Abstract
Purpose
The aim of the study was to determine the optimum time for administration of neostigmine during recovery from atracurium-induced neuromuscular blockade.
Methods
The study comprised 103 patients anaesthetised with midazolam, fentanyl, thiopentone, halothane, and nitrous oxide. Relaxation was induced with atracurium 0.5 mg·kg−1 and maintained with supplements of 0.15 mg·kg−1. The ulnar nerve was stimulated with train-of-four (TOF) and double burst stimulation (DBS). Evoked MMG responses were recorded. Patients were randomized to spontaneous recovery (n = 20) or to assisted recovery by neostigmine (0.07 mg ·kg−1) at varying intervals (6–50 min) from the last atracurium dose (n = 83).
Results
The reversal time (time from administration of neostigmine to TOF ratio 0.7) was always < 13 min, when T1 (first twitch in TOF) was detectable or when D1 (first twitch in DBS) was > 5%. Total assisted recovery time (time from last supplemental atracurium dose to TOF ratio 0.7) increased with increasing T1 and D1 twitch heights (P < 0.05). The curve fitted to the scattergram with total assisted recovery time vs time from last atracurium supplement to neostigmine administration decreased to reach a minimum after which it increased to approach the line of identity. The minimum of the curve (total assisted recovery time 30.7 min) was reached when neostigmine was given 18.6 min after last atracurium supplement. At this time the T1 and D1 twitch height averaged 4 and 8% respectively. If prolongation of the minimum total recovery time of 2.5% is accepted, neostigmine can be given at T1 and D1 twitch height values of 0 to 8% and 4 to 15%, respectively.
Conclusion
The optimum time for neostigmine administration, taking both the reversal time and total recovery time into consideration, is when 0 < T1 < 8% or when 5 < D1 < 15%. Giving neostigmine at more profound degrees of blockade prolongs reversal time, while giving neostigmine later in the recovery phase prolongs total recovery time.
Résumé
Objectif
Déterminer le moment idéal pour l’administration de la néostigmine pendant la phase de récupération du bloc neuromusculaire induit par l’atracurium.
Méthodes
Cette étude évaluait 103 patients anesthésiés au midazolam, fentanyl, thiopentone, halothane et protoxyde d’azote. La relaxation était induite par l’atracurium (0,5 mg·kg−1) et entretenue avec des suppléments de 0,15 mg·kg−1. Le nerf cubital était stimulé avec le train-de-quatre (TOF) et la suppression du double burst (DBS). Les réponses MMG évoquées étaient enregistrées. Les patients étaient répartis au hasard entre récupération spontanée (n = 20) et assistée par la néostigmine (0,07 mg·kg−1) à intervalles variés (6–50 min) après la derniére doses d’atracurium (n = 83).
Résultats
Le temps de neutralisation (l’intervalle entre l’administration de la néostigmine et le retour du rapport TOF 0,7) était toujours < 13 min, au moment où T1 (premier twitch du TOF) était détecté ou quand D1 (premier twitch du DBS) était > 5%. Le temps de la récupération assistée (l’intervalle entre la dernire dose supplémentaire d’atracurium et le rapport TOF = 0,7) augmentait simultanément avec l’ampleur de T1 et D1 (P < 0,05). La courbe du diagramme de dispersion ajustée à la récupération totale assistée vs l’intervalle entre le dernier supplément d’atracurium et l’administration de la néostigmine diminuait pour atteindre un minimum après quoi elle augmentait pour s’approcher de la ligne d’identité. Le creux de la courbe (temps total de récupération assistée 30,7 min) était atteint quand la néostigmine était administrée 18,6 min après le dernier supplément d’atracurium. À ce moment, la hauteur des twitch T1 et D1 était respectivement de 4 et 8%.
Conclusion
En considérant à la fois le temps de neutralisation et le temps total de récupération, le moment idéal pour administrer la néostigmine se situe quand 0 < T1 < 0,8% ou quand 5 < D1 < 15%. L’administration de la néostigmine à des niveaux de bloc plus profonds prolonge le temps de neutralisation; l’administration plus tardive de néostigmine pendant la période de récupération prolonge le temps de récupération totale.
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References
Hennart D, d’Hollander A, Plasman C, De Jonckheere M. Importance of the level of paralysis recovery for a rapid antagonism of atracurium neuromuscular blockade with moderate doses of edrophonium. Anesthesiology 1986; 64: 384–7.
Rupp SM, McChristian JW, Miller RD, Taboada JA, Cronnelly R. Neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium. Anesthesiology 1986; 64:711–7.
Donati F, Lahoud J, McCready D, Bevan DR. Neostigmine, pyridostigmine and edrophonium as antagonists of deep pancuronium blockade. Can J Anaesth 1987; 34: 589–93.
Engbœk J, Østergaard D, Skovgaard LT, Viby-Mogensen J. Reversal of intense neuromuscular blockade following infusion of atracurium. Anesthesiology 1990; 72: 803–6.
Beemer GH, Bjorksten AR, Dawson PJ, Dawson RJ, Heenan PJ, Robertson BA. Determinants of the reversal time of competitive neuromuscular block by anticholinesterases. Br J Anaesth 1991; 66: 469–75.
Payne JP, Hughes R. Evaluation of atracurium in anaesthetized man. Br J Anaesth 1981; 53: 45–54.
Basta SJ, Ali HH, Savarese JJ, et al. Clinical pharmacology of atracurium besylate (BW 33A): a new non-depolarizing muscle relaxant. Anesth Analg 1982; 61: 723–9.
Astley BA, Hughes R, Payne JP. Antagonism of atracurium-induced neuromuscular blockade by neostigmine or edrophonium. Br J Anaesth 1986; 58: 1290–5.
Harper NJN, Wallace M, Hall IA. Optimum dose of neostigmine at two levels of atracurium-induced neuromuscular block. Br J Anaesth 1994; 72: 82–5.
Caldwell JE, Robertson EN, Baird WLM. Antagonism of profound neuromuscular blockade induced by vecuronium or atracurium. Br J Anaesth 1986; 58: 1285–9.
Magorian TT, Lynam DP, Caldwell JE, Miller RD. Can early administration of neostigmine, in single or repeated doses, alter the course of neuromuscular recovery from a vecuronium-induced neuromuscular blockade? Anesthesiology 1990; 73: 410–4.
Delisle S, Bevan DR. Impared neostigmine antagonism of pancuronium during enflurane anaesthesia in man. Br J Anaesth 1982; 54: 441–5.
Baurain MJ, d’Hollander AA, Melot C, Dernovoi BS, Barvais L. Effects of residual concentrations of isoflurane on the reversal of vecuronium-induced neuromuscular blockade. Anesthesiology 1991; 74: 474–8.
Kirkegaard-Nielsen H, May O. Prediction of reversal time and optimal time of neostigmine administration in atracurium blockade. (German) Anaesthesist 1994; 43: 528–33.
Kirkegaard-Nielsen H, May O. Double burst stimulation for monitoring profound neuromuscular blockade: a comparison with posttetanic count and train of four. Acta Anaesthesiol Belg 1992; 43: 253–7.
Kirkegaard-Nielsen H, Helbo-Hansen HS, Lindholm P, Krogh Severinsen I, Bülow K, Jensen EW. Stabilization of the neuromuscular response when switching between different modes of nerve stimulation at surgical degrees of neuromuscular blockade. J Clin Monit 1995; 11: 317–23.
Donati F, Smith CE, Bevan DR. Dose-response relationships for edrophonium and neostigmine as antagonists of moderate and profound atracurium blockade. Anesth Analg 1989; 68: 13–9.
Caldwell JE, Robertson EN, Baird WLM. Antagonism of vecuronium and atracurium: comparison of neostigmine and edrophonium administered at 5% twitch height recovery. Br J Anaesth 1987; 59: 478–81.
Bartkowski RR. Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium. Anesth Analg 1987; 66: 594–8.
Kirkegaard-Nielsen H, Helbo-Hansen HS, Lindholm P, Severinsen IK, Bülow K. Time to peak effect of neostigmine at antagonism of atracuriumor vecuronium-induced neuromuscular block. J Clin Anesth 1995; 7: 635–9.
Fox MA, Keens SJ, Utting JE. Neostigmine in the antagonism of the action of atracurium. Br J Anaesth 1987; 59: 468–72.
Jones JE, Hunter JM, Utting JE. Use of neostigmine in the antagonism of residual neuromuscular blockade produced by vecuronium. Br J Anaesth 1987; 59: 1454–8.
Ali HH, Wilson RS, Savarese JJ, Kitz, RJ. The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth 1975; 47: 570–4.
Brand JB, Cullen DJ, Wilson NE, Ali HH. Spontaneous recovery from nondepolarizing neuromuscular blockade: correlation between clinical and evoked responses. Anesth Analg 1977; 56: 55–8.
Kirkegaard-Nielsen H, Helbo-Hansen HS, Severinsen IK, Lindholm P, Bülow K. Response to double burst appears before response to train-of-four stimulation during recovery from non-depolarizing neuromuscular blockade. Acta Anaesthesiol Scand, in press.
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Kirkegaard-Nielsen, H., Helbo-Hansen, H.S., Lindholm, P. et al. Optimum time for neostigmine reversal of atracurium-induced neuromuscular blockade. Can J Anaesth 43, 932–938 (1996). https://doi.org/10.1007/BF03011807
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DOI: https://doi.org/10.1007/BF03011807