A Population Pharmacokinetic Analysis to Study the Effect of Therapeutic Hypothermia on Vancomycin Disposition in Children Resuscitated From Cardiac Arrest.

OBJECTIVES: Limited data exist on the effects of therapeutic hypothermia on renal function and pharmacokinetics in pediatric patients after cardiac arrest. The objective was to describe the differences in vancomycin disposition in pediatric patients following cardiac arrest treated with either therapeutic hypothermia or normothermia using population pharmacokinetic modeling.

DESIGN: Single-center, retrospective cohort study.

SETTING: A tertiary care hospital pediatric and cardiac ICU.

PATIENTS: Fifty-two pediatric patients (30 d to 17 yr old) who experienced a cardiac arrest, received vancomycin, and were treated with therapeutic hypothermia (32-34°C) or normothermia (36.3-37.6°C) between January 1, 2010, and September 30, 2014, were reviewed.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data despite high variability due to the small sample size. The typical value of clearance in this study was 4.48 L/hr (0.19 L/hr/kg) for a normothermic patient weighing 70 kg and a glomerular filtration rate of 90 mL/min/1.73 m. Patients treated with normothermia but with reduced or poor renal function (≤ 90 mL/min/1.73 m) had up to an 80% reduction in vancomycin clearance compared to those with normal renal function (90-140 mL/min/1.73 m). Patients with normal renal function but treated with therapeutic hypothermia versus normothermia experienced up to 25% reduction in vancomycin clearance. Patients treated with therapeutic hypothermia and with poor renal function experienced up to an 84% reduction in vancomycin clearance.

CONCLUSIONS: Patients receiving hypothermia and/or with decreased renal function had lower vancomycin clearances based on a retrospectively fitted two-compartment model in children who experience cardiac arrest.