Kidney Week

Abstract: SA-PO499

Tris(hydroxymethyl)aminomethane Reverses Tumor-Induced Lactic Acidosis

Session Information

• Acid-Base, Calcium, Potassium, and Magnesium Disorders: Clinical
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Szendrey, John Alexander, Baystate Medical Center, Springfield, Massachusetts, United States

John Alexander Szendrey, MD, MS

• Landry, Daniel L., Baystate Medical Center, Springfield, Massachusetts, United States

Daniel L. Landry, DO, FASN

• Braden, Gregory Lee, Baystate Medical Center, Springfield, Massachusetts, United States

Gregory Lee Braden, MD

• Mulhern, Jeffrey, Baystate Medical Center, Springfield, Massachusetts, United States

Jeffrey Mulhern, MD

Group or Team Name

• Kidney Care and Transplant Services of New England.

Introduction

Tumor-induced(TI) lactic acidosis (LA) occurs in lymphomas due to impaired liver L metabolism & the Warburg effect of anaerobic glyolysis in the tumor. We describe a patient with large B cell lymphoma with severe respiratory distress & Kussmaul breathing from TI LA. The use of tris-hydroxymethyl aminomethane (THAM) which provides HCO3 without the generation of CO2, rapidly cleared his lactic acidosis.

Case Description

A 73 yr old man had severe dyspnea after 1 month of an enlarging groin mass He had a RR of 30/min with Kussmaul respirations. Lungs were clear & heart exam normal. A V/Q scan showed no pulmonary embolus.Table 1 shows a severe anion gap LA on admission. His glucose, BUN & creatinine, CPK, aspirin, acetaminophen & beta-hydroxybutyrate levels were normal. He was transfered to the ICU due to severe respirtory fatigue. THAM at a dose of 575 ml via a 0.3 mmo/L solution was given. Four hours later his LA dropped from 14.7 to 8.7 & his HCO3 rose to 20 mEq/L with markedly improved breathing & no intubation. The next day this same THAM dose was repeated with a greater fall in LA. A biopsy showed diffuse large cell B-lymphoma.& methylprednisolone was started. By the fourth day his LA was gone.

Discussion

Sodium bicarbonate IV in TI LA worsens LA. We chose to use THAM in our patient as it rapidly alkalinizes tissue & the liver within three minutes. This patient's LA quickly reversed with THAM doses calculated to increase the serum bicarbonate by 5 mmol/L per dose, prreventing intubation. We conclude that THAM can reverse TI LA without liver mets by the following mechanisms: a) alkalosis Increases lactate uptake & metabolism by hepatocytes, b) alkalosis increases liver conversion of lactate to pyruvate by stimulation of lactate dehydogenase (LHD) A and inhibition of LDH B, & c) reversal of the Warburg effect by increasing pyruvate dehydogenase(PDH) by inhibition of (PDH) kinase its breakdown enzyme with enhanced shuttling of pyruvate into the alkalosis-stimulated Krebs cycle. THAM is a new therapy for TI LA.