Antidotal Sodium Bicarbonate Therapy: Delayed QTc Prolongation and Cardiovascular Events

J Med Toxicol. 2021 Jan;17(1):27-36. doi: 10.1007/s13181-020-00799-z. Epub 2020 Jul 31.

Abstract

Background: Sodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)-based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE.

Methods: This was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2).

Results: Out of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6-24.1), DQTP (aOR 126.7, CI 9.8-1646.2), and death (aOR 11.9, CI 2.4-58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8-14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16-61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19).

Conclusion: In ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.

Keywords: Adverse cardiovascular events; Overdose; Sodium bicarbonate.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antidotes / adverse effects*
  • Dose-Response Relationship, Drug
  • Drug Overdose / diagnosis
  • Drug Overdose / drug therapy*
  • Drug Overdose / mortality
  • Emergency Service, Hospital
  • Female
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiopathology
  • Heart Rate / drug effects
  • Humans
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / mortality
  • Long QT Syndrome / physiopathology
  • Male
  • Middle Aged
  • Risk Assessment
  • Risk Factors
  • Sodium Bicarbonate / adverse effects*
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antidotes
  • Sodium Bicarbonate