Recovery of neuromuscular function after atracurium and pancuronium maintenance of pancuronium block

David G. Whalley Ma Cha 0 Brenda Lewis oo 0 Nita Marie Bedocs MSNRN 0 0 From the Cleveland Clinic Foundation, Department of General Anesthesiology ,9500 Euclid Ave., M-26, Cleveland, Ohio , USA 44195 . land Clinic Foundation , Department of General Anesthesiology , 9500 Euclid Ave., M-26, Cleveland, Ohio , USA 44195 . Acceptedf o r publication 1st October , 1993 The study was undertaken to determine whether a neuromuscular blockade induced with pancuronium but maintained with atracurium was associated with a shorter time to complete recovery after administration o f neostigmine than i f the blockade was maintained with pancuronium alone. Anaesthesia consisted o f thiopentone, N20/ O2/enflurane and fentanyl, and the neuromuscular blockade, induced by pancuronium 0.1 mg" kg - t was monitored by the force o f contraction o f adductor pollicis during major abdominal surgery lasting 2-5 hr. In 24 patients - Group 1 - atracurium 0.07 rag" kg - t was repeated when the first twitch o f the train-of-four (TOF) returned to 25% o f control (Tt/ TC 25). In 28 patients- Group 2 - pancuronium 0.015 mg" kg - I was given at similar recovery o f Tt/TC. At the end o f surgery, neostigmine 0.07 rag" kg - t and glycopyrrolate 0.015 mg" kg -1 were given to reverse the residual neuromuscular blockade which was indicated by a Tt~ TC o f less than 25% in all patients. The time from injection o f the reversal drugs to a TOF ratio o f 70% was similar in both groups (Group 1, 1L6 + 7.6 min; Group 2, 10.1 + 6 rain; P = NS), but the recovery index was smaller in Group 2 (Group I, 4 42.6 rain; Group 2, 2.61 + 1.2 rain; P < 0.05). Furthermore, there was no difference between groups in the duration o f action o f each redose. The study showed that when compared with pancuronium, equipotent doses o f atracurium were not associated with (a) a shorter time to complete recovery from a neuromuscular blockade induced with pancuronium or Co) a shorter duration o f action. - Cette &ude vise ~ dOterminer si la cumrisation initi~e par le pancuronium mais maintenue ,~l'atracurium pr$sente une r~cup~ration complete plus rapide apr~s l'administration de n~ostigmine que lorsque la curarisation est maintenue par le pancuronium seul. L'anesth~sie est r~alisde avec une association de thiopentone, de NzO/ O2 avec enflurane et du fentanyl; le bloc neuromusculaire est induit par le pancuronium 0,1 mg" kg -1. Le monitorage consiste fi mesurer laforce de contraction de l'adducteur du pouce pendant une chirurgie abdominale majeure d'une dur~e de 2 ~ 5 h. Chez 24 patients (groupe 1), de l'atracurium 0,07 rag" kg - t est rdp~td quand le premier twitch du train-de-quatre (TOF) revient ~ 25% du contrtle (TI/ TC25). Chez 28 patients (groupe 2), du pancuronium 0,015 mg" kg - I e s t administr$ au moment oft la r~cup~ration atteint le trdme degrd. A la fin de la chirurgie, de la n$ostigmine 0,07 tng" kg -~ et du glycopyrrolate 0,015 rag" kg - t sont administr$s pour renverser le bloc neuromusculaire tel que d~montr~ par un Tt/ TC moindre que 25% chez tous lepatients. Le moment de l'injection des antagonistes pour atteindre un TOF de 70% est le mdme pour les deux groupes (groupe 1, 11,6 -4- 7,6 rain; groupe 2, 10,1 + 6 rain; P = NS) mais l'index de r$cupdration est moins ~levd dans le groupe 2 (groupe 1,4 + 2,6 rain; groupe 2, 2,61 5:1,2 min; P < 0.05). On ne note pas non plus de diffdrence entre la durde d'action de chaque dose r$p$Me. Cette ~tude montre qu'on le compare au pancuronium, l'atracurium ?J doses $quipotentes n'est pas associd a) ~ un diminution du temps requis pour une r~cupdration complete du bloc induit au pancuronium ou b) ~ une dur~e d'action plus courte. There have been numerous studies both in adults and children which have documented prolonged neuromuscular blockade that extended into the postanaesthesia recovery period despite diligent intraoperative monitoring and seemingly adequate reversal, i-4 The incidence of impaired neuromuscular function upon arrival in the recovery room has been shown to be approximately 40% following the use of pancuronium but less than 5% after vecuronium or atracurium suggesting the greater safety of these intermediate-acting muscle relaxants. 2.3 Both vecuronium and atracurium have been used to prolong a neuromuscular blockade induced by a longacting muscle relaxant in situations where the shorter duration of action of the former drugs might prove to be advantageous, e.g., during a peritoneal closure. 5-9This has resulted in reduced dose requirements and prolongation of action of the intermediate-acting drugs such that the drug first administered appeared to play a dominant role in influencing the duration of action of the subsequent neuromuscular blocker. 6-9 mps and Inglis have suggested that supplementary doses of atracurium 5-10 mg in an adult patient originally paralyzed with pancuronium provide enhanced neuromuscular blockade without the fear of inadequate reversal at the end of surgery. 5 However, the time to complete recovery after sequential administration of a long- and intermediateacting nondepolarizing muscle relaxant has not been investigated. The hypothesis of the present study was that a neuromuscular blockade induced with pancuronium but maintained by atracurium is associated with a shorter time to complete recovery after neostigmine than if the blockade is maintained by pancuronium alone. The interaction between the two drugs was subsequently examined. Methods With approval of the Institutional Review Board and informed consent, 42 adult patients without hepatic, renal or neuromuscular disease were studied during major colorectal or gynaecological surgery. Each patient received premedication with midazolam 1-3 mg/v before surgery, and anaesthesia was induced with thiopentone 3-5 mg. kg -~ and fentanyl 100-200 ~g. A control recording of neuromuscular transmission was obtained and pancuronium 0.1 mg. kg-J was subsequently given. Neuromuscular function was monitored using a Myograph 2000| (Biometer International A/S, Odense, Denmark). The force of contraction of the adductor pollicis muscle was recorded after stimulation of the ulnar nerve at the wrist by four supramaximai square wave impulses of 200 ~tsec duration delivered at 2 Hz every 12 see through surface electrodes. The outstretched arm was enveloped in a cotton blanket and plastic bag in an attempt to minimize heat loss. After ablation of the twitch response, the patient's trachea was intubated and anaesthesia maintained with nitrous oxide 60% in oxygen, enflurane to a maximum end tidal concentration of 1%, and additional fentanyl as required. Patients were randomly allocated to two groups and received either atracurium 0.07 m g - k g -I or pancuronium 0.015 mg. kg -l mg to maintain muscle relaxation whenever the first twitch (TI) of the train-of-four (TOF) recovered to 25% of control (TI/TC 25). Enflurane was discontinued at the end of surgery at which time neostigmine 0.07 m g . k g -~ and glycopyr (...truncated)