Otoacoustic emission screen results in critically ill neonates who received gentamicin in the first week of life.

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.