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

Abstract

Objective To examine the impact of a change in the empiric gentamicin dose from 5 mg/kg every 24h to 5 mg/kg every 36h 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 gentamicin 5 mg/kg every 24h (Q24h period). During the second treatment period (January 2011 to May 2012; n=23), the dose was changed to 5 mg/kg every 36h (Q36h period). Cooling criteria and protocol remained the same between treatment periods. Gentamicin drug concentrations including achievement of target trough concentrations (<2 mg/L) were compared between treatment periods. Individual Bayesian estimates of gentamicin clearance were also compared. Result Neonates with an elevated trough concentration >2 mg/L decreased from 38% to 4% with implementation of a Q36h dosing interval (P<0.007). The mean gentamicin trough concentration was 2.0 ± 0.8 mg/L during the Q24h period and 0.9 ± 0.4 mg/L during the Q36h period (P<0.001). Peak concentrations were minimally impacted (Q24h 11.4 ± 2.3 mg/L vs. Q36h 10.0 ± 1.9 mg/L; 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 every 36h gentamicin dosing strategy in neonates with HIE receiving therapeutic hypothermia improved achievement of target trough concentration <2 mg/L while still providing high peak concentration exposure.

Side Effects of Culture Media Antibiotics on Cell Differentiation

“…During the adipocyte differentiation, gentamicin 5 μg/ml significantly increased leptin production (244 %, P = 0.0441), but it had not effect on triglyceride levels ( Figure 1). This gentamicin concentration is within the range of concentrations (0.9-11.4 μg/ml) found in the blood of some patients, for example in neonates with hypoxic ischemic encephalopathy treated for presumptive infection and, therefore, it could have physiologic consequences on medicated individuals (13).…”

Decreased Morphine Clearance in Neonates With Hypoxic Ischemic Encephalopathy Receiving Hypothermia

“…For example, when standard gentamicin doses of 4–5 mg/kg every 24 hours were given to neonates with HIE receiving hypothermia, potentially toxic trough concentrations frequently occurred . In contrast, a customized every‐36‐hour dosing strategy that was developed based on an in‐depth quantitative pharmacokinetic understanding of gentamicin in neonates with HIE receiving hypothermia, reliably achieved target drug exposures . Similarly, a detailed examination of morphine pharmacokinetics in neonates with HIE receiving hypothermia is essential to help to understand optimal dosing strategies of morphine in this population.…”

“…Therefore, it is critical to consider the unique clinical pharmacologic needs of this vulnerable population. For example, a recent clinical study examined the pharmacokinetics of gentamicin in neonates with HIE receiving hypothermia that demonstrated a marked reduction in gentamicin clearance and the need for extended dosing intervals . Careful inquiry into the pharmacokinetics of other drugs used in the HIE population can help to further advance customized evidenced‐based dose recommendations…”

Hypoxic-Ischemic Encephalopathy in Neonates Born to Severe Birth Asphyxia

“…Общая гипотермия не влияет на фенобарбитал [46]. Гипо-термия уменьшает выведение антибактериальных средств, поэтому необходимо увеличивать интервал используемых доз [22].…”