Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines.

Background: High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning.Methods: This was a retrospective study from a single poison center. Cases were identified via the generic code "Calcium Antagonists" in which the therapy "High Dose Insulin/Glucose" was "performed, whether or not recommended" from 2019-2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia.Results: Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil n = 10, diltiazem n = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2-5; range 0-6) and 2 in the non-DHP group (IQR: 1-3; range 0-5; p = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0-2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min; p = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0; p = 0.009).Conclusions: Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.

Persistent Hyperinsulinemia Following High-Dose Insulin Therapy: A Case Report.

INTRODUCTION: Overdoses of beta-adrenergic antagonists and calcium channel antagonists represent an uncommonly encountered but highly morbid clinical presentation. Potential therapies include fluids, calcium salts, vasopressors, intravenous lipid emulsion, methylene blue, and high-dose insulin. Although high-dose insulin is commonly used, the kinetics of insulin under these conditions are unknown. CASE REPORT: We present a case of a 51-year-old male who sustained a life-threatening overdose after ingesting approximately 40 tablets of a mixture of amlodipine 5 mg and metoprolol tartrate 25 mg. Due to severe bradycardia and hypotension, he was started on high-dose insulin (HDI) therapy; this was augmented with epinephrine. Despite the degree of his initial shock state, he ultimately recovered, and HDI was discontinued. Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter. CONCLUSION: The kinetics of insulin following discontinuation of high-dose insulin therapy are largely unknown, but supraphysiologic insulin levels persist for some time following therapy; this may allow for simple discontinuation rather than titration of insulin at the end of therapy. Dextrose replacement is frequently needed; although the duration is often difficult to predict, prolonged infusions may not be necessary.

High dose insulin for beta-blocker and calcium channel-blocker poisoning.

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 1U/kg/h and titrated to 10U/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 ≥0.5U/kg/h. RESULTS: In total 199 patients met final inclusion criteria. Median age was 48years (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 70mmHg (range, 30-167). Forty-one patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus was 1U/kg (range, 0.5-10). Median starting insulin infusion was 1U/kg/h (range 0.22-10); median peak infusion was 8U/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.