重症患者复方磺胺甲[口恶]唑血药峰浓度与不良反应的相关性研究

The relationships of peak plasma concentration with toxicity of trimethoprim-sulfamethoxazole in ICU patients

目的:评估重症患者使用复方磺胺甲[口恶]唑发生的不良反应与血药峰浓度(Cmax)的相关性及其毒性阈值。方法:采用回顾性研究的方法,收集2016年1月至2021年12月某三甲医院重症监护室使用复方磺胺甲[口恶]唑治疗并进行治疗药物监测的患者信息,使用Naranjo评分量表评价复方磺胺甲[口恶]唑与不良反应的关联性,并分析磺胺甲[口恶]唑及甲氧苄啶Cmax与不良反应发生之间的相关性。结果:本研究共获得109人次磺胺甲[口恶]唑的浓度数据及87人次甲氧苄啶的浓度数据,未发现皮疹、恶心呕吐、肝毒性及肾毒性的发生与磺胺甲[口恶]唑及甲氧苄啶Cmax有相关性(P>0.05),发生血液系统毒性及高钾血症的患者其甲氧苄啶Cmax显著高于未发生的患者(P<0.05),进一步通过受试者工作特征曲线分析得到高钾血症的甲氧苄啶Cmax最佳阈值为8.75μg·mL^(-1)。结论:有必要对使用复方磺胺甲[口恶]唑的重症患者进行治疗药物监测,甲氧苄啶Cmax>8.75μg·mL^(-1)时可能导致发生高钾血症的概率增加。

OBJECTIVE To evaluate the correlation between the adverse reactions of sulfamethoxazole(SMX)/trimethoprim(TMP)and the peak plasma concentration(Cmax)and its toxicity threshold in critically ill patients.METHODS A retrospective analysis was conducted on patients who were continuously treated with SMX/TMP for severe infection and underwent therapeutic drug monitoring(TDM)in the intensive care unit of a tertiary hospital from January 2016 to December 2021.The occurrence of SMX/TMP-related adverse reactions was judged by Naranjo scale.The obtained adverse reactions data and the Cmaxof SMX/TMP were subjected to analysis of the correlation. RESULTS A total of 109 concentration data of SMX and 87 concentration data of TMP were respectively obtained in this study.The Cmaxof TMP in patients with hematological toxicity and hyperkalemia were significantly higher than that in patients without toxicity(P<0.05),but no correlation was found between the occurrence of rash, nausea and vomiting, hepatotoxicity, nephrotoxicity and the Cmaxof SMX/TMP(P>0.05).Further receiver operating characteristic analysis showed that the threshold of TMP peak concentration for hyperkalemia was Cmax>8.75 μg·mL^(-1).CONCLUSION It is necessary to monitor the drug concentration of critical patients using SMX/TMP,which may increase the probability of hyperkalemia at Cmax>8.75 μg·mL^(-1).