超剂量服用甲氨蝶呤引起骨髓抑制和多器官衰竭致死亡

Death due to myelosuppression and multiple organ failure associated with over dose of methotrexate

1例77岁男性类风湿性关节炎患者医嘱予甲氨蝶呤10 mg口服、1次/周,雷公藤多苷20 mg口服、2次/d,甲泼尼龙8 mg口服、1次/d,但患者将甲氨蝶呤的用药频次与雷公藤多苷混淆,误服为甲氨蝶呤5 mg、2次/d。服药4 d后(服用7次,共35 mg)出现严重口腔溃疡、全身皮疹、发热、咳嗽、咳痰。实验室检查示白细胞计数1.21×10^(9)/L,血清肌酐288μmol/L,γ⁃谷氨酰转移酶163 U/L,丙氨酸转氨酶82 U/L,碱性磷酸酶235 U/L。6 d后实验室检查示白细胞计数0.13×10^(9)/L,中性粒细胞计数0.01×10^(9)/L,血清肌酐317μmol/L,估算肾小球滤过率18 ml/(min·1.73 m^(2)),C反应蛋白233.8 mg/L,降钙素原14.31μg/L。诊断为甲氨蝶呤中毒,骨髓抑制,肾功能不全,肺部感染。立即停用所有药物,给予血液灌流,亚叶酸钙静脉注射,以及抗感染、升白细胞、输血、补液和口腔护理等对症治疗。但患者感染和骨髓抑制持续加重,12 d后因多器官衰竭死亡。

A 77⁃year⁃old male patient with rheumatoid arthritis was given methotrexate 10 mg once a week,tripterygium glycosides 20 mg twice daily,and methylprednisolone 8 mg once daily orally.However,the patient confused the medication frequency of methotrexate with tripterygium glycosides and mistakenly took methotrexate 5 mg twice daily.After 4 days of medication(taking methotrexate 7 times,35 mg in total),the patient developed severe oral ulcers,generalized rash,fever,cough,and expectoration.Laboratory tests showed white blood cell count 1.21×10^(9)/L,serum creatinine 288μmol/L,γ⁃glutamyltransferase 163 U/L,alanine transaminase 82 U/L,and alkaline phosphatase 235 U/L.After 6 days of medication,laboratory tests showed white blood cell count 0.13×10^(9)/L,neutrophil count 0.01×10^(9)/L,serum creatinine 317μmol/L,estimated glomerular filtration rate 18 ml/(min·1.73 m^(2)),C⁃reactive protein 233.8 mg L,and procalcitonin 14.31μg/L.The patient was diagnosed as having methotrexate poisoning,myelosuppression,renal insufficiency,and pulmonary infection.All drugs were discontinued immediately.Blood perfusion,intravenous injection of calcium folinate,and symptomatic treatments such as anti⁃infection,elevation of white blood cells,blood transfusion,rehydration,and mouth care were given.However,the patient′s infection and myelosuppression continued to worsen,and he died of multiple organ failure 12 days later.