Every 36-h gentamicin dosing in neonates with hypoxic–ischemic encephalopathy receiving hypothermia

Objective:to examine the impact of a change in the empiric gentamicin dose from 5 mg kg−1 every 24 h (q24 h period) to 5 mg kg every 36 h (q36 h period) on target drug concentration achievement in neonates with hypoxic ischemic encephalopathy (hie) receiving therapeutic hypothermia.study design:gentamicin drug concentrations in neonates with hie receiving therapeutic hypothermia were examined during two time periods in a retrospective chart review. during the initial treatment period (november 2007 to march 2010; n=29), neonates received q24 h period. during the second treatment period (january 2011 to may 2012; n=23), the dose was changed to q36 h period. cooling criteria and protocol remained the same between treatment periods. gentamicin drug concentrations including achievement of target trough concentrations (<2 mg l−1) were compared between treatment periods. individual bayesian estimates of gentamicin clearance were also compared.result:neonates with an elevated trough concentration >2 mg l−1 decreased from 38 to 4% with implementation of a q36-h dosing interval (p<0.007). the mean gentamicin trough concentration was 2.0±0.8 mg l−1 during the q24 h period and 0.9±0.4 mg l−1 during the q36 h period (p<0.001). peak concentrations were minimally impacted (q24 h 11.4±2.3 mg l−1 vs q36 h 10.0±1.9 mg l−1; p=0.05). the change in gentamicin trough concentration could not be accounted for by differences in gentamicin clearance between treatment periods (p=0.9).conclusion:a 5 mg kg−1 every 36-h gentamicin dosing strategy in neonates with hie receiving therapeutic hypothermia improved achievement of target trough concentration <2 mg l−1, while still providing high peak concentration exposure.