Reed Daniel R, Pierce Eric J, Sen Jeremy M, Keng Michael K
Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Cancer Manag Res. 2019 Aug 30;11:8065-8072. doi: 10.2147/CMAR.S190084. eCollection 2019.
Intravenous (IV) sodium bicarbonate is typically used in alkalization regimens for the safe use of the chemotherapeutic agent high-dose methotrexate (HDMTX). Urine parameters including urine output and pH are important in order to minimize the risk of kidney injury, which increases adverse effects and hospital length of stay following HDMTX. IV sodium bicarbonate has been on shortage, and there are limited literature describing the safety of alternative regimens.
A single institution, prospective analysis of non-Hodgkin's lymphoma and acute lymphoblastic leukemia patients receiving HDMTX for central nervous system (CNS) prophylaxis or disease. Patients received an oral (PO) regimen of sodium bicarbonate and acetazolamide to achieve a urine pH >7. This cohort was compared to a subsequent IV sodium bicarbonate control cohort. Multiple co-primary safety outcomes assessed the incidences of acute kidney injury and delayed methotrexate clearance as well as change in liver function tests. Secondary outcomes included time to urine pH, time to urine output, and length of stay.
A total of 126 encounters were studied for the primary safety outcome. There was no difference between AKI incidence in patients receiving the PO alkalization regimen compared to patients receiving IV sodium bicarbonate (14.5% vs 9.3%, respectively, =0.41). There was no difference in methotrexate clearance between the PO and IV groups (26.5% vs 37.2%, respectively, =0.21). The use of PO alkalization regimen is estimated to have saved 2002 vials of IV sodium bicarbonate and was approximately US$226 less expensive per encounter.
This analysis supports the use of PO regimens to achieve urine alkalization necessary for safe administration of HDMTX during periods of IV sodium bicarbonate shortage. Further studies may determine optimal dosing strategies that decrease length of stay and ensure noninferiority of efficacy outcomes with PO regimens for urine alkalization with HDMTX.
静脉注射碳酸氢钠通常用于碱化治疗方案，以安全使用化疗药物大剂量甲氨蝶呤（HDMTX）。包括尿量和pH值在内的尿液参数对于将肾损伤风险降至最低很重要，肾损伤会增加HDMTX治疗后的不良反应和住院时间。静脉注射碳酸氢钠一直短缺，且描述替代方案安全性的文献有限。
对一家机构中接受HDMTX进行中枢神经系统（CNS）预防或治疗的非霍奇金淋巴瘤和急性淋巴细胞白血病患者进行前瞻性分析。患者接受口服（PO）碳酸氢钠和乙酰唑胺方案，以使尿液pH值>7。将该队列与随后的静脉注射碳酸氢钠对照队列进行比较。多个共同主要安全结局评估急性肾损伤和甲氨蝶呤清除延迟的发生率以及肝功能检查的变化。次要结局包括达到尿液pH值的时间、达到尿量的时间和住院时间。
共对126例患者进行了主要安全结局研究。接受PO碱化方案的患者与接受静脉注射碳酸氢钠的患者相比，急性肾损伤发生率无差异（分别为14.5%和9.3%，P=0.41）。PO组和静脉注射组之间甲氨蝶呤清除率无差异（分别为26.5%和37.2%，P=0.21）。估计使用PO碱化方案节省了2002瓶静脉注射碳酸氢钠，每次治疗费用约便宜226美元。
该分析支持在静脉注射碳酸氢钠短缺期间使用PO方案来实现HDMTX安全给药所需的尿液碱化。进一步的研究可能会确定最佳给药策略，以缩短住院时间，并确保PO方案在HDMTX尿液碱化方面的疗效结果不劣于其他方案。
