Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery

Objectives: To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. Design: Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. Setting: A 16-bed cardiac ICU at an university-affiliated hospital. Patients: Forty-two patients (20 Down syndrome, 22 controls) were enrolled. Interventions: None. Measurements and Main Results: The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. Conclusions: This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease. Supported, in part, by funding ($50,000) from the Linda Crnic Institute for Down Syndrome Seed Grant, University of Colorado Anschutz Medical Campus, Aurora, CO. This funding was used for purchasing materials used in data collection and data analysis. No honoraria were perceived. Dr. Goot’s institution received funding from a Linda Crnic Institute for Down Syndrome Seed Grant (used for laboratory materials and specimen processing). Dr. da Cruz received support for article research from a Linda Crnic Institute for Down Syndrome Seed Grant. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: eduardo.dacruz@childrenscolorado.org ©2018The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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