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 5mg kg(-1) every 24 h (Q24 h period) to 5mg 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 (<mg l(-1)) were compared between treatment periods. Individual Bayesian estimates of gentamicin clearance were also compared. RESULT: Neonates with an elevated trough concentration 42mg 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 +/- 0.8mgl(-1) during the Q24 h period and 0.9 +/- 0.4mgl(-1) during the Q36 h period (P<0.001). Peak concentrations were minimally impacted (Q24 h 11.4 +/- 2.3 mgl(-1) vs Q36 h 10.0 +/- 1.9 mgl(-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 5mgkg(-1) every 36-h gentamicin dosing strategy in neonates with HIE receiving therapeutic hypothermia improved achievement of target trough concentration <mg l(-1), while still providing high peak concentration exposure.