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Antidotal Sodium Bicarbonate Therapy: Delayed QTc Prolongation and Cardiovascular Events

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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.

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Funding

The study was made possible, in part, by grant DA037317 (PI: Manini) from the National Institute on Drug Abuse of the National Institutes of Health. Dr. Shastry is supported by an institutional training grant, 1T32 HL129974-01 (PI: Richardson), from the National Heart, Lung & Blood Institute of the National Institutes of Health. Dr. Manini is currently supported by grant R01DA048009 from the National Institute on Drug Abuse of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, 3 East 101st Street, 2nd Floor, New York, NY, 10029, USA

    Siri Shastry, George Loo & Lynne D. Richardson

  2. Brown University, Providence, RI, USA

    Judson Ellis

  3. Department of Population Health, New York University, New York, NY, USA

    Rajesh Vedanthan

  4. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Lynne D. Richardson

  5. Division of Medical Toxicology, Department of Emergency Medicine, Icahn School of Medicine, Elmhurst Hospital Center, New York, NY, USA

    Alex F. Manini

Authors
  1. Siri Shastry
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  2. Judson Ellis
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  4. Rajesh Vedanthan
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  6. Alex F. Manini
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Contributions

SS performed data analysis and drafted the manuscript. JE assisted with data collection and analysis. RV assisted with data analysis. LDR provided assistance with funding and data collection. AM conceived the study, obtained funding, and oversaw data collection, analysis, and manuscript preparation. All authors helped edit the manuscript and approved the final version of the manuscript.

Corresponding author

Correspondence to Siri Shastry.

Ethics declarations

IRB approval was obtained with waiver of consent prior to data collection at the study institutions.

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None.

Additional information

Supervising Editor: Maryann Elizabeth Amirshahi, PharmD, MD, MPH, PhD

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Presentations

Data from this study were presented at the American College of Medical Toxicology (ACMT) Annual Scientific Meeting in San Francisco, CA in April 2019, at the Society for Academic Emergency Medicine (SAEM) Annual Meeting in Las Vegas, NV in May 2019, and at the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) Congress in Naples, Italy in May 2019.

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Shastry, S., Ellis, J., Loo, G. et al. Antidotal Sodium Bicarbonate Therapy: Delayed QTc Prolongation and Cardiovascular Events. J. Med. Toxicol. 17, 27–36 (2021). https://doi.org/10.1007/s13181-020-00799-z

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  • DOI: https://doi.org/10.1007/s13181-020-00799-z

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