Original ContributionHigh dose insulin for beta-blocker and calcium channel-blocker poisoning☆
Introduction
Cardiovascular drugs cause a substantial number of poisoning deaths each year, primarily from acute overdose. In 2016, cardiovascular drugs as a class were the second leading cause of poisoning deaths reported to the National Poison Data System (NPDS), the vast majority of which were beta-blockers and calcium channel-blockers [1].
High dose insulin (HDI) has become a standard therapy for poisoning from both beta-blockers and calcium channel-blockers [2]. Despite basic science evidence that HDI is superior to vasopressors for poisoning from both calcium channel-blockers [3,4] and beta-blockers [5,6], consensus does not yet exist regarding which therapy to start first after basic supportive care, such as IV fluids and calcium salts, has failed [7,8]. As such, emergency physicians may be unfamiliar with HDI and the implementation of this complex therapy.
In our regional poison center, the clinical guideline for the treatment of beta-blocker and calcium channel-blocker poisoning recommends starting HDI prior to vasopressors after basic supportive care has failed. The guideline (Fig. 1) recommends titrating HDI from 1 to 10 U/kg/h, based on data suggesting cardiac output increases approximately 50% from an HDI dose of 1 U/kg/h to 10 U/kg/h [9].
Though expert consensus guidelines recommend HDI if basic supportive care has failed [8], there is a relative paucity of human case experience with HDI. In fact, HDI use in humans is poorly described. The largest published series to date is a brief analysis of 46 poison center cases for which HDI was recommended for calcium channel-blocker poisoning [10]. Case reports and smaller series of successful HDI use exist, but frequently are reported by medical toxicologists performing bedside consultation and may suffer from positive reporting bias [[11], [12], [13], [14], [15], [16]]. As of 2015, published human case experience describing the use of insulin for drug-induced cardiac toxicity was limited to under 100 cases [17]. Emergency physicians may be hesitant to use HDI in lieu of more familiar therapies such as vasopressors given the relative scarcity of published clinical experience. A larger study more clearly describing HDI use, administration, and outcomes may better define the role for HDI in the emergency department (ED).
The primary purpose of this study was to describe the clinical characteristics of patients receiving HDI for beta-blocker or calcium channel-blocker poisoning as recommended by our regional poison center including HDI dosing, concomitant therapies, clinical outcomes, and adverse effects associated with HDI.
Section snippets
Study design and setting
This was a structured [18,19] single poison center chart review of patients treated with HDI for beta-blocker or calcium channel-blocker poisoning treated from 2000 to 2016. Our human subjects research committee approved this study.
The study setting is an American Association of Poison Control Centers (AAPCC) accredited regional poison center covering 3 U.S. states. In 2016, our poison center handled 64,468 calls, of which 58,838 were exposure calls. This poison center is pharmacist-based; 100%
Characteristics of study subjects
A total of 506 patients met initial screening criteria. There were 307 patients excluded leaving 199 patients meeting final inclusion criteria; study enrollment is further delineated in Fig. 2. Kappa for drug class and specific exposure medications was 0.9; kappa for clinical interventions and adverse events was 0.93. HDI usage and adherence to poison center recommendations increased steadily over time (Fig. 3).
Median age was 48 years (range 14–89); 50% were male. There were 88 patients (44%)
Discussion
Based upon the large number of cases, increased utilization, and high doses used, our data suggest emergency physicians can feasibly initiate HDI titrated to a median peak infusion of 8 U/kg/h with the aid of a regional poison center. Our data also suggest HDI is feasible for physicians providing critical care on inpatient units as HDI was routinely continued far into the patients' hospitalizations. Though emergency and critical care physicians are generally more familiar with insulin infusions
Conflicts of interest/declarations
No authors report any relevant conflicts of interest.
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Cited by (27)
Cardiotoxic Medication Poisoning
2022, Emergency Medicine Clinics of North AmericaCitation Excerpt :It is therefore critical, from a hemodynamic standpoint, to establish the optimal HDI dose for each individual patient by carefully monitoring both cardiac output and systemic vascular resistance to optimize HDI dosing. HDI is also associated with other adverse effects that require careful monitoring in a critical care environment, including hypoglycemia, hypokalemia, and volume overload.78,88,89 Unlike vasodilation, hypoglycemia and hypokalemia associated with HDI do not seem to be dose dependent.80,88
The Crashing Toxicology Patient
2020, Emergency Medicine Clinics of North AmericaCitation Excerpt :Recent consensus guidelines on treatment of calcium channel blocker poisoning recommend HIET as part of first-line therapies.39 Once initiated, insulin infusion rates can be titrated to clinical effect.40,41 A concentrated dextrose infusion, often dextrose 50% at 25 g/h, is used to maintain euglycemia.
Phenibut exposures and clinical effects reported to a regional poison center
2019, American Journal of Emergency MedicineCitation Excerpt :All exposure calls from January 2000 through December 2018 were included with stated concerns for phenibut ingestion; this search was completed by the primary author. Data collection was performed in a manner similar to a prior study which included three of our authors [21]. A search was completed for the following terms: “phenibut” and “4-amino-phenylbutyrate.”
Beta-blocker and calcium-channel blocker toxicity: current evidence on evaluation and management
2024, European Heart Journal: Acute Cardiovascular CareUse of Concentrated Insulin in the Management of Calcium Channel Blocker Overdose: A Case Report
2023, Journal of Pharmacy Practice
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Prior presentations: This work was presented in abstract form as a poster presentation at the 2017 North American Congress of Clinical Toxicology in Vancouver, BC, Canada (abstract #52).