Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine

Abstract

Background: Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia.

Methods: Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events.

Results: Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group.

Conclusions: Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694).

Figure 1

Patient disposition. One patient randomized to sugammadex/vecuronium was mistakenly given neostigmine/rocuronium and excluded from the AST population, but included in the ITT population according to the proposed randomization.*Data for patients randomized to the rocuronium arm have been reported elsewhere [5]. AST, all-subjects-treated; ITT, intent-to-treat; TOF, train-of-four.

Figure 2

Examples of recovery profiles for vecuronium 0.1 mg/kg after administration of (A) sugammadex 4 mg/kg or (B) neostigmine 70 μg/kg at a target of 1-2 PTC. Bars represent first twitch (T₁) values (twitch height %) and dots represent the TOF ratio. PTC, post-tetanic-counts; TOF, train-of-four.

Figure 3

Time (min) from start of administration of sugammadex or neostigmine to recovery of the TOF ratio to 0.9 (intent-to-treat population, imputed data, n = 47 for sugammadex and n = 36 for neostigmine). TOF, train-of-four.