RESUMO
STUDY OBJECTIVE: To characterize the extent that serum gentamicin concentrations are associated with hearing loss indicated by otoacoustic emission (OAE) screen failure in critically ill neonates receiving gentamicin in accordance with a high-dose, extended-interval dosing protocol. DESIGN: Retrospective medical record review. SETTING: Two neonatal intensive care units in a pediatric tertiary care system. PATIENTS: Sequential sample of 528 critically ill neonates who were admitted between February 2003 and January 2008 and who received a gentamicin pharmacokinetic consultation during the first week of life and an OAE hearing screen before hospital discharge. Neonates were stratified into two groups: very low birth weight (VLBW [≤ 1500 g]) and non-VLBW (> 1500 g). MEASUREMENTS AND MAIN RESULTS: Gentamicin was dosed intravenously to achieve a target calculated gentamicin peak serum concentration (C(max)) of 7-10 µg/ml and a target trough serum concentration (C(min)) of less than 2 µg/ml. The dosage administered was 4 mg/kg/dose every 48 hours if the neonate's birth weight was less than 1250 g or if the neonate was receiving indomethacin. Otherwise, the dosing interval was every 24 hours. Initial OAE screen results were obtained from the medical records, and follow-up results were collected for neonates who failed the initial OAE screen. The overall rate of OAE screen failure was 13.1% (69/528 patients). The rate of OAE screen failure was 34.1% (29/85 patients) in the VLBW neonates, which was significantly higher than the failure rate in non-VLBW neonates (9.0% [40/443 patients], p=0.001). Multivariate analysis of non-VLBW neonates determined that each 1-µg/ml increase in gentamicin C(max) was associated with an increased risk of OAE screen failure (odds ratio [OR] 1.4, 95% confidence interval (CI) 1.1-1.7, p=0.003). Further, the non-VLBW neonate subpopulation had an increased rate of OAE screen failure if the gentamicin C(max) exceeded 10 µg/ml (OR 2.2, 95% CI 1.1-4.2, p=0.022) compared with neonates whose C(max) was 10 µg/ml or lower. No association between serum gentamicin concentration and OAE screen failure could be determined among the VLBW neonates. CONCLUSION: Neonates weighing more than 1500 g at birth and whose gentamicin C(max) exceeded 10 µg/ml were at an increased risk for OAE screen failure. Monitoring and maintaining gentamicin C(max) at or below 10 µg/ml may minimize hearing impairment; however, further studies are necessary.
