Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys

Anesthesiology. 2006 Apr;104(4):718-23. doi: 10.1097/00000542-200604000-00016.

Abstract

Background: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the anesthetized rhesus monkey using train-of-four stimulation.

Methods: Four female rhesus monkeys each underwent three experiments. In each experiment, first, a 100-microg/kg dose of rocuronium was injected and spontaneous recovery was monitored. After full recovery, a 500-microg/kg dose of rocuronium was injected. Up to this point, all three experiments in a single monkey were identical. One minute after this rocuronium injection, either one of the two tested dosages of sugammadex (1.0 or 2.5 mg/kg) was injected or saline was injected.

Results: Injection of 100 microg/kg rocuronium resulted in a mean neuromuscular blockade of 93.0% (SD = 4%), and profound blockade was achieved by injection of 500 microg/kg. In all experiments, a 100% neuromuscular blockade was achieved at this dose. After injection of the high rocuronium dose, the 90% recovery of the train-of-four ratio took 28 min (SD = 7 min) after saline, 26 min (SD = 9.5 min) after 1 mg/kg sugammadex, and 8 min (SD = 3.6 min) after 2.5 mg/kg sugammadex. Signs of residual blockade or recurarization were not observed. Injection of sugammadex had no significant effects on blood pressure or heart rate.

Conclusions: Chemical encapsulation of rocuronium by sugammadex is a new therapeutic mechanism allowing effective and rapid reversal of profound neuromuscular blockade induced by rocuronium in anesthetized rhesus monkeys.

MeSH terms

  • Androstanols / antagonists & inhibitors*
  • Androstanols / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Cholinesterase Inhibitors / pharmacology
  • Female
  • Heart Rate / drug effects
  • Macaca mulatta
  • Neuromuscular Blockade*
  • Neuromuscular Nondepolarizing Agents / antagonists & inhibitors*
  • Rocuronium
  • Sugammadex
  • gamma-Cyclodextrins / pharmacology*

Substances

  • Androstanols
  • Cholinesterase Inhibitors
  • Neuromuscular Nondepolarizing Agents
  • gamma-Cyclodextrins
  • Sugammadex
  • Rocuronium