Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing.
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.
Eikermann
M
M
Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. meikermann@partners.org
Zaremba
S
S
Malhotra
A
A
Jordan
A S
AS
Rosow
C
C
Chamberlin
N L
NL
D000732:Androstanols / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000762:Anesthesia Recovery Period; D018685:Anesthetics, Inhalation; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004576:Electromyography / Q000187:drug effects; D007530:Isoflurane; D008297:Male; D009388:Neostigmine / Q000494:pharmacology*; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D012132:Respiratory Muscles / Q000187:drug effects* / Q000502:physiology; D000077123:Rocuronium; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000494:pharmacology*
D000732:Androstanols; D018685:Anesthetics, Inhalation; D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D009388:Neostigmine; D007530:Isoflurane; D000077123:Rocuronium