Abstract
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.
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Acknowledgements
We thank Susan Peloquin, RN, MS, Clinical Coordinator of the UCSF Neuro-Intensive Care Nursery and members of the UCSF Neuro-Intensive Care Nursery leadership and nursing teams for helping support this project. AF received support, in part, by the National Institutes of Health Grant R01 AI50587. DV received support, in part, by National Institutes of Health Grant R01 AI50587, GM26696. SLB received support by the National Center for Advancing Translational Sciences and National Institutes of Health through UCSF-CTSI Grant KL2TR000143.
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AF wrote the first draft of the manuscript and NO honorarium, grant or other form of payment was given to anyone to produce the manuscript. Each author listed on the manuscript has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript. Each author clearly meets authorship criteria as described at http://www.icmje.org.
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Previously presented: (1) data from the Q24 h period were used for a published population pharmacokinetic analysis and formed the basis for the every 36-h gentamicin dose change under study; (2) Preliminary findings of this work, in part, will be presented as abstract and poster for the Pediatric Academic Societies Annual Meeting, Washington, DC, 4–7 May 2013.
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Frymoyer, A., Lee, S., Bonifacio, S. et al. Every 36-h gentamicin dosing in neonates with hypoxic–ischemic encephalopathy receiving hypothermia. J Perinatol 33, 778–782 (2013). https://doi.org/10.1038/jp.2013.59
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DOI: https://doi.org/10.1038/jp.2013.59
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