A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants

W Joseph Herring,Aobo Wang,Manfred Blobner,Yuki Mukai,John F Lombard,David M Broussard,Molly Watkins,Li Lin,Jeannine Lutkiewicz

doi:10.1186/s12871-021-01477-5

Abstract

BackgroundThe aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest.MethodsParticipants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias.ResultsOf 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study.ConclusionsCompared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants.Trial registrationClinicalTrials.gov Identifier: NCT03346057.

Highlights

The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria
Studies confirm the safety and efficacy of sugammadex for reversal of moderate or deep, rocuronium- or vecuronium-induced neuromuscular block [6,7,8,9,10,11]; randomized clinical trial data are limited in higher surgical risk ASA Physical Class 3 or 4 participants [2, 6]
No clinically meaningful imbalances in the types of anesthetics used was observed across the treatment groups, mitigating the concern that differences in types of anesthesia administered may have impacted the outcomes seen in this study

Summary

Introduction

The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Studies confirm the safety and efficacy of sugammadex for reversal of moderate or deep, rocuronium- or vecuronium-induced neuromuscular block [6,7,8,9,10,11]; randomized clinical trial data are limited in higher surgical risk ASA Physical Class 3 (defined as severe disease) or 4 (defined as severe systemic disease that is a constant threat to life) participants [2, 6]. In clinical studies involving surgical patients, the rates of bradycardia observed with sugammadex administration consistently appeared lower than that of comparator neostigmine, a reversal agent for which coadministered countermeasures against bradycardia are typically given [16]

Methods

Results

Conclusion