The optimal administration time for neostigmine following atracurium blockade. Kinetics of antagonists

Abstract

The aims of the study were: (1) to predict reversal time from intensive atracurium blockade; and (2) to determine the optimal time of neostigmine administration during recovery from atracurium blockade, i.e., the time at which the administration of neostigmine results in the shortest total recovery time (time from administration of last supplemental dose of atracurium to train-of-four [TOF] ratio 0.70), and at the same time results in the shortest time from administration of neostigmine to TOF ratio 0.70. The spontaneous and neostigmine-facilitated recovery in 52 healthy women anaesthetised with thiopentone, fentanyl, droperidol, and nitrous oxide was followed. Post-tetanic count (PTC) of TOF stimulation of the ulnar nerve and mechanomyography were used for monitoring neuromuscular transmission. The neuromuscular blockade was induced with atracurium 0.6 mg/kg and supplemental doses of 0.15 mg/kg were given when the first twitch response in the TOF (TH1) had recovered to 20%. Neostigmine 0.036 mg/kg body weight was given at different levels of neuromuscular blockade to 37 of the patients. Multiple regression analyses including pre-reversal time (time from administration of the last atracurium dose to neostigmine administration), PTC, weight, and age of the patients suggest that pre-reversal time is the best predictor of reversal time: reversal time = 27.3 min - (0.89 x pre-reversal time [min]; (SEE = 6.0 min). If pre-reversal time is unknown, PTC can be used: reversal time = 24 min - (4.5 x ln PTC) at time of reversal); (SEE = 6.8 min). Total recovery time was 47 min (SEM = 2.0 min, n = 15) in the patients allowed to recover spontaneously, and 29 min (SEM = 1.2 min, n = 29) in the patients reversed by neostigmine; the difference of 18 min (SE diff 2.0 min) was significant (P < 0.0005). The level of blockade indicated by PTC (1-24) at the time of reversal had no influence on the total recovery time. The spontaneous recovery times from reappearance of TH1 and TH1 = 10% to TOF ratio 0.70 were 29.2 min (SEM = 1.7 min) and 24.4 min (SEM = 2.6 min), respectively. The results suggest that pre-reversal time is the strongest predictor of reversal time when neostigmine is administered during intense atracurium blockade. To achieve the optimal time-saving effect, neostigmine must be given 18 min (the time saved by giving neostigmine) plus 7 to 11 min (needed for neostigmine to reach its peak effect), giving a total of 25 to 29 min before TOF ratio 0.70. As TH1 is between 1% and 10% 25 to 29 min before TOF ratio 0.70 is reached during spontaneous recovery, the optimal level of neuromuscular blockade for neostigmine administration in atracurium blockade is when TH1 is between 1% and 10%. Reversal time can be predicted as 27.3 min - (0.89 x prereversal time (min), and the optimal time of neostigmine administration in atracurium blockade appears to be when TH1 is 1%-10%.