Page 106 - 中国药房2021年11期

ABSTRACT OBJECTIVE：To investigate the role of clinical pharmacists in the treatment of delayed excretion of acute renal
failure （ARF） with epileptic seizure caused by HD-MTX in a patient，and to provide reference for rational drug use and
pharmaceutical care in such type of patients. METHODS：A patient with diffuse large B-cell lymphoma was given HD-MTX for
chemotherapy，and ARF caused by delayed methotrexate excretion occurred on the second day after methotrexate administration.
Clinical physicians adjusted the rescue dose and frequency of calcium folinate but the effect was poor. Clinical pharmacists analyzed
the causes of delayed methotrexate excretion by reviewing literature and combining with the patient’s condition. It was suggested to
monitor the blood concentration of methotrexate，strengthen alkalization and hydration，increase the volume of intravenous sodium
bicarbonate from 125 mL to 250 mL，take Sodium bicarbonate tablets orally，and monitor the pH value of urine（pH value of urine
maintained above 7）. In addition，the pharmacist told the patient to drink water as much as possible to ensure the daily urine output
reached 3 000 to 4 000 mL. The blood concentration of methotrexate was 16.14 μmol/L 44 h after administration，which proved to
be excretion delay. The patient had epileptic seizure on the 13th day after methotrexate medication. The physician gave sodium
valproate 0.8 g intravenously to control epilepsy. The clinical pharmacist conducted pharmaceutical care for the patient，and found
that the compliance of the patient taking Sodium bicarbonate tablets and Sodium valproate tablets orally was not good，so
medication education and pharmaceutical care were conducted，then the patient accepted and took the drugs on time. RESULTS：
The physician adopted the suggestions of the pharmacist to monitor the blood concentration of methotrexate and performed
symptomatic treatment. The urine volume of the patient increased，the edema was reduced，serum creatinine gradually returned to
normal，and renal function recovered gradually；the symptoms of epilepsy was controlled. CONCLUSIONS：In the treatment
process of ARF complicated with epileptic seizure caused by excretion delay of HD-MTX，the clinical pharmacist assisted physician
to improve the treatment plan and conducted pharmaceutical care and medication education for the patient，therefore ensure the safe
and rational use of drugs.
KEYWORDS HD-MTX；Central diffuse large B-cell lympHoma；Acute renal failure；Epileptic seizure；Pharmaceutical care

甲氨蝶呤是经典的叶酸拮抗剂，可竞争性地抑制二 病理活检示：弥漫大B细胞淋巴瘤[非生发中心来源B细
氢叶酸还原酶，阻止二氢叶酸还原为具有生理活性的四 胞淋巴瘤（Non-GCB）亚型]，未予特殊治疗。7 月 26 日
氢叶酸，从而影响嘌呤核苷酸和胸腺嘧啶核苷酸生物合 患者于上海某三级甲等医院就诊，完善相关检查后诊断
成中一碳单位的转移，抑制DNA合成，最终抑制肿瘤细 为“中枢弥漫大 B 细胞淋巴瘤 Ⅳ期 A 组，国际预后指数
胞的增殖和复制，其在临床上通常用于治疗急性淋巴细 （IPI）3 分”，予利妥昔单抗和来那度胺联合地塞米松方
2
[1]
胞白血病 。大剂量甲氨蝶呤（HD-MTX，＞1 g/m）冲击 案治疗2个周期，具体为：利妥昔单抗注射液800 mg，静
治疗可使药物透过常规剂量下无法突破的血脑屏障和 脉滴注，d0+来那度胺胶囊25 mg，口服，d1～21+醋酸地塞米
血睾屏障发挥疗效，但同时也会引起严重的药物不良反 松片20 mg，口服，d1～4 （每21天为1个周期）。此后，患者
应，如肝肾毒性、骨髓抑制、严重的黏膜炎以及中枢神经 因“确诊中枢弥漫大 B 细胞淋巴瘤 3 个月”于 2019 年 10
系统毒性等 。因此，临床上应用 HD-MTX 时常辅以水 月16日就诊于上海某三级甲等医院，行进一步治疗。
[2]
化、碱化和亚叶酸钙解救等预防措施，但因甲氨蝶呤在 2 主要治疗经过
体内的代谢和排泄个体差异很大，其排泄延迟常会引起 2019 年 10 月 16 日，患者入院完善相关检查。体格
[3]
急性肾损伤（ARF） 。甲氨蝶呤排泄延迟造成ARF在临 检查结果显示：体温36.6 ℃、脉搏78 次/min、呼吸18 次/
床上相对较常见，但伴发癫痫大发作的情况较少见。本 min、血压 130/80 mmHg（1 mmHg＝0.133 kPa）。实验室
文通过报道临床药师参与1例中枢弥漫大B细胞淋巴瘤 检查结果显示：白细胞 6.3×10 L ，中性粒细胞 46.6％，
－1
9
患者使用HD-MTX后排泄延迟导致的ARF伴癫痫发作 血红蛋白 136 g/L，血小板 133×10 L ，超敏 C 反应蛋白
－1
9
的诊疗过程，分析甲氨蝶呤发生排泄延迟的相关因素， 0.81 mg/L，总胆红素12.4 μmol/L，直接胆红素1.8 μmol/L，
提出应对措施以及进行药学监护，旨在为临床安全合理 总蛋白66.1 g/L，白蛋白34.8 g/L，谷丙转氨酶40 U/L，谷
用药提供参考。 草转氨酶 23 U/L，肌酐 70 μmol/L，乳酸脱氢酶 268 U/L，
1 病例资料 尿液pH 6.5。患者入院诊断为：（1）中枢弥漫大B细胞淋
患者，男性，66 岁，身高 180 cm，体质量 87.5 kg。 巴瘤Ⅳ期 A 组，IPI 3 分；（2）冠心病；（3）房颤射频消融
2019 年 6 月患者以左手指麻木起病。6 月 26 日，出现左 术后。
上肢麻木加重伴左侧脸部及肢体间断抽搐，每次持续约 10 月 17 日，患者行抗肿瘤治疗，具体为：利妥昔单
10 s，可自行缓解，左下肢肌力减退，不能抵抗重力，予丙 抗注射液800 mg，静脉滴注 +注射用阿糖胞苷80 mg，鞘
戊酸钠缓释片控制癫痫发作。7 月 8 日，患者颅内穿刺 内注射+地塞米松磷酸钠注射液5 mg，鞘内注射；辅以奥

·1376 · China Pharmacy 2021 Vol. 32 No. 11 中国药房 2021年第32卷第11期