Morning Report: 10/3/2013 - The Original Kings of County

Here’s Dr. Basile with today’s Morning Report!

Case: 60 yo female with pmh of htn, ESRD on HD presents as notification for syncope and hypotension. BP of 75/40, HR of 45. Afebrile Rectally. Bedside sono, no large pericardial effusion.

Calcium Channel Blocker Toxicity

Epidemiology:

– In 1986: more than 1200 exposures and seven deaths.

– In 2007: 10,084 exposures and 17 deaths.

Pathophysiology:

– Toxicity is an extension of the therapeutic effects

– Inhibition of calcium channels has a significant effect on myocardium and smooth muscle

– In myocardium –> decreased force of contraction and decreased HR (affects SA and AV node)

– In vascular smooth muscle –> arterial vasodilation

– Verapamil (greater affinity for myocardium) has the most marked effects in the myocardium, whereas dihydropyridines have the greatest decrease in systemic vascular resistance.

Clinical Manifestations:

– Bradycardia, hypotension, AV conduction abnormalities, heart block, Cardiogenic shock

– Hypotension is the most common abnormal vital sign in an overdose

– Dizziness, fatigue, lightheadedness, lethargy, syncope, AMS, etc all occur as a result of decreased perfusion

– GI symptoms are uncommon

– Deaths are much more common with verapamil and diltiazem, but can also occur with the dihydropyridines

– Hyperglycemia can be seen in an overdose –> Calcium is required for insulin release

– With regular release formulations –> toxicity within 2-3 hours of ingestion

– With sustained release –> initial signs and symptoms can be delayed for 6-8 hours (reports of delays for 15 hours reported) and the half-life is prolonged causing toxicity that can last longer than 48 hours

– Elderly and patients with underlying cardiovascular disease are more sensitive

– VERY dangerous in pediatrics

Management:

– ABCs; IV, Oxygen, cardiac monitor, EKG, IVF

– Importance of GI decontamination even for well-appearing patients with history of sustained-release ingestion using charcoal and whole bowel irrigation

– Atropine:

Largely ineffective in improving heart rate in severely poisoned patients
Should still be used at dose of 0.5 mg every 2-3 minutes up to a maximum dose of 3 mg in patients with symptomatic bradycardia

– Calcium:

Also controversial as to whether it works
13 to 25 mEq of Ca²⁺ (10 to 20 mL of 10% calcium chloride or 30 to 60 mL of 10% calcium gluconate) followed by either repeat boluses every 15 to 20 minutes up to three to four doses or a continuous infusion of 0.5 mEq/kg/h of Ca²⁺ (0.2 to 0.4 mL/kg/h of 10% calcium chloride or 0.6 to 1.2 mL of 10% calcium gluconate

– Inotropes and Vasopressors:

Epinepherine or Norepinephrine appears to be the appropriate initial catecholamine to use in hypotensive CCB-poisoned patients

– Glucagon:

Should not offer any advantage over direct B-adrenergic agents because the problem is “downstream” from the B-adrenergic receptor (as opposed to B-Blocker toxicity)
An initial dose of 3 to 5 mg IV (SLOWLY) and if there is no hemodynamic improvement within 5 minutes, retreatment with a dose of 4 to 10 mg may be effective.

– Insulin and Glucose:

Hyperinsulinemia euglycemia therapy has become the treatment of choice for patients with severe CCB poisoning.
therapy typically begins with a bolus of 1 Unit/kg of regular human insulin along with 0.5 g/kg of dextrose (dextrose not necessary if glucose is greater than 400)
infusion of regular insulin should follow the bolus starting at 0.5 Units/kg/h titrated up to 2 Units/kg/h if no improvement after 30 minutes and a continuous dextrose infusion, beginning at 0.5 g/kg/h
monitor glucose every half hour
response to insulin usually takes 15-60 minutes (may need to start pressors prior)

– Intravenous fat emulsions (IFE) –> incorporates the drug and lowers the free or effective drug concentrations

– Adjunctive Hemodynamic Support:

Transthoracic or transvenous cardiac pacing
Intraaortic balloon pump
Extracorporeal membrane oxygenation (ECMO)

Disposition Pearls:

– Patients with signs/symptoms of toxicity should be admitted to an ICU

– Any patient ingesting sustained-release products should be admitted for 24 hours to monitored setting (even if asymptomatic)
References:

DeRoos FJ. Chapter 60. Calcium Channel Blockers. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accessemergencymedicine.com/content.aspx?aID=6516947. Accessed June 18, 2013.

The views expressed on this blog are the author's own and do not reflect the views of their employer. Please read our full disclaimer here. Any references to clinical cases refer to patients treated at a virtual hospital, Janus General Hospital.

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Jay Khadpe MD

Editor in Chief of "The Original Kings of County" Assistant Professor of Emergency Medicine Assistant Residency Director SUNY Downstate / Kings County Hospital