Canadian Journal of Anaesthesia

, Volume 45, Issue 6, pp 515–520 | Cite as

Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery

  • Buvanendran Asokumar
  • Davy Cheng
  • Frances Chung
  • Charles Peniston
  • Alan Sandler
  • France Varin
Reports of Investigation

Abstract

Purpose

To compare the pharmacokinetic behaviour of doxacurium in patients undergoing normothermic or hypothermic cardiopulmonary bypass (CPB) for coronary artery bypass graft surgery.

Methods

Twenty patients in two equal groups were studied. Anaesthesia was induced with sufentanil and midazolam after a standard premedication. Doxacurium was administered at 3 × ED95 (80μ·kg−1), and anaesthesia was maintained with 0.5 μg·kg−1 hr−1 sufentanil, 0.05 mg·kg−1 midazolam and isoflurane 0.5–1%. Systemic temperature for patients in the normothermic and hypothermic groups was maintained at 33–36C and 26–30C respectively. Timed blood and urine samples were collected and pharmacokinetic parameters were estimated using a non-compartmental approach.

Results

For the normothermic and hypothermie groups, terminal elimination half-life (t1/2B) was 100.1 ± 28 and 183.8 ± 60 min (P < 0.05) respectively, elimination half-life during the CPB phase (T1/2 CPB) 114.5 ± 10 and 183.8 ± 60 min (P < 0.05), mean residence time 108.8 ± 25 and 164.8 ± 34 min (P < 0.05) and apparent volume of distribution at steady state 0.20 ± 0.03 and 0.26 ± 0.04 L·kg−1 (P < 0.05). Compared with the hypothermie group, the normothermic group had a higher rate of renal clearance (1.40 ± 0.4 vs 0.93 ± 0.3 ml·min−1·kg−1;P < 0.05) and a higher value for renal clearance as a percentage of the total clearance (76.2 ± 10 vs 58.3 ± 20%).

Conclusion

The elimination rate of doxacurium during normothermic CPB is faster than that in hypothermic CPB.

Keywords

Renal Clearance Sufentanil Mean Residence Time Doxacurium Hypothermic Group 
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.

Résumé

Objectif

Comparer le comportement pharmacocinétique du doxacurium chez des patients subissant une CEC normothermique ou une CEC hypothermique lors d’une chirurgie pour un pontage coronaire.

Méthodes

Vingt patients répartis en deux groupes égaux ont été étudiés. Lanesthésie a été induite avec du sufentanil et du midazolam après une prémédication standard. Le doxacurium a été administré à raison de 3 × ED95 (80 μg·kg−1). et l’anesthésie a été maintenue avec 0,5 μg·kg−1hr−1 de sufentanil, 0,05 mg·kg−1 de midazolam et de l’isoflurane 0,5 – 1 %. La température systémique pour les patients des groupes normothermique et hypothermique a été maintenue à 33–36 °C et 26–30 °C respectivement. Les échantillons de sang et d’urine ont été prélevés à des moments déterminés et les paramètres pharmacocinétiques ont été estimés selon une approche non compartimentale.

Résultats

Pour les groupes normothermique et hypothermique, la demi-vie d’élimination finale (t1/2ß) était de 100,1 ± 28 et de 183,8 ± 60 min (P < 0,05) respectivement, la demi-vie d’élimination durant la phase de CEC (T1/2 CEC) était de 114,5 ± 10 et de 183,8 ± 60 min (P < 0,05), la durée de séjour moléculaire moyenne (MRT) était de 108,8 ± 25 et de 164,8 ± 34 min (P < 0,05) et le volume de distribution à l’état d’équilibre était de 0,20 ± 0,03 et de 0,26 ± 0,04 L·kg−1 (P < 0,05). Comparé au groupe hypothermique, le groupe normothermique avait une clairance rénale à un taux plus élevé (1,40 ± 0,4 vs 0,93 ± 0,3 ml·min−1·kg−1,P < 0,05) et une valeur de clairance rénale plus grande en proportion de la dairance totale (76,2 ± 10 vs 58,3 ± 20 %).

Conclusion

Le taux d’élimination du doxacurium pendant la CEC nonmothermique est plus élevé que pendant la CEC hypothermique.

References

  1. 1.
    Bigelow WG, Lindsay WK, Greenwood WF. Hypothermia. Its possible role in cardiac surgery: an investigation of factors governing survival in dogs at low body temperatures. Ann Surg 1950; 132: 849–66.PubMedCrossRefGoogle Scholar
  2. 2.
    Buylaert WA, Herregods LL, Mortier EP, Bogaert MG. Cardiopulmonary bypass and the pharmacokinetics of drugs. An update. Clin Pharmacokinet 1989; 17: 10–26.PubMedCrossRefGoogle Scholar
  3. 3.
    McDonagh P, Dupuis J-Y, Curran M, Kitts J, Wynands JE. Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardiopulmonary bypass. Can J Anaesth 1996; 43: 134–40.PubMedGoogle Scholar
  4. 4.
    Lichtenstein SV, Ashe KA, El Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg 1991; 101: 269–74.PubMedGoogle Scholar
  5. 5.
    The Warm Heart Investigators. Randomised trial of normothermic versus hypothermic coronary bypass surgery. Lancet 1994; 343: 559–63.CrossRefGoogle Scholar
  6. 6.
    Gariepy LP, Varin F, Donati F, Salib Y, Bevan DR. Influence of ageing on the pharmacokinetics and pharmacodynamics of doxacurium. Clin Pharmacol Ther 1993; 53: 340–7.PubMedGoogle Scholar
  7. 7.
    DeAngelis R, Loebs P, Maehr R, Savarese J, Welch R. High-performance liquid chromatographic analysis of doxacurium, a new long-acting neuromuscular blocker. J Chromatogr 1990; 525: 389–400.PubMedCrossRefGoogle Scholar
  8. 8.
    Gibaldi M, Perrier D. Pharmacokinetics in Drugs and the Pharmaceutical Science, Vol 15, 2nd ed. Marcel Dekker, 1982: 494.Google Scholar
  9. 9.
    Hall R. The pharmacokinetic behaviour of opioids administered during cardiac surgery. Can J Anaesth 1991; 38: 747–56.PubMedCrossRefGoogle Scholar
  10. 10.
    Dresner DL, Basta SJ, Ali HH, et al. Pharmacokinetics and pharmacodynamics of doxacurium in young and elderly patients during isoflurane anesthesia. Anesth Analg 1990; 71: 498–502.PubMedCrossRefGoogle Scholar
  11. 11.
    Walker JS, Brown KF, Shanks CA. Akuronium kinetics in patients undergoing cardiopulmonary bypass surgery. Br J Clin Pharmacol 1983; 15: 237–44.PubMedGoogle Scholar
  12. 12.
    Kavanagh BP, Mazer CD, Panos A, Lichtenstein SV. Effect of warm heart surgery on perioperative management of patients undergoing urgent cardiac surgery. J Cardiothorac Vasc Anesth 1992; 6: 127–31.PubMedCrossRefGoogle Scholar
  13. 13.
    Lazenby WD, Ko W, Zelano JA, et al. Effects of temperature and flow rate on regional blood flow and metabolism during cardiopulmonary bypass. Ann Thoac Surg 1992; 53: 957–64.CrossRefGoogle Scholar
  14. 14.
    Sessler DI. Temperature monitoring.In: Miller RD (Ed.). Anesthesia, 2nd ed. New York: Churchill Livingstone Inc., 1990: 1227–42.Google Scholar
  15. 15.
    Stoopes CM, Curtis CA, Kovach DA, et al. Hemodynamic effects of doxacurium chloride in patients receiving oxygen sufentanil anesthesia for coronary artery bypass grafting or valve replacement. Anesthesiology 1988; 69: 365–70.CrossRefGoogle Scholar
  16. 16.
    Cook R, Freeman JA, Lai AA, et al. Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure. Anesth Analg 1991; 72: 145–50.PubMedGoogle Scholar

Copyright information

© Canadian Anesthesiologists 1998

Authors and Affiliations

  • Buvanendran Asokumar
    • 3
  • Davy Cheng
    • 4
  • Frances Chung
  • Charles Peniston
    • 1
  • Alan Sandler
  • France Varin
    • 2
  1. 1.Department of Anaesthesia and Division of Cardiovascular SurgeryThe Toronto Hospital, University of TorontoCanada
  2. 2.Faculty of PharmacyUniversity of MontrealCanada
  3. 3.Department of AnesthesiologyRush-Presbyterian-St.Luke’s Medical Center, Rush UniversityChicagoUSA
  4. 4.Department of AnaesthesiaThe Toronto Hospital BW 4-646TorontoCanada

Personalised recommendations