Original Contribution
High dose insulin for beta-blocker and calcium channel-blocker poisoning

https://doi.org/10.1016/j.ajem.2018.02.004Get rights and content

Abstract

Background/objectives

High dose insulin (HDI) is a standard therapy for beta-blocker (BB) and calcium channel-blocker (CCB) poisoning, however human case experience is rare. Our poison center routinely recommends HDI for shock from BBs or CCBs started at 1 U/kg/h and titrated to 10 U/kg/h. The study objective was to describe clinical characteristics and adverse events associated with HDI.

Methods

This was a structured chart review of patients receiving HDI for BB or CCB poisoning with HDI defined as insulin infusion of ≥0.5 U/kg/h.

Results

In total 199 patients met final inclusion criteria. Median age was 48 years (range 14–89); 50% were male. Eighty-eight patients (44%) were poisoned by BBs, 66 (33%) by CCBs, and 45 (23%) by both. Median nadir pulse was 54 beats/min (range 12–121); median nadir systolic blood pressure was 70 mm Hg (range, 30–167). Forty-one patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus was 1 U/kg (range, 0.5–10). Median starting insulin infusion was 1 U/kg/h (range 0.22–10); median peak infusion was 8 U/kg/h (range 0.5–18). Hypokalemia occurred in 29% of patients. Hypoglycemia occurred in 31% of patients; 50% (29/50) experienced hypoglycemia when dextrose infusion concentration ≤10%, and 30% (31/105) experienced hypoglycemia when dextrose infusion concentration ≥20%.

Conclusions

HDI, initiated by emergency physicians in consultation with a poison center, was feasible and safe in this large series. Metabolic abnormalities were common, highlighting the need for close monitoring. Hypoglycemia was more common when less concentrated dextrose maintenance infusions were utilized.

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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    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).

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