Original article
Postoperative analgesia and sedation following pediatric cardiac surgery using a constant infusion of ketamine

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Abstract

Constant rate infusions of ketamine supplemented with intermittent doses of midazolam were given postoperatively to 10 children in order to provide analgesia and sedation during mechanical ventilation after cardiac surgery as well as during weaning from the ventilator and during spontaneous breathing. The aims of the study were to determine the pharmacokinetics of ketamine and evaluate the suitability of ketamine as an analgesic and sedative in postoperative pediatric cardiac patients. The children were between one week and 30 months old. Five children were given 1 mg/ kg/h of ketamine and five children had 2 mg/kg/h. Blood was sampled during infusion and up to 24 hours after infusion for plasma concentrations of ketamine and the main plasma metabolite, norketamine, which were determined by gas chromatography and were compared to the degree of sedation. The children were arousable when ketamine concentrations were below 1.0 to 1.5 μg/mL. Plasma ketamine concentrations at steady state were within a narrow range for each infusion regimen and the calculated pharmacokinetic parameters were similar. Mean plasma clearance of ketamine was 0.94 ± 0.22 L/kg/h. The elimination half-life was 3.1 ± 1.6 hours, but in some children late samples indicated an even longer elimination half-life. Norketamine did not reach a steady state, but at the end of the infusion, the mean plasma concentration was higher than that of ketamine. The elimination half-life of norketamine was estimated to be 6.0 ± 1.8 hours. Both ketamine infusion regimens were supplemented with midazolam and provided similarly acceptable analgesia and sedation during mechanical ventilation and during and after weaning from the ventilator. Spontaneous breathing was readily resumed and was adequate as judged by acceptable blood gas values during the ketamine infusion, which was continued well beyond extubation. No adverse effects of ketamine were seen.

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    Citation Excerpt :

    However, CYP 3A4 has been shown to be the major contributor to ketamine metabolism (Hijazi and Boulieu, 2002). The high ketamine clearance rate suggests that its elimination is susceptible to factors affecting hepatic blood flow (Brunette et al., 2011; Hartvig et al., 1993; Malinovsky et al., 1996). Despite the common use of ketamine in children with cardiac disease, pharmacokinetic (PK) data in this population are sparse.

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Supported by grants from Parke-Davis, Division of Warner Lambert Company, Solna, Sweden.

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