Case Study 2: Symptomatic Bradycardia

1. Case Study 2: Symptomatic Bradycardia Robert S. Hoffman, MD Director New York City Poison Center

2. Objectives • Understand the differential diagnosis of drug-induced bradycardia • Explain the use of the laboratory in cases of unknown bradycardia • Discuss the treatment of patients with known and unknown causes of bradycardia

3. Differential Diagnosis • A 42 year old man presents to the hospital complaining of weakness and dizziness following an intentional drug overdose • He is pale and diaphoretic appearing but awake • Blood pressure 62/30 mm Hg • Pulse 40/minute; slightly irregular • Physical examination otherwise normal

4. ECG

5. EAPCCT Investigation of the Poisoned Patient-Case Studies Bordeaux, May 2010

6. Question 1 • The most likely etiology of this patient’s toxicity is: • A. Digoxin • B. Calcium channel blocker • C. Beta blocker • D. Clonidine • E. Organophosphate

7. Answer 1 • You can not be certain at this point: • A. Digoxin • B. Calcium channel blocker • C. Beta blocker • D. Clonidine • Sedation • E. Organophosphate • Muscarinic and nicotinic findings

8. Physiology

9. Physiology

10. Physiology

11. Physiology

12. Beta Blocker

13. Digoxin Toxicity

14. EAPCCT Investigation of the Poisoned Patient-Case Studies Bordeaux, May 2010

15. Question 2 • Which laboratory tests might be useful to help narrow the differential diagnosis • A. Glucose • B. Calcium • C. Potassium • D. Sodium • E. Both A and C

16. Answer 2 • Which laboratory tests might be useful to help narrow the differential diagnosis • A. Glucose • B. Calcium • C. Potassium • D. Sodium • E. Both A and C

17. Diagnosis and Prognosis Bismuth C, et al: Clin Toxicol 1973; 6:153-162

18. Composite endpoints • Death • Vasoactive drugs (epinephrine, etc) • Pacemaker

20. 22.2 mmol/L

21. EAPCCT Investigation of the Poisoned Patient-Case Studies Bordeaux, May 2010

22. Question 3 • Which ECG finding is MOST characteristic of digoxin toxicity: • A. Scooped ST segment • B. Sinus bradycardia • C. Atrial tachycardia with high degree A-V block • D. Bidirectional ventricular tachycardia • E. Slow atrial fibrillation

23. Digoxin Effect

24. Bradycardia

25. Atrial Tachycardia with A-V Block

26. More

27. Bidirectional Ventricular Tachycardia

28. Answer 3 • Which ECG finding is MOST characteristic of digoxin toxicity: • A. Scooped ST segment • B. Sinus bradycardia • C. Atrial tachycardia with high degree A-V block • D. Bidirectional ventricular tachycardia • E. Slow atrial fibrillation

29. EAPCCT Investigation of the Poisoned Patient-Case Studies Bordeaux, May 2010

30. Question 4 • Which rhythm is inconsistent with digoxin toxicity • A. Sinus tachycardia • B. Rapid atrial fibrillation • C. Supraventricular tachycardia at 150/min • D. Multifocal atrial tachycardia • E. All of the above

31. Answer 4 • Which rhythm is inconsistent with digoxin toxicity • A. Sinus tachycardia • B. Rapid atrial fibrillation • C. Supraventricular tachycardia at 150/min • D. Multifocal atrial tachycardia • E. All of the above

32. More Case Information • ECG: As shown previously • Glucose: 300 mg/dL (16.16 mmol/L) • Serum potassium: 4.8 mmol/L • A fluid bolus of 1L of saline is given without response • Blood pressure 72/40 mm Hg • Pulse 45/min

33. EAPCCT Investigation of the Poisoned Patient-Case Studies Bordeaux, May 2010

34. Question 5 • Which of the following therapies is most appropriate at this point? • A. Digoxin antibodies • B. Epinephrine • C. Glucagon • D. Calcium • E. Milrinone

35. General Treatment

36. Answer 5 • Which of the following therapies is most appropriate at this point? • A. Digoxin antibodies • B. Epinephrine • C. Glucagon • D. Calcium • E. Milrinone

37. Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM: Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther 1993;267:744-50

38. More Case Information • A serum digoxin concentration is reported as non-detectable. • The patient is given the following with little improvement: • 3 grams of calcium chloride • Escalating doses of glucagon (up to 10 mg) • Amrinone • Dopamine continuous infusion

39. EAPCCT Investigation of the Poisoned Patient-Case Studies Bordeaux, May 2010

40. Question 6 • Which therapies might be indicated next: • A. Hemodialysis/hemoperfusion • B. Pacemaker • C. Intra-aortic balloon pump • D. High-dose insulin euglycemia therapy • E. Intravenous fat emulsion

41. Answer 6 • Which therapies might be indicated next: • A. Hemodialysis/hemoperfusion • B. Pacemaker • C. Intra-aortic balloon pump • D. High-dose insulin euglycemia therapy • E. Intravenous fat emulsion

42. Cardiac Energy Dynamics • Normal Function • Preferred Substrate • Fatty Acids • High energy • Stable pool

43. Cardiac Energy Dynamics • Sick hearts • Convert to glucose • Immediate energy • Limited availability • Large swings • Basis for: • Tight glucose control • High dose insulin/euglycemia therapy

44. Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM: Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther 1993;267:744-50

45. Kline JA, et al. Cardiovasc Res 1997;34:289-298

46. Yuan TH, et al: Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. J Toxicol Clin Toxicol 1999;37:463-474

47. Technique • Bolus 1 unit/kg of regular insulin • Follow with a continuous infusion • 0.5-2.0 units/kg/hour of regular insulin • Add glucose as necessary • 0.5-1 gm/kg/hr • Allow mild hypokalemia (only mild)

48. Lipid Emulsion Therapy • Mechanism of action • 2 Prevailing hypotheses • “Lipid sink theory” • Bioenergetic theory

49. Lipid Emulsion Therapy • Lipid sink theory • Intralipid partitions the drug into a lipid phase creating a concentration gradient for removal of the drug from the target organ Weinberg GL: Reg Anesth Pain. 2006;31:296

50. Tebutt S: Intralipid prolongs survival in a rat model of verapamil toxicity. Acad Emerg Med 2006;13:134