1. Hypokalemic Arrest Eric Lavonas, MD, FACEP Carolinas Medical Center Charlotte, NC

2. Patient presents with… H/O schizophrenia Acute-on-chronic overdose 100 pills of a single medication Time of ingestion: ~45 min PTA No symptoms

3. Vital Signs P 70 R 16 BP 120/80 T 36.1  C

5. Now the Fun Begins Sudden cardiac arrest  Wide complex tachydysrhythmia  No pulse  Unknown if Torsades de Pointes Rapid defibrillation & intubation P 60 BP 70/50

7. Pre-ArrestPost-Arrest 200 msec240 msec

8. Laboratory Abnormalities Profound hypokalemia Mild metabolic acidosis  Respiratory alkalosis from vent Other minor abnormalities  Creatinine 1.2 mg/dl  Glucose 178 mg/dl

9. Post-Arrest Therapy Dopamine  Poor response Norepinephrine  BP improved 4 gm MgSO 4 Potassium, potassium, potassium 300 ml (154 mEq) hypertonic NaCl

10. Effect of Hypertonic Saline After Before 200 80

11. QT Prolongation QT =.640s; QTc =.500 QT.440; QTc.469 Before After

12. Inpatient Course Potassium still low  Aggressive replacement over 11 hours Weaned off pressors Did well

13. Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

14. Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

15. Anti-Dysrhythmics Class I: Block Na entry  Ia: Block Na in and K out  Ib: Block Na in  Ic: Block Na in, Ca in, and K out Class II: β receptor antagonists Class III: Block K out Class IV: L-type Ca channel antagonists Vaughn-Williams EM and Singh BN, Cardiovasc Res 6:109 (1972)

16. Na inK out Ca in, K out Na channel blockade

18. Sodium Channel States Resting (Closed) Open Inactivated (Closed)  Refractory

19. Sodium Channel States

20. Frequency-Dependent Block Weirich J, Antoni H, J Cardiovasc Pharmacol 15:998-1009 (1990) Class Ia: τ recovery 1-10 sec Class Ib: τ recovery < 1 sec Class Ic: τ recovery > 10 sec

21. Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

22. QT Prolongation QT =.640s; QTc =.500

23. Na inK out Ca in, K out K efflux blockade

25. Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

26. Relative Bradycardia β-receptor antagonists Calcium channel antagonists Digitalis and related glycosides Central α-2 agonists Cholinesterase inhibitors Mitochondrial toxins (e.g. CN) Sedative-hypnotics End-stages of cocaine, TCA’s, etc.

27. Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

28. Increased urinary losses  Most diuretics  Renal toxins (toluene, aminoglycosides)  Licorice Extra-renal losses (diarrhea) Exchange with another cation  Sodium polystyrene sulfate (Kayexalate™)  Sodium penicillins

29. Hypokalemia Intracellular sequestration  Enhanced entry Catecholamines Insulin/glucose Barium salts Thyrotoxicosis

30. Hypokalemia Intracellular sequestration  Blocked release from I K channels  “Pure”: Dofetilide, Ibutilide

31. Hypokalemia Intracellular sequestration  Blocked release from I K channels  “Pure”: Dofetilide, Ibutilide  “Less selective”: Disopyramide, flecainide, procainamide, quinidine

32. Hypokalemia Intracellular sequestration  Blocked release from I K channels  “Pure”: Dofetilide, Ibutilide  “Less selective”: Disopyramide, flecainide, procainamide, quinidine 

33. Hypokalemia Intracellular sequestration  Blocked release from I K channels  “Pure”: Dofetilide, Ibutilide  “Less selective”: Disopyramide, flecainide, procainamide, quinidine  Amiodarone, bretylium, propafenone, sotalol

34. Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

35. The Sicilian Gambit Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Circulation 1991;84:1831-51.

36. Hints & Clues Pill form Medication  Prescription? Herbal?  Available in bottle of 100 Cardiac arrest precedes AMS Recovery in 26 hours

37. Closing in… Quinine Quinidine Disopyramide Chloroquine Antipsychotics Amiodarone Procainamide Sotalol

38. Closing in… Quinine Quinidine Disopyramide Chloroquine Antipsychotics Amiodarone Procainamide Sotalol GI Effects Tachycardia Tachycardia, sedation Onset delayed No Na Ch block; no hypoK

39. Chloroquine Na channel blockade  Present at low heart rate K efflux blockade  QT prolongation  Profound hypokalemia Relative bradycardia Hypotension

40. Drug Information Chloroquine Trade NameAralen™ Common UseMalaria Dose500 mg PO Q week Half-lifeDays-weeks

41. Patient presents with… H/O schizophrenia Acute-on-chronic overdose 100 pills of a single medication Time of ingestion: ~45 min PTA No symptoms

42. Drug Information ChloroquineHydroxychloroquine Trade nameAralen™Plaquenil™ Common useMalariaAutoimmune disease Dose500 mg PO Q week 200 mg PO 1-2 daily-BID Half lifeDays-weeks15-31 hours

44. Hydroxychloroquine Overdose