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.

Pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol in critically ill neonates.

STUDY OBJECTIVE: To determine the pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates. DESIGN: Retrospective medical record review with pharmacokinetic analysis. SETTING: Two neonatal intensive care units in a pediatric tertiary care system. PATIENTS: Sequential sample of 644 critically ill neonates less than 7 days old without evidence of renal dysfunction who received gentamicin, dosed by using a simplified, weight-based, extended-interval dosing protocol, on the first day of life for suspected sepsis between February 2003 and January 2008, and who had subsequent gentamicin plasma concentrations measured during their first week of life. MEASUREMENTS AND MAIN RESULTS: Data were collected on birth weight, gestational age at birth, serum creatinine concentration during the first 10 days of life, medical conditions, and concomitant drugs. Gentamicin dosing and its pharmacokinetic parameters were noted for each patient. A mean dose of 3.96 mg/kg/dose of gentamicin was administered intravenously every 48 hours in neonates weighing less than 1250 g at birth and every 24 hours in those weighing 1250 g or more. If the neonate received concurrent indomethacin, however, gentamicin was given every 48 hours. Protocol success was defined as a peak gentamicin plasma concentration of 7-10 mg/L and a trough concentration less than 2 mg/L. Mean gentamicin peak and trough concentrations were 9.38 mg/L (95% confidence interval [CI] 9.24-9.52 mg/L) and 1.00 mg/L (95% CI 0.96-1.04 mg/L), respectively. With use of the protocol, 361 neonates (56.1%) achieved gentamicin peak plasma concentrations in the range defined as successful and 610 neonates (94.7%) achieved successful trough concentrations. The mean gentamicin apparent volume of distribution and half-life were 0.48 L/kg (95% CI 0.47-0.49 L/kg) and 8.31 hours (95% CI 8.09-8.52 hrs), respectively. CONCLUSION: This simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates was effective in achieving therapeutic peak plasma concentrations of gentamicin in most of the patients and, as a high proportion of patients had acceptable trough concentrations, may minimize the potential for toxicity.