Clinical and literature case analysis on cyclophosphamide-associated severe hyponatremia
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
Abstract：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 sodium returned to normal 8 h ~ 24 d (median time 48-h) after drug withdrawal, and returned to normal within 5 d in 27 cases (79.4%). Of them, one patient was still in coma after blood sodium returned to normal, and was diagnosed with central pontine myelinolysis one week later. Conclusions CTX-associated severe hyponatremia mostly occurs within 48-h of intravenous administration and the latency of oral administration is longer. It occurs usually in patients with large amount of hydration and rehydration in a short time before and after medication. The prognosis in most patients is good when CTX is stopped, sodium is supplemented and water is limited.
贺飞，梁锌，梅志红，李国辉. 环磷酰胺相关重度低钠血症临床及文献病例分析[J]. 药物不良反应杂志, 2021, 23(8): 424-432.
He Fei, Liang Xin, Mei Zhihong, Li Guohui. Clinical and literature case analysis on cyclophosphamide-associated severe hyponatremia. Adverse Drug Reactions Journal, 2021, 23(8): 424-432.
