Neuromuscular Blocking Agents and Neuromuscular Dysfunction Acquired in Critical Illness: A Systematic Review and Meta-Analysis

Objective: The relationship between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness remains unclear. We examined the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, and critical illness myopathy. Data Sources: PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and bibliographies of included studies were searched from database inception until September 24, 2015. Study Selection: Randomized controlled trials and prospective observational studies examining the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, or critical illness myopathy. Data Extraction: One author screened titles/abstracts. Two authors independently reviewed full text and extracted data from included studies. Meta-analysis was performed using the DerSimonian-Laird random effects model (OpenMetaAnalyst 10.10 for OS.X). We assessed reporting bias with funnel plots and heterogeneity with the I 2 statistic. Data Synthesis: Of 2,170 titles/abstracts screened, 99 full texts were selected for review, yielding one randomized controlled trial and 18 prospective observational studies, for a total of 2,254 patients. The randomized controlled trial did not show an association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness (odds ratio, 1.21; 95% CI, 0.67–2.19), but pooled data from all included studies suggested a modest association (odds ratio, 1.25; 95% CI, 1.06–1.48; I 2 = 16%). Funnel plots suggested reporting bias, and sensitivity analyses showed a disproportionate contribution from critical illness polyneuropathy/critical illness myopathy and severe sepsis/septic shock studies. Conclusions: This meta-analysis suggests a modest association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness; limitations include studies with a high risk of bias and a disproportionate contribution from studies examining patients for critical illness polyneuropathy/critical illness myopathy and those with severe sepsis/septic shock.