Department of Pharmacy, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota 55404, USA.
Pharmacotherapy. 2011 Jul;31(7):649-57. doi: 10.1592/phco.31.7.649.
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.
Retrospective medical record review.
Two neonatal intensive care units in a pediatric tertiary care system.
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).
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.
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.
描述根据高剂量、延长间隔给药方案接受庆大霉素治疗的危重病新生儿中，血清庆大霉素浓度与耳声发射（OAE）筛查失败导致的听力损失之间的关联程度。
回顾性病历审查。
儿科三级护理系统中的两个新生儿重症监护病房。
2003 年 2 月至 2008 年 1 月期间入院的 528 例危重病新生儿的连续样本，他们在生命的第一周接受了庆大霉素药代动力学咨询，并在出院前接受了 OAE 听力筛查。新生儿分为两组：极低出生体重（VLBW [≤1500g]）和非 VLBW（>1500g）。
静脉内给予庆大霉素以达到目标计算的庆大霉素峰值血清浓度（C（max））为 7-10μg/ml 和目标谷值血清浓度（C（min））小于 2μg/ml。如果新生儿的出生体重小于 1250g 或正在接受吲哚美辛，则给予 4mg/kg/剂量，每 48 小时给药一次。否则，给药间隔为每 24 小时一次。初始 OAE 筛查结果从病历中获得，对首次 OAE 筛查失败的新生儿进行了随访。OAE 筛查失败的总体发生率为 13.1%（69/528 例患者）。VLBW 新生儿的 OAE 筛查失败率为 34.1%（29/85 例），明显高于非 VLBW 新生儿的失败率（9.0%[40/443 例]，p=0.001）。对非 VLBW 新生儿的多变量分析确定，庆大霉素 C（max）每增加 1μg/ml，OAE 筛查失败的风险就会增加（比值比[OR] 1.4，95%置信区间[CI] 1.1-1.7，p=0.003）。此外，与 C（max）为 10μg/ml 或更低的新生儿相比，庆大霉素 C（max）超过 10μg/ml 的非 VLBW 新生儿亚群的 OAE 筛查失败率更高（OR 2.2，95%CI 1.1-4.2，p=0.022）。VLBW 新生儿的血清庆大霉素浓度与 OAE 筛查失败之间无法确定关联。
出生体重超过 1500g 的新生儿和庆大霉素 C（max）超过 10μg/ml 的新生儿发生 OAE 筛查失败的风险增加。监测和维持庆大霉素 C（max）在 10μg/ml 或以下可能最大限度地减少听力损伤；然而，还需要进一步的研究。
