硫酸丁胺卡那霉素对新生儿耳毒性作用的研究

Ototoxicity of amikacin on newborn infants

目的 观察常规剂量硫酸丁胺卡那霉素 (阿米卡星 ,amikacin ,AMK)对新生儿的耳毒性作用并探讨其与血药浓度的关系。方法 以脑干听觉诱发电位 (BAEP)监测AMK[10mg/ (kg·d) ,连用7d]治疗组 (2 6例 )与对照组 (2 0例 )足月新生儿的听功能变化 ,并以荧光偏振免疫法对治疗组进行血药浓度监测。结果 治疗第 7天 ,治疗组有 3例BAEP异常 (12 % ) ,对照组未发现异常 ,两组差异无显著性 (P >0 .0 5 )。经随访 ,治疗组 3例异常者有 2例恢复正常 ,1例失访 ,假设其未恢复 ,则异常率为4% ,与对照组比较 ,差异仍无显著性 (P >0 .0 5 )。治疗后Ⅴ波反应阈值 :治疗组为 (38± 8)dBnHL ,对照组为 (34± 11)dBnHL ,差异无显著性 (P >0 .0 5 ) ;治疗组治疗前后比较 ,差异亦无显著性 (P >0 .0 5 )。治疗组异常的 3例BAEP均表现为Ⅰ波潜伏期 (PLⅠ )延长 ,治疗组治疗后反映听通路外周段功能的PLⅠ [(1.6 0± 0 .2 4)ms]较对照组 [(1.48± 0 .12 )ms]显著延长 (P <0 .0 5 ) ;较治疗前 [(1.5 3± 0 .14)ms]也显著延长 (P <0 .0 5 ) ;而反映听通路中枢段功能的Ⅰ Ⅴ波峰间潜伏期 (IPLⅠ Ⅴ )、Ⅴ波与Ⅰ波的振幅比 (AmpⅤ /Ⅰ ) ,治疗组与对照组差异无显著性 (P >0 .0 5 )。治疗组AMK血药峰浓度第 3天为 (17± 3)mg/L ,73%在?

Objective To study the ototoxicity of routine dose amikacin in newborn infants and the relationship with amikacin blood concentration and to provide a possible rule for safely using amikacin in neonates. Methods Brainstem auditory evoked potential (BAEP) was carried out to monitor auditory function in amikacin [10 mg/(kg·d)×7 days] treated group (26 cases) and control group (20 cases) of newborn infants before and after treatments. Blood amikacin concentrations were measured in amikacin treated group by fluorescence polarization immunoassay. Results BAEP monitoring showed abnormal in 3 cases (12%) in amikacin treated group , while no abnormal case was found in the control group at the 7 th day of the study course. The difference was not significant ( P >0.05). Two abnormal cases recovered, and one missed during follow-up observation. If the missed case was still abnormal, the abnormality rates of amikacin treated group could be 4%. And there was still no statistical difference between two groups after follow-up ( P >0.05). Threshold Ⅴ (THRⅤ) was (38±8) dBnHL in amikacin treated group and (34±11) dBnHL in control group after treatments. There was no statistical difference between them ( P >0.05). THRⅤ in amikacin treated group after treatment did not increase significantly comparing to the baseline ( P >0.05). Three cases with abnormal BAEP presented prolonged peak latency Ⅰ (PL Ⅰ). After the treatment, PLⅠ which reflects the peripheral function of the hearing conduction route was (1.60±0.24)ms in amikacin treated group, which was significantly higher than that in control (1.48±0.12) ms and the baseline (1.53±0.14) ms, respectively ( P <0.05). But there were significant differences in interpeak latency Ⅰ-Ⅴ(IPL Ⅰ-Ⅴ)and the ratio amplitude Ⅴ to Ⅰ (AmpⅤ/Ⅰ), which reflect the central function of the hearing conduction route ,between amikacin treated group and control group ( P >0.05). The amikacin peak concentration was (17±3)mg/L in 10 cases at the 3 rd day and (16±3) mg/L in 18 cases at the 7 th day of the treatment. Blood peak concentrations were all lower than 35 mg/L, and blood trough concentrations were all lower than 5 mg/L (0～1.51 mg/L). Conclusion The intravenous administration of amikacin with a dosage of 10 mg/kg once a day may reach the efficient blood concentration in most term neonates, and the peak and the trough blood concentrations were within the safe range. The 7 day course of amikacin in the dose of 10 mg/kg once a day does not cause clinical ototoxicity in term neonates, but it may result in reversible mild peripheral hearing dysfunction. It is necessary to monitor ototoxicity with BAEP when the treatment exceeds 7 days.