Morning Report: 10/3/2013

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.