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QTc Prolongation in Poison Center Exposures to CredibleMeds List of Substances with “Known Risk of Torsades de Pointes”

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Abstract

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as “Known Risk of TdP” but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the “Known Risk” substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common “Known Risk” substances were citalopram, escitalopram and cocaine. Although not in the “Known Risk” category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2–55.8) and methadone (OR 7.1, 95% CI 2.1–23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of “Known Risk of TdP” QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.

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Change history

  • 06 September 2022

    Kaitlin Ryan author ORCID number has been updated to 0000-0003-1587-9815.

References

  1. Yates, C., & Manini, A. F. (2012). Utility of the electrocardiogram in drug overdose and poisoning: Theoretical considerations and clinical implications. Current Cardiology Reviews, 8(2), 137–151.

    Article  Google Scholar 

  2. Woosley, R. L., Heise, C. W., & Romero, K. A. (2018). QTdrugs list, AZCERT, Inc. 1822 Innovation Park Dr., Oro Valley, AZ 85755 Retrieved July 6, 2018, from www.Crediblemeds.org

  3. Drew, B. J., Ackerman, M. J., Funk, M., Gibler, W. B., Kligfield, P., Menon, V., Philippides, G. J., Roden, D. M., Zareba, W., American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology, the Council on Cardiovascular Nursing, and the American College of Cardiology Foundation. (2010). Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation, 121(8), 1047–1060.

    Article  Google Scholar 

  4. Tisdale, J. E., Jaynes, H. A., Kingery, J. R., Overholser, B. R., Mourad, N. A., Trujillo, T. N., & Kovacs, R. J. (2014). Effectiveness of a clinical decision support system for reducing the risk of QT interval prolongation in hospitalized patients. Circulation Cardiovascular Quality and Outcomes, 7(3), 381–390.

    Article  Google Scholar 

  5. Isbister, G. K. (2015). Risk assessment of drug-induced QT prolongation. Australian Prescriber, 38(1), 20–24.

    Article  Google Scholar 

  6. Pourmand, A., Mazer-Amirshahi, M., Chistov, S., Sabha, Y., Vukomanovic, D., & Almulhim, M. (2017). Emergency department approach to QTc prolongation. American Journal of Emergency Medicine, 35(12), 1928–1933.

    Article  Google Scholar 

  7. Heemskerk, C. P. M., Pereboom, M., van Stralen, K., Berger, F. A., van den Bemt, P. M. L. A., Kuijper, A. F. M., van der Hoeven, R. T. M., Mantel-Teeuwisse, A. K., & Becker, M. L. (2018). Risk factors for QTc interval prolongation. European Journal of Clinical Pharmacology, 74(2), 183–191.

    Article  CAS  Google Scholar 

  8. Berling, I., & Isbister, G. K. (2015). Prolonged QT Risk assessment in antipsychotic overdose using the QT nomogram. Annals of Emergency Medicine, 66(2), 154–164.

    Article  Google Scholar 

  9. Baker, W. L. (2017). Treating arrhythmias with adjunctive magnesium: Identifying future research directions. European Heart Journal Cardiovascular Pharmacother, 3(2), 108–117.

    Google Scholar 

  10. Schwartz, P. J., & Woosley, R. L. (2016). Predicting the unpredictable: Drug-induced QT prolongation and torsades de pointes. Journal of the American College of Cardiology, 67(13), 1639–1650.

    Article  Google Scholar 

  11. Pérez-Riera, A. R., Barbosa-Barros, R., Raimundo, R. D., de Rezende, M. P. D. C., Sorpreso, I. C. E., & de Abreu, L. C. (2018). The congenital long QT syndrome Type 3: An update. Indian Pacing Electrophysiology Journal, 18(1), 25–35.

    Article  Google Scholar 

  12. von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gøtzsche, P. C., & Vandenbroucke, J. P. (2014). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. International Journal of Surgery, 12(12), 1495–1499.

    Article  Google Scholar 

  13. Campleman, S. L., Brent, J., Pizon, A. F., Shulman, J., Wax, P., & Manini, A. F. (2020). Drug-specific risk of severe QT prolongation following acute drug overdose. Clinical Toxicology. https://doi.org/10.1080/15563650.2020.1746330

    Article  PubMed  Google Scholar 

  14. van Gorp, F., Whyte, I. M., & Isbister, G. K. (2009). Clinical and ECG effects of escitalopram overdose. Annals of Emergency Medicine, 54(3), 404–408.

    Article  Google Scholar 

  15. Berling, I., & Isbister, G. K. (2014). Mirtazapine overdose is unlikely to cause major toxicity. Clinical Toxicology (Philadelphia, PA), 52(1), 20–24.

    Article  CAS  Google Scholar 

  16. Manini, A. F., Nair, A. P., Vedanthan, R., Vlahov, D., & Hoffman, R. S. (2017). Validation of the Prognostic Utility of the Electrocardiogram for Acute Drug Overdose. Journal of the American Heart Association, 6(2), e004320.

    Article  Google Scholar 

  17. Othong, R., Devlin, J. J., & Kazzi, Z. N. (2015). Medical toxicologists’ practice patterns regarding drug-induced QT prolongation in overdose patients: A survey in the United States of America, Europe, and Asia Pacific region. Clinical Toxicology (Philadelphia, PA), 53(4), 204–209.

    Article  CAS  Google Scholar 

  18. Manini, A. F., Nelson, L. S., Skolnick, A. H., Slater, W., & Hoffman, R. S. (2010). Electrocardiographic predictors of adverse cardiovascular events in suspected poisoning. Journal of Medical Toxicology, 6(2), 106–115.

    Article  Google Scholar 

  19. Jang, D. H., Spyres, M. B., Fox, L., & Manini, A. F. (2014). Toxin-induced cardiovascular failure. Emergency Medicine Clinics of North America, 32(1), 79–102.

    Article  Google Scholar 

  20. Berling, I., Hatten, B. W., Hoffman, R. S., Othong, R., Roberts, D. M., Mustafa, R. A., Yates, C., Cormier, M., & Gosselin, S. (2020). Guidelines for reporting case studies and series on drug-induced QT interval prolongation and its complications following acute overdose. Clinical Toxicology (Philadelphia, PA), 58(1), 20–28. https://doi.org/10.1080/15563650.2019.1605077 Epub 2019 Apr 24.

    Article  Google Scholar 

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Authors and Affiliations

  1. Pharmacy Department, Children’s Wisconsin, 8915 West Connell Court, Milwaukee, WI, 53226, USA

    Kaitlin Ryan

  2. Department of Emergency Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Paul Benz, Amy Zosel, Andrew Farkas & Jillian Theobald

  3. Wisconsin Poison Center, Children’s Wisconsin, 999 N 92nd St, Suite 660, Milwaukee, WI, 5226, USA

    Amy Zosel, Andrew Farkas & Jillian Theobald

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  1. Kaitlin Ryan
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  5. Jillian Theobald
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Contributions

The authors confirm contribution to the paper as follows: All authors contributed to the study conception and design. KR and PB completed the data collection. All authors analyzed the data, interpreted the results, and contributed to manuscript revisions. All authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Kaitlin Ryan.

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Ryan, K., Benz, P., Zosel, A. et al. QTc Prolongation in Poison Center Exposures to CredibleMeds List of Substances with “Known Risk of Torsades de Pointes”. Cardiovasc Toxicol 22, 866–877 (2022). https://doi.org/10.1007/s12012-022-09764-4

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