Actual versus ideal body weight dosing of sugammadex in morbidly obese patients offers faster reversal of rocuronium- or vecuronium-induced deep or moderate neuromuscular block: a randomized clinical trial

Abstract

Background: This randomized, double-blind trial evaluated sugammadex-mediated recovery time from rocuronium- or vecuronium-induced moderate (M-) or deep (D-) neuromuscular block in morbidly obese adults dosed by actual (ABW) or ideal body weight (IBW).

Methods: Adults with BMI ≥40 kg/m2 were randomized to 1 of 5 groups: M-neuromuscular block, sugammadex 2 mg/kg ABW; M-neuromuscular block, sugammadex 2 mg/kg IBW; M-neuromuscular block, neostigmine 5 mg, and glycopyrrolate 1 mg; D-neuromuscular block, sugammadex 4 mg/kg ABW; or D-neuromuscular block, sugammadex 4 mg/kg IBW. Supramaximal train of four (TOF) stimulation of the ulnar nerve (TOF-watch SX®) monitored recovery. Primary endpoint was time to TOF ratio ≥ 0.9 for ABW and IBW groups pooled across neuromuscular blocking agent (NMBA)/blocking depth, analyzed by log-rank test stratified for agent and depth. Prespecified safety outcomes included treatment-emergent bradycardia, tachycardia, and other arrhythmias, and adjudicated hypersensitivity and anaphylaxis.

Results: Of 207 patients randomized, 188 received treatment (28% male, BMI 47 ± 5.1 kg/m2, age 48 ± 13 years). Recovery was 1.5 min faster with ABW vs IBW dosing. The sugammadex 2 mg/kg groups recovered 9-fold faster [time 0.11-fold, 95% CI 0.08 to 0.14] than the neostigmine group. ABW (5.3%) and IBW (2.7%) groups had similar incidences of recovery time > 10 min (95% CI of difference: - 4.8 to 11.0%); 84% for neostigmine group. Re-curarization occurred in one patient each in the 2 mg/kg IBW and neostigmine groups. Prespecified safety outcomes occurred with similar incidences.

Conclusions: ABW-based sugammadex dosing yields faster reversal without re-curarization, supporting ABW-based sugammadex dosing in the morbidly obese, irrespective of the depth of neuromuscular block or NMBA used.

Trial registration: Registered on November 17, 2017, at ClinicalTrials.gov under number NCT03346070 .

Keywords: Bradycardia; Multicenter trial; Neostigmine; Recurarization.

Conflict of interest statement

JCH is a former employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. WL, JL, MS, MD, and WJH are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. MB received grants and personal fees from MSD, Haar, Germany, personal fees from Grünenthal, Aachen, Germany, and personal fees from GE Healthcare, Helsinki, Finland. JCH is currently Clinical Professor of Anesthesiology & Critical Care Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Figures

Fig. 1

Modified CONSORT diagram showing patient flow during the study

Fig. 2

Cumulative percentage of patients achieving TOF ratio ≥ 0.9 pooled across depth of block. The 50th and 90th percentile times, in minutes, are marked for the ABW and IBW pooled groups. A given patient’s results were censored if monitoring terminated or data became unreliable

Fig. 3

Recovery time to TOF ratio ≥ 0.9 for subgroups. Point estimates and 95% CI presented for respective pooled ABW and IBW groups