伏立康唑使用早期出现精神症状不良反应特点及影响因素分析

Voriconazole induced psychological side-effect and analysis of probable affective factors

目的总结伏立康唑致精神症状不良反应的表现特点，并探讨出现该类不良反应的可能影响因素及处理对策。方法统计我院呼吸内科2011年7月至2012年5月使用伏立康唑治疗的患者，排除使用伏立康唑前有痴呆等精神障碍、电解质紊乱等代谢性脑病病例，根据是否出现精神症状分为精神症状不良反应组及对照组，分析总结伏立康唑精神症状不良反应的表现形式、持续时间、缓解方式及处理方法，并对比两组患者年龄、性别比例、用药方式及剂量、肝肾功能的差异，探寻伏立康唑出现精神症状不良反应的可能影响因素。结果我院呼吸内科2011年7月至2012年5月使用伏立康唑抗真菌治疗的患者共31例，除外用药前有痴呆病史者1例，纳入病例30例，其中出现精神症状不良反应者6例（发生率为200）。所有患者均使用伏立康唑静脉制剂200mg，每12小时1次静点，部分患者首日剂量加倍。精神症状多在使用伏立康唑后1～4d出现，表现为兴奋、躁动、谵妄、言语混乱无逻辑、幻觉、梦呓等，3例患者因该不良反应不能耐受用药2d后停药，另外3例维持用药，精神症状持续2～5d后自行缓解。精神症状不良反应组血清丙氨酸氨基转移酶水平高于对照组[（45．50±27．60）U／Lvs（21．63±17．67）U／L，t=2．641，P=0．013]；精神症状不良反应组血清总胆红素水平高于对照组[（18．10±13．10）／μmol／Lvs（10．84±3．96）μmol／L，t=2．411，P=0．023]；精神症状不良反应组血清直接胆红素水平高于对照组[（6．10±4．95）gmol／Lvs（2．38±1.22）μmol／L，t=-2．816，P=0．012]；精神症状不良反应组血清碱性磷酸酶水平高于对照组[（134．67±106．57）U／Lvs（65．50±16．42）U／L，t=2．771，P=0．013]；精神症状不良反应组与对照组年龄、性别比例及首日剂量是否加倍、血清天门冬氨酸氨基转移酶、总蛋白、白蛋白、谷氨酰转肽酶、肌酐及尿素氮水平差异无统计学意义（P值均〉0．05）。结论肝功能异常的患者使用伏立康唑出现精神症状不良反应的可能性增加；如临床症状不重者无需特殊处理，多数可以自行缓解。

Objective To summarize the manifestation of voriconazole induced psychological sideeffect, to analyse the probable affective factors and management. Methods The patients who hadpsychological diseases before using voriconazole and the ones who had metabolic encephalopathy were excluded. The patients who had used voriconazole during July 2011 and May 2012 were divided into twogroups： psychological side effect group and contrasting group. The performance of psychological sideeffect,lasting period, relieving and management were analyzed, the differences of age, gender, deliverymode and dose, hepatic and renal functions between the two groups were compared to analyse the probable affective factors and management. Results Thirty patients were included and six of them hadpsychological side-effect. Hallucination, restlessness, delirium, and nightmare were observed after using vorieonazole for one to four days,and the symptoms relieved after two to five days. The levels of alanineaminotrans/erase, total bilirubin, direct bilirubin, and alkaline phosphatase in psychological sideeffect group were higher than those of the contrasting group. Conclusions The probability of psychological sideeffect after using voriconazole is higher among patients with abonormal hepatic functions. Most of them need no further management and relieve automatically.