title: Antagonism of mivacurium-induced neuromuscular blockade in humans. Edrophonium dose requirements at threshold train-of-four count of 4.
abstract: BACKGROUND
  Mivacurium's rapid rate of recovery has led to the suggestion that routine reversal of its residual effects may be unnecessary once signs of spontaneous recovery are evident. When antagonism is attempted at 90% twitch depression, the time saved to return to train-of-four (TOF) ratios > 0.70 compared to control has been reported to average < or = 8 min. This study was an attempt to determine whether similar savings in time could be achieved once spontaneous recovery was well underway. Also investigated was the ability of a TOF count of 4 to serve as a marker that might predict the dose of edrophonium necessary for satisfactory antagonism of mivacurium.
  
  
  METHODS
  Fifty-eight adult patients were studied under nitrous oxide/propofol/opioid anesthesia. Neuromuscular block was monitored electromyographically and maintained by infusion of mivacurium at a level sufficient to abolish any palpable response of the thumb. TOF stimuli were delivered to the ulnar nerve at the wrist every 20 s throughout the period of observation. When the infusion was terminated, an observer was asked to note the time when the 1st through the 4th twitches first became detectable. In group 1, recovery to a TOF ratio > 0.90 was allowed to proceed spontaneously. In groups 2, 3, and 4, 0.3, 0.5, and 0.75 mg/kg edrophonium, respectively, was administered when the 4th response to TOF stimulation first became palpable. Times to TOF ratios of 0.70 and 0.90 were recorded in all groups.
  
  
  RESULTS
  TOF counts of 1, 2, 3, and 4 first became palpable at 8 +/- 4% (SD), 20 +/- 6%, 33 +/- 9%, and 44 +/- 10% of control twitch height. Fade on TOF stimulation could no longer be detected once the TOF ratio exceeded a value of 0.41 +/- 0.07 (range 0.25-0.51). Once the 1st evoked response was palpable, the 2nd, 3rd, and 4th responses could be detected 2.5 +/- 1.1 (SD), 4.6 +/- 1.6, and 6.1 +/- 1.6 min later. Spontaneous recovery to TOF fade ratios of 0.7 and 0.9 occurred on average 10.7 +/- 2.3 and 16.9 +/- 4.7 min, respectively, after a threshold count of 4. Administration of 0.3 mg/kg edrophonium shortened the recovery process by about 7.5 min. Increasing the dose of edrophonium beyond 0.3 mg/kg did not further accelerate recovery.
  
  
  CONCLUSIONS
  After recovery from profound mivacurium-induced neuromuscular block, TOF counts of 1, 2, 3, and 4 approximate 10%, 20%, 30%, and 40% return to control twitch height, respectively. Finally, > or = 0.3 mg/kg edrophonium will accelerate recovery from mivacurium by approximately 7-8 min.
authors.affiliation: Department of Anesthesiology, St. Vincent's Hospital and Medical Center of New York, New York City 10011.
authors.forename: A F
authors.initials: AF
authors.lastname: Kopman
authors.forename: M U
authors.initials: MU
authors.lastname: Mallhi
authors.forename: M D
authors.initials: MD
authors.lastname: Justo
authors.forename: P
authors.initials: P
authors.lastname: Rodricks
authors.forename: G G
authors.initials: GG
authors.lastname: Neuman
mesh_terms: D000328:Adult; D000368:Aged; D000762:Anesthesia Recovery Period; D004305:Dose-Response Relationship, Drug; D004491:Edrophonium / Q000494:pharmacology*; D004576:Electromyography; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D009469:Neuromuscular Junction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009609:Nitrous Oxide; D015742:Propofol; D013997:Time Factors
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D004491:Edrophonium; D000077590:Mivacurium; D009609:Nitrous Oxide; D015742:Propofol