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The Role of Insulin and Glucose (Hyperinsulinaemia/Euglycaemia) Therapy in Acute Calcium Channel Antagonist and β-Blocker Poisoning

  • Review Article
  • Published:
Toxicological Reviews

Abstract

The inotropic effect of insulin has been long established. High-dose (0.5–1 IU/kg/hour) insulin, in combination with a glucose infusion to maintain euglycaemia (hyperinsulinaemia/euglycaemia therapy), has been proposed as a treatment for calcium channel antagonist (CCA) and β-adrenoceptor antagonist (β-blocker) poisonings. However, the basis for its beneficial effect is poorly understood.

CCAs inhibit insulin secretion, resulting in hyperglycaemia and alteration of myocardial fatty acid oxidation. Similarly, blockade of β2-adrenoceptors in β-blocker poisoning results in impaired lipolysis, glycogenolysis and insulin release. Insulin administration switches cell metabolism from fatty acids to carbohydrates and restores calcium fluxes, resulting in improvement in cardiac contractility.

Experimental studies in verapamil poisoning have shown that high-dose insulin significantly improved survival compared with calcium salts, epinephrine or glucagon. In several life-threatening poisonings in humans, the administration of high-dose insulin produced cardiovascular stabilisation, decreased the catecholamine vasopressor infusion rate and improved the survival rate.

In a canine model of propranolol intoxication, high-dose insulin provided a sustained increase in systemic blood pressure, cardiac performance and survival rate compared with glucagon or epinephrine. In contrast, insulin had no effect on heart rate and electrical conduction in the myocardium. In another study, high-dose insulin reversed the negative inotropic effect of propranolol to 80% of control function and normalised heart rate. High-dose insulin produced a significant decrease in the left ventricular end-diastolic pressure and a significant increase in the stroke volume and cardiac output. The vasodilator effect was explained by an enhanced cardiac output leading to withdrawal of compensatory vasoconstriction. No clinical studies have yet been performed.

Although not effective in all cases, we recommend hyperinsulinaemia/euglycaemia therapy in patients with severe CCA poisoning who present with hypotension and respond poorly to fluid, calcium salts, glucagon and catecholamine infusion. However, careful monitoring of blood glucose and serum potassium concentrations is required to avoid serious adverse effects. More clinical data are needed before this therapy can be recommended in β-blocker poisoning. There is a need for large prospective clinical trials to confirm safety and efficacy of hyperinsulinaemia/euglycaemia therapy in both CCA and β-blocker poisoning.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The author has no conflicts of interest that are directly relevant to the content of this review.

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  1. Réanimation Médicale et Toxicologique, Hôpital Lariboisière - Université Paris 7, Paris, France

    Bruno Mégarbane, Souheil Karyo & Frédéric J. Baud

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  1. Bruno Mégarbane
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  2. Souheil Karyo
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  3. Frédéric J. Baud
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Correspondence to Bruno Mégarbane.

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Mégarbane, B., Karyo, S. & Baud, F.J. The Role of Insulin and Glucose (Hyperinsulinaemia/Euglycaemia) Therapy in Acute Calcium Channel Antagonist and β-Blocker Poisoning. Toxicol Rev 23, 215–222 (2004). https://doi.org/10.2165/00139709-200423040-00002

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