How To Manage Severe Allergic Reactions And Hypoglycemia In Your Office

In a previous article "Why Glucagon Should Never, Ever Be in Your Drug Kit", I responded to a client who had inquired about adding glucagon to her kit for the purposes of combating anaphylaxis refractory to epinephrine due to beta blockade.  In my piece, I highlighted the actions of how glucagon works to circumvent beta blocker actions, but also presented conservative calculations to show that the probability of encountering this event is extremely low– too rare to justify the cost of glucagon. In addition, I showed that proper administration requires IV insertion, a skill that a vast majority of dentists are not familiar with, and additional equipment that you’ll probably never use in your regular practice.  The article went on to discuss the three pronged attack in which you can combat anaphylactoid-like reactions without the addition of glucagon.  It has been a few years since that article, and since medicine is constantly evolving I thought it would be worthwhile to review the current science.  Perhaps this would lead me to reconsider my previous position with a lens on treating severe allergic reactions and hypoglycemia.

Medical emergencies can happen to young, healthy people.

Treating Severe Allergic Reactions

To clarify, as early as 2005 Emergency Cardiac Care (ECC) Guidelines included a recommendation for glucagon in anaphylaxis that is refractory to epinephrine, especially when the patient takes beta blockers (1).  However, this should be a tertiary thought.  As I stated in my previous article, it is important to remember that anaphylactic shock is a distributive shock that results from cardiovascular collapse.  All the beta in the world won’t help keep the blood pressure up without sufficient vascular tone and volume.  Fighting beta blockade in the first several minutes of the event is simply chasing after the wrong waterfall. 

Early epinephrine is lifesaving.  At the higher doses you would administer,  epinephrine exhibits alpha-1 properties, as well as beta.  Alpha-1 works to constrict peripheral vasculature, thus raising blood pressure by decreasing the volume of the vascular compartment.  Increased pressure means increased delivery of oxygen to the cells. A second dose of epinephrine is recommended in five minutes if symptoms worsen. 

During an allergic reaction, MAST cells degranulate and release histamines.  Histamines recruit additional cells from the humoral immune system, causing fluid to move out of the blood and cells into the “third space”.  This causes swelling (especially in the face, neck, and upper airway) and sudden hypovolemia, which in turn leads to hypotension. Diphenhydramine prevents this cascade of events from occurring. 

Since, epinephrine peaks at about 20 minutes and does not address the cause of the allergic reaction, diphenhydramine must be part of your first line of attack.  Patients will often regress without diphenhydramine.  In addition, due to the amount of time it will take for enteral medication to pass through the liver before entering systemic circulation, diphenhydramine must be provided in the form of intramuscular injections. 

The next line of treatment is to keep the pressure up by increasing the volume of fluid in the vasculature.  Paramedics replace that missing volume by administering an IV/IO fluid bolus.  Without having sufficient volume to circulate, increasing the rate and strength of the pump is simply ineffective. 

Considering average EMS response time nationwide is 7 minutes (median time increases to 14 minutes in rural areas) (2), you probably won’t get this far down the algorithm.  However, if you do actually find yourself 15 or 20 minutes into an event with a patient you are very unlikely to have, EMS is nowhere to be found, and you still want to perform additional, likely ineffective treatments, glucagon can be administered.  The recommendations are for 1-2 mg every 5 minutes IM or IV (when volume and vasculature has already been addressed). To accomplish this,  you would need at least 2mg of glucagon (at >$250 per mg) to maintain your treatment for another 5-10 minutes. 

Treating Severe Hypoglycemia

But what about glucagon’s utility in managing hypoglycemic patients?  Afterall, it has been prescribed as a rescue device to patients who are not medical professionals for decades.  Why not add this to your emergency medical kit?  Imagine this scenario: 

A 24 year-old patient who did not disclose their Type I diabetes mellitus seeks your services for (insert your favorite 30-minute procedure here).  You did not give them instructions to do so, but they figured since there would be anesthetics involved, it is better to fast the night before the procedure.  Afterall, they were told to fast for another minor surgery they underwent a few months ago.  To adjust for fasting, they decided they should take a little less of  their morning insulin.

The patient walks into your office for the procedure scheduled at 11 am, but since you are slightly behind today,  your assistant gets the patient into your chair at 11:15, and you arrive to apply a topical anesthetic at 11:23.  Feeling the pressure, you leave the room momentarily to perform a quick oral cancer screening.  You return at 11:29 and begin your infiltration.  The procedure begins at 11:36.  Your patient begins to exhibit signs of confusion at 11:44 am. 

It is extremely difficult to identify signs of hypoglycemia when performing dental procedures.

Of course this is very easy to miss, because your patient cannot have any meaningful conversation with you while you are working inside their mouth.  All you have to go on is body language  and only if you are not hyper-focused on the task you have at hand. 

Thinking the patient is simply nervous, or is just feeling the effect of a mild sedative they may have gotten from their physician, you continue the procedure.  At 11:53, the patient begins to squirm around– they can’t sit still and they are becoming difficult to manage– combative, even.  Your sixth sense tells you something is not right.  Suspecting the patient may be hypoglycemic, you activate the emergency response plan in your office. EMS is called and your emergency medication kit, oxygen assembly and AED are all brought to the patient’s side in seconds.  You grab the tube of oral glucose gel and try to get the patient to ingest it.  You’ve practiced this drill before, and everything is running like clockwork.

Except . . . a nearby apartment fire with multiple casualties has tied up units, and a paramedic ambulance is dispatched from a distance.  Fifteen minutes later, you are still waiting for EMS and your patient is teetering on unconsciousness.  You know that unconscious people cannot protect their own airway if given anything PO.  You remember the lecture you attended where the presenter (with little experience responding to emergencies themselves) told you that as serum glucose levels continue to drop, there is an increased risk that the patient will have a seizure and could possibly die. If only there were something else that could be done?  The lecturer’s voice is still in your head.  Why didn’t you listen and just buy the over $850 glucagon autoinjector pen?  Wait!  Didn’t they say epinephrine could work in a pinch?!

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I think most of us could agree that while maybe a bit far-fetched, a perfect storm of events could make the above scenario plausible.  I can imagine the feeling of helplessness any clinician might have, watching the progression of an emergent condition go sideways.  I have felt it myself, more than once.  But I’ve also come to realize and accept that even I, a flight paramedic with over 30 years experience in 911 EMS, cannot be prepared for EVERY unlikely situation.

For as long as I can remember, I have encountered patients who have been prescribed glucagon to inject in emergency situations, similar to the theory behind epinephrine autoinjectors.  They consist of a powder that needs to be reconstituted with 1 mL of sterile water.  The mixture is then injected IM.  Newer versions consist of liquid that does not need to be reconstituted, and may even be administered by spraying it in someone’s nose.  The glucagon acts on liver glycogen stores, converting it to glucose, thus temporarily raising concentrations in the blood.  Easy-peasy, problem solved . . . .right? 

Well, maybe.  There is a wealth of literature supporting the use of glucagon, in any of its many forms (intramuscular,  intranasal, autoinjector) in severe hypoglycemia (3).  However, it has not been shown to be superior to dextrose (3).  One study has shown that glucagon may not be effective in preventing hypoglycemia when insulin levels are high (4).  Interestingly, the 2020 American Heart Association and American Red Cross Focused Update for First Aid (5) does not mention glucagon at all.

But even if glucagon does do the trick, a severe hypoglycemic event is avoided, and your patient is ready to go home, I implore you to call EMS anyway.  It is important to understand that without also administering insulin, serum potassium levels have been shown to increase (6,7).  If the patient's potassium was at the high end of normal (a very narrow range) before the glucagon injection, hyperkalemia may ensue.  Hyperkalemia can lead to a lethal cardiac dysrhythmia that may require your AED.

Paramedics will bring glucometers, cardiac monitors and waveform capnography to the patient’s side.  These devices will provide indirect clues about acid/base balance and dysrhythmias as well as a direct measurement of serum glucose.  Critical care paramedics can also use albuterol to shift potassium back into the intracellular space.  However, this is done as a careful titration, and after lab results and / or electrophysiology provide indication for this treatment.  You do not (nor should you) have the laboratory equipment (or time) required to make this determination. 

So what about your Epipen? 

Epinephrine does temporarily increase serum glucose levels.  However, a 2001 Yale New Haven study suggested epinephrine is not an adequate substitute for glucagon, at least in children (8).  This makes sense, as epinephrine also increases the rate and strength of  myocardial contractions, thus myocardial glucose and oxygen demand is increased.  As an aside, increased myocardial oxygen demand should compel the practitioner to administer oxygen to this patient.   Since endogenous adrenaline has also been shown to cause hypokalemia (9), cardiac monitoring may, at the very least, be a good idea.

Science aside, these types of events seem to be rare enough, and the expense of epinephrine and glucagon autoinjectors is not palatable.  I currently sell the only FDA approved epinephrine autoinjector device for about $335.  The Gvoke hypopen (glucagon injection) retails on Amazon for $859 and does not need to be reconstituted.  It can simply be injected in a similar manner as an epinephrine autoinjector.  Glucagon that needs to be reconstituted is also available from Amazon for $268.  The shelf life of the Gvoke device is 24 (pediatric) - 30 (adult) months.  If you’re thinking you can stretch that out a little bit by keeping it in the fridge, don’t. The manufacturer’s website has an explicit warning not to refrigerate the medication– it must be stored at 68-77 F (10).  The conventional glucagon has a shelf life of 12 - 24 months when kept at 68-77 F (11). 

Even if we disregarded the Gvoke warning, and stored the hypopen in a refrigerator, it would be away from the rest of the emergency equipment.  During an emergency, all equipment should be at the patient's side, which means that all equipment should be stored together, in as few carrying vessels as possible.  One person in the office should be able to fetch EVERYTHING (AED, Oxygen, Drug Kit) whether you think you will need it or not, with only two hands, in a single trip.  The rest of these items are not ordinarily kept in a refrigerator. 

This brings us back to the issue of reconstitution.  You may fear that this process is time consuming, especially in an emergency.  I disagree.  Unless you manage emergencies on a regular basis, you would understandably (and thankfully) have a limited amount of experience being immersed in one.  If a person presented to me on the street with signs and symptoms of hypoglycemia, not only would I take the time to measure their blood glucose first, I would also take the time to attempt to start an IV with the purpose of dripping in D10.  If I missed the IV twice, I would also take additional time to draw sterile water into a syringe, inject it into another vial containing the powdered glucagon, swirl to ensure all is dissolved, and redraw from the vial for an IM injection. Then, I find my target, clean it with an alcohol wipe and inject. 

But what about hypoglycemic seizures? 

The occurrence of seizures in hypoglycemia is rare.  Instead, the most common neurological symptom is coma (12).  In one 12-month-long  study, only 9 of 125 visits to Harlem Hospital for symptomatic hypoglycemia resulted in seizures while 65 were obtunded, 38 were confused or exhibited bizarre behavior and 10 were dizzy or tremulous (13).  Another retrospective study (14) investigated 53,505 patients treated by EMS for seizures and who had their blood glucose recorded.  Only 1.2% (638) of those patients had a blood glucose level less than 60 mg/dL.  Keep in mind, tonic clonic muscle twitching decreases glucose levels as well.

In my over 30 years of responding to 911 emergencies, I can count on one hand the number of hypoglycemic seizures I’ve encountered.  In every one of the cases, altered mental status preceded any tonic-clonic movements, and there were many minutes- perhaps an hour or two or more of time from the onset of AMS to the seizure.  There is a progression of disease pathology that takes time to evolve.  I’m not saying that we should dilly-dally, but I am saying there are VERY FEW emergencies in which we do not have some time to take a step back, take a deep breath,  and respond carefully and purposefully.  An untrained, unpracticed, and reactionary approach to emergency management out of fear and inexperience increases your potential of freezing, or making a mistake under undue duress. 

 Although anecdotal, I also offer you my experience with administering glucagon to patients suffering hypoglycemic emergencies.  As mentioned above, I have administered IM glucagon when getting an IV is not possible, so it is my third line of defense. 

For the Type I diabetics, hypoglycemia is most usually a result of too much insulin being injected.  Their calculations are off, or perhaps their pump is overactive.  In either case they tend to have less glycogen stores in their liver, and so a dose of glucagon does not seem to be very effective.  In my own personal experience, it works about half the time.

I have found that Type II diabetics often do not experience hypoglycemia, probably due to the insulin-resistant nature of their disease.  Their problem is not that too much glucose is entering the cells and leaving the blood serum, but that not enough glucose can get into the cells due to insulin resistance.  This would increase glucose concentrations in the vascular compartment, not decrease it.  Increasing the concentration of serum glucose with glucagon does allow more uptake, but only temporarily as it also causes spilling into the urine as a compensatory measure.

For the Type I diabetics, hypoglycemia is most usually a result of too much insulin being injected.  Their calculations are off, or perhaps their pump is overactive.  In either case they tend to have less glycogen stores in their liver, and so a dose of glucagon does not seem to be very effective.  In my own personal experience, it works about half the time.

I also discourage the use of expensive “pen” type devices for convenience.  Drawing fluid from a vial and injecting it intramuscularly is a skill that every dentist MUST have.  This is non-negotiable.  The ADA (15), AGD (16) and British Dental Journal (17) all recommend an injectable antihistamine.  In the US, Benadryl (diphenhydramine) is the choice.  This cannot be in pill form, as PO meds must pass through the liver first (ASA is an exception because it is absorbed in the stomach) before entering general circulation.  This can take upwards of 20 minutes.  Diphenhydramine is not available in an autoinjector “pen” style device.

You could also have a glucometer in your office. Hand-held devices are relatively inexpensive and will provide reasonably accurate measurements.  However, if you use these devices in a clinical setting, you need to  consider that glucometers should be calibrated every so often.  Afterall, they are laboratory devices.  Keeping AED pads within expiry is an easy task to forget about.  What is the probability you will eagerly maintain a careful monthly glucometer calibration log? 

Revisiting the original scenario, here are a few things that can be done to avoid and/or treat a severe hypoglycemic event without glucagon.

1. Understand that Type I diabetics may not be forthcoming with their condition due to embarrassment (18).  Instead of asking people to fill in a form that you will look at briefly and then file away, have that uncomfortable conversation with your patient.  Ask them point blank, “Are you diabetic?”,  “Type I or Type II?”, “Is your glucose under control?”, “Do you have a pump?”, “Do you check your sugar regularly?”, “When was the last time you checked?”, “What was it?” 

2. Make it a habit to tell people not to do anything differently for an upcoming procedure, unless they should.  Tell them to “make sure you eat breakfast” (19) or “remember, there’s no need to fast for this procedure”. 

3. Try to schedule diabetics earlier in the morning, if possible.  If they do fast, finishing their procedure earlier allows them to eat earlier, and may prevent a severe hypoglycemic event.

4. Talk to your patient about the procedure.  Are they nervous?  Will they seek a mild sedative from their physician?  Is there something you can prescribe or advice you can offer to help them through?

5. Screen your diabetic patient just before the procedure.  Ask if they ate and / or adjusted their insulin.  Are they feeling normal now, before the procedure?  If you choose to have a glucometer in your office, and it is maintained regularly, why not check their level before beginning the procedure?

6. Know the signs and symptoms of a hypoglycemic emergency.  Remember that altered mental status is a major sign that the brain is not getting glucose and/or oxygen.  As soon as any bit of confusion sets in, take a step back and reevaluate. 

7. Keep your emergency kit up to date and compliant with the recommendations of the ADA (15) and AGD (16).  Be sure all medications (even your glucose) are within expiry.  Use my free service to help you manage and make sure your kit is always ready to go.

8. Make sure you have glucose gel, not tablets, beverages or anything that needs chewing.  A severely confused or unconscious patient will not be able to protect their own airway with something in their oropharynx.  At the very least, glucose gel can be placed in small amounts in the buccal mucosa where some absorption can occur.

9. Update the 9-1-1 dispatcher if the patient’s condition worsens.  If the dispatcher hangs up before the ambulance gets there, you are allowed to call 911 again.  Whoever answers the call will be able to update the dispatch notes, and the paramedics enroute will be advised.  Dispatchers will use real-time information to upgrade the call’s priority, so help may arrive faster.  In extreme cases, they may dispatch additional resources. 

10. Practice, practice, practice.  Call us in once per year to engage your team in a dynamic, fun-filled event that requires them to work together through a series of realistic simulations.  For the same reasons we do fire drills in schools, after a few iterations, everyone will know what to do, and the emergency will be handled with calm and confidence. 

11. Debrief with your team after any emergency event, no matter how small.  Here again, I offer my expertise to reconstruct and dissect the event in a Just Culture.  Let me help find the kinks in the armor, figure out where more training can help, and then design a custom program to make you and your team confident and well prepared to manage any emergency that comes your way. 

I know that feeling of helplessness is incredibly uncomfortable and scary.  Even worse, you may be in a situation where you can’t avoid it.  While factors that cause medical emergencies are often out of your control, you can respond to them in a calm and confident manner, without unnecessarily spending a ton of money.  Have Dummy Will Travel is dedicated to helping.

Erik Zalewski is a Nationally Registered Paramedic and former New York State EMS Certified Instructor Coordinator with over 30 years experience responding to 9-1-1 calls for medical emergencies.  Erik has taught EMTs and paramedics at Stony Brook University, Borough of Manhattan Community College, and the Suffolk County, NY EMS academy.  Erik is also a certified flight paramedic.  He and his team at Have Dummy Will Travel, Inc. are dedicated to helping medical professionals respond to emergencies safely, efficiently and in the most cost-effective manner possible.  Call or text 631-849-4978 or email erik@havedummy.com for additional information.

References:

1. 2005 American Heart Association Guidelines For Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.Circulation,2005;112(24):IV-143-IV-145.

2.. Mell, H. et al. Emergency Medical Services Response Times in Rural, Suburban, and Urban Areas. JAMA Surg. 2017;152(10):983-984.

3. Boido, A, Ceriani, V. & Pontiroli, A. Glucagon for hypoglycemic episodes in insulin-treated diabetic patients: a systematic review and meta-analysis with a comparison of glucagon with dextrose and of different glucagon formulations. Acta Diabetologica, 2014;52:405-412.

4. Castle JR, et al. Factors Influencing the Effectiveness of Glucagon for Preventing Hypoglycemia. Journal of Diabetes Science and Technology. 2010;4(6):1305-1310. doi:10.1177/193229681000400603

5.  Pellegrino, J. et al. 2020 American Heart Association and American Red Cross Focused Update for First Aid, Circulation. 2020;142(17):e287-e303.

6. Massara, F. et al. Influence of glucagon on plasma levels of potassium in man. Diabetologica. 1980;19:414-417.

7. Viera, A. & Wouk, N. Potassium disorders: Hypokalemia and Hyperkalemia. American Family Physician. 2015;92(6):487-495.

8. Monsod, T. Epipen as an Alternative to Glucagon in the Treatment of Hypoglycemia in Children with Diabetes. Diabetes Care. 2021;24(4):701-704.

9. Reid, J., Whyte, K. & Struthers, A. Epinephrine-induced hypokalemia: The role of beta adrenoceptors. The American Journal of Cardiology. 1986;57(12):F23-F27.

10. https://www.gvokeglucagon.com/wp-content/uploads/2023/07/Gvoke_HypoPen_Patient_FAQs.pdf

11. https://www.novomedlink.com/diabetes/products/treatments/glucagen-hypokit/storage.html

12. Halawa, I., Zelano, J. &  Kumlien, E. Erratum to “Hypoglycemia and risk of seizures: A retrospective cross-sectional study” [Seizure (2015) 147–149]. Seizure. 2017(45):132.

13. Malof, R. & Brust, J. Hypoglycemia: Causes, neurological manifestations, and outcome. Neurological Review. 1985;17(5)-421-430.

14. Beskind, D. et al. When Should You Test For and Treat Hypoglycemia in Prehospital Seizure Patients? Prehospital Emergency Care. 2014;18(3):433-441.

15. ADA Council on Scientific Affairs. Office emergencies and emergency kits. J Am Dent Assoc. 2002;133:364-365.

16. Roberson, J. & Rothman, C. Supplying Safety: The Importance of Drug Kits. AGD Impact. 2008;36(7).

17. Jevon, P. Medical emergencies in the dental practice poster: revised and updated. British Dental Journal. 2020;229(2):97-104

 18. Pearson T. Glucagon as a Treatment of Severe Hypoglycemia. The Diabetes Educator. 2008;34(1):128-134. 

19. Rees T.  The Diabetic Dental Patient. Dental Clinics of North America. 1994; 38(3):447-463. 

17. Jevon, P. Medical emergencies in the dental practice poster: revised and updated. British Dental Journal. 2020;229(2):97-104

 18. Pearson T. Glucagon as a Treatment of Severe Hypoglycemia. The Diabetes Educator. 2008;34(1):128-134. 

19. Rees T.  The Diabetic Dental Patient. Dental Clinics of North America. 1994; 38(3):447-463.