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Canadian Journal of Anesthesia

, Volume 49, Issue 4, pp 353–360 | Cite as

Rocuronium pharmacokinetic-pharmacodynamic relationship under stable propofol or isoflurane anesthesia

  • Alexandrina Dragne
  • France Varin
  • Benoît Plaud
  • François Donati
General Anesthesia

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.

Keywords

Isoflurane Rocuronium Isoflurane Anesthesia Effect Compartment Rocuronium Bromide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

La relation pharmacocinétique-pharmacodynamique du rocuronium pendant une anesthésie avec propofol ou isoflurane

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.

References

  1. 1.
    Van der Broek L, Wierda JMKH, Smeulers NJ, et al. Clinical pharmacology of rocuronium (Org 9426); study of the time course of action, dose requirement, reversibility and pharmacokinetics. J Clin Anesth 1994; 6: 288–96.PubMedCrossRefGoogle Scholar
  2. 2.
    Cannon JE, Fahey MR, Castagnoli KP, et al. Continuous infusion of vecuronium: the effect of anesthetic agents. Anesthesiology 1987; 67: 503–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Zhu Y, Audibert G, Donati F, Varin F. Pharmacokinetic-pharmacodynamic modeling of doxacurium: effect of input rate. J Pharmacokinet Biopharm 1997; 25: 23–37.PubMedCrossRefGoogle Scholar
  4. 4.
    Gariepy LP, Varin F, Donati F, Salib Y, Bevan DR. Influence of aging on the pharmacokinetics and pharmacodynamics of doxacurium. Clin Pharmacol Ther 1993; 53: 340–7.PubMedGoogle Scholar
  5. 5.
    Yasuda N, Lockhart SH, Eger IIEI, et al. Kinetics of desflurane, isoflurane, and halothane in humans. Anesthesiology 1991; 74: 489–98.PubMedCrossRefGoogle Scholar
  6. 6.
    Ducharme J, Varin F, Bevan DR, Donati F. Importance of early blood sampling on vecuronium pharmacokinetic and pharmacodynamic parameters. Clin Pharmacokinet 1993; 24: 507–18.PubMedGoogle Scholar
  7. 7.
    Ducharme J, Varin F, Bevan DR, Donati F, Théorêt T. High-performance liquid chromatography-electrochemical detection of vecuronium and its metabolites in human plasma. J Chromatogr 1992; 573: 79–86.PubMedCrossRefGoogle Scholar
  8. 8.
    Unadkat JD, Bartha F, Sheiner LB. Simultaneous modeling of pharmacokinetics and pharmacodynamics with nonparametric kinetic and dynamic models. Clin Pharmacol Ther 1986; 40: 86–93.PubMedGoogle Scholar
  9. 9.
    Ducharme J, Varin F, Donati F. Pharmacokinetics and pharmacodynamics of a second dose of atracurium in anaesthetised patients. Clin Drug Invest 1995; 9: 95–110.Google Scholar
  10. 10.
    Cooper RA, Mirakhur RK, Wierda JMKH, Maddineni VR. Pharmacokinetics of rocuronium bromide in patients with and without renal failure. Eur J Anaesth 1995; 12(Suppl. 11):43–4.Google Scholar
  11. 11.
    Szenohradszky J, Fisher DM, Segredo V, et al. Pharmacokinetics of rocuronium bromide (ORG 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation. Anesthesiology 1992; 77: 899–904.PubMedCrossRefGoogle Scholar
  12. 12.
    Magorian T, Wood P, Caldwell J, et al. The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease. Anesth Analg 1995; 80: 754–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Davis L, Jayarajah MJ, Toner CC, Flynn PJ. Evaluation of neuromuscular effects and antagonism of rocuronium bromide: a preliminary report. Eur J Anaesth 1995; 12(Suppl. 11): 65–8.Google Scholar
  14. 14.
    Ali HH, Savarese JJ. Stimulus frequency and dose-response curve to d-tubocurarine in man. Anesthesiology 1980; 52: 36–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Cooper RA, Mirakhur RK, Elliot P, McCarthy GJ. Estimation of the potency of ORG 9426 using two different modes of nerve stimulation. Can J Anaesth 1992; 39: 139–42.PubMedGoogle Scholar
  16. 16.
    Lambalk LM, De Wit APM, Wierda JMKH, Hennis PJ Agoston S. Dose-response relationship and time course of action of Org 9426. A new muscle relaxant of intermediate duration evaluated under various anaesthetic techniques. Anaesthesia 1991; 46: 907–11.PubMedCrossRefGoogle Scholar
  17. 17.
    Lowry DW, Mirakhur RK, McCarthy GJ, Carroll MF, McCourt KC Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia. Anesth Analg 1998; 87: 936–40.PubMedCrossRefGoogle Scholar
  18. 18.
    Oris B, Crul JF, Vandermeersch E, Van Aken H, Van Egmond J, Sabbe MB. Muscle paralysis by rocuronium during halothane, enflurane, isoflurane, and total intravenous anesthesia. Anesth Analg 1993; 77: 570–3.PubMedCrossRefGoogle Scholar
  19. 19.
    Khalil M, D’Honneur G, Duvaldestin P, Slavov V, De Hys C, Gomeni R. Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. Anesthesiology 1994; 80: 1241–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Plaud B, Proost JH, Wierda JMKH, Barre J, Debaene B, Meistelman C. Pharmacokinetics and pharmacodynamics of rocuronium at the vocal cords and the adductor pollicis in humans. Clin Pharmacol Ther 1995; 58: 185–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Kansanaho M, Olkkola KT, Wierda JMKH. Doseresponse and concentration-response relation of rocuronium infusion during propofol-nitrous oxide and isoflurane-nitrous oxide anaesthesia. Eur J Anaesth 1997; 14: 488–94.CrossRefGoogle Scholar

Copyright information

© Canadian Anesthesiologists 2002

Authors and Affiliations

  • Alexandrina Dragne
    • 1
  • France Varin
    • 1
  • Benoît Plaud
    • 2
  • François Donati
    • 2
  1. 1.De la Faculté de pharmacieUniversité de MontréalCanada
  2. 2.Département d’anesthésiologieUniversité de Montréal et Centre Hospitalier de l’Université de Montréal (Hôtel-Dieu)MontréalCanada

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