Glucagon + EpiPen?

[BB8730]

In my physiology class we're learning about the synergistic effects of glucagon and epinephrine. It seems pretty significant. Anyone have any input on the potential benefits of administering an EpiPen along with glucagon? This would of course only apply to BLS services with no other hypoglycemia management options, such as D50.

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[alpinism]

Good question. The majority of pts w/ hypo in the field are due to diabetics taking insulin and then not eating, ie poor sugar control, or just ODing on the stuff. From my limited knowledge on the subject (im by no means an expert), the problem w/ giving epi or glucagon or both in that instance is that insulin acts to antagonize the effects of both drugs on the liver/kidney. Insulin will inhibit AC and activate PDE which will inhibit cAMP production and PKA activation etc... which is how both epi (via beta-2/G-alpha s) and glucagon act to stimulate glycogenolysis, gluconeogenesis, and lipolysis. Thus w/ high insulin levels, the effect of both drugs will be much less than oral glucose or D50 (best option). You can still give glucagon, esp w/ severe hypo or if you don't have D50 as BLS, but oral glucose should be more than enough most of the time.

The other problem w/ epi is the cardiovascular side effects in hypo pts, esp since you'd need higher systemic doses to have any effect on the liver. The SNS activation (incr HR via beta1 and localized vasoconstriction via alpha1) would increase glucose/fuel requirements in the heart and other tissues when there isnt enough to being with. (why physiologically its only released in short bursts and meant to be a fight or flight response only when physical activity is needed, even w/ hypo) That in addition to autonomic instability and the increased risk of MI, stroke and tissue ischemia in pts who usually aren't very healthy (w/ multiple medical conditions) to begin with.

Hope this answers why its not currently used in EMS.

 

[BB8730]

The SNS activation (incr HR via beta1 and localized vasoconstriction via alpha1) would increase glucose/fuel requirements in the heart and other tissues when there isnt enough to being with. (why physiologically its only released in short bursts and meant to be a fight or flight response only when physical activity is needed, even w/ hypo) That in addition to autonomic instability and the increased risk of MI, stroke and tissue ischemia in pts who usually aren't very healthy (w/ multiple medical conditions) to begin with.

That makes sense. Giving epi to a severely hypoglycemic PT would just ramp up the SNS and burn more energy.

the problem w/ giving epi or glucagon or both in that instance is that insulin acts to antagonize the effects of both drugs on the liver/kidney

Yeah, we always keep that one in the back of our minds when we're giving glucagon. Also, the really strung out diabetics who haven't eaten in days can have very little glycogen (or intermediates for gluconeo) left, rendering glucagon pretty much useless. On our BLS service, it's a last resort for PT's who are either unconscious or have such an altered LOC that they can't take oral glucose. That's why I was thinking about the EpiPen + glucagon combo as a last ditch effort to ramp up circulating glucose levels faster to possibly avoid some permanent neural damage, but what you posted makes a lot of sense and I can see why it wouldn't be very beneficial, if at all beneficial. I appreciate your detailed response! Thanks!

 

[tremulousNeedle]

From the perspective of a practicing senior EM resident and former EMT, while epi plus glucagon may sound intriguing from a physiology standpoint, this combination is not realistic clinically.

First, physiologically, I would be very concerned about the cardiovascular side effects of epinephrine. Consider the usual indications for subQ epinephrine, cardiovascular or respiratory collapse following an allergen exposure or an exposure previously known to cause cardiovascular or respiratory collapse.

Second, in current times, practitioners would be exposing themselves to medicolegal risk if they just started using medications for indication that may be biochemically sound, but never actually tested inclinical trials. Of course there are many off-label uses for many drugs, but itis always risky to be that trailblazer. People at the frontline always argue what’s the difference if the person is going to die anyways. Unfortunately, that defense usually does not pan out. For example, lawyers would argue that the hypoglycemic grandmother would not have had a heart attack if you hadn’t given epinephrine and instead waited the extra 10 minutes for a more advance level of care to arrival.

Keep up the innovative thinking though, maybe you will be the trailblazer to start the glucagon + epi movement.

 

[pianoman511]

More from a resource standpoint, can't have a patient sign off(refuse) after epinephrine. Pretty much guarantees a ride to the hospital and a few hours on a monitor.

Sent from my PC36100 using Tapatalk

 

[BB8730]

From the perspective of a practicing senior EM resident and former EMT, while epi plus glucagon may sound intriguing from a physiology standpoint, this combination is not realistic clinically.

First, physiologically, I would be very concerned about the cardiovascular side effects of epinephrine. Consider the usual indications for subQ epinephrine, cardiovascular or respiratory collapse following an allergen exposure or an exposure previously known to cause cardiovascular or respiratory collapse.

Second, in current times, practitioners would be exposing themselves to medicolegal risk if they just started using medications for indication that may be biochemically sound, but never actually tested inclinical trials. Of course there are many off-label uses for many drugs, but itis always risky to be that trailblazer. People at the frontline always argue what’s the difference if the person is going to die anyways. Unfortunately, that defense usually does not pan out. For example, lawyers would argue that the hypoglycemic grandmother would not have had a heart attack if you hadn’t given epinephrine and instead waited the extra 10 minutes for a more advance level of care to arrival.

Keep up the innovative thinking though, maybe you will be the trailblazer to start the glucagon + epi movement.

More from a resource standpoint, can't have a patient sign off(refuse) after epinephrine. Pretty much guarantees a ride to the hospital and a few hours on a monitor.

Sent from my PC36100 using Tapatalk

Thanks for the replies.