The morning after Christmas Day, we found ourselves in some suburban Chicago emergency room. My teenage son had thrown up after ingesting some pine nuts, and his throat and stomach still felt bad after an hour and two Benadryls, so we went to wait in the ER to be safe. However, I opted just to sit in the waiting room and not to check in unless his condition worsened. He said he felt safer there, and frankly so did I. About an hour later — three hours after the incident — we were contemplating leaving. I called the allergist to be safe, and got an earful. “You should have used the Epi-Pen immediately,” she said, “and gone straight to the hospital.”
I asked why, and she gave me an astonishing figure: she claimed that around four in ten allergic reactions result in a worse reaction sometime within six hours after symptoms appear to dissipate.
“That much?” I asked. “Can you repeat that? I’d like to look into it.” It sounded improbably high. It did not jibe with my 50 years’ experience with my own peanut and egg allergies, nor with my son’s history, nor with the experience of many friends I know. I’d never heard of an allergic reaction spiking a second time: they all went downhill. Though we were on the phone only four minutes, I had the vague feeling that she was spouting just enough high-quality nonsense to be able to hang up on this jerk and get back to her holidays. Although my son was feeling better after three hours, the allergist instructed me to get him checked in, to get him an epinephrine injection and steroids. And so, despite the fact that he was almost back to normal, we were stuck there for three more hours while my son sat through a hypodermic injection, three catheterizations (two had collapsed), the hour of shivering that results from an increased adrenaline rush, repeated prodding and poking, and a generally bizarre, disorienting environment.
The ER doctor was very good. I complained to her that we’ve all been trained many times in the use of the Epi-Pen, and while the mechanical aspects of its use have always been repeatedly made crystal clear to us, up until now we have not had a clear indication of the scenarios calling for its use. We and most other Epi-Pen owners, it appears, believe that it is only in life-and-death situations that we should administer it, and yet we were just told by the allergist that anytime there is even mild discomfort, even a minimal sensation in the throat, the device should be used. The ER doctor concurred.
The implication, and the source of the confusion, is that doctors seemingly want us to consider every allergic reaction due to ingestion to be a life-and-death moment. The ER doctor said that skin rash would not be a concern, but whenever irritation affects the “core” (throat, chest, stomach, lungs, vomiting), the airway is at potential risk and we should always administer epinephrine and then follow up with a visit to the emergency room. In effect, the Epi-Pen gives us an hour or so to get there. If we had two Epi-Pens, we would effectively have twice as much time.
I interpreted this to mean that using the Epi-Pen, which is to say, taking a shot of epinephrine, should not be viewed as responding to an existing moment of clear and present danger, only a precautionary step to forestall potential danger and gain time to reach a hospital. We should have a more liberal sense of it, and far from being afraid of the Epi-Pen, we should use it whenever in doubt. But we should also realize that in doing so we must then hurry to an emergency room immediately.
The nurse, for his part, was one of those wonderfully smart, gregarious, heavy-set types with a big mouth. I do not see a lot of doctors like him. Even the best doctors always have their minds on the next patient’s chart or on their own personal lives, and most display mild annoyance the moment your effort for them to justify their position surpasses a certain low threshold. Like other unsung heroes, there is far less arrogance in many nurses: even as they are wiping up our shit or vomit and changing our sheets, and although they are thinking about the next chart as much as the doctors, nurses seem to have much more spirit to listen, open up, and explain. There was some of this in the ER doctor as well, but she would not admit what I was pressing for.
The nurse said a little too much. He told me that the 30% to 40% figure of our allergist had to be wrong. He pointed out that what our allergist probably meant was that the risk shoots up when you use epinephrine and then don’t administer any buffering medications soon afterward. He explained that this is probably what the “rebound effect” refers to (technically called biphasic anaphylaxis).
But, then, we hadn’t used any epinephrine when we called the allergist, and of course the allergist was well aware of this because I had told her.
This is the crucial point. The upshot is that if you do not use epinephrine, there is far less possibility of a rebound within six hours; the risk usually decays naturally over time as the body’s own immune system defuses the allergen. Apparently (see the Ellis articles below), rebound or biphasic anaphylaxis can occur in some cases when insufficient epinephrine or steroid are administered. But the nurse suggested it may be the epinephrine followed by steroids that in fact creates the increased risk of rebound. Either our allergist was deliberately equivocating and making us stay in order to discipline me, or she was innocently mistaken — both of which are dangerous things. Or the nurse is all wrong. One thing is certain, and that is that nobody is sure of anything.
As you will see, I am not arguing here that we should never resort to epinephrine.
The problem of risk here appears to be a semantic one involving statistics and time. Some fevers or infections can become life-threatening, in some limited cases, if left completely untreated for too long. An allergic reaction also has certain signs and symptoms that should be monitored. It might be better to say that most allergic reactions, even ones in which there is some core effect, begin with almost zero risk of actual danger; in limited instances, the risk rises, and if treated improperly (such as in cases after taking epinephrine without following up with buffering) it could react at higher levels. Discomfort and swelling of the esophagus with an allergic reaction is a natural and routine response, and yet only in the rarest instances does the constriction become so extreme as to truly endanger life. Nobody wants anyone to stop breathing, but today we have emergency provisions for essentially every moment of allergic discomfort — not because there is a warranted risk of death, but primarily because doctors would rather not have a mess on their hands if something bad were to happen.
It would be proper to point out here the upshot of these facts: while avoiding epinephrine will almost never increase the risk of life-threatening anaphylaxis, taking epinephrine in fact almost always will increase the risk, due to the danger of rebound. But this is not what the allergist represented to me. Doctors hate to explain risk curves and factors, perhaps because they fear being misinterpreted, perhaps because they have no patience. Occasionally, they may lie outright. The allergists I have spoken to over the years have never bothered to make any of this very clear. I’d not heard of the rebound effect until that day when my ex told me to ask about it.
This is to point up the dilemma that most allergic reactions — even ones affecting the core — are never emergencies, and yet more often than not we all must now get to the emergency room, thanks to the Epi-Pen.
Both ER doctor and nurse emphasized that epinephrine is not usually a dangerous drug. It is artificial adrenaline, naturally produced in our adrenal glands. It is chemically identical, so the pharmaceutical industry can legally call it adrenaline, and the dosage is what we manufacture in our bodies every now and then whenever we experience a sudden fight-or-flight situation. Almost hit by a car? Threatened by a superior? Running for your departure gate? Fell down some stairs? If one of these things were to happen right after you ingested something you were allergic to, oddly enough, it could conceivably save your life. Epinephrine greatly increases our metabolism and as a result encourages a stronger histamine response. Though we may have the fear that we are in danger of asphyxiation, causing that necessary increase in adrenaline, in rare instances a body may not generate enough of it naturally to cause the throat swelling to go down. Because this has happened a few times to a few people, we administer epinephrine all the time to all of the people; because we cannot be trusted with syringes, it must be packaged in a very costly delivery system; and when we use this delivery system we must also go to the emergency room for further antihistamines and steroids.
If we were to use an Epi-Pen accidentally, as the ER doctor said she sometimes sees, it is arguably of no greater concern than if we accidentally cut ourselves with a kitchen knife, a common enough occurrence. But even accidentally taking epinephrine, at least in our world, still necessitates going to the emergency room. In the case of no allergic reaction, this would not truly be necessary. In the case of an allergic reaction, it is due to the danger of the rebound effect.
Part of the problem here, it seems to me, is the very fact of the emergency room. In addition to the adrenaline, what my son was given there were fluids, antihistamines, and steroids. Like adrenaline, all are generally safe things that we can, and often do, administer ourselves. Naturally, as this was a hospital, they did everything through a mainline catheter in fluid form, which offers better control over dosage (eliminating such variables as throwing up some unknown amount of the antihistamine or steroid), and so it could take effect more rapidly (eliminating such variables as the contents of the stomach that could slow down uptake of the antihistamine or steroid).
Inserting a venous catheter is probably not something everyone should need to know how to do. But taking these things in pill or liquid form after epinephrine would have a similar effect; it would merely take somewhat longer, and in case of vomiting or full/empty stomach, one would have to take into account dosage. There is, apparently, no medical danger in taking these things together. It would not endanger anyone to take a shot of epinephrine and chase it with reasonable doses of Benadryl and steroid pills. In fact, it would be exactly what one could and should do after taking epinephrine following an allergic reaction.
This is to say that in another universe, or a different America, it would be considered safe to do all of this at home, and it would be safe — and even advisable — to have all of these things available more or less over the counter. In another universe, our doctors would be more readily available over the phone without the pomp and circumstance, or perhaps we might be told by some doctors that we don’t even need them at that moment. If we knew what we were doing, in most cases it would be only for our peace of mind.
In the case of a real emergency, naturally we would jump in the car or call 911 and get to an emergency room. But how much less often in our world would that need occur, if we only had such things in our medicine cabinets? In the event of even a strong allergic reaction, could it ever happen? How many of today’s simple procedures could be safely done at home if the world were just a little different?
A tiny number of people are saved from the brink of death with the Epi-Pen. It can be argued that many more, likely thousands upon thousands of times a year, are put at unnecessary risk due to doctors’ overeagerness to protect us from ourselves by giving us the wrong sense that every allergic reaction is, ipso facto, a life-or-death situation. The truth is that most unmedicated allergic reactions are probably no more risky than crossing the street, and yet a microscopic minority are as risky as crawling across a busy highway. Closer to the point, most are similar in terms of risk to having a fever, and yet a vanishingly small number are as risky as, say, a gunshot wound to the torso. This is the case whether we go the epinephrine route or not.
I am in a logical quandary in my mind whether the “rebound” risk makes taking epinephrine perhaps more dangerous than just relaxing, throwing up a few times, going through the motions of discomfort, letting it pass, as billions of humans did in the millennia up until the 1970’s. (Naturally, we have epinephrine on hand just in case.) I say this because it seems allergy doctrine insists that epinephrine must always be followed by a three-hour stay in an emergency room for the additional drugs and observation — and this involves additional risks, not the least of which are the major threats to our autonomy.
There is an infantilizing aspect to our doctors’ tone of voice. Much has been said about bedside manner. Patients are full of layers of questions, and doctors are full of complicated answers, including misinformed ones. In most cases, not enough is said, because the harried doctor simply wants to get the discussion over with. I can understand that it would be impossible for a doctor or nurse to sit patiently over the phone or in a clinic and give a two-hour interactive discussion at a sixth-grade literacy level, on the pharmacological history of autoimmunity and justification for emergency procedure. However, many doctors wish simply to pat us on the head and tell us not to fret about our bodies. The bold ones encourage us to look it up online. And yet I have browbeaten dentists, orthopedic surgeons, allergists, and others over the years to justify, at least in capsule form, the crap they seem to be spewing, and more often than not I have found grave equivocations at the bottom of it all. This tends to happen when I research a doctor’s claims after his or her patronizing lecture and exasperated exit from the examining room. I am tempted to feel that some doctors are such busy, vicious, money-grubbing people they don’t even realize where their words are coming from.
I believe that the self interest has been institutionally channeled into a reflexive response, a kind of easy self-administering drug, a soma. This response is constructed through the regulatory morass created by big medicine. The architectural revisions are based on decades-deep layers of often conflicting medical research. Every malpractice suit helped build the edifice, and so every allegedly or truly negligent move made by every doctor through history was a stone in the huge ziggurat listed on maps as medical paraonia. I must admit that every irresponsible patient through history provided a the mortar, and that the AMA and insurance lobby have done their part by securing landmark status for the structure.
While they’re all taken care of and have left the neighborhood as millionaires, ordinary people like us have been forced to keep up the property taxes on the ziggurat all these decades, in the form of bloated insurance provisions and perversely overcautious medical procedures.
I’m sorry. I didn’t mean “vicious, money-grubbing” above in a hostile way. I meant to indicate that the doctor’s immune response described above has become a vice, a kind of drug addiction; the fact that this response happens to result in significantly greater revenue for the medical industry may simply be called a salutary side-effect of the paranoia. If there were not greater victims than the doctors, and if the doctors did not truly have their reward, I might have pity on them.
One might also call this the money problem in medicine. I don’t mean this simplistically. I mean the wool over the eyes business. I mean the thin, gluey, transparent membrane that doctors freely escape through whenever they speak to us, but that neither we nor they can easily see or comprehend. They use it whenever a patient asks a little more than they are entitled to ask or than doctors are comfortable hearing. It is in their patient tone of voice that is actually impatience, in the standing there in a relaxed posture by your bed that really means they want to get the hell over to the next room. The billed value for this expert and his body language typically far exceeds the time actually expended.
In shorthand, the money problem is in the extraordinarily bounteous compensation for an often less-than-extraordinary human mind and spirit. The field of medicine attracts generous people, but it also attracts selfish people. The fact is that that we can never tell anymore which doctors have entered this field primarily to save lives and which to make money hand over fist. Are they communicating their mandates to us out of tender concern and a Hippocratic duty to human life, or for the serious green? It is a psycho-social condition, but impossible to diagnose. It presents in these doctor-patients in exactly the same way whether they are social or selfish, and we can only treat their suffering symptomatically, by just shutting the fuck up and letting them go.
I don’t want to lose sight of the 150 lives per year ended prematurely by the tragedy of untreated anaphylactic shock. In fact, in a way I am arguing that, paradoxically, many if not all of these people lost their lives not when they failed to have an Epi-Pen or get help in time, but because of the Epi-Pen’s very existence as the modern world’s only available way to mitigate the risk. And of course when I say Epi-Pen I mean not only the little plastic spring-loaded stick but all of the mechanisms and assumptions surrounding it, spreading out as far as the eye can see, but touching nowhere near that remote provincial settlement known as autonomous care.
Something here makes me very angry: The medical priesthood is persuading me that epinephrine is a good thing, and I can certainly see great value in it. What irritates me is not the debate about epinephrine, nor even the emergency room quandary, but that the care community feels it has done its duty by giving us this little technological curiosity called the Epi-Pen. The fact is, the Epi-Pen is not epinephrine in a syringe. The Epi-Pen all on its own is a Rube Goldberg device eminently prone to failure and human error. The Epi-Pen and the complex surrounding it are not to be trusted on their own to save lives.
Doctors tell us that an Epi-Pen is good, and that two are even better. The fine print is that we are trusting the lives of our loved ones to these extremely dubious, expensive, and hard-to-find devices. They should be in our medicine cabinets, but often they are not. Or they have expired. Or there was some other mishap. This solitary device could save our lives. If that one packaged, mechanized hope should fail, we are alone, facing premature death.
From this fact screams a great hypocrisy in industrial medicine. Either it is fully committed to saving lives, or else it has failed in its duty. The Epi-Pen, not being as cheap, ubiquitous, and reliable as a disposable toothbrush, is inadequate alone in our medicine cabinets to solve the anaphylactic shock problem. In fact, because we can afford only one or at most two a year, it puts our loved ones at risk to have only that many available. After that, our child is only moments from death. Perhaps it failed, or it fired improperly. Perhaps it wasn’t where it should have been. Who can tell who was to blame? A misplaced phone, a too-late call, a wrong address, a traffic jam, a slow ambulance, and our child is lifeless. All of the life-saving epinephrine in the world is three miles away, safely locked up in a hospital or pharmacy.
We should therefore be very angry at the Epi-Pen. We should be clamoring for the right of access to the hypodermic needle, proper training in its use, and several vials of cheap, ubiquitous manmade adrenaline in every home and every neighbor’s home. Our allergists and pediatricians should be fighting for this kind of world, not the kind that now exists.
Up until now in similar arguments, people (other than the specialists I am indicting) tend to nod and agree with me. However, when I get down to the real nitty-gritty of the philosophy, I do start getting the bizarre sidelong looks, even from more or less reasonable people. You can practice that look, too, right here. Here is my outlandish thought, my prescription.
I feel that somewhere a few decades ago we lost a fundamental human right, the right to the personal power of self-determination, of personal risk. We abandoned it to the ziggurat. This risk-protection appears in the tyvek-wrapped individual candy packets for Halloween and other events, objects that tell us that we shouldn’t cook for ourselves or pass out apples to strangers or trust our neighbors anymore. It appears in all of the disposable medical packaging and its waste laws. It has drifted into the Changing of the Disposable Gloves two or three times whenever we order a Potbelly sandwich. It appears hundreds of times a day in similar things, most prevalently beginning in hermetic sealing and ending in poorly redeemable waste, but also beginning in filling a form for something we need and ending in crickets, or beginning in a nice day and ending in some numbing frustration due to yet another wayward, worthless appliance once thought of as a convenience. We are so numb to this world that we do not even notice as it hits us square in the face a hundred or a thousand times a day.
It also appears in the notion that a mere mortal can’t be trusted with a needle any more than he or she can with a gun. There is also that lock-in at the registration desk in an emergency room: if you announce your presence, though you may have a simple headache, you or your insurance (which ultimately comes back to you) are in for a bare minimum of $500. If you stay outside and take care of yourself, you are defying all of that physical and moral packaging industry. But it is relatively cold and lonely out there. Our Christmas trip for the allergic reaction billed over $4,000.
Finally, it appears with clear and present danger in the story of the medical industry’s faith in the Epi-Pen and its mechanical distrust of patients.
These are all examples of the controlled individuated processing of man’s everyday life. It begins with any given basic idea (getting lunch, parking a car, seeking medical attention), proceeds with unit necessities within those procedures (packets to microwave, transactions to swipe, forms and fields to complete, disposable catheters to tear open, brochures to feed to patients), and ends in waste, externalized byproduct, and death. All of this has evolved not for man’s benefit, only to reduce risk and increase profit. Wherever it appears to redound to mankind’s benefit, one can identify social and environmental externalities, as well as basic system losses, all of which negate most and probably all of the gross gains.
The neat little logical Russian nesting dolls that the medical industry (and every other industry) has created, where we can’t know what we can’t know, are a big part of this. What doctors and nurses were telling me yesterday without actually telling me, you see, is that the world would actually be much better off if we all learned to load a needle. Epi-Pens are too costly and too specialized. Having only one around is highly risky, and often there isn’t even one. Beyond basic first aid — an undeniable good — we really should have some other essential medical skills for things that have the potential to spiral into life-and-death situations but that in actuality are not, things that couldn’t spiral if we only knew and could do just a bit more. Doctors will violently shake their heads here and say that I’m insane, perhaps even bring me up on charges of some kind of terrorism — but sooner or later they will have to come back and admit that parts of this idea are quite sound.
Aside from what the Red Cross currently teaches, I wonder if every middle schooler might have a few hours of class time to be taught and drilled in the use of the hypodermic needle — both subcutaneous or intramuscular, what diabetes patients are taught, and intravenous, what drug abusers are taught. They should be taught how to identify situations of low blood sugar or anaphylaxis or any of the half-dozen other things that call for an injection. They should be taught not to be afraid, and such skills should feel as righteous and rewarding as driving a car. Every refrigerator should have a few vials of insulin and adrenaline, and every medicine cabinet should have a few sterile syringes. (I’ll concede that the syringes should be single-use.) In an urgent situation, one should be able to call a neighbor and get backup materials and skills in seconds. One should know how to equip a medical kit for such things. These things should be encouraged in carry-on luggage.
You can see a glimpse of the pride of having arcane knowledge in popular culture. In a dystopian movie, out in the desperate wasteland, we are often treated to an aggrandizing heroic device: the rough-and-ready protagonist is busy, sewing perfect sutures with whisky as anesthetic; administering a curative injection; or displaying other field surgical skills, often on himself (or, even better, herself). It inspires us, makes us want to be more like them — it even looks like something we could vaguely do and be proud of, like baking bread — but of course we cannot do it in the real world, because our doctor and culture forbid us, warning us that it is too dangerous. It remains, ironically, locked inside the fantasy world of the dystopian, far from utopia. But in these furtive wishes lies the frustration of mankind’s subjection to unreasonable technical controls, wishing to escape through Freudian dreams.
We are only what we are capable of. When we know nothing, we are nobodies. Whenever we surrender even more knowledge to the pushbutton, we lose a little more of our self-confidence, which is in fact our sense of self. But this pervades our world far beyond first aid and medicine. In first aid, today we are warned never, ever to tie a tourniquet, tie off and suction a snakebite wound, or move a victim with any back injury — techniques that until 30 years ago were taught to youth. It is not that this knowledge is no longer valuable, it is that in a few remote cases a few people have inadvertently caused more harm than good due to a lack of data or knowledge, and so specialists have instructed us simply to stay away from them entirely and not even to think of them. But even in the city, relinquishing this responsibility is not universally a good thing, since in many cases proper training and readiness could save a good deal of trouble and reduce risk.
These notions of the erosion of technical self-sufficiency are everywhere in our world, not only in the first-aid business. To once again become human, we must somehow venture back to that visceral world, at least know it and re-experience it somehow every now and then. There are connections here in industries as diverse as food, camping, transportation, education, dental hygiene. It is why bicycles are considered toys in most states and also why we’re morbidly obese. It rears its head when we are afraid to lift the hood of our car or even change a tire, and so we call AAA instead. We see it in the meat section of the American supermarket, since modern butchers know that we couldn’t possibly stomach the sight of a chicken or cow or pig head, much less slaughter our own meat. In fact, there are connections here to all modern human activity: it pervades our world. These restrictions pull out our self-determination and wrap it in convenient opaque packaging that would sooner suffocate us than empower us.
My New Year’s resolution is to get out there and renew my Red Cross certification. I can already hear the applause from doctors: “Yes, that’s quite charming and noble; everyone should learn how to treat for shock.” But for me this will be to build confidence for feeling bolder about the above things. What brave doctor or national medical association will risk admitting that every American should know a great deal more than CPR and how to treat for shock? Doctors should not be reading this and benignantly nodding down at me in that avuncular way that they do; they should feel threatened by it. The AMA has its standard response for dangerous nonsense like this, and I expect to be treated to it.
These instincts do not originate from isolated concerns about the medical industry: I come at this from a critical view of the entire world of technique. But it so happens that my childhood pediatrician was none other than Robert Mendelson, the so-called “medical heretic.” This is the Chicago doctor who in the 1960’s was roundly criticized by the AMA and others for saying similar things. Mendelson’s bestsellers argued that we should keep our distance from doctors and hospitals, that the only time we should ever see one is when we are keeling over.
Like Mendelson, I feel the relationship with medicine should be much more open and collegial, like a true partnership. As much as doctors claim it is, today’s medicine is only a twisted version of this. I’d really like to be able to stop in and chat for a few minutes with my neighborhood nurse or physican’s assistant, perhaps see her or him standing outside a simple storefront between the shoe-repair man and the dry cleaner. I would also have the nurse’s cell phone number, and the numbers for one or two others within a couple blocks’ walk from my house in case the nearest one is unavailable.
If I had questions about injecting my son with epinephrine and observation while buffering its effects, the nurse or PA would be just around the corner and we could practice with saline. She would certify my authorization to purchase epinephrine, syringes, steroids, and other such supplies. I’d need to stay in her good graces and out of trouble to renew these rights. And she would offer the same opportunity to all of my neighbors as well, and many neighbors would take her up on it, and we’d all know who had done so. That wouldn’t put epinephrine in every medicine cabinet, it wouldn’t free us entirely, but it would be a safe first step toward truly ubiquitous epinephrine and other life-saving remedies.
Bock SA, Munoz-Furlong A,Sampson HA. “Further fatalities caused by anaphylactic reactions to food, 2001–2006.” J Allergy Clin Immunol 2007;119:1016–8.
Ellis, A.K. “Incidence and characteristics of biphasic anaphylaxis: A prospective evaluation of 103 patients.” Ann Allergy Asthma Immunol. 2007 Jan;98(1):64-9. (Suggests correlation between too little epinephrine P = 0.048 and/or corticosteroid P = 0.06 with biphasic anaphylaxis.)
Ellis, A.K. “Priority role of epinephrine in anaphylaxis further underscored – the impact on biphasic anaphylaxis.” Ann Allergy Asthma Immunol. 2015 115(3):65. (Can’t see the abstract or article on this for some reason.)
Greenberger PA, Rotskoff BD, Lifschultz B. “Fatal anaphylaxis: postmortem findings and associated comorbid diseases.” Ann Allergy Asthma Immunol2007; 98:252–7.
Guerlain S, Hugine A, Wang, L. “A comparison of 4 epinephrine autoinjector delivery systems: usability and patient preference.” Ann Allergy Asthma Immunol. 2010 Feb; 104(2): 172–177.
Lee, JK; Vadas, P (July 2011). “Anaphylaxis: mechanisms and management.” Clinical and Experimental Allergy 41 (7): 923–38. PMID 21668816. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2011.03779.x/full
Lee, JK; Vadas, P (July 2011). “Anaphylaxis: mechanisms and management.” Clinical and Experimental Allergy 41 (7): 923–38. doi:10.1111/j.1365-2222.2011.03779.x. PMID 21668816.
Luckhurst HM, Tuthill D, Brown J, Spear E, Pitcher J. “G86 Anapen, EpiPen and Jext Auto-Injectors; Assessment of Successful Use After Current Training Package.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954079/ (Only 28% of participants were able to perform the individual device’s 10 steps correctly. Overall the trainer devices fired in 88%, with a failure rate of 2 to 30%; a clinically and statistically significant result. The Epipen’s swing and hit delivery method may affect its successful delivery compared to the Jext and Anapen’s methods.)
Marx, John (2010). Rosen’s emergency medicine: concepts and clinical practice 7th edition. Philadelphia, PA: Mosby/Elsevier. p. 15111528.ISBN 978-0-323-05472-0.
Neugut AI, Ghatak AT, Miller RL. “Anaphylaxis in the United States: an investigation into its epidemiology.” Arch Intern Med 2001; 161:15–21. (Estimated 500–1,000 deaths per year (2.4 per million) in the United States.)
Pumphrey R. “Anaphylaxis: Can we tell who is at risk of a fatal reaction?” Curr Opin Allergy Clin Immunol 2004;4:285–90. (Death from anaphylaxis is most commonly triggered by medications??? doesn’t show in this article despite in Wiki?)
Pumphrey RS. “Fatal anaphylaxis in the UK, 1992–2001.” Novartis Found Symp 2004; 257:116–28, discussion 128–132, 157–160, 276–185.
Pumphrey RS. “Lessons for management of anaphylaxis from a study of fatal reactions.” Clin Exp Allergy 2000; 30:1144–50.
Sampson HA, Mendelson L, Rosen JP. “Fatal and near-fatal anaphylactic reactions to food in children and adolescents.” N Engl J Med 1992;327:380–4. (Early administration of epinephrine within 30 min of allergen ingestion is key to preventing fatal anaphylaxis. A delay in access to epinephrine is also a prominent and consistent risk factor in fatal anaphylaxis as it seen in 80–87% of fatalities.)
Triggiani, M; Patella, V; Staiano, RI; Granata, F; Marone, G (September 2008). “Allergy and the cardiovascular system”. Clinical and Experimental Immunology. 153 Suppl 1 (s1): 7–11.doi:10.1111/j.1365-2249.2008.03714.x. PMC 2515352.PMID 18721322.
Wikipedia, Anaphylaxis article. (Approximately 2.4 per million Americans annually die from anaphylaxis episodes. Estimated 0.7-20% of anaphylactic reactions do cause death. A second dose of epinephrine rebound is required in 16% to 35% of episodes [some of these, but perhaps not all, must be rebounds].)