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Abstract

Hyperinsulinaemia/euglycaemia therapy (HIET) consists of the infusion of high-dose regular insulin (usually 0.5 to 1 IU/kg per hour) combined with glucose to maintain euglycaemia. HIET has been proposed as an adjunctive approach in the management of overdose of calcium-channel blockers (CCBs). Indeed, experimental data and clinical experience, although limited, suggest that it could be superior to conventional pharmacological treatments including calcium salts, adrenaline (epinephrine) or glucagon. This paper reviews the pathophysiological principles underlying HIET. Insulin administration seems to allow the switch of the cell metabolism from fatty acids to carbohydrates that is required in stress conditions, especially in the myocardium and vascular smooth muscle, resulting in an improvement in cardiac contractility and restored peripheral resistances. Studies in experimental verapamil poisoning in dogs have shown that HIET significantly improves metabolism, haemodynamics and survival in comparison with conventional therapies. Clinical experience currently consists only of a few isolated cases or short series in which the administration of HIET substantially improved cardiovascular conditions in life-threatening CCB poisonings, allowing the progressive discontinuation of vasoactive agents. While we await further well-designed clinical trials, some rational recommendations are made about the use of HIET in severe CBB overdose. Although the mechanism of action is less well understood in this condition, some experimental data suggesting a potential benefit of HIET in β-adrenergic blocker toxicity are discussed; clinical data are currently lacking. IntroductionHyperinsulinaemia/euglycaemia therapy (HIET) consists of the infusion of high-dose regular insulin (most commonly 0.5 to 1 IU/kg per hour). Of course, frequent blood glucose monitoring by bedside capillary testing is needed to minimise the likelihood of hypoglycaemia. Glucose infusion is adapted to maintain euglycaemia (6 to 8 mmol/l, or 110 to 150 mg/dl). Adults may require 15 to 30 g of glucose per hour (as glucose 10% or more), associated with potassium supplements to maintain normokalaemia.Pathophysiological bases, as well as experimental data and clinical observations, suggest that HIET might be useful in cases of severe overdose of calcium-channel blockers (CBBs). Conventional measures that consist of intravenous fluids, calcium salts, dopamine, dobutamine, noradrenaline (norepinephrine), phosphodiesterase inhibitors or glucagon often fail to improve the haemodynamic condition of the patient, so that more invasive procedures such as intra-aortic balloon counterpulsation or extracorporeal circulatory support may be needed [1][2][3]. Until now, HIET has mainly been used as a rescue therapy and as an alternative to invasive procedures. However, HIET seems to ensure a more favourable energetic balance in the myocardium than other conventional treatment. It has few side effects provided that glycaemia is frequently checked, and it uses only widely av...

Critical Management of Severe Hypotension Caused by Amlodipine Toxicity Managed With Hyperinsulinemia/Euglycemia Therapy Supplemented With Calcium Gluconate, Intravenous Glucagon and Other Vasopressor Support: Review of Literature

“…Supplemental potassium is required only to prevent severe hypokalemia [ 20 ]. The duration of HIET should be guided by the clinical response, especially hemodynamic parameters: the goal should be hemodynamic stability after the withdrawal of vasoactive agents [ 20 , 21 ]. Methylene blue has been used as a novel approach to treat refractory CCB overdose based on reports of its use to counteract post-coronary artery bypass vasoplegia when added to vasopressors and HIET.…”

A multifaceted approach to calcium channel blocker overdose: a case report and literature review

“…The proposed mechanism involves improved smooth muscle contractility by increased efficiency of carbohydrate uptake and utilization which counteracts CCBs blockade of indigenous insulin release and decreased myocardial free fatty acid extraction. This optimizes the glucose-dependent energy formation required to overcome CCBs overdose 14 . Both glucose and potassium should be frequently monitored on this therapy and potassium should be replaced if the level falls below 3 mmol/L 10 .…”

High dose insulin therapy, an evidence based approach to beta blocker/calcium channel blocker toxicity

“…Although many sources recommend a 1 unit/kg bolus dose followed by a continuous infusion at 0.5-1 unit/kg per hour [9,15,21], no ceiling effect has ever been established and higher doses have been postulated to be more effective [38], with good outcomes documented in patients receiving insulin boluses as high as 10 U/kg [39] and infusions as high as 22 U/kg/h [25]. …”