doses, produces potent inotropic and vasodilatory effects, improving cardiac contractility, increasing myocardial glucose uptake, and enhancing perfusion to the heart.
Special Considerations With Calcium Channel Blocker Toxicity
Non-dihydropyridine (non-DHP) calcium channel blockers such as verapamil and diltiazem exert their primary effects on the myocardium. In the setting of overdose, this can result in marked myocardial depression, making HIET particularly effective because of its inotropic effect. In contrast, dihydropyridine (DHP) calcium channel blockers such as amlodipine act mainly on vascular smooth muscle with minimal effects on the myocardium at usual dosages. In overdose, however, most notably with amlodipine, synthesis of nitric oxide is increased in a dosedependent manner, which produces profound vasoplegia rather than the myocardial depression commonly associated with non-DHPs. Because HIET can also produce peripheral vasodilatory effects, it does not address this vasoplegic physiology and may even exacerbate distributive shock. For this reason, HIET may not be prioritized as highly in the management algorithm for DHP calcium channel blocker toxicity compared with treatment of nonDHP toxicity. When a DHP calcium channel blocker is the predominant ingestant, vasopressors play the main role in addressing vasoplegia, with HIET often reserved for cases where
myocardial depression is evident. It should be mentioned, however, that pharmacological selectivity between DHP and non-DHP calcium channel blockers can become blurred in the midst of excessively high levels in systemic circulation, such as in overdose.
Patient’s Clinical Status
Clinical status ultimately guides therapy decisions regardless of the ingested agent (beta blocker, DHP calcium channel blocker or non-DHP calcium channel blocker), and HIET is likely appropriate for initiation when there is evidence of reduced cardiac contractility. If a bedside echocardiogram or ultrasound reveals a reduced ejection fraction, initiating HIET for inotropic support may be beneficial, even with DHP calcium channel blocker toxicity, to improve contractility and perfusion. Other therapies that have been tried in cases of refractory vasoplegia include nitric oxide scavengers such as methylene blue and hydroxocobalamin.
HIET Dosing and Titration
Reported dosing strategies for HIET vary in the literature, but the usual dose is approximately 10 times higher than what is needed for managing diabetic ketoacidosis. This can understandably lead to practitioner hesitation when considering HIET; however, with frequent lab monitoring and judicious supplementation of glucose and electrolytes, this resource-intensive therapy can be implemented safely as a potentially life-saving treatment for cardiac drug poisonings.
Examples
Primary Sites of Action
Main Therapeutic Effects
Amlodipine, Nifedipine, Dihydropyridines Nicardipine, Clevidipine
Vascular smooth muscle
Potent arterial vasodilation ↓SVR, ↓BP (minimal cardiac conduction effect)
Verapamil
Myocardium & AV node
↓HR (negative chronotropy), ↓contractility (negative inotropy), ↓AV conduction
Diltiazem
Intermediate (AV node + some vascular)
Slows AV conduction, modest ↓HR, moderate vasodilation
Subclass
Nondihydropyridines
SVR, systemic vascular resistance; BP, blood pressure; HR, heart rate; AV, atrioventricular
Before starting the insulin infusion, obtain baseline blood glucose and serum potassium. If blood glucose is less than 200 milligrams per deciliter, administer 25 to 50 grams of IV dextrose. A continuous IV infusion of 10 percent dextrose (peripheral line) or 20 percent dextrose (central line) should also be initiated and titrated during HIET to maintain glucose between 100 and 200 milligrams per deciliter. If potassium is less than 3 milliequivalents per liter at baseline, provide supplementation before starting HIET. When ready to begin, administer an IV bolus of 1 unit per kilogram of regular insulin using actual body weight (no consensus on a maximum weight), followed by a continuous IV infusion of 1 unit per kilogram per hour. HIET should be titrated every 15 to 30 minutes as needed, based on cardiac output parameters (contractility and perfusion) and blood pressure: •C ontractility: Assess by bedside ultrasound in the emergency department. Increase HIET rate if ejection fraction is less than 50 percent. • Perfusion: Target urine output greater than 0.5 milliliters per kilogram per hour, warm skin with normal color, palpable peripheral pulses and improving serum markers (basic metabolic panel, lactate, venous blood gas). • Blood pressure: Goal is systolic blood pressure 90 millimeters of mercury or higher, or mean arterial pressure 60 millimeters of mercury or higher. Clinicians should not rely solely on blood pressure goals to guide therapy. HIET can lower vascular tone, while vasopressors may raise mean arterial pressure without improving tissue perfusion. HIET should instead be titrated based on contractility, perfusion and blood pressure goals, up to 10 units per kilogram per hour.
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