Oral sodium bicarbonate protocol for high-dose methotrexate urine alkalinization: A pediatric experience

Methotrexate (MTX) is a cytotoxic antimetabolite. Intravenous (IV) hydration and urine alkalinization with sodium bicarbonate (NaHCO₃) can mitigate nephrotoxicity associated with high-dose MTX (HDMTX, doses ≥500 mg/m²). A shortage of IV NaHCO₃ in 2017 prompted Alberta Children's Hospital (ACH) and Stollery Children's Hospital (SCH) to adopt an alternative protocol including oral NaHCO₃ and IV hydration with Lactated Ringer's (LR).

A retrospective chart review was conducted for ACH and SCH inpatients who received HDMTX between January and December 2017. The primary outcome was the proportion of cycles with delayed HDMTX clearance within the IV and oral cohorts. Secondary outcomes include NaHCO₃ administered until clearance, NaHCO₃ required to reach pH ≥7, time to reach pH ≥7, incidence of pH <7, time to clearance, and time to discharge. Adverse effects associated with delayed clearance or NaHCO₃ administration were also reported.

112 MTX cycles were included, 50 and 62 from the IV and oral cohorts, respectively. Clearance delays beyond protocol expectations occurred in 10 cycles (8.9%), 5 from each cohort (p = 0.72). Differences between cohorts were not statistically significant, except the amounts of NaHCO₃ required until clearance (383 vs. 277 mmol/m², p = 0.005) and to reach pH ≥7 (52 vs. 40 mmol/m², p = 0.004) were lower in the oral cohort. Incidences of adverse effects were not different.

Oral NaHCO₃ with LR is a feasible alternative for urine alkalinization. The total dose of NaHCO₃ utilized was lower in the oral cohort, with no additional delays in clearance.