Pharmacodynamics and Pharmacokinetics of Morphine after Cardiac Surgery in Children with and Without Down Syndrome

Objective: To compare the pharmacodynamics and pharmacokinetics of IV morphine after cardiac surgery in two groups of children - those with and without Down syndrome. Design: Prospective, single-center observational trial. Setting: PICU in a university-affiliated pediatric teaching hospital. Patients: Twenty-one children with Down syndrome and 17 without, 3-36 months old, scheduled for cardiac surgery with cardiopulmonary bypass. Interventions: A loading dose of morphine (100 μg/kg) was administered after coming off bypass; thereafter, morphine infusion was commenced at 40 μg/kg/hr. During intensive care, nurses regularly assessed pain and discomfort with validated observational instruments (COMFORT-Behavior scale and Numeric Rating Scale - for pain). These scores guided analgesic and sedative treatment. Plasma samples were obtained for pharmacokinetic analysis. Measurements and Main Results: Median COMFORT-Behavior and Numeric Rating Scale scores were not statistically significantly different between the two groups. The median morphine infusion rate during the first 24 hours after surgery was 31.3 μg/kg/hr (interquartile range, 23.4-36.4) in the Down syndrome group versus 31.7 μg/kg/hr (interquartile range, 25.1-36.1) in the control group (p = 1.00). Population pharmacokinetic analysis revealed no statistically significant differences in any of the pharmacokinetic variables of morphine between the children with and without Down syndrome. Conclusions: This prospective trial showed that there are no differences in pharmacokinetics or pharmacodynamics between children with and without Down syndrome if pain and distress management is titrated to effect based on outcomes of validated assessment instruments. We have no evidence to adjust morphine dosing after cardiac surgery in children with Down syndrome.

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