环磷酰胺相关重度低钠血症临床及文献病例分析  

Clinical and literature case analysis on cyclophosphamide-associated severe hyponatremia

作　　者：贺飞 梁锌 梅志红 李国辉 He Fei;Liang Xin;Mei Zhihong;Li Guohui(Department of Pharmacy,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Medical Statistics Office,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Medicine,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China)

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院药剂科,北京100021 [2]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院统计室,北京100021 [3]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院内科,北京100021

出　　处：《药物不良反应杂志》2021年第8期424-432,共9页Adverse Drug Reactions Journal

摘　　要：目的了解环磷酰胺(CTX)相关重度低钠血症的临床特点。方法报道中国医学科学院北京协和医学院肿瘤医院收治的1例乳腺癌患者应用CTX后出现重度低钠血症的诊治经过,并对该例以及检索PubMed、Embase、中国知网、万方数据库(截至2021年1月26日)收集到的相关病例主要临床资料[性别、年龄、CTX用药指征、CTX用法用量、应用CTX至发生低钠血症时间(潜伏期)以及重度低钠血症临床表现、治疗及转归等]进行描述性统计分析。结果纳入分析的患者共34例,男性4例,女性30例;年龄27~87岁,中位年龄56岁;原发疾病为恶性肿瘤者22例(乳腺癌17例),系统性红斑狼疮6例,肾小球肾炎3例,硬皮病2例,单克隆丙种球蛋白病1例。34例患者中,31例静脉应用CTX者中有22、8、1例患者分别在第1、2、7剂次用药后发生重度低钠血症,其中27例有潜伏期记录,为用药后3~96 h(中位时间24 h),25例潜伏期≤48 h;3例口服用药者潜伏期分别为1、21和30 d。34例患者血钠最低值为102~124 mmol/L,<120 mmol/L者30例(88.2%);主要临床表现为意识障碍(20例)、恶心、呕吐(17例)和癫痫样发作(15例);22例(64.7%)给予CTX前后短时间内进行了水化补液,1例未行水化补液,11例无相关描述。出现重度低钠血症后,34例患者均停止CTX治疗,经补钠、限水等处理,血钠在停药后8 h~24 d(中位时间48 h)恢复正常,5 d内恢复正常者27例(79.4%),其中1例血钠恢复正常后仍处于昏迷状态,1周后诊断为桥脑中央髓鞘溶解症。结论CTX相关重度低钠血症多发生于静脉用药后48 h内,口服用药者潜伏期延长;易发生于用药前后短时间内大量水化补液者。停用CTX并补钠、限水,多数患者预后较好。Objective To explore the clinical characteristics of hyponatremia associated with cyclophosphamide(CTX).Methods The diagnosis and management of a breast cancer patient with severe hyponatremia after CTX treatment in Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College was reported.The main clinical data of this patient and the relevant cases collected by searching PubMed,Embase,CNKI,and Wanfang database(as of January 26,2021),including gender,age,indications of CTX,usage and dosage of CTX,time from the application of CTX to the occurrence of hyponatremia(latency),and clinical manifestations,treatment and outcome of severe hyponatremia,etc.,was descriptively analyzed.Results A total of 34 patients were included in the analysis,including 4 males and 30 females,aged from 27 to 87 years with the median age of 56 years.The primary disease were malignant tumor in 22 cases(17 cases of breast cancer),systemic lupus erythematosus in 6 cases,glomerulonephritis in 3 cases,scleroderma in 2 cases,and monoclonal gamma globulinosis in 1 case.Among the 34 patients,22,8 and 1 of 31 patients who received CTX intravenously developed severe hyponatremia after the first,second and seventh dose of treatments,respectively.Among them,27 cases had latency records,which were 3⁃96 h(median time 24 h)and 25 cases had latency≤48 h.The latency of severe hyponatremia induced by oral CTX was 1 d,21 d and 30 d,respectively.The lowest value of blood sodium in 34 patients was 102⁃124 mmol/L,and in 30 patients(88.2%)were less than 120 mmol/L.The main clinical manifestations were disturbance of consciousness(20 cases),nausea and vomiting(17 cases),and epileptic seizures(15 cases).Twenty⁃two cases(64.7%)underwent hydration rehydration in a short time before and after CTX treatment,1 case did not undergo hydration rehydration,and 11 cases had no relevant descriptions.After severe hyponatremia occurrence,CTX treatment was discontinued in all 34 patients.After sodium supplementation and water restriction,blood sod

关 键 词：低钠血症 环磷酰胺 药物相关副作用和不良反应 

分 类 号：R969.3[医药卫生—药理学]