Take Home Points Management of severe beta-blocker and calcium-channel blocker toxicity should occur in a stepwise fashion: potential gastric decontamination, multiple lines of access, judicious fluids, calcium, glucagon, and vasopressors as needed. Initiation of high dose insulin therapy requires a tremendous amount of logistical and cognitive resources as it requires cross-disciplinary collaboration and is prone to mismanagement. If the patient doesn’t respond to maximum pharmacologic therapy, venous-arterial ECMO should be considered. REBEL Core Cast 124.0 – Hyperinsulinemia Euglycemia Therapy Click here for Direct Download of the Podcast. Background and Physiology Shock secondary to beta-blocker (BB) or calcium-channel blocker (CCB) toxicity bears a tremendous degree of morbidity and mortality. According to the 2022 Annual Report of the National Poison Data System from America’s Poison Center, CCBs and BBs account for the sixth and seventh largest number of fatalities from overdose.1 Recall that cardiac output is a function of both stroke volume and heart rate. The natural response to diminishing stroke volume is a compensatory rise in heart rate (tachycardia). Keep a low threshold to search a patient’s medication list for BB/CCBs, when a hypotension is seen with a “normal heart rate.” Clinical Manifestations Both BBs and CCBs ultimately cause reduced levels of intracellular calcium within myocytes. Depending on the degree of toxicity, subsequent effects include: decreased systemic vascular resistance, vasodilation, bradycardia, various conduction delays, and ultimately hypotension and cardiogenic shock. In addition to abnormal vital signs, look for surrogates of poor clinical perfusion: acidemia, lactate, decreasing urinary output Traditional Management Consider GI decontamination to reduce systemic absorption: 1g/kg up to 50g of activated charcoal. Patient must be alert or the airway must be secured as to avoid aspiration. Obtain multiple lines of intravenous access (3 PIVs or triple lumen CVC) and provide a judicious amount of fluids. (more on this below) Pharmacotherapy Calcium Gluconate: 1-3g intravenous Glucagon: 3mg-5mg slow intravenous push. Rapid administration may induce nausea and emesis. Vasopressors as a bridge to… HIET Mechanism of action is still not fully elucidated however several factors are implicated: Insulin augments cardiac contractility by activating “reverse-mode” Na-Ca exchange and subsequently increasing calcium concentration in the sarcoplasmic reticulum. 2 At a resting physiologic state, the heart utilize free fatty acids as its primary energy course. Under stressed conditions, glucose is used instead. Insulin helps to facilitate glucose metabolism. HIET Dosing: 1 unit/kg IV bolus. Then infusion starting at 1 unit/kg/hr infusion and titrate q30-60 minutes, keeping in mind that effects are not instant. Relative maximum is ~10 unit/kg/hr. If glucose 250 mg/dL, administer a bolus of dextrose 25-50 g (or 0.5-1 g/kg) IV. Ask pharmacy to concentrate insulin from 1 unit/mL to 10 units/ml. Patients often succumb to volume overload given pre-existing cardiac disease and the volume of medical resuscitation through their hospital stay. Once HIET is initiated, dextrose and potassium infusions should simultaneously be started to obviate hypoglycemia and hypokalemia Dextrose: 0.5-1 g/kg/hr via D50/D20 Replete potassium to a minimum of 3.5mEq/L A central venous catheter (often a triple lumen) is often needed to emergently replete potassium and provide D50/D20 safely (given its high osmolarity) Serial monitoring of dextrose (q15-30 minutes) and potassium (q1 hour) is critical HIET has been demonstrated to improve perfusion without necessarily increasing SVR/MAP – while MAPs may not markedly increase dramatically in the short term, obtain serial blood gases, lactate, and track urinary output to track perfusion. 3 Hyperinsulinemia Euglycemia Therapy (HIET) for BB/CCB Toxicity Management of severe beta-blocker and calcium-channel blocker toxicity should occur in a stepwise fashion: potential gastric decontamination, multiple lines of access, judicious fluids, calcium, glucagon, and vasopressors as needed. Initiation of high dose insulin therapy requires a tremendous amount of logistical and cognitive resources as it requires cross-disciplinary collaboration and is prone to mismanagement. HIET Dosing: 1 unit/kg IV bolus. Then infusion starting at 1 unit/kg/hr infusion and titrate q30-60 minutes, keeping in mind that effects are not instant. Relative maximum is ~10 unit/kg/hr. HIET therapy requires simultaneous dextrose and potassium infusions as insulin will induce hypoglycemia and shift potassium intracellularly. If the patient doesn’t respond to maximum pharmacologic therapy, venous-arterial ECMO should be considered. References Gummin DD, Mowry JB, Beuhler MC, et al. 2022 Annual Report of the National Poison Data System® (NPDS) from America’s Poison Centers®: 40th Annual Report. Clin Toxicol (Phila). 2023;61(10):717-939. doi:10.1080/15563650.2023.226898 von Lewinski D, Bruns S, Walther S, Kögler H, Pieske B. Insulin causes [Ca2+]i-dependent and [Ca2+]i-independent positive inotropic effects in failing human myocardium. Circulation. 2005;111(20):2588-2595. doi:10.1161/CIRCULATIONAHA.104.497461 Holger JS, Engebretsen KM, Fritzlar SJ, Patten LC, Harris CR, Flottemesch TJ. Insulin versus vasopressin and epinephrine to treat beta-blocker toxicity. Clin Toxicol (Phila). 2007;45(4):396-401. doi:10.1080/15563650701285412 Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie) The post REBEL Core Cast 124.0 – Hyperinsulinemia Euglycemia Therapy appeared first on REBEL EM - Emergency Medicine Blog.
