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

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

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

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

Pre-ArrestPost-Arrest 200 msec240 msec

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

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

Effect of Hypertonic Saline After Before

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

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

Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

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)

Na inK out Ca in, K out Na channel blockade

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

Sodium Channel States

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

Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

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

Na inK out Ca in, K out K efflux blockade

Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

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.

Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

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

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

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

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

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

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

Key Elements Wide QRS Prolonged QTc Relative bradycardia Hypokalemia

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:

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

Closing in… Quinine Quinidine Disopyramide Chloroquine Antipsychotics Amiodarone Procainamide Sotalol

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

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

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

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

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

Hydroxychloroquine Overdose