Ketamine anesthesia in children – exploring infusion regimens

Abstract

We aimed to produce a racemic ketamine manual infusion regimen capable of maintaining a steady-state blood concentration associated with anesthesia in children aged 1.5-12 years. The literature was searched for a ketamine blood concentration associated with anesthesia in humans. Pharmacokinetic parameter estimates were taken from published studies of infusion data in children and used in a pharmacokinetic simulation program to predict likely ketamine blood concentrations during infusions. A variability of 10% was allowed about the chosen target concentration. A target concentration of 3 mg.l(-1) was chosen for simulation modeling. This target is greater than that associated with anesthesia when supplemented by nitrous oxide or midazolam in adults. Arousal to light touch or voice appears to occur at a mean plasma concentration of 0.5 mg.l(-1) in both children and adults. A loading dose of 2 mg.kg(-1) followed by an infusion rate of 11 mg.kg(-1).h(-1) for the first 20 min, 7 mg.kg(-1).h(-1) from 20 to 40 min, 5 mg.kg(-1).h(-1) from 40 to 60 min and 4 mg.kg(-1).h(-1) from 1 to 2 h resulted in a steady-state target concentration of 3 mg.l(-1) in children 1.5-12 years. Arousal, either spontaneous or to speech, is anticipated 3 h 47 min after a 2 h infusion in an average 6-year-old child. The context sensitive half-time in children was shorter than in adults after 1.5 h, rising from 30 min at 1 h to 55 min at 5 h after an infusion of 3 mg.kg(-1).h(-1) in a 10 kg child. Children require higher infusion rates than adults to maintain steady-state concentrations of 3 mg.l(-1) and have shorter context sensitive half-times than adults after prolonged infusion. These differences can be attributed to age-related pharmacokinetics. We anticipate slow return to full consciousness after prolonged infusion, suggesting that a lower target concentration with supplementation from adjuvant short acting anesthetic drugs may be advantageous.