The Poison Review

High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.  Engebretsen KM et al.  Clin Toxicol 2011;49:277-283.

Abstract

This is a very well done review article of high dose insulin (HDI) therapy, and must-reading for anyone who treats poisoned patients.  I would have rated it even higher than 4 skulls had the authors not overreached in their goals and conclusions.  I’ll explain that in a bit.

The authors point out that standard therapy in poisoning from beta-blockers (BB) or calcium channel-blockers (CCB) include supportive care, fluids, calcium, glucagon, atropine, catecholamines, inotropes, and vasopressors.  However, in serious intoxications, these measures often fail.  The authors searched multiple databases for the years 1975-2010 for articles and abstracts related to the use of HDI in BB and/or CCB overdose.  They identified 72 papers they considered relevant, including animal studies, case reports, and case series.  As they note, there were no published clinical trials. (Despite their claim to have identified 72 relevant papers, for some reason the paper has only 63 references.)

In their review, the authors make the following points:

• Possible mechanisms for the beneficial effects of HDI in these cases include increased inotropy, increased intracellular glucose transport providing nutritional substrate for myocardial cells, and vascular dilatation leading in increased tissue perfusion.
• In contrast to catecholamines, HDI increases coronary blood flow without increasing myocardial oxygen requirements.
• There are a number of experimental studies indicating that vasopressors are not beneficial in CCB poisoning, and may in fact be detrimental.
• Some authors have hypothesized that increased insulin doses are needed when vasopressors have been given, to counteract increased systemic vascular resistance and decreased cardiac output.
• Titrating treatment to blood pressure and pulse alone can be misleading, since the real goal of therapy is to maintain essential tissue perfusion.
• Better clinical parameters to follow include mental status, skin warmth and color, peripheral pulses, and urine output, as well as vital signs. Following lactate levels may also be helpful.
• And most importantly: “In order for HDI to be of greatest benefit, it should be used early on in therapy rather than as rescue therapy.”

The authors conclude that although more clinical data is needed, HDI is “a superior treatment in terms of safety and survival in both beta-blocker and calcium-channel blocker poisoning.” However, of all the articles they cite, only 2 case reports describe an isolated BB overdose.  In one, a patient with a massive metoprolol overdose received multiple treatments and interventions, and to my view any possible effect of HDI was not clearly evident in the case details.  In the other paper, a 48-year-old man who overdosed on Nebivolol was treated with standard interventions, as well as intravenous fat emulsion and HDI.  Again, I find it impossible to tease out exactly what intervention(s) were responsible for his good outcome.  In my opinion, although HDI may indeed have a role in treating BB overdose, the authors had precious little clinical data to support their conclusion that it is a superior treatment in this setting.  As for CCB overdose, there is no doubt. Keeping this limitation in mind, I highly recommend this article.