Low-dose neostigmine to antagonise shallow atracurium neuromuscular block during inhalational anaesthesia

Abstract

Even shallow residual neuromuscular block [i.e. train-of-four (TOF) ratio around 0.6] is harmful. It can be effectively antagonised by small doses of neostigmine, but reports are limited to intravenous anaesthesia. Inhalational anaesthesia may enhance neuromuscular block and delay recovery. It is not known whether low doses of neostigmine are still effective in the context of inhalational anaesthesia. To assess the effectiveness of low doses of neostigmine to antagonise shallow atracurium block during desflurane anaesthesia. Randomised controlled trial, four groups. Single centre, University Hospital, May 2010 to March 2011. Forty-eight American Society of Anesthesiologists I-III patients undergoing desflurane anaesthesia. At TOF ratio 0.6, patients were randomised to one of four treatments (physiological saline, 10, 20 or 30 µg kg(-1) neostigmine, n = 12 for each). Primary efficacy endpoint: time interval between study drug injection and a TOF ratio more than 0.9 using acceleromyography. Secondary efficacy endpoint: neuromuscular recovery after 5 and 10 min. After physiological saline, the time interval [median (range)] between a TOF ratio of 0.6 and 0.9 was 14 (7 to 18) min. After 10, 20 and 30 µg kg(-1) neostigmine, it was reduced to 5 (3 to 8) min, 5 (3 to 10) and 4 (2 to 6) min, respectively (P < 0.001 compared to physiological saline). At 5 min after physiological saline, the TOF ratio [mean (SD)] was 0.73 (0.05) and 0.91 (0.06), 0.90 (0.10), 0.96 (0.02) after neostigmine 10, 20 or 30 µg kg(-1), respectively (P < 0.01 compared to physiological saline). At 10 min after physiological saline, the TOF ratio was 0.86 (0.08) and 1.0 (0), 0.98 (0.03), 1.0 (0) after neostigmine 10, 20 or 30 µg kg(-1), respectively (P < 0.01 compared to physiological saline). Under desflurane anaesthesia, neostigmine 10 µg kg(-1) is effective in antagonising shallow atracurium block. Compared to no neostigmine, the time to a TOF ratio more than 0.9 was shortened and neuromuscular recovery at 5 and 10 min was more advanced. EudraCT Nr. is 2009 -018214-19.