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

BMC Anesthesiol. 2021 Oct 28;21(1):259. doi: 10.1186/s12871-021-01477-5.


Background: 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. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest.

Methods: Participants 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.

Results: Of 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.

Conclusions: Compared 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 registration: ClinicalTrials.gov Identifier: NCT03346057 .

Keywords: ASA physical class 3 or 4; Sugammadex: safety.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bradycardia / chemically induced*
  • Cholinergic Agents / administration & dosage
  • Cholinergic Agents / adverse effects
  • Double-Blind Method
  • Female
  • Glycopyrrolate / administration & dosage
  • Glycopyrrolate / adverse effects
  • Humans
  • Male
  • Neostigmine / administration & dosage
  • Neostigmine / adverse effects
  • Neuromuscular Blockade*
  • Neuromuscular Nondepolarizing Agents / administration & dosage
  • Rocuronium / administration & dosage
  • Rocuronium / adverse effects
  • Sugammadex / administration & dosage
  • Sugammadex / adverse effects*
  • Tachycardia / chemically induced*
  • Vecuronium Bromide / administration & dosage
  • Vecuronium Bromide / adverse effects


  • Cholinergic Agents
  • Neuromuscular Nondepolarizing Agents
  • Sugammadex
  • Neostigmine
  • Vecuronium Bromide
  • Glycopyrrolate
  • Rocuronium

Associated data

  • ClinicalTrials.gov/NCT03346057