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

Abstract

Introduction 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). Methods 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. Results 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. Conclusions 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.

Comparison of Sodium Bicarbonate and Lactated Ringers Hydration for High-dose Methotrexate Chemotherapy in Children

“…8 Similar to our cohort, those that used enteral alkalinization found no difference in time to methotrexate clearance as compared IV sodium bicarbonate. 8,[10][11][12] Others have also reported no difference in percentage of patients or methotrexate cycles with delayed clearance for enteral alkalinization versus IV sodium bicarbonate. 8,13 Diachinski et al described 29 children receiving highdose methotrexate with either regularly scheduled enteral sodium bicarbonate or sodium citrate with Lactated Ringers (62 cycles) or IV sodium bicarbonate (50 cycles).…”

“…IV fluids, when described, were usually sodium containing fluids, with or without dextrose 12–14. Only one cohort described using Lactated Ringers for IV hydration 8. Similar to our cohort, those that used enteral alkalinization found no difference in time to methotrexate clearance as compared IV sodium bicarbonate 8,10–12.…”

“…8,13 Diachinski et al described 29 children receiving highdose methotrexate with either regularly scheduled enteral sodium bicarbonate or sodium citrate with Lactated Ringers (62 cycles) or IV sodium bicarbonate (50 cycles). 8 Similar to our cohort, they found no difference in the percentage of methotrexate cycles that were delayed (8% vs. 10%) or the mean time to methotrexate clearance (57 vs. 61 h). Our cohort, however, had a larger percentage of cycles that were delayed (36.8% vs. 38.3%) and a longer mean time to clearance (71.3 vs. 69.7 h).…”

“…There was also a shortage of sodium acetate, an alternative for urine alkalinization 7. Across Canada, oncology centers handled the shortage by either switching to Lactated Ringers or sodium acetate, if it was available 8. Standard of care at our institution for hydration and urine alkalinization changed to Lactated Ringers solution.…”

Evaluation of an oral sodium bicarbonate protocol for high-dose methotrexate urine alkalinization

“…Despite the lower sodium bicarbonate dose, no differences in time to MTX clearance or the rates of increased serum creatinine were seen between the two cohorts. This nding of an overall lower enteral sodium bicarbonate dose being comparable to a higher IV sodium bicarbonate dose is re ected in the literature, both in the pediatric and adult populations [9][10][12][13]. Consideration to whether lower IV sodium bicarbonate doses have comparable outcomes to those currently prescribed may be of interest.…”