An Overview of Hyperinsulinemic‐Euglycemic Therapy in Calcium Channel Blocker and β‐blocker Overdose

Abstract

Both calcium channel blockers (CCBs) and β blockers (BBs) are associated with fatal substance exposures within the United States. Cases of overdose with these agents have the potential to be both complex and difficult to manage. A variety of pharmacologic treatment options are available for clinicians to use to help mitigate harm from these poisonings. Hyperinsulinemic-euglycemic therapy (HIET) was once regarded as a last-ditch effort to treat patients in highly refractory cases. In recent years, this therapy has become a routine therapy in the treatment of CCB/BB overdose. This article provides a literature review regarding HIET in cases of overdose with CCB and BB agents. Relevant literature articles from 1997-2018 were identified and reviewed using the PubMed and Embase databases. The following search terms were used to identify potential articles: "hyperinsulinemic-euglycemic therapy," "overdose," "calcium channel blocker," "beta blocker," and "insulin." Articles published in the English language were included in this review. A manual search of reference lists was also conducted. Much of the literature is limited to case reports, series, retrospective chart reviews, and small prospective studies. The success rate observed in published case series ranged from 80.4-100%. Regular insulin is most commonly dosed at an initial bolus of 1 unit/kg followed by a regular insulin infusion of 0.5-1 unit/kg/hour. Euglycemia is often maintained using intravenous fluids containing dextrose. Hyperinsulinemic-euglycemic therapy exhibited a promising safety profile, provided close monitoring is conducted. More research is needed to determine optimal strategies for maintaining euglycemia, ideal monitoring parameters, and consistent efficacy goals.

Management of Severe Beta-Blockers Toxicity with High Dose Insulin Euglycemic Therapy: A Case Report

“…The use of high dose insulin euglycemic therapy (HDIET) in betablockers overdoses is supported by experimental evidence in animals' studies and case reports [3][4][5]. It was usually reserved as a last rescue therapy, however, it is being frequently used early in treating calcium channel blockers overdose, beta-blockers overdose, as well as mixed overdose [6]. In our case report, we demonstrated the quick improvement of betablockers induced cardiogenic shock after starting the HDIET.…”

“…In the heart, blocking of beta-1 adrenoceptors leads to reduction of calcium influx in cardiac myocytes due to reduction in adenylate cyclase activity decreasing the synthesis of cyclic adenosine momophosphate (cAMP) which control L-type calcium channel opening. Excessive beta-adrenergic antagonism seen in beta-blockers toxicity leads to significant myocardial depression and cardiogenic shock due to depressed contractility in myocytes, reduced spontaneous depolarization in pacemaker cells as well as blocking of impulses transmission through the conduction pathway [6].…”

“…Krenz et al recommended in their review an intravenous dose of 1 IU.Kg -1 of insulin followed by continuous infusion of 0.5 -1 IU.Kg -1 .hour -1 , titrated upward every 15 minutes if no clinical response up to 10 IU.Kg -1 .hour -1[6].…”

Can hypoinsulinemia induced by calcium channel blockers be associated with cardiac events?

“…Eventually, the impaired conduction and impulse generation in the sinoatrial and atrioventricular nodes may lead to bradycardia or atrioventricular block. 3 As discussed above, CCBs poisoning may cause cardiovascular consequences or even cardiogenic shock. 4 It is generally believed that all cardiovascular consequences are due to the blockage of calcium channels in the heart.…”

A Case of Massive Metoprolol Overdose Successfully Managed

“…Treatment with calcium salts may provide benefit for hypotensive patients who overdosed. High-dose insulin with euglycemia is a safe and simple way to augment cardiac contractility and does not need invasive monitoring 3 . High-dose insulin with euglycemia can cause profound hypokalemia and hypoglycemia that can potentiate the cardiotoxicity.…”