Abstract
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 (TI 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−1P<0.001); similarly the clearances showed a bimodal distribution (mean±SD; 5.08±0.94; 11.51±0.2 ml·min−1·kg−1P<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.
Résumé
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 (TI 4–10% avec un électromyographe 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−1P<0,001); les clairances ont affiché une distribution bimodale (moyenne ± écart type: 5,08±0,94; 11,51±0,2 ml·min−1·kg−1P<0,001), chez différents patients cependant. Pendant la CEC, cette distribution bimodale a disparu. La vitesse de perfusion du vécuronium (VPR) a diminué de 84% et 92%, comparée à celle de la pré-CEC chez les patients avec hypothermie profonde et modérée, respectivement (P<0,05), parallèlement à une baisse des Cpss de 36% (P>0,05) et de 52% (P<0,05).
Conclusion: Les besoins différents de vécuronium et les changements de concentrations plasmatiques pendant la CEC montrent que la pharmacocinétique et la pharmacodynamie du vécuronium sont influencées par une CEC hypothermique chez l’enfant. La découverte de distributions bimodales de vécuronium plasmatique et de clairance du vécuronium, souligne la nécessité d’un monitorage du blocage neuromusculaire chez les patients de cet âge.
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Withington, D., Menard, G., Harris, J. et al. Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children. Can J Anesth 47, 1188–1195 (2000). https://doi.org/10.1007/BF03019867
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DOI: https://doi.org/10.1007/BF03019867