亚胺培南西司他丁钠致未成年住院患者肝功能异常发生情况及影响因素分析

Occurrence of hepatic dysfunction and the influencing factors among preadult inpatients treated with imipenem-cilastatin sodium

目的 了解亚胺培南西司他丁钠致未成年住院患者肝功能异常的发生情况并分析相关影响因素. 方法 收集2016年1月1日至12月31日在中南大学湘雅医院接受亚胺培南西司他丁钠治疗且治疗前肝功能正常的未成年住院患者的病历资料进行回顾性分析.记录患者一般情况、亚胺培南西司他丁钠用药情况、联用药物情况、临床疗效和肝功能情况等,分析亚胺培南西司他丁钠致肝功能异常特别是严重肝损害的影响因素. 结果 纳入分析的患者为143例,男性86例,女性57例;年龄〈1岁者61例,1~3岁9例,4~10岁6例,11~18岁67例,中位年龄9岁.143例患者住院期间共有176例次感染,感染类型以下呼吸道感染、脓毒症和败血症居多.亚胺培南西司他丁钠均为静脉滴注给药,日剂量不变情况下给药频率为1次/6 h者30例（21.0%）,1次/8 h者79例（55.2%）,1次/12 h者31例（21.7%）,1次/d者3例（2.1%）.85例患者联用了可致肝功能异常药物（万古霉素、伏立康唑、氟康唑、阿奇霉素）.143例患者中出现肝功能异常者59例（41.3%）,肝损害者24例（16.8%）,严重肝损害者11例（7.7%）,有34例肝功能异常患者在使用亚胺培南西司他丁钠期间联用了可致肝功能异常药物.患者性别、年龄、是否患恶性肿瘤,是否患急性全身性感染、日剂量不变情况下给药频率、是否联用可致肝功能异常药物以及是否预先应用护肝药物等因素均与肝功能异常的发生无相关性（均P〉0.05）;但〈1岁与11~18岁患者严重肝损害发生率差异有统计学意义[18.0%（11/61）比0（0/67）,P〈0.001],患与未患恶性肿瘤患者严重肝损害发生率差异有统计学意义[0（0/46）比11.3%（11/97）,P〈0.01],给药频率为1次/6 h和1次/d患者之间差异有统计学意义[0（0/30）比1/3,P=0.001]. 结论 未成年住院患者应用亚胺培南西司他丁钠治疗后易发生肝功能异常,年龄〈1岁和单次给药剂量高者可能更容易发生严重肝损害.

Objective To understand the occurrence of hepatic dysfunction induced by imipenem-cilastatin sodium in preadult inpatients and analyze the influencing factors. Methods Data of inpatients receiving imipenem-cilastatin sodium treatment in Xiangya Hospital of Central South University from January 1st,2016 to December 31st,2016 were collected and analyzed retrospectively. The patients＇ general condition,utilization of imipenem-cilastatin sodium,combined medication,clinical effect,and liver function etc. were recorded. The influencing factors of hepatic dysfunction,especially severe liver injury caused by imipenem-cilastatin sodium were analyzed. Results A total of 143 preadult inpatients were enrolled into this study. Of them,86 patients were males and 57 were females;61 of them were 〈1 year old,9 were 1-3 years old,6 were 4-10 years old,67 of them were 11-18 years old,and their median age was 9 years. There were 176 infections in the 143 patients. Most of the infections were respiratory tract infection,sepsis, and septicemia. Imipenem-cilastatin sodium was given via intravenous infusion in all patients. At the same daily dosage,the drug was given every 6 hours in 30 patients（21.0%）,every 8 hours in 79 patients （55.2%）,every 12 hours in 31 patients（21.7%）,once daily in 3 patients（2.1%）. Eighty-five patients were given combined drugs that could cause liver dysfunction,such as vancomycin,voriconazole, fluconazole,and azithromycin etc. Of the 143 patients,59 had hepatic dysfunction（41.3%）,24 had liver injury（16.8%）,and 11 had severe liver injury（7.7%）. Thirty-four patients with hepatic dysfunction received drugs that could cause liver dysfunction during the imipenem-cilastatin sodium treatment. Occurrence of liver dysfunction was not correlated with any of the following factors：patients′ gender,ages, whether or not having malignant tumor,systemic infections,frequency of administration at the same daily dosage,combination drugs that could cause liver dysfunction,liver-protective drugs use before imipenem-cilastatin sodium treatment（all P〉0.05）. However,the difference in the incidence of severe liver injury between the 〈1 year old and 11-18 years old patients was statistically significant[18.0%（11/61）vs. 0（0/67）,P〈0.001],the difference in the incidence of severe liver injury between the inpatients with malignancies or not was statistically significant[0（0/46）vs. 11.3%（11/97）,P〈0.01],the difference in the incidence of severe liver injury between the inpatients whose administration frequency was every 6 hours and once daily was statistically significant[0（0/30）vs. 1/3,P=0.001]. Conclusions Non-adult inpatients who were treated with imipenem-cilastatin sodium were prone to develop hepatic dysfunction. Inpatients at age 〈1 year or receiving higher single dose are more likely to have severe liver injury.