Serum gentamicin concentrations in encephalopathic infants are not affected by therapeutic hypothermia.
OBJECTIVE
Mild hypothermia for 72 hours is neuroprotective in newborns with moderate or severe hypoxic-ischemic encephalopathy. A core temperature of 33.5 degrees C might reduce drug clearance leading to potential toxicity. Gentamicin is nephrotoxic and ototoxic at high serum concentrations. No study has investigated the influence of 72 hours of hypothermia on serum gentamicin concentrations (SGCs) in children of any age. We aimed to compare the SGCs in encephalopathic infants who underwent intensive care with therapeutic hypothermia or normothermia.


METHODS
Data were collected retrospectively from 2 NICUs in Bristol, United Kingdom, that offered cooling therapy within clinical trials since 1998. Eligible infants (n = 55) developed grade 2/3 encephalopathy after birth and fulfilled the entry criteria defined in the CoolCap trial. Encephalopathic infants with similar demographic values were either nursed under normothermia or 72 h-hypothermia. Once-daily gentamicin dosage (4-5 mg/kg) was administered, and trough SGC was recorded with corresponding creatinine concentrations. The time and number of omitted drug doses were noted.


RESULTS
Mean trough SGC (pre-second dose) and mean plasma creatinine concentrations for both treatment groups were similar (gentamicin: 2.19 +/- 1.7 [hypothermia] and 2.30 +/- 2.0 [normothermia] mg/L; creatinine: 115.6 +/- 42.8 [hypothermia] and 121.0 +/- 45.1 [normothermia] mumol/L). Forty percent of the trough SGCs in both groups were above the recommended trough concentration of 2.0 mg/L. A significant correlation (r(2) = 0.36) was found between high SGCs and impaired renal function assessed by raised plasma creatinine levels regardless of treatment options.


CONCLUSIONS
Our data confirm that impaired renal function is strongly associated with high SGCs. Reduced body temperatures do not affect the clearance of gentamicin.
Liu
Xun
X
Department of Child Health, St Michael's Hospital, University of Bristol, Bristol, United Kingdom.
Borooah
Manobi
M
Stone
Janet
J
Chakkarapani
Ela
E
Thoresen
Marianne
M
D001831:Body Temperature / Q000502:physiology*; D003404:Creatinine / Q000097:blood; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D005839:Gentamicins / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000097:blood*; D007231:Infant, Newborn; D007677:Kidney Function Tests; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous; D012189:Retrospective Studies
D005839:Gentamicins; D003404:Creatinine