improved survival (RR 0.72; 95% CI 0.58-0.91) and a decreased frequency of barotrauma (RR 0.43; 95% CI 0.20-0.90) in those receiving NMBAs [395].…”

“…Pooled analysis of the RCT data did not show an increase in neuromuscular weakness in those who received NMBAs (RR 1.08; 95% CI 0.83-1.41); however, this was based on very low quality of evidence [395]. Given the uncertainty that still exists pertaining to these important outcomes and the balance between benefits and potential harms, the panel decided that a weak recommendation was most suitable.…”

Should Early Prone Positioning Be a Standard of Care in ARDS With Refractory Hypoxemia?

“…9 In that trial, both groups received a statistically similar number of therapeutic co-interventions, such as prone positioning (NMBA 42% vs placebo 48%, P ϭ .31), suggesting that these co-interventions were not key factors in demonstrating a clinical effect. Similarly a meta-analysis by Alhazzani et al 56 56 the reduced early use of NMBAs might have affected mortality in the supine group of Guérin et al 20 Complications can occur with prone positioning. Multiple studies have reported an increased risk of pressure ulcers in the prone group.…”

Prescribing Patterns of Drugs in Acute Respiratory Distress Syndrome (ARDS): An Observational Study

“…In comparison with placebo or no intervention, systematic review and meta-analysis of RCTs examining the effect of using NMBA (cisatracurium) resulted in a significant reduction in risk of death at 28 days and at ICU and hospital discharge [26]. Improvements in mortality and gas exchange by NMBs could be related to a decrease in ventilator induced lung injury, as suggested by the decreased incidence of barotrauma and pneumothoraces in the cisatracurium group [27], One of the main complications of corticosteroid treatmentis ICU acquired weakness [28], which is responsible for difficulty in weaning from ventilator.…”