1Department of Anaesthesiology, Surugadai Nihon University Hospital, 1-8-13, Kanda-Surugadai, Chiyoda-Ku, Tokyo, Japan. Departments of 2Hygiene and 3Anaesthesiology, Nihon University School of Medicine, Tokyo, Japan
Accepted for publication: June 26, 2000
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Abstract |
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Br J Anaesth 2000; 85: 7324
Keywords: pharmacology, doseresponse relationship; neuromuscular block, vecuronium; anaesthetics volatile, sevoflurane
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Introduction |
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Methods |
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All patients were premedicated with pethidine 50 mg and atropine 0.5 mg i.m. approximately 45 min before induction of anaesthesia. An intravenous infusion of Ringers acetated solution was started and electrocardiogram, pulse oximeter and non-invasive arterial pressure were continuously monitored after arrival in the operating theatre. Anaesthesia was induced with fentanyl 24 µg kg1 and propofol 2.02.5 mg kg1. After topical anaesthesia with lidocaine 2%, the patients trachea was intubated without the use of an NMBA. Anaesthesia was maintained with an end-tidal concentration of 1.7% sevoflurane and 67% nitrous oxide in oxygen which was monitored throughout the study with an anaesthetic gas analyser (Capnomac Ultima; Datex, Helsinki, Finland). Additional fentanyl was administered as required. Ventilation was adjusted to keep end-tidal PCO2 within the range 3538 mm Hg. Oesophageal and skin temperature over the thenar muscles were kept above 35°C and 33°C respectively, with a heating mattress and cotton wool.
The patients were allocated at random using the sealed envelope method to receive vecuronium after 15, 30, 60 or 90 min exposure to sevoflurane (10 patients per group). At least 15 min before the administration of vecuronium, stimulation of the ulnar nerve was commenced at the wrist with square-wave supramaximal stimuli of 0.2 ms duration, delivered in a train-of -four (TOF) mode at 2 Hz every 15 s using a TOF guard (Organon Teknika NV, Turnhout, Belgium). The contraction of the ipsilateral adductor pollicis muscle was measured by accelerometry. When baseline neuromuscular responses had stablized, patients were given vecuronium by a cumulative dose technique. Vecuronium 10 µg kg1 was administered repeatedly via a rapidly running infusion until 95% depression of the first twitch response (T1) in each TOF sequence was achieved. Repeated doses were administered when stable responses, defined as three equal consecutive T1 responses, had been obtained after the previous dose, or when no further depression of the T1 response had been obtained for at least 5 min after the last dose. The individual doseresponse relationship was examined by plotting the log dose against the logit transformation of T1 depression relative to baseline. Regression lines were constructed by least-squares regression analysis and parallelism of the lines was determined between groups. The effective doses of vecuronium that depressed the amplitude of T1 in each TOF sequence by 50%, 90% and 95% (ED50, ED90 and ED95, respectively) were calculated from the regression lines and compared between the groups.
Data are presented as mean (SD or SEM). Statistical analysis was performed using the KruskalWallis test. A P value of <0.05 was considered statistically significant. If a significant P value was obtained, further group comparisons were made using Scheffes F-test or Fishers PLSD test.
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Results |
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Discussion |
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Sevoflurane has a low blood/gas and tissue/gas solubility,1012 so equilibration between the end-tidal concentration and the neuromuscular junction should be reached more rapidly with this agent than with other inhalational anaesthetics. We found a lower potency of vecuronium using doseresponse studies after 15 min exposure to sevoflurane than after longer time periods. We suggest that the duration of sevoflurane anaesthesia influences the doseresponse of vecuronium significantly and 30 min inhalation of an end-tidal concentration of 1.7% sevoflurane with nitrous oxide is sufficient to achieve a stable potentiating effect on vecuronium. The maximum potentiating effect of sevoflurane is therefore established more quickly than with other inhalational agents,6 7 except for desflurane,18 which is less soluble in blood and tissue than sevoflurane.11 12 Meretoja and colleagues6 showed that 1 MAC end-tidal concentration of halothane and isoflurane produced a maximal neuromuscular effect in 3080 min. Withington and colleagues7 indicated that a longer exposure to 1 MAC end-tidal concentration of enflurane (45120 min) was required to obtain a steady neuromuscular potentiating effect. In fact, the time course of augmentation by inhalational anaesthetics on NMBA differs markedly among the agents and sevoflurane seems to achieve the fastest onset of stable neuromuscular inhibition.
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Footnotes |
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References |
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