The combination of sugammadex and neostigmine can reduce the dosage of sugammadex during recovery from the moderate neuromuscular blockade

Abstract

Background: Sugammadex is a novel neuromuscular reversal agent, but its associated hypersensitivity reaction and high cost have been obstacles to its widespread use. In the interest of reducing the necessary dosage of sugammadex, the reversal time of the combined use of sugammadex and neostigmine from moderate neuromuscular blockade were investigated.

Methods: The patients enrolled ranged in age from 18 to 65 years old with American Society of Anesthesiologists class 1 or 2. The subjects were randomly assigned into one of the four groups (Group S2, S1, SN, and N; n = 30 per group). The reversal agents of each groups were as follows: S2 - sugammadex 2 mg/kg, S1 - sugammadex 1 mg/kg, SN - sugammadex 1 mg/kg + neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg, N - neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg. The time to recovery of the train-of-four (TOF) ratio was checked in each group.

Results: The time to 90% recovery of TOF ratio was 182.6 ± 88.9, 371.1 ± 210.4, 204.3 ± 103.2, 953.2 ± 379.7 sec in group S2, S1, SN and N, respectively. Group SN showed a significantly shorter recovery time than did group S1 and N (P < 0.001). However, statistically significant differences between the S2 and SN groups were not be observed (P = 0.291). No hypersensitivity reactions occurred in all groups.

Conclusions: For the reversal from rocuronium-induced moderate neuromuscular blockade, the combined use of sugammadex and neostigmine may be helpful to decrease the recovery time and can also reduce the required dosage of sugammadex. However, the increased incidence of systemic muscarinic side effects must be considered.

Keywords: Neostigmine; Neuromuscular blockade; Rocuronium; Sugammadex.

Fig. 1. CONSORT flow diagram.

Fig. 2. The time to 70, 80 and 90% recovery of TOF ratio. Group N showed significantly longer time to 70, 80 and 90% recovery of TOF ratio than the other groups (P < 0.001). Group S2 and Group SN did not show significant difference in time to 70, 80 and 90% recovery of TOF ratio. The thick lines represent the median values, boxes indicate the interquartile range, whiskers represent the 10^th and 90^th percentiles, and block dots represent outliers. Group S2: sugammadex 2 mg/kg, Group S1: sugammadex 1 mg/kg, Group SN: sugammadex 1 mg/kg + neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg, Group N: neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg (^*P < 0.05 when compared with group S1, ^†P < 0.001 when compared with the other groups, ^‡P < 0.001 when compared with group S1).

Fig. 3. The trend of the (A) mean blood pressure (MBP), and (B) heart rate (HR) after administration of neuromuscular reversal agents. (A) Immediately after the reversal agents administration, the MBP of group SN was significantly lower than group S2 and N (P < 0.05). After 5 min of the reversal agents administration, the MBP of the group SN and N were significantly lower than that of group S1 (P < 0.05), and the MBP of group SN was significantly lower than that of S2 (P < 0.05). After 10 min of the reversal agents administration, group N showed significantly lower MBP than group S2 and S1 (P < 0.05). (B) The HR of the group N were significantly lower than group S1 and S2 after 5 and 10 min of the reversal agents administration (P < 0.001). The group SN showed significantly lower HR than group S2 and S1 (P < 0.05) after 5 min, and significantly higher HR than group N (P < 0.05) and lower HR than group S2 (P < 0.05) after 10 min of the reversal agents administration. The thick lines represent the median values, boxes indicate the interquartile range, whiskers represent the 10^th and 90^th percentiles, and block dots represent outliers. Group S2: sugammadex 2 mg/kg, Group S1: sugammadex 1 mg/kg, Group SN: sugammadex 1 mg/kg + neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg, Group N: neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg (^*P < 0.05, ^†P < 0.001 when compared between groups).