Skip to main content
Log in

Management of the Cardiovascular Complications of Tricyclic Antidepressant Poisoning

Role of Sodium Bicarbonate

  • Review Article
  • Published:
Toxicological Reviews

Abstract

Experimental studies suggest that both alkalinisation and sodium loading are effective in reducing cardiotoxicity independently. Species and experimental differences may explain why sodium bicarbonate appears to work by sodium loading in some studies and by a pH change in others. In the only case series, the administration of intravenous sodium bicarbonate to achieve a systemic pH of 7.5–7.55 reduced QRS prolongation, reversed hypotension (although colloid was also given) and improved mental status in patients with moderate to severe tricyclic antidepressant poisoning. This clinical study supports the use of sodium bicarbonate in the management of the cardiovascular complications of tricyclic antidepressant poisoning. However, the clinical indications and dosing recommendations remain to be clarified.

Hypotension should be managed initially by administration of colloid or crystalloid solutions, guided by central venous pressure monitoring. Based on experimental and clinical studies, sodium bicarbonate should then be administered. If hypotension persists despite adequate filling pressure and sodium bicarbonate administration, inotropic support should be initiated. In a non-randomised controlled trial in rats, epinephrine resulted in a higher survival rate and was superior to norepinephrine both when the drugs were used alone or when epinephrine was used in combination with sodium bicarbonate. Sodium bicarbonate alone resulted in a modest increase in survival rate but this increased markedly when sodium bicarbonate was used with epinephrine or norepinephrine. Clinical studies suggest benefit from norepinephrine and dopamine; in an uncontrolled study the former appeared more effective. Glucagon has also been of benefit. Experimental studies suggest extracorporeal circulation membrane oxygenation is also of potential value.

The immediate treatment of arrhythmias involves correcting hypoxia, electrolyte abnormalities, hypotension and acidosis. Administration of sodium bicarbonate may resolve arrhythmias even in the absence of acidosis and, only if this therapy fails, should conventional antiarrhythmic drugs be used. The class 1b agent phenytoin may reverse conduction defects and may be used for resistant ventricular tachycardia. There is also limited evidence for benefit from magnesium infusion. However, class 1a and 1c antiarrhythmic drugs should be avoided since they worsen sodium channel blockade, further slow conduction velocity and depress contractility. Class II agents (β-blockers) may also precipitate hypotension and cardiac arrest.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I

Similar content being viewed by others

References

  1. Walsh DM. Cyclic antidepressant overdose in children: a proposed treatment protocol. Pediatr Emerg Care 1986; 2: 28–35

    Article  PubMed  CAS  Google Scholar 

  2. Hoffman JR, McElroy CR. Bicarbonate therapy for dysrhythmia and hypotension in tricyclic antidepressant overdose. West J Med 1981; 134: 60–4

    PubMed  CAS  Google Scholar 

  3. Nee PA, Hodgkinson DW, Gwinnutt CL. Treatment of severe tricyclic antidepressant poisoning by alkalinisation. Care Crit Ill 1994; 10: 125–7

    Google Scholar 

  4. Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J 2001; 18: 236–41

    Article  PubMed  CAS  Google Scholar 

  5. Blackman K, Brown SG, Wilkes GJ. Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. Emerg Med 2001; 13: 204–10

    Article  CAS  Google Scholar 

  6. Goldfrank LR, Flomenbaum NE, Lewin NA, et al., editors. Goldfrank’s toxicologic emergencies. 6th ed. Stamford (CT): Appleton & Lange, 1998

    Google Scholar 

  7. Hoffman JR, Votey SR, Bayer M, et al. Effect of hypertonic sodium bicarbonate in the treatment of moderate-to-severe cyclic antidepressant overdose. Am J Emerg Med 1993; 11: 336–41

    Article  PubMed  CAS  Google Scholar 

  8. Brown TCK, Barker GA, Dunlop ME, et al. The use of sodium bicarbonate in the treatment of tricyclic antidepressant-induced arrhythmias. Anaesth Intensive Care 1973; 1: 203–10

    PubMed  CAS  Google Scholar 

  9. Brown TCK. Sodium bicarbonate treatment for tricyclic antidepressant arrhythmias in children. Med J Aust 1976; 2: 380–2

    PubMed  CAS  Google Scholar 

  10. Liebelt EL, Ulrich A, Francis PD, et al. Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med 1997; 25: 1721–6

    Article  PubMed  CAS  Google Scholar 

  11. Shannon MW. Duration of QRS disturbances after severe tricyclic antidepressant intoxication. J Toxicol Clin Toxicol 1992; 30: 377–86

    Article  PubMed  CAS  Google Scholar 

  12. Seger DL, Hantsch C, Zavoral T, et al. Variability of recommendations for serum alkalinization in tricyclic antidepressant overdose: a survey of US Poison Center medical directors. J Toxicol Clin Toxicol 2003; 41: 331–8

    Article  PubMed  Google Scholar 

  13. Nattel S, Mittleman M. Treatment of ventricular tachyarrhythmias resulting from amitriptyline toxicity in dogs. J Pharmacol Exp Ther 1984; 231: 430–5

    PubMed  CAS  Google Scholar 

  14. Pentel P, Benowitz N. Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats. J Pharmacol Exp Ther 1984; 230: 12–9

    PubMed  CAS  Google Scholar 

  15. Nattel S, Keable H, Sasyniuk BI. Experimental amitriptyline intoxication: electrophysiologic manifestations and management. J Cardiovasc Pharmacol 1984; 6: 83–9

    Article  PubMed  CAS  Google Scholar 

  16. Hedges JR, Baker PB, Tasset JJ, et al. Bicarbonate therapy for the cardiovascular toxicity of amitriptyline in an animal model. J Emerg Med 1985; 3: 253–60

    Article  PubMed  CAS  Google Scholar 

  17. Stone CK, Kraemer CM, Carroll R, et al. Does a sodium-free buffer affect QRS width in experimental amitriptyline overdose. Ann Emerg Med 1995; 26: 58–64

    Article  PubMed  CAS  Google Scholar 

  18. Baselt RC. Disposition of toxic drugs and chemicals in man. 5th ed. Foster City (CA): Chemical Toxicology Institute, 2000

    Google Scholar 

  19. Levitt MA, Sullivan Jr JB, Owens SM, et al. Amitriptyline plasma protein binding: effect of plasma pH and relevance to clinical overdose. Am J Emerg Med 1986; 4: 121–5

    Article  PubMed  CAS  Google Scholar 

  20. Javaid JI, Hendricks K, Davis JM. α1-Acid glycoprotein involvement in high affinity binding of tricyclic antidepressants to human plasma. Biochem Pharmacol 1983; 32: 1149–53

    Article  PubMed  CAS  Google Scholar 

  21. Seaberg DC, Weiss LD, Yealy DM, et al. Effects of alpha-1-acid glycoprotein on the cardiovascular toxicity of nortriptyline in a swine model. Vet Hum Toxicol 1991; 33: 226–30

    PubMed  CAS  Google Scholar 

  22. Ma Y-L, Henry JA. The antidotal effect of α1-acid glycoprotein on amitriptyline toxicity in cardiac myocytes. Toxicology 2001; 169: 133–44

    Article  PubMed  CAS  Google Scholar 

  23. Bou-Abboud E, Nattel S. Molecular mechanisms of the reversal of imipramine-induced sodium channel blockade by alkalinization in human cardiac myocytes. Cardiovasc Res 1998; 38: 395–404

    Article  PubMed  CAS  Google Scholar 

  24. Adamantidis MM, Adnet-Bonte C, Adnet P, et al. Sodium lactate reversal of electrophysiological effects of imipramine in guinea-pig ventricular myocardium. Fundam Clin Pharmacol 1992; 6: 113–21

    Article  PubMed  CAS  Google Scholar 

  25. McCabe JL, Cobaugh DJ, Menegazzi JJ, et al. Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med 1998; 32: 329–33

    Article  PubMed  CAS  Google Scholar 

  26. McCabe JL, Menegazzi JJ, Cobaugh DJ, et al. Recovery from severe cyclic antidepressant overdose with hypertonic saline/dextran in a swine model. Acad Emerg Med 1994; 1: 111–5

    Article  PubMed  CAS  Google Scholar 

  27. Bou-Abboud E, Nattel S. Relative role of alkalosis and sodium ions in reversal of class I antiarrhythmic drug-induced sodium channel blockade by sodium bicarbonate. Circulation 1996; 94: 1954–61

    Article  PubMed  CAS  Google Scholar 

  28. Sasyniuk BI, Jhamandas V. Mechanism of reversal of toxic effects of amitriptyline on cardiac Purkinje fibers by sodium bicarbonate. J Pharmacol Exp Ther 1984; 231: 387–94

    PubMed  CAS  Google Scholar 

  29. Sasyniuk BI, Jhamandas V, Valois M. Experimental amitriptyline intoxication: treatment of cardiac toxicity with sodium bicarbonate. Ann Emerg Med 1986; 15: 1052–9

    Article  PubMed  CAS  Google Scholar 

  30. Liebelt EL. Toxicology reviews: targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: the pivotal role for alkalinization and sodium loading. Pediatr Emerg Care 1998; 14: 293–8

    Article  PubMed  CAS  Google Scholar 

  31. Weld FM, Bigger Jr JT. Electrophysiological effects of imipramine on ovine cardiac Purkinje and ventricular muscle fibers. Circ Res 1980; 46: 167–75

    Article  PubMed  CAS  Google Scholar 

  32. Pentel PR, Benowitz NL. Tricyclic antidepressant poisoning: management of arrhythmias. Med Toxicol 1986; 1: 101–21

    PubMed  CAS  Google Scholar 

  33. Lomholt BS. Hyperventilationsbehandling ved Akut forgiftning med tricykliske antidepressiva. En kontrolleret klinisk undersogelse. Ugeskr Laeger 1975; 138: 4–9

    PubMed  CAS  Google Scholar 

  34. Bessen HA, Niemann JT. Improvement of cardiac conduction after hyperventilation in tricyclic antidepressant overdose. J Toxicol Clin Toxicol 1985; 23: 537–45

    Article  PubMed  Google Scholar 

  35. Kingston ME. Hyperventilation in tricyclic antidepressant poisoning. Crit Care Med 1979; 7: 550–1

    Article  PubMed  CAS  Google Scholar 

  36. Nousaine DA. Hyperventilation versus bicarbonate therapy for alkalinization in tricyclic antidepressant overdose. West J Med 1981; 135: 160–1

    PubMed  CAS  Google Scholar 

  37. Wrenn K, Smith BA, Slovis CM. Profound alkalemia during treatment of tricyclic antidepressant overdose: a potential hazard of combined hyperventilation and intravenous bicarbonate. Am J Emerg Med 1992; 10: 553–5

    Article  PubMed  CAS  Google Scholar 

  38. Koppel C, Wiegreffe A, Tenczer J. Clinical course, therapy, outcome and analytical data in amitriptyline and combined amitriptyline/chlordiazepoxide overdose. Hum Exp Toxicol 1992; 11: 458–65

    Article  PubMed  CAS  Google Scholar 

  39. McKinney PE, Rasmussen R. Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution. Ann Emerg Med 2003; 42: 20–4

    Article  PubMed  Google Scholar 

  40. Teba L, Schiebel F, Dedhia HV, et al. Beneficial effect of norepinephrine in the treatment of circulatory shock caused by tricyclic antidepressant overdose. Am J Emerg Med 1988; 6: 566–8

    Article  PubMed  CAS  Google Scholar 

  41. Buchman AL, Dauer J, Geiderman J. The use of vasoactive agents in the treatment of refractory hypotension seen in tricyclic antidepressant overdose. J Clin Psychopharmacol 1990; 10: 409–13

    Article  PubMed  CAS  Google Scholar 

  42. Knudsen K, Abrahamsson J. Epinephrine and sodium bicarbonate independently and additively increase survival in experimental amitriptyline poisoning. Crit Care Med 1997; 25: 669–74

    Article  PubMed  CAS  Google Scholar 

  43. Tran TP, Panacek EA, Rhee KJ, et al. Response to dopamine vs norepinephrine in tricyclic antidepressant-induced hypotension. Acad Emerg Med 1997; 4: 864–8

    Article  PubMed  CAS  Google Scholar 

  44. Sensky PR, Olczak SA. High-dose intravenous glucagon in severe tricyclic poisoning. Postgrad Med J 1999; 75: 611–2

    PubMed  CAS  Google Scholar 

  45. Sener EK, Gabe S, Henry JA. Response to glucagon in imipramine overdose. J Toxicol Clin Toxicol 1995; 33: 51–3

    Article  PubMed  CAS  Google Scholar 

  46. Farah AE. Glucagon and the circulation. Pharmacol Rev 1983; 35: 181–217

    PubMed  CAS  Google Scholar 

  47. Williams JM, Hollingshed MJ, Vasilakis A, et al. Extracorporeal circulation in the management of severe tricyclic antidepressant overdose. Am J Emerg Med 1994; 12: 456–8

    Article  PubMed  CAS  Google Scholar 

  48. Goodwin DA, Lally KP, Null DM. Extracorporeal membrane oxygenation support for cardiac dysfunction from tricyclic antidepressant overdose. Crit Care Med 1993; 21: 625–7

    Article  PubMed  CAS  Google Scholar 

  49. Larkin GL, Graeber GM, Hollingsed MJ. Experimental amitriptyline poisoning: treatment of severe cardiovascular toxicity with cardiopulmonary bypass. Ann Emerg Med 1994; 23: 480–6

    Article  PubMed  CAS  Google Scholar 

  50. Frommer DA, Kulig KW, Marx JA, et al. Tricyclic antidepressant overdose: a review. JAMA 1987; 257: 521–6

    Article  PubMed  CAS  Google Scholar 

  51. Davison ET. Amitriptyline-induced torsade de pointes: successful therapy with atrial pacing. J Electrocardiol 1985; 18: 299–301

    Article  PubMed  CAS  Google Scholar 

  52. Knudsen K, Abrahamsson J. Magnesium sulphate in the treatment of ventricular fibrillation in amitriptyline poisoning. Eur Heart J 1997; 18: 881–2

    Article  PubMed  CAS  Google Scholar 

  53. Orr DA, Bramble MG. Tricyclic antidepressant poisoning and prolonged external cardiac massage during asystole. BMJ 1981; 283: 1107–8

    Article  PubMed  CAS  Google Scholar 

  54. Southall DP, Kilpatrick SM. Imipramine poisoning: survival of a child after prolonged cardiac massage. BMJ 1974; 4: 508

    Article  PubMed  CAS  Google Scholar 

  55. Sandeman DJ, Alahakoon TI, Bentley SC. Tricyclic poisoning: successful management of ventricular fibrillation following massive overdose of imipramine. Anaesth Intensive Care 1997; 25: 542–5

    PubMed  CAS  Google Scholar 

  56. Citak A, Soysal DD, Ucsel R, et al. Efficacy of long duration resuscitation and magnesium sulphate treatment in amitriptyline poisoning. Eur J Emerg Med 2002; 9: 63–6

    Article  PubMed  CAS  Google Scholar 

  57. Brown TCK. Tricyclic antidepressant overdosage: experimental studies on the management of circulatory complications. J Toxicol Clin Toxicol 1976; 9: 255–72

    Article  CAS  Google Scholar 

  58. Knudsen K, Abrahamsson J. Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat. Crit Care Med 1994; 22: 494–8

    Article  PubMed  CAS  Google Scholar 

  59. Langou RA, Van Dyke C, Tahan SR, et al. Cardiovascular manifestations of tricyclic antidepressant overdose. Am Heart J 1980; 100: 458–64

    Article  PubMed  CAS  Google Scholar 

  60. Boehnert M, Lovejoy Jr FH. The effect of phenytoin on cardiac conduction and ventricular arrhythmias in acute tricyclic antidepressant (TCA) overdose. Vet Hum Toxicol 1985; 28: 297

    Google Scholar 

  61. Hagerman GA, Hanashiro PK. Reversal of tricyclic-antidepressant-induced cardiac conduction abnormalities by phenytoin. Ann Emerg Med 1981; 10: 82–6

    Article  PubMed  CAS  Google Scholar 

  62. Cantrill S. Prophylactic phenytoin in tricyclic overdose. J Emerg Med 1983; 1: 169–77

    Article  Google Scholar 

  63. Mayron R, Ruiz E. Phenytoin: does it reverse tricyclic-antidepressant-induced cardiac conduction abnormalities? Ann Emerg Med 1986; 15: 876–80

    Article  PubMed  CAS  Google Scholar 

  64. Freeman JW, Loughhead MG. Beta blockade in the treatment of tricyclic antidepressant overdosage. Med J Aust 1973; 1: 1233–5

    PubMed  CAS  Google Scholar 

  65. Roberts RJ, Mueller S, Lauer RM. Propranolol in the treatment of cardiac arrhythmias associated with amitriptyline intoxication. J Pediatr 1973; 82: 65–7

    Article  PubMed  CAS  Google Scholar 

  66. Thorstrand C. Clinical features in poisonings by tricyclic antidepressants with special reference to the ECG. Acta Med Scand 1976; 199: 337–44

    Article  PubMed  CAS  Google Scholar 

  67. Freeman JW, Mundy GR, Beattie RR, et al. Cardiac abnormalities in poisoning with tricyclic antidepressants. BMJ 1969; 2: 610–1

    Article  PubMed  CAS  Google Scholar 

  68. Dziukas LJ, Vohra J. Tricyclic antidepressant poisoning. Med J Aust 1991; 154: 344–50

    PubMed  CAS  Google Scholar 

  69. Barrueto Jr F, Chuang A, Cotter BW, et al. Amiodarone fails to improve survival in amitriptyline-poisoned mice. Clin Toxicol 2005; 43: 147–9

    CAS  Google Scholar 

  70. Casazza F, Fiorista F, Rustici A, et al. Torsade de pointes caused by tricyclic antidepressive agents. Description of a clinical case [in Italian]. G Ital Cardiol 1986; 16: 1058–61

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bradberry, S.M., Thanacoody, H.K.R., Watt, B.E. et al. Management of the Cardiovascular Complications of Tricyclic Antidepressant Poisoning. Toxicol Rev 24, 195–204 (2005). https://doi.org/10.2165/00139709-200524030-00012

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00139709-200524030-00012

Keywords

Navigation