Antagonism of low degrees of atracurium-induced neuromuscular blockade: dose-effect relationship for neostigmine.
BACKGROUND
Low degrees of residual paralysis (i.e., a train-of-four [TOF] ratio > 0.4) are relatively frequent, difficult to detect, and still potentially harmful. Unfortunately, the appropriate dose of anticholinesterase for this situation has not been determined. This may be of clinical interest because a high dose of neostigmine given at a shallow level of neuromuscular block may produce neuromuscular weakness. The purpose of this study was to investigate the dose-effect relationship of neostigmine to antagonize residual paralysis corresponding to a TOF ratio of 0.4 and 0.6.


METHODS
Recovery after 10, 20, 30 microg/kg neostigmine or placebo given at either 0.4 or 0.6 TOF ratio was assessed by acceleromyography in 120 patients undergoing intravenous anesthesia. Time to a 0.9 and 1.0 TOF ratio was measured, and the probability of successful reversal within 10 min after the respective neostigmine doses was calculated. In addition, the dose of neostigmine needed to achieve the recovery targets in 5 or 10 min was also determined.


RESULTS
When given at a TOF ratio of either 0.4 or 0.6, time to 0.9 and 1.0 TOF ratio was significantly shorter with any dose of neostigmine than without. The probability of successful reversal after 20 microg/kg neostigmine was 100% when a TOF ratio of 0.9 was the target; for a TOF ratio of 1.0, the probability was 93% and 67%, dependent on whether the dose of neostigmine was given at TOF ratio of 0.6 or 0.4, respectively. With a dose of 30 microg/kg, a TOF ratio of 1.0 is expected to be reached within approximately 5 min. Low doses of neostigmine are required to reach a TOF ratio of 0.9 or to accept an interval of 10 min.


CONCLUSIONS
Reduced doses (10-30 microg/kg) of neostigmine are effective in antagonizing shallow atracurium block. For successful reversal within 10 min, as little as 20 microg/kg neostigmine may be sufficient. These dose recommendations are specific for atracurium and an intravenous anesthetic background.
Fuchs-Buder
Thomas
T
Department of Anesthesia and Critical Care, Centre Hospitalier Universitaire, Institut de la Sante et de la Recherche Medicale, CIC-EC CIE6, Nancy, France. t.fuchs-buder@chu-nancy.fr
Meistelman
Claude
C
Alla
François
F
Grandjean
Arnaud
A
Wuthrich
Yann
Y
Donati
François
F
D000758:Anesthesia; D000762:Anesthesia Recovery Period; D001279:Atracurium / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006801:Humans; D016343:Monitoring, Intraoperative; D009388:Neostigmine / Q000494:pharmacology*; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010243:Paralysis / Q000139:chemically induced
D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D009388:Neostigmine