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

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 (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...

Serum Gentamicin Concentrations in Encephalopathic Infants are Not Affected by Therapeutic Hypothermia

“…Drugs such as phenobarbital, morphine, and vecuronium, which are metabolized by the temperature-dependent cytochrome P450 enzymes system, have significantly longer t 1/2 in patients undergoing therapeutic hypothermia. [21][22][23] Renal function has the greatest influence on gentamicin elimination. 9,23 Plasma creatinine concentrations indirectly reflect glomerular filtration rate and may thus be used as an indicator of renal function.…”

“…[21][22][23] Renal function has the greatest influence on gentamicin elimination. 9,23 Plasma creatinine concentrations indirectly reflect glomerular filtration rate and may thus be used as an indicator of renal function. We found that a high predose serum drug concentration correlated to a high creatinine plasma concentration and/or reduced urine output (Ͻ1 mL/kg per hour).…”

Effect of Therapeutic Moderate Hypothermia on Multi-drug Resistance Protein 1-Mediated Transepithelial Transport of Drugs

“…Therefore, this study indicated that therapeutic moderate hypothermia causes the suppression of drug transport via MDR1 rather than via passive diffusion. Hypothermia is reported to change the pharmacokinetics of various drugs, including phenytoin, 21) vecuronium, 8,50) and neostigmine 17) in humans, and flesinoxan 54) and fentanyl 12) in experimental animals. Such changes are thought to be due to decrease in blood flow, 39) hepatic metabolism, 5,12) and biliary excretion.…”

Beta-Normal Distribution: Bimodality Properties and Application

“…Withington et al (2000), in their study of cardiopulmonary bypass in infants showed that plasma vecuronium and vecuronium clearance requirements have bimodal distributions. They concluded that their findings on bimodal distributions for plasma vecuronium and vecuronium clearance requirements highlight the need for individual monitoring of neuromuscular blockade.…”