Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing

Abstract

Background: Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown.

Methods: Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg(-1) and neostigmine 0.06 mg kg(-1) to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing.

Results: During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively (sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable.

Conclusions: In contrast to neostigmine, which significantly impairs upper airway dilator muscle activity when given after recovery from neuromuscular block, a reversal dose of sugammadex given under the same conditions does not affect genioglossus muscle activity and normal breathing. Human studies will be required to evaluate the clinical relevance of our findings.

Fig 1

Effects of reversal of partial paralysis (T4/T1=0.5) on breathing and T4/T1 ratio (efficacy data). Recovery time of minute volume to baseline values observed before administration of neuromuscular blocking agents was significantly shorter with sugammadex and neostigmine compared with placebo. The accelerating effect was significantly stronger with sugammadex compared with neostigmine. The effect of reversal agents on breathing paralleled those on T4/T1 recovery. In the placebo group, the T4/T1 recovery time was significantly longer than the time to recovery of the minute volume. *P<0.05 vs placebo; ^#P<0.05 vs neostigmine; ^XP<0.05 vs T4/T1 (placebo group).

Fig 2

Effects of sugammadex and neostigmine reversal after recovery of T4/T1 to 1 (safety data). Drugs were given after spontaneous recovery of the T4/T1 to 1. Values are given as per cent of values observed immediately after injection of reversal agents. (a) Primary outcome. Effects on upper airway dilator muscle activity. Neostigmine significantly decreases EMG activity of the genioglossus muscle, whereas sugammadex does not have significant effects. Individual values, means and sem. (b and c) Effects on ventilation. Tidal volume was significantly lower, and minute volume tended to be lower after neostigmine reversal compared with sugammadex. *P<0.05 vs sugammadex; ^#P<0.1 vs sugammadex.