Abstract
Introduction
In ED patients with acute drug overdose involving prescription medication and/or substances of abuse, severe QTc prolongation (> 500 ms) is predictive of adverse cardiovascular events (ACVE), defined as myocardial injury, ventricular dysrhythmia, shock, or cardiac arrest. However, it is unclear whether delayed severe QTc prolongation (dsQTp) is a risk factor for ACVE and if specific clinical factors are associated with occurrence of dsQTp.
Methods
A secondary analysis of a prospective cohort of consecutive adult ED patients with acute drug overdose was performed on patients with initial QTc < 500 ms. The predictor variable, dsQTp, was defined as initial QTc < 500 ms followed by repeat QTc ≥ 500 ms. The primary outcome was occurrence of ACVE. Multivariable logistic regression was performed to test whether dsQTp was an independent predictor of ACVE and to derive clinical factors associated with dsQTp.
Results
Of 2311 patients screened, 1648 patients were included. The dsQTp group (N = 27) was older than the control group (N = 1621) (51.6 vs 40.2, p < 0.001) and had a higher number of drug exposures (2.92 vs 2.16, p = 0.003). Following adjustment for age, sex, race/ethnicity, number of exposures, serum potassium, and opioid exposure, dsQTp remained an independent predictor of ACVE (aOR: 12.44, p < 0.0001). Clinical factors associated with dsQTp were age > 45 years and polydrug (≥ 3) overdoses.
Conclusion
In this large secondary analysis of ED patients with acute drug overdose, dsQTp was an independent risk factor for in-hospital occurrence of ACVE.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Wilson N, Kariisa M, Seth P, Smith H IV, Davis NL. Drug and opioid-involved overdose deaths — United States, 2017–2018. MMWR Morb Mortal Wkly Rep. 2020;69(11):290–7. https://doi.org/10.15585/mmwr.mm6911a4.
Vivolo-Kantor AM, Hoots BE, Scholl L, Pickens C, Roehler DR, Board A, et al. Nonfatal drug overdoses treated in emergency departments — United States, 2016–2017. MMWR Morb Mortal Wkly Rep. 2020;69(13):371–6. https://doi.org/10.15585/mmwr.mm6913a3.
Manini AF, Nelson LS, Stimmel B, Vlahov D, Hoffman RS. Incidence of adverse cardiovascular events in adults following drug overdose. Acad Emerg Med. 2012;19(7):843–9. https://doi.org/10.1111/j.1553-2712.2012.01397.x.
Manini AF, Hoffman RS, Stimmel B, Vlahov D. Clinical risk factors for in-hospital adverse cardiovascular events after acute drug overdose. Acad Emerg Med. 2015;22(5):499–507. https://doi.org/10.1111/acem.12658.
Gummin DD, Mowry JB, Spyker DA, Brooks DE, Beuhler MC, Rivers LJ, et al. 2018 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 36th Annual Report. Clin Toxicol (Phila). 2019;57(12):1220–413. https://doi.org/10.1080/15563650.2019.1677022.
Campleman SL, Brent J, Pizon AF, Shulman J, Wax P, Manini AF, et al. Drug-specific risk of severe QT prolongation following acute drug overdose. Clin Toxicol (Phila). 2020;58(12):1326–34. https://doi.org/10.1080/15563650.2020.1746330.
Manini AF, Nair AP, Vedanthan R, Vlahov D, Hoffman RS. Validation of the prognostic utility of the electrocardiogram for acute drug overdose. J Am Heart Assoc. 2017;6(2):e004320. https://doi.org/10.1161/jaha.116.004320.
Manini AF, Nelson LS, Skolnick AH, Slater W, Hoffman RS. Electrocardiographic predictors of adverse cardiovascular events in suspected poisoning. J Med Toxicol. 2010;6(2):106–15. https://doi.org/10.1007/s13181-010-0074-x.
Tampi RR, Balderas M, Carter KV, Tampi DJ, Moca M, Knudsen A, May J. Citalopram, QTc Prolongation, and Torsades de Pointes. Psychosomatics. 2015;56(1):36–43. https://doi.org/10.1016/j.psym.2014.09.002.
Beach SR, Celano CM, Sugrue AM, Adams C, Ackerman MJ, Noseworthy PA, Huffman JC. QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update. Psychosomatics. 2018;59(2):105–22. https://doi.org/10.1016/j.psym.2017.10.009.
Kim Y, Kim A, Chung JY. Population pharmacokinetic/pharmacodynamic modeling of delayed effect of escitalopram-induced QT prolongation. J Affect Disord. 2021;285:120–6. https://doi.org/10.1016/j.jad.2021.02.048.
Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95(7):915–8. https://doi.org/10.1016/j.amjcard.2004.11.055.
Fraley DS, Adler S. Correction of hyperkalemia by bicarbonate despite constant blood pH. Kidney Int. 1977;12(5):354. https://doi.org/10.1038/ki.1977.122.
Blumberg A, Weidmann P, Shaw S, Gnädinger M. Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure. Am J Med. 1988;85(4):507. https://doi.org/10.1016/s0002-9343(88)80086-x.
Manini AF, Brent J, Campleman S, et al. Validation of a prediction rule for adverse cardiovascular events from drug overdose. Ann Emerg Med. 2020;76(4):S6. https://doi.org/10.1016/j.annemergmed.2020.09.024
Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta D, Steiner J. Chart reviews in emergency medicine research: where are the methods? Ann Emerg Med. 1996;27(3):305–8. https://doi.org/10.1016/s0196-0644(96)70264-0.
Carreiro S, Miller S, Wang B, Wax P, Campleman S, Manini AF. Clinical predictors of adverse cardiovascular events for acute pediatric drug exposures. Clin Toxicol (Phila). 2020;58(3):183–9. https://doi.org/10.1080/15563650.2019.1634272.
Hollander JE, McCracken G, Johnson S, Valentine SM, Shih RD. Emergency department observation of poisoned patients: how long is necessary? Acad Emerg Med. 1999;6(9):887–94. https://doi.org/10.1111/j.1553-2712.1999.tb01235.x.
Gottlieb M, Long B, Koyfman A. Approach to the agitated emergency department patient. J Emerg Med. 2018;54(4):447–57. https://doi.org/10.1016/j.jemermed.2017.12.049.
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.
Author information
Authors and Affiliations
Contributions
SS performed data analysis and drafted the manuscript. ER provided assistance with data collection, drafted the abstract, and preliminary data analysis. RV assisted with data analysis and interpretation. LDR provided assistance with study design and data collection. AM conceived the study; obtained funding; and oversaw data collection, analysis, as well as manuscript preparation. All authors helped edit the manuscript and approved the final version of the manuscript.
Corresponding author
Ethics declarations
Conflict of Interest
None.
Additional information
Supervising Editor: David M. Wood, MD
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This study was previously presented at the North American Congress of Clinical Toxicology (NACCT) Annual Meeting (Nashville, TN, September 2019) and American College of Emergency Physicians (ACEP) Annual Meeting (Denver, CO, October 2019).
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Shastry, S., Aluise, E.R., Richardson, L.D. et al. Delayed QT Prolongation: Derivation of a Novel Risk Factor for Adverse Cardiovascular Events from Acute Drug Overdose. J. Med. Toxicol. 17, 363–371 (2021). https://doi.org/10.1007/s13181-021-00855-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13181-021-00855-2