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.
Similar content being viewed by others
References
Wax PM. Antidotes in depth (A5): sodium bicarbonate. In: Nelson L, Lewin N, Howland M, editors. Goldfranks toxicological emergencies, vol. 9. New York: McGraw Hill; 2010. p. 528–35.
Bradberry SM, Thanacoody HKR, Watt BE, Thomas SHL, Vale JA. Management of the cardiovascular complications of tricyclic antidepressant poisoning: role of sodium bicarbonate. Toxicol Rev. 2005;24:195–204.
Boyer EW, Weibrecht KW. Salicylate (aspirin) poisoning in adults. In: Traub SJ, editor. UpToDate. Waltham: UpToDate; 2017.
Bruccoleri RE, Burns MM. A literature review of the use of sodium bicarbonate for the treatment of QRS widening. J Med Toxicol. 2016;12(1):121–9.
Garella S, Dana CL, Chazan JA. Severity of metabolic acidosis as a determinant of bicarbonate requirements. N Engl J Med. 1973;289:121–6.
Velissaris D, Karamouzos V, Pierrakos C, Koniari I, Apostolopoulou C, Karanikolas M. Use of sodium bicarbonate in cardiac arrest: current guidelines and literature review. J Clin Med Res. 2016;8(4):277–83.
Mark NH, Leung JM, Arieff AI, Mangano DT. Safety of low-dose intraoperative bicarbonate therapy: a prospective, double-blind, randomized study. The Study of Perioperative Ischemia (SPI) Research Group. Crit Care Med. 1993;21:659–65.
Hoste EA, Colpaert K, Vanholder RC, Lameire NH, De Waele JJ, Blot SI, et al. Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis. J Nephrol. 2005;18:303–7.
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.
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.
Blackman K, Brown SG, Wilkes GJ. Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. Emerg Med (Fremantle). 2001;13:204–10.
Hoffman JR, Votey SR, Bayer M, Silver L. Effect of hypertonic sodium bicarbonate in the treatment of moderate-to-severe cyclic antidepressant overdose. Am J Emerg Med. 1993;11(4):336–41.
Gummin DD, Mowry JB, Spyker DA, Brooks DE, Osterthaler KM, et al. Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 35th Annual Report. Clin Toxicol (Phila). 2017;2018:1–202.
Hedegaard H, Miniño AM, Warner M. Drug overdose deaths in the United States. In: NCHS data brief, no 329. Hyattsville: National Center for Health Statistics; 1999–2017. p. 2018.
Boehnert MT, Lovejoy FH. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med. 1985;313:474–9.
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;27:305–8.
Manini AF, Nelson LS, Stimmel B, Vlahov D, Hoffman RS. Incidence of adverse cardiovascular events in adults following drug overdose. Acad Emerg Med. 2012 Jul;19(7):843–9.
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 May;22(5):499–507.
Lugassy DM. Salicylates. In: Nelson LS, Howland MA, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS, editors. Goldfrank's Toxicologic Emergencies, vol. 11e. New York: McGraw-Hill; 2019.
Groleau G, Jotte R, Barish R. The electrocardiographic manifestations of cyclic antidepressant therapy and overdose: a review. J Emerg Med. 1990 Sep-Oct;8(5):597–605.
Ghauri SK, Javaeed A, Mustafa KJ, Podlasek A, Khan AS. Bicarbonate therapy for critically ill patients with metabolic acidosis: a systematic review. Cureus. 2019;11(3):e4297.
Becker RA, Ankley GT, Edwards SW, Kennedy SW, Linkov I, Meek B, et al. Increasing scientific confidence in adverse outcome pathways: application of tailored Bradford-Hill considerations for evaluating weight of evidence. Regul Toxicol Pharmacol. 2015;72(3):514–37.
Lawson AA, Proudfoot AT, Brown SS, MacDonald RH, Fraser AG, Cameron JC, et al. Forced diuresis in the treatment of acute salicylate poisoning in adults. Q J Med. 1969;38(149):31–48.
Hindman BJ. Sodium bicarbonate in the treatment of subtypes of acute lactic acidosis: physiologic considerations. Anesthesiology. 1990;72(6):1064–76.
Adeva-Andany MM, Fernandez C, Mourino-Bayolo D, Castro-Quintela E, Domínguez-Montero A. Sodium bicarbonate therapy in patients with metabolic acidosis. Sci World J. 2014;2014:1–10.
Espejo MS, Orlowski A, Ibañez AM, Di Mattía RA, Velásquez FC, Rossetti NS, et al. The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility. Pflugers Arch. 2019;22 [Epub ahead of print].
Buchanan N, Kundig H, Eyberg C. Experimental salicylate intoxication in young baboons. A preliminary report. J Pediatr. 1975;86(2):225–32.
Hill JB. Experimental salicylate poisoning: observations on the effects of altering blood pH on tissue and plasma salicylate concentrations. Pediatrics. 1971;47(4):658–65.
Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001;18:236–41.
Abeyaratne DD, Liyanapathirana C, Gamage A, Karunarathne P, Botheju M, Indrakumar J. Survival after severe amitriptyline poisoning with prolonged ventricular tachycardia and cardiac arrest. BMC Res Notes. 2016;9:167.
Hoffman JR, McElroy CR. Bicarbonate therapy for dysrhythmia and hypotension in tricyclic antidepressant overdose. West J Med. 1981;134(1):60–4.
Campleman SL, Brent J, Pizon AF, et al. Drug-specific risk of severe QT prolongation following acute drug overdose. Clin Toxicol (Phila). 2020; https://doi.org/10.1080/15563650.2020.1746330.
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.
Author information
Authors and Affiliations
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
Ethics declarations
IRB approval was obtained with waiver of consent prior to data collection at the study institutions.
Conflict of Interest
None.
Additional information
Supervising Editor: Maryann Elizabeth Amirshahi, PharmD, MD, MPH, PhD
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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.
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13181-020-00799-z