危重患者ECMO生命支持期间抗真菌药物TDM与剂量调整

Therapeutic drug monitoring and dose adjustment of antifungal drugs in critically ill patients undergoing extracorporeal membrane oxygenation life support

目的:分析危重患者体外膜肺氧合(ECMO)生命支持期间治疗药物监测(TDM)的意义,提供抗真菌药物剂量调整方案。方法:检索PubMed、Cochrane Library至今有关ECMO期间抗真菌药物TDM相关文献进行分析综述。结果:ECMO对伏立康唑、泊沙康唑、艾沙康唑、两性霉素B脂质体的药动学影响明显,TDM结果显示,ECMO支持期间药物暴露明显降低,需要增加剂量以达到预期临床效果,推荐依据TDM结果进行个体化药物治疗方案调整;氟康唑、阿尼芬净、两性霉素B脱氧胆酸盐受ECMO影响小,可使用常规剂量并进行必要的TDM;TDM有助于提高抗真菌治疗的成功率。结论:ECMO支持期间抗真菌药物的药动学呈现复杂变化,推荐进行TDM并依次调整临床药物治疗方案。

OBJECTIVE To explore the value of therapeutic drug monitoring(TDM)of antifungal drugs in critically ill patients undergoing extracorporeal membrane oxygenation(ECMO)life support and optimize antifungal treatment regimens.METHODS A literature search was performed using PubMed and Cochrane Library regarding TDM of antifungal drugs during ECMO up to the present.And the relevant results were reviewed.RESULTS The pharmacokinetics of voriconazole,posaconazole,isavuconazole and liposomal amphotericin B were significantly affected by ECMO circuit.And the results of TDM indicated that the exposure decreased dramatically during ECMO support.A higher dose should be offer to attain target clinical effects and TDM based individualized drug adjustment was highly recommended.By contrast,the pharmacokinetics of fluconazole,anidulafungin and amphotericin B deoxycholate were less affected by ECMO,routine dosage was selected and TDM could be performed when necessary.TDM was helpful for improving the recovery rates of antifungal treatment.CONCLUSION The pharmacokinetic profiles of antifungal drugs undergo complex changes during ECMO support.Antifungal treatment should be modified base upon the TDM results of antifungal drugs.