In this episode, I’ll discuss how to use high dose insulin therapy for beta-blocker or calcium channel blocker overdose.
An overdose of beta-blockers or calcium channel blockers often induces life-threatening cardiogenic shock.
Traditional therapies for beta-blockers or calcium channel blocker toxicity are:
Glucagon
Calcium
Atropine
Electricity (pacing)
Vasopressors
Unfortunately, these therapies often fail or are transiently or minimally effective.
High-dose insulin therapy has emerged as a preferred treatment of cardiogenic shock induced by calcium channel blockers or beta blockers.
When used at doses 10 times that of the normal antidiabetic dose, insulin has positive inotropic effects even in the presence of beta-blocker or calcium channel blocker toxicity.
High-dose insulin therapy also improves the poisoned patient’s response to vasopressors and provides lasting effects on hemodynamic stability.
It is important to note that the hemodynamic response to high dose insulin does not occur until 15-45 minutes after initiation. Maximal use of other therapies must be employed while the effects of high dose insulin therapy kick in.
Dosing recommendations for high-dose insulin therapy are provided in the Consensus recommendations for the management of calcium channel blocker poisoning in adults. To start high dose insulin therapy give a bolus of 1 unit/kg IV of regular insulin followed by an infusion of 1 unit/kg/hr.
Based on animal data, high dose insulin therapy appears to have a linear dose-response curve where increasing doses of insulin produce increasing positive hemodynamic effects. Therefore high dose insulin therapy may be titrated to effect. A maximum of 10 units/kg/hr is suggested but no ceiling dose has been established.
Goals for treatment can be a heart rate of at least 50 beats per minute and a systolic blood pressure of at least 100 mmHg.
You’ll need to proactively treat against the development of hypoglycemia with such high doses of insulin. A central line should be obtained if there is not one already so that more concentrated solutions of dextrose can be given to avoid fluid overload.
If the initial blood glucose level is less than 400 mg/dL, give an IV dextrose bolus of 0.5 g/kg and continuous infusion of 0.5g/kg/hr at the start of high dose insulin therapy.
Check the blood glucose every 20 minutes x 3, then hourly. Titrate the dextrose infusion to maintain blood glucose at the upper end of normal.
The patient should be monitored for the development of hypokalemia, although this will not always occur. Check serum potassium hourly until insulin dose and potassium level are stable; then check the potassium at least every 6 hours.
Because hypokalemia is due to intracellular shifting and not potassium depletion, the goal potassium level is lower than usual. A suggested goal is 2.8 to 3.2 mEq/L with replacement not indicated until the potassium drops below 2.8 mEq/L.
Before you use high dose insulin therapy, find out the fastest way to get potassium results back from your lab. At my hospital, adding on a potassium level to a blood gas gets results in 15 minutes or less. It shouldn’t matter whether it is an arterial or venous sample for the purpose of checking the potassium level.
The optimal duration of high dose insulin therapy has not been determined.
It is unknown whether slow weaning of the insulin infusion is preferred to abrupt cessation. It is possible that lipid stores of insulin provide a self-tapering effect that allows for abrupt cessation. If hemodynamic instability recurs when high dose insulin is weaned, restart the insulin infusion.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Great stuff.
I have implemented this quite a few times, with varying degrees of success. I will say that in pure OD it has worked out pretty well.
A few more points:
1) Important to continue to monitor glucose for 24 hr POST High Dose Insulin Injection. This is when patients are at high risk of hypoglycemia.
(when high doses of regular insulin are given I’ve noticed a delayed response IE pts glucose don’t typically drop in ED but rather tank later in ICU. Almost like a U500 effect.)
Also the aggressive treatment of glucose will be typically different with Beta Blocker vs Calcium Blocker OD as you may already know.
2) There seems to be significant debate on what to do with pressors. Mortality data (particularly with animal studies) suggests that pressors do not help, they help the numbers but not the patient. On one hand you have increased perfusion with HDI and improvement in capillary leaking and with pressors the numbers improve but pt doesn’t always improve clinically. The hard part is ‘how long do you hold pressors?’. Often times as the pressor does is increased, you will need to increase the Insulin rate and the cycle begins. What I typically recommend is try and minimize the use of pressors as much as possible until you reach ‘danger zones’ with respect to vitals. There is an interesting review of this which I included here:https://www.ncbi.nlm.nih.gov/pubmed/21819291
(sorry I couldn’t attach the whole article electronically)
3. Work closely with nursing staff. People often ‘freak out’ when they see these doses of insulin being used. Education is really important on what to mntr for and why this is being used. I have also noticed that once you reach 100 units/hr MDs/RNs are reluctant to titrate up. Again ED/ICU PharmD education is a must.
As an ED Pharmacist I love these cases. One of the coolest pharm interventions you can be involved in. It is important to know this really well as the team will really look to you for support during these situations.
– Ash
Great article worth reading and sharing. A question one may raise regarding role of insulin in treating CCB or BB overdose pertains to our traditional understanding of its role to lower blood glucose. Glucagon, a hormone commonly used in reversing CCB or BB overdose, has an antagonistic effect to insulin with respect to regulating glucose level, causing some confusion in understanding the latter’s role in overdose of the said agents without predisposing one to major risks. Clearly, Insulin’s positive inotropic effect via shifting potassium intracellularly may partly help explain its unique role in this case. May be that in a case of cardiogenic shock, the clinical benefits of using Insulin far outweighs the risks. Nonetheless, these are some of the questions clinicians be prepared to answer.
Just to clarify – I meant it is just as important to closely monitor glucose 24 hr AFTER the insulin infusion has been turned off.
Thanks again Joe for bringing up another interesting topic.
Ash