Abstract
Purpose
To compare the pharmacokinetics, pharmacodynamics and the concentration-effect relationship of rocuronium in patients under stable propofol or isoflurane anesthesia.
Methods
Ten patients were randomized to receive fentanyl, propofol and nitrous oxide (60%) or fentanyl, thiopental, isoflurane (1.2% end-tidal concentration) and nitrous oxide (60%). To obtain good intubation conditions and maintain adequate muscle relaxation during surgery patients received two bolus doses of rocuronium: 0.5 mg·kg−1 (1,7 × ED95) at induction followed one hour later by 0.3 mg·kg−1 (1 × ED95). Arterial blood samples were obtained over six hours after the second bolus dose. Plasma concentrations of rocuronium were measured using high pressure liquid chromatography. Muscle twitch tension was monitored by mechanomyography for the two doses. Pharmacokinetic and pharmacodynamic parameters were determined.
Results
No differences in rocuronium pharmacokinetic parameters were observed between both groups. After the second bolus, clinical duration was 20 ± 6 min in the propofol group vs 39 ± 8 min in the isoflurane group (P < 0.05). The effect compartment concentration corresponding to 50% block, EC50 was higher under propofol anesthesia: 1008 vs 592 μg·L−1 (P < 0.05).
Conclusion
Rocuronium body disposition is similar under stable propofol or isoflurane anesthesia. In contrast to isoflurane, propofol does not prolong the neuromuscular block. Therefore, the potentiating effect of isoflurane is of pharmacodynamic origin only, as explained by an increased sensitivity at the neuromuscular junction. In contrast with isoflurane anesthesia where the dose of rocuronium has to be decreased under stable conditions, no dose adjustment is required under propofol anesthesia.
Résumé
Objectif
Comparer la pharmacocinétique, la pharmacodynamie et la relation concentration-effet du rocuronium chez les patients sous anesthésie équilibrée avec propofol ou isoflurane.
Méthodes
Dix patients ont été randomisés pour recevoir fentanyl, propofol et oxide nitreux (60 %) ou fentanyl, thiopental, isoflurane (1,2 % concentration télé-expiratoire) et oxyde nitreux (60 %). Pour obtenir de bonnes conditions d’intubation et maintenir une relaxation musculaire adéquate pendant la chirurgie, les patients ont reçu deux doses de rocuronium : 0,5 mg·kg−1 (1,7 × ED95) à l’induction, suivi de 0,3 mg·kg−1 ( 1 × ED95) une heure plus tard. Des échantillons sanguins artériels ont été prélevés jusqu’à six heures après l’administration du deuxième bolus et les concentrations plasmatiques du rocuronium mesurées par chromatographie liquide haute performance (CLHP). La fonction neuromusculaire a été enregistrée pour les deux doses. On a déterminé les paramètres pharmacocinétiques et pharmacodynamiques.
Résultats
Aucune différence n’a été observée entre les deux groupes pour les paramètres pharmacocinétiques. Après la deuxième dose, la durée clinique a été de 20 ± 6 min pour le groupe propofol comparativement à 39 ± 8 min pour le groupe isoflurane (P < 0,05). La concentration dans le compartiment effet correspondant à 50 % de blocage neuromusculaire, la EC50 a été plus élevée sous anesthésie avec propofol: 1008 vs 592 μg·L−1 (P < 0,05).
Conclusion
L’élimination corporelle du rocuronium est semblable pour les deux types d’anesthésie. Contrairement à l’isoflurane, le propofol ne prolonge pas le blocage neuromusculaire. Par conséquent, l’effet de potentialisation de l’isoflurane serait uniquement d’origine pharmacodynamique et s’expliquerait par une augmentation de la sensibilité au niveau de la jonction neuromusculaire. Contrairement à l’isoflurane qui nécessite une diminution de la dose de rocuronium dans des conditions d’anesthésie équilibrée, aucun ajustement n’est nécessaire sous anesthésie avec propofol.
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This study was supported by the Canadian Institutes of Health Research.
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Dragne, A., Varin, F., Plaud, B. et al. Rocuronium pharmacokinetic-pharmacodynamic relationship under stable propofol or isoflurane anesthesia. Can J Anesth 49, 353–360 (2002). https://doi.org/10.1007/BF03017322
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DOI: https://doi.org/10.1007/BF03017322