Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

McDonagh, Paul F.; Dupuis, Jean‐Yves; Curran, Michael; Kitts, John B.; Wynands, J. Earl

doi:10.1007/bf03011254

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children TUDIES performed both in animals and humans during hypothermic CPB have indicated that hypothermia below 32°C increases sensitivity to vecuronium, 1-5 pancuronium 1,4,6 atracurium, 5,7-9 rocuronium, 10-12 metocurine 13 and doxacurium 14 but not to alcuronium 15,16 or d-tubocurarine. 1,17 Some studies have examined pharmacodynamic parameters only 1,4,5,7,18 but other authors have performed a complete pharmacokinetic-pharmacodynamic study.…”

Section: Methodsmentioning

confidence: 99%

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Withington

Ménard

Harris

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children. Methods:We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (T1 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteadystate during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion.Results: Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean ± SD: 330 ± 42 ng·ml -1 ; 127 ± 27 ng·ml -1 ; P < 0.001); similarly the clearances showed a bimodal distribution (mean ± SD: 5.08 ± 0.94; 11.51 ± 0.2 ml·min -1 ·kg -1 P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05). Conclusion: Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.Objectif: Déterminer l'effet d'une circulation extracorporelle (CEC) avec hypothermie modérée ou profonde sur les paramètres pharmacocinétiques et pharmacodynamiques du vécuronium chez des nourrissons et des enfants.Méthode : Nous avons étudié 12 patients opérés pour cardiopathie congénitale sous anesthésie avec un mélange de narcotique et de protoxyde d'azote. Le blocage neuromusculaire a été maintenu constant (T1 4-10 % avec un élec-tromyographe Datex) en ajustant une perfusion de vécuronium. Les concentrations plasmatiques de vécuronium (Cpss) ont été analysées par chromatographie liquide haute performance (CLHP) afin de définir l'état pseudo-équilibre pendant chacune des étapes pré-CEC, CEC et post-CEC. Des échantillons appariés de sang artériel ont été prélevés à intervalles de 20 min, après au moins 20 min de perfusion constante.Résultats: Neuf cas ont été analysés, âgés de 20 ms et pesant 9 kg en moyenne. Trois patients avaient une hypothermie profonde et six, une modérée. Pendant la pré-CEC, les Cpss se séparent en deux groupes (moyenne ± écart type : 330 ± 42 ng·ml -1 ; 127 ± 27 ng·ml -1 ; P < 0,001); les clairances ont affiché une distribution bimodale (moyenne ± écart type : 5,08 ± 0,94; 11,51 ± 0,2 ml·min -1 ·kg -1 P < 0,001), chez différents patients cependant. Pendant la CEC, cette distribution bimodale a disparu. La vitesse de perfus...

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Section: Methodsmentioning

confidence: 99%

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Withington

Ménard

Harris

et al. 2000

Can J Anesth/J Can Anesth

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Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery

Buvanendran

Cheng²,

Chung³

et al. 1998

Can J Anaesth

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Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgeryPurpose: To compare the pharmacokinetic behaviour of doxacurium in patients undergoing normotherrnic 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 x EDgs (80/~g-kg-~), and anaesthesia was maintained with 0.5/ag'kg -I hr -I sufentanil, 0.05 mg'kg -l midazolam and isoflurane 0.5-I %. 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 norrnothermic and hypothermic groups, terminal elimination half-life (ti/213) was I00. I __+ 28 and 183.8 ---60 rain (P < 0.05) respectively, elimination half-life during the CPB phase CTlr2 CPB) 114.5 _ I 0 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 -I (P < 0.0S). Compared with the hypothermic group, the normothermic group had a higher rate of renal clearance (1.40 _+ 0.4 vs 0.93 ___ 0.3 ml'min -1'kg-l; P < 0.05) and a higher value for renal clearance as a percentage of the total clearance (76.2 _ I0 vs 58.3 ---20%). Conclusion: The elimination rate of doxacurium during normothermic CPB is faster than that in hypothermic CPB.

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Cardiopulmonary bypass and the systemic inflammatory response: Effects on drug action

Hall

2002

Journal of Cardiothoracic and Vascular Anesthesia

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Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

Abstract: In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED95. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.

Cited by 3 publications

References 23 publications

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery

Cardiopulmonary bypass and the systemic inflammatory response: Effects on drug action

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