Early neuromuscular blockade for acute respiratory distress syndrome: a systematic review with meta-analysis and trial sequential analysis

Abstract

Background To assess the effect of neuromuscular blockade on outcomes in adults with acute respiratory distress syndrome who are receiving mechanical ventilation.Methods We searched from inception to 24 may 2019 in MEDLINE, EMBASE and CENTRAL. We included randomized clinical trials comparing early neuromuscular blockade to placebo or usual care in adults with moderate to severe ARDS (PaO2/FiO2≤150mmHg). The primary outcome was 90-day and 28-day mortality. Secondary outcomes included oxygenation, driving pressure, incidence of barotrauma and pneumothorax, ventilator-free days at 28 days and ICU-acquired weakness by 28 days. In addition, a trial sequential analysis was performed.Results Four trials were included with a total of 1437 patients. For the primary outcomes, there was no effect of neuromuscular blocking agent (NMBA) on 90-day mortality [relative risk (RR) 0.91, 95%CI 0.72-1.15, p=0.41] or 28-day mortality [RR 0.55, 95%CI 0.22-1.12, p=0.08], or ventilator-free days at 28 days [mean difference (MD) 0.86, 95%CI -0.61-2.33, p=0.25]. NMBA improved PaO2/FiO2 at 72h [MD 15.21, 95%CI 1.90-28.52, p=0.03]. NMBA reduced the incidence of barotrauma [RR 0.55, 95%CI 0.35-0.85, p=0.007] and pneumothorax [RR 0.46, 95%CI 0.28-0.76, p=0.002] and increased the driving pressure at 24 hours [MD 0.75, 95%CI 0.24-1.26, p=0.004] and 48 hours [MD 0.75, 95%CI 0.08-1.43, p=0.03]. There is no statistically significant difference in ICU-acquired weakness by 28 days [RR 1.20, 95%CI 0.72-1.98, p=0.49].Conclusions In adults with moderate to severe ARDS treated with early neuromuscular blockade, oxygenation increase, incidence of barotrauma and pneumothorax are reduced, ICU-acquired weakness are not increased, but 90-day and 28-day mortality are not decreased. Further large-scale, multicenter studies are needed to confirm our results.Trial Registry PROSPERO (ID: CRD42019137832)