Continuous Neuromuscular Blockade Following Successful Resuscitation From Cardiac Arrest: A Randomized Trial

Abstract

Background Neuromuscular blockade (NMB) agents are often administered to control shivering during targeted temperature management following cardiac arrest. In this study, we hypothesized that early, continuous NMB would result in a greater reduction in serum lactate levels among comatose patients after cardiac arrest. Methods and Results Randomized trial of continuous NMB for 24 hours versus usual care following cardiac arrest conducted at 5 urban centers in the United States. Adult patients who achieved return of spontaneous circulation, remained unresponsive, and underwent targeted temperature management after cardiac arrest were included. The primary outcome was change in lactate over 24 hours. A total of 83 patients were randomized, and 80 were analyzed (37 and 43 in the NMB and usual care arms, respectively). There was no significant interaction between time and treatment group with respect to change in lactate over 24 hours (median lactate change from 4.2 to 2.0 mmol/L [-2.2 mmol/L] in the NMB arm versus 4.0 to 1.7 mmol/L [-2.3 mmol/L] in the usual care arm; geometric mean difference, 1.3 [95% CI, 1.0-1.8]; P=0.07 for the interaction term). There was no difference in hospital survival (38% [NMB] versus 33% [usual care]; P=0.63) or survival with good functional outcome (30% [NMB] versus 21% [usual care]; P=0.35). There were no adverse events in either arm attributed to study interventions. Conclusions Continuous NMB compared with usual care did not reduce lactate over the first 24 hours after enrollment compared with usual care. There was no difference in overall hospital survival, hospital survival with good neurologic outcome, or adverse events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02260258.

Keywords: biomarkers; cardiopulmonary resuscitation; clinical trial; heart arrest; hypothermia; neuromuscular blockade.

Figure 1. Consolidated Standards of Reporting Trials diagram.

LAR indicates legally authorized representative; mRS, modified Rankin Scale; and NMB, neuromuscular blockade.

Figure 2. Longitudinal plot of lactate over time.

Figure 3. Biomarkers of neurologic injury over time.

Change in biomarker levels over time assessed via mixed model, controlling for shock stratification as a fixed effect and study site as a random effect. Biomarker values log transformed for the analysis as their distributions visually deviated from normal. P values reflect the interaction between randomization group and time. NMB indicates neuromuscular blockade; and NSE, neuron‐specific enolase.