Substitution of sodium acetate for sodium bicarbonate for urine alkalinization in high-dose methotrexate therapy

Purpose Methotrexate is an antifolate agent used in treatment of several malignancies. Many toxicities accompany methotrexate that are minimized with urine alkalinization. Parenteral sodium bicarbonate is the historical standard alkalinizing agent, but use has been limited by intermittent shortages. However, intravenous sodium acetate may be considered as a chemically equivalent alternative. The primary objective of this study is to determine the efficacy of sodium acetate versus sodium bicarbonate for urine alkalinization for high-dose methotrexate (HDMTX). Methods This is a retrospective cohort study including adults admitted to Barnes-Jewish Hospital to receive HDMTX for lymphoma, breast cancer with leptomeningial spread, or osteosarcoma. Patients must have received intravenous sodium acetate or sodium bicarbonate alkalinization. Results Of 192 HDMTX encounters, 154 (sodium bicarbonate, n = 86; sodium acetate, n = 68) were evaluated for efficacy and safety. Safety outcomes were not significantly different between groups except for higher peak methotrexate level in the bicarbonate group (2.9 mcmol/L vs. 1.7 mcmol/L, p = 0.023), and increased incidence of grade 3–4 ALT in the sodium bicarbonate group (23.5% vs. 9%, p = 0.02). Time from alkalinizer initiation to pH ≥7 was significantly shorter with sodium bicarbonate (4 vs. 5.15 h, p = 0.021). Nonetheless, outcomes such as length of stay (4.4 vs. 4 days respectively, p = 0.037) and time to methotrexate clearance (3.6 vs. 3.2 days respectively, p = 0.023) reveal that inpatient time was shorter with sodium acetate overall. Conclusion This retrospective analysis suggests that sodium acetate has similar efficacy and safety to sodium bicarbonate for alkalinization and may be considered as an alternative in future shortage situations.

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

Supportive Care in Cancer ◽

10.1007/s00520-021-06503-3 ◽

2021 ◽

Author(s):

Rachel D. Heisler ◽

Jordan J. Kelly ◽

Sara Abedinzadegan Abdi ◽

Jennifer L. Hawker ◽

Leanne G. Fong ◽

...

Keyword(s):

Sodium Bicarbonate ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate ◽

Urine Alkalinization ◽

Oral Sodium

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Evaluation of an Oral Sodium Bicarbonate Protocol for High-Dose Methotrexate Urine Alkalinization

10.21203/rs.3.rs-328004/v1 ◽

2021 ◽

Author(s):

Rachel Heisler ◽

Jordan Kelly ◽

Sara Abedinzadegan Abdi ◽

Jennifer Hawker ◽

Leanne Fong ◽

...

Keyword(s):

Serum Creatinine ◽

Sodium Bicarbonate ◽

Retrospective Chart Review ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate ◽

Urine Alkalinization ◽

Nausea And Emesis ◽

Alberta Health ◽

Oral Sodium

Abstract Purpose: Intravenous (IV) sodium bicarbonate is considered standard therapy for high-dose methotrexate (HDMTX) urine alkalinization. Due to a national IV sodium bicarbonate shortage, an oral (PO) sodium bicarbonate protocol was implemented by Alberta Health Services (AHS) for HDMTX urine alkalinization. This study aims to evaluate the efficacy and safety of the PO sodium bicarbonate protocol compared to IV sodium bicarbonate for HDMTX urine alkalinization. Methods: A retrospective chart review of adult patients who received HDMTX (>500 mg/m2) with sodium bicarbonate for urine alkalinization at 4 hospitals in Alberta was conducted. Patients who received IV sodium bicarbonate between January-June 2017 and PO sodium bicarbonate between July-December 2017 were compared for the primary outcome of time to methotrexate clearance. Results: A total of 84 and 78 HDMTX cycles were included in the IV and PO cohorts, respectively. No difference in time to methotrexate clearance was seen between the IV and PO cohorts, 91.6 (± 35.4) hours and 95.2 (± 44) hours respectively; p=0.5. The proportion of HDMTX cycles that experienced a >25% increase in serum creatinine was not statistically significant, IV protocol 12% and PO protocol 5%; p=0.13. Nausea and emesis occurred more frequently in the PO cohort than the IV cohort, though rarely resulted in refused doses or change to alternate sodium bicarbonate formulations.Conclusions: The results of this study indicate that the AHS PO sodium bicarbonate protocol was no different in time to methotrexate clearance or rates of increased serum creatinine when compared to IV sodium bicarbonate.

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Short-term, High-dose Methotrexate Therapy in a Case of Severe Psoriatic Arthritis

Rheumatology ◽

10.1093/rheumatology/27.2.160 ◽

1988 ◽

Vol 27 (2) ◽

pp. 160-162 ◽

Cited By ~ 1

Author(s):

E. EECKHOUT ◽

E. SUYS ◽

P. BUYDENS ◽

S. VAN BELLE ◽

L. A. VERBRUGGEN

Keyword(s):

Psoriatic Arthritis ◽

Methotrexate Therapy ◽

High Dose ◽

High Dose Methotrexate ◽

Short Term ◽

Dose Methotrexate

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Early Recognition of Renal Toxicity of High-dose Methotrexate Therapy

Journal of Pediatric Hematology/Oncology ◽

10.1097/mph.0b013e318182e73e ◽

2008 ◽

Vol 30 (12) ◽

pp. 950-952 ◽

Cited By ~ 7

Author(s):

Theodore Scott Nowicki ◽

Kari Bjornard ◽

David Kudlowitz ◽

Claudio Sandoval ◽

Somasundaram Jayabose

Keyword(s):

Renal Toxicity ◽

Early Recognition ◽

Methotrexate Therapy ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate

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Acute urticaria and hepatitis complicating high-dose methotrexate therapy

Medical and Pediatric Oncology ◽

10.1002/mpo.2950240215 ◽

1995 ◽

Vol 24 (2) ◽

pp. 137-140 ◽

Cited By ~ 8

Author(s):

Zakiya Al-Lamki ◽

Eileen Thomas ◽

Nagwa El-Banna ◽

Norman Jaffe

Keyword(s):

Methotrexate Therapy ◽

High Dose ◽

High Dose Methotrexate ◽

Acute Urticaria ◽

Dose Methotrexate

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P0008CASE REPORT: METABOLIC ALKALOSIS RESULTING IN RESPIRATORY COMPROMISE IN A PATIENT UNDERGOING HIGH DOSE METHOTREXATE THERAPY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0008 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Darragh O'Donoghue ◽

Heather Truong ◽

Heidi Finnes ◽

Jennifer McDonald ◽

Nelson Leung

Keyword(s):

Metabolic Alkalosis ◽

B Cell Lymphoma ◽

Methotrexate Therapy ◽

High Dose ◽

Close Monitoring ◽

High Dose Methotrexate ◽

Respiratory Compromise ◽

Dose Methotrexate ◽

Adequate Hydration ◽

Bicarbonate Infusion

Abstract Background and Aims High dose Methotrexate (HDMTX) is an important component of several modern oncological/haematological treatment protocols due to its central nervous system penetrance. Nephrotoxicity represents a significant adverse effect and can limit therapeutic options. Therefore, strategies to prevent this are paramount. Urinary alkalinisation and large volume resuscitation to maintain adequate hydration and urine output are the typical strategies. Urinary alkalinisation prevents tubular precipitation of methotrexate and therefore, a strict urinary pH target of 7 is maintained via a continuous bicarbonate infusion. Method We describe a case report, of Iatrogenic metabolic alkalosis leading to respiratory compromise in a patient receiving HDMTX from Mayo Clinic, Rochester. Results We present the case of a 76-year-old woman with a Diffuse Large B-Cell Lymphoma with CNS involvement who presented for elective admission for her 1st cycle of HDMTX. She received 7g of Methotrexate at dosing of 8 g/m2. She received the standard urinary alkalinisation with pre- and post-hydration. Her baseline HCO3- was 28 mEq/L. Her 48 hour MTX level was elevated at 1.2 so the urinary alkalinisation protocol was continued until <0.1 mcmol/L. On day 4, she developed frequent episodes of apnoea. Her ABG demonstrated a metabolic alkalaemia pH 7.54, pCO 53, pO2 91, HCO3 45. She was transferred to the ICU for close monitoring. Her bicarbonate infusion was discontinued and she received acetazolamide. Her bicarbonate improved to 31 after 12 hours. She had a significant improvement in her respiratory status with no further episodes of apnoea. Her bicarbonate infusion was restarted due to elevated MTX levels. She was discharged home with no further complications. Conclusion Iatrogenic Metabolic alkalosis leading to respiratory compromise represents a rare but important complication of urinary alkalinsation protocols for High-dose Methotrexate therapy.

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