Anaphylaxis and Its Treatment

Anaphylaxis and Its Treatment

By Ian D. Brasted, BS Aug 02, 2016

This CE activity is approved by EMS World, an organization accredited by the Continuing Education Coordinating Board for Emergency Medical Services (CECBEMS), for 1 CEU upon successful completion of the post-test available at EMSWorldCE.com. Test costs $6.95. Questions? E-mail editor@EMSWorld.com.

Objectives

  • Review how to identify anaphylaxis
  • Discuss the need for all EMS providers to be able to treat anaphylaxis emergently
  • Learn how agencies are moving the scope of practice and treating anaphylaxis with a syringe and vial rather than an autoinjector

A 5-year-old approaches her mother at the convenience store counter and asks if she can pick a snack. The mother, aware of her child’s severe peanut allergy, ensures the snack doesn’t contain nuts. A few bites in, though, and the child stops chewing and tells her mother she “feels funny.” Suddenly concerned, the mother double-checks the snack’s packaging and sees the unfortunately common message: May contain traces of peanuts.

Quickly searching her purse, the mother realizes she must have left her child’s prescribed epinephrine auto-injector at home for the quick trip to the store. Knowing she does not have time to drive all the way home, she dials 9-1-1. In the next few minutes, the child begins wheezing, and her face begins to swell. As the ambulance pulls up, the child loses consciousness.

Described above is a classic presentation of an anaphylactic reaction. Anaphylaxis is a life-threatening allergic reaction that requires prompt recognition and treatment.1 Rapid-onset respiratory compromise, skin/mucosal involvement and hypotensive end-organ dysfunction are all characteristic presentations. Most anaphylactic reactions are triggered by exposure to a known or unknown allergen. Many foods, medications and insect stings are well-known culprits. Although allergen exposure did occur in the outlined case, it is not required. Nonimmunologic triggers have been identified as well. 

Symptoms of anaphylaxis are mediated by a sudden, massive release of a wide variety of inflammatory signals.2 The most common mechanism in humans involves immunoglobulin E (IgE). Classically a patient is exposed to an antigen (allergen) that activates an allergen-specific IgE. This causes a cascade response in which nearby mast cells and basophils bind the allergen to their available allergen-specific IgE.

Whether the trigger is a known allergen, unknown allergen or independent of any allergen, the result is a chain reaction of inflammation. As long as the exposure is sufficiently noxious, the mast cell or basophil degranulates, releasing multiple preformed mediators, cytokines and enzymes. The list of inflammatory mediators hypothesized to contribute to anaphylaxis is long. Major players include histamine, tryptase, platelet activating factor, tumor necrosis factor, nitric oxide and arachidonic acid metabolites. These mediators continue to aggravate nearby mast cells, basophils and eosinophils. The body initiates an inflammatory cascade, leading to diffuse cell recruitment and systemic pathology. From what may start as a local exposure, this cascade ultimately leads to a systemic response. The most common clinical presentations are outlined in Table 1. These clinical criteria are commonly used to make an initial diagnosis and have been found to be 97% sensitive and 82% specific in a retrospective cohort study of 214 emergency department patients.3 While the numbers indicate reasonable reliability, clinical judgment in recognizing anaphylaxis is key to early diagnosis.

The wide variety of possible presentations is what makes clinical judgement so important. Skin and mucosal involvement are the most common and widely recognized symptoms but can be deceptively absent in as many as 10% of cases.1 Gastrointestinal symptoms such as nausea, vomiting, diarrhea and crampy abdominal pain can mimic food poisoning. Hypotonia, syncope, incontinence and dizziness can raise concern of a neurologic event. It is important to treat anaphylaxis as a multisystem disease. The anaphylaxis patient may present as an “unconscious unknown,” and after addressing the immediately life-threatening compromise to airway or circulation, your evaluation may lead to recognition of anaphylaxis. Even more important, if you consider the nonspecific symptoms with which anaphylaxis can present, early identification can lead to treatment before it becomes life-threatening.

The cardiovascular and respiratory effects are often what cause immediate threat to life. Due to an increase in vascular permeability, fluid shift from the intravascular to extravascular space can occur within minutes, resulting in edema, respiratory arrest and circulatory collapse. This is caused in part by all of the mediators, but nitric oxide is thought to play a large role.4 In small exposures to the skin only, histamine causes urticaria (hives). In systemic release, as in anaphylaxis, histamine will increase the heart rate, lower the diastolic blood pressure and therefore increase the pulse pressure. Edema of the face and airway can exacerbate breathing difficulty caused by other inflammatory mediators, and airway compromise poses a significant risk of death. The loss of intravascular volume also results in shock, deemed anaphylactic shock. Perfusion pressure of vital organs falls. Thus, almost every organ system is potentially compromised. With diffuse vasodilation and fluid shift out of the intravascular space, end-organ damage potentially can be fatal. Such a wide variety of presentations can complicate both recognition and management.

Biphasic reactions can also complicate management. These occur when primary anaphylaxis is followed by an asymptomatic period with subsequent return of anaphylactic symptoms. Symptoms can recur anywhere from 1 to 30 hours after the initial reaction, usually in less than 12 hours. These can occur even if treatment has been provided and are why all patients who have been treated with epinephrine must go to the hospital. Biphasic reactions occur in as many as 21% of cases.5 They are a major reason for continued observation after symptom resolution.

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How Common?

Estimates of lifetime prevalence of anaphylaxis in the general population are between 0.05% and 2% in industrialized countries, more specifically 1.6% in the United States.6,7 For comparison, this is about a third of the lifetime prevalence of colorectal cancer, one of the most common cancers in the U.S.8 Many are not aware that anaphylaxis is this common. With the possibility of death within minutes of allergen exposure, this lack of awareness must be remedied.

Treatment

The local basic life support ambulance crew arrives within minutes. Although she’s unconscious and wheezing, the child’s chest is still rising and falling. After the mother explains what happened, an EMT checks the child’s mouth for any remaining food. This ensures removal of any trigger the child didn’t spit out. The other reaches for the pediatric epinephrine auto-injector, which is quickly administered to the child’s lateral thigh. In the 5 minutes it takes to load the patient into the ambulance and begin transport to a nearby emergency department, the child’s condition continues to worsen. A second auto-injector is administered. The crew begins to ventilate the patient with a bag-valve mask and oxygen.

For an EMS call for an allergic reaction, after ensuring there are no potential threats to the crew, patient care must begin with a rapid assessment of the patient’s airway. If respiratory arrest (apnea) is present, support ventilations and consider intubation if available. Stridor and wheezes may be the initial symptoms, and epinephrine is the first line of treatment with no absolute contraindications if anaphylaxis is identified.1 Intramuscular administration in a location that minimizes the chance of accidental injection directly into circulation is ideal, most commonly to the anterolateral thigh.

Epinephrine treats symptoms of anaphylaxis on multiple levels. First, it is a potent alpha-1 adrenergic agonist, and it vasoconstricts and increases the peripheral vascular resistance. This increases blood pressure and reduces mucosal edema, especially relevant in alleviation of upper airway obstruction. Epinephrine’s beta-1 adrenergic effect increase inotropy and chronotropy, improving cardiac output by increasing heart rate and stroke volume. It additionally directly bronchodilates and decreases release of inflammatory mediators, which is a beta-2 adrenergic effect.9

Because epinephrine has so many systemic effects, its list of potential adverse reactions is long. They include tachycardia, anxiety, headache, tremor and palpitations. This is due to epinephrine being a potent activator of the human “fight or flight” response. Humans, along with many other animals, release endogenous epinephrine in life-threatening situations.

While epinephrine is lifesaving in anaphylaxis, use caution in certain patient populations. First, those with cardiovascular disease are at risk. Anaphylaxis itself can cause coronary artery vasoconstriction, but epinephrine augments this effect. Therefore, patients with high-risk atherosclerosis of the coronary arteries are at risk for acute myocardial infarction. Patients who’ve had recent brain surgery, uncontrolled hypertension or aortic aneurysm are also at risk due to epinephrine’s ability to increase blood pressure. Last, patients with coingestion of stimulants (cocaine or amphetamines, for example) are at risk of adverse events. In all of these cases, the risk of anaphylaxis is significant, and epinephrine should still be given. One choice for high-risk patients would be to give half of the usual dose: 0.15 mg in an adult, repeated as needed, instead of a full 0.3 mg initially.

Accidental IV administration of a relatively large concentrated dose of epinephrine can be fatal. This is why care is taken to ensure the IM dose is not injected intravascularly. In common IM training for paramedics and nurses, the plunger on the syringe is withdrawn before the injection is completed to assure the needle is not in a vessel. Obviously this is not done with an auto-injector, so select the injection site carefully. A suggestion is the anterolateral thigh, where there are few large blood vessels.

Following the rapid administration of epinephrine, there are many adjunct therapies for patients in anaphylactic shock. Since these patients are often hypotensive due to loss of intravascular volume, patient positioning is paramount. Patients will be most comfortable supine, or with their head slightly elevated for respiratory comfort. Some suggest Trendelenburg positioning, believing this will maximize venous return to the heart and perfusion of vital organs, although this likely does not offer significant benefit.10

When ALS or hospital care is involved, place at least one large-bore IV catheter (14- to 18-gauge for an adult) for fluid resuscitation. In hypotensive patients, large fluid boluses are indicated. Normotensive patients should receive fluids at slower rates due to the possibility of worsening disease. Medications including steroids and histamine blockers are given to reduce the derangement in immunological response. All providers should administer supplemental oxygen either through nasal cannula or a nonrebreather to maintain adequate saturation and ensure a reserve of oxygen in case respiratory distress worsens.

Epinephrine Auto-Injectors

Upon arrival at the ED, the child’s blood pressure has plummeted precipitously. She receives additional epinephrine, along with other medications. Her blood pressure quickly improves, and respirations became less labored. Soon the child regains consciousness. She is admitted to the hospital for a night of observation to ensure a second reaction does not occur.

When the EMTs return to their ambulance, they discuss what might have gone wrong and why their epinephrine auto-injectors didn’t work. Upon further deliberation, they recall that a couple years ago, their department budget was reevaluated, and the cost of annually replacing expired auto-injectors was deemed excessive. As the EMTs cleaned up from the call, they checked the remaining auto-injectors—indeed, their epinephrine had expired.

The gold standard in treatment of anaphylaxis is IM injection of epinephrine. Epinephrine auto-injectors like the EpiPen are a widely recognized and easily used method of administration. An auto-injector generally includes a plastic case, some form of spring-loaded needle, trigger mechanism and solution of epinephrine. The head of the device is pressed firmly against the desired injection site, and the needle is automatically pushed forward. There are two commercially available sizes, a 0.3-mg adult size and a 0.15-mg pediatric size for patients under 66 lbs (30 kg). The ideal dose is 0.01 mg of epinephrine per kilogram of patient weight; this leads to a medically acceptable underestimation of the safe appropriate dose for most patients.

The needle length of a standard EpiPen is reported to be 14.3 mm. In practice this appears slightly less when measured. Regardless, the subcutaneous tissue depth in a variety of patients may preclude these from actually deploying their epinephrine intramuscularly because in many patients, particularly women, the tissue depth at the anterolateral thigh is greater than 14 mm.11 The clinical relevance of this remains questionable, but interestingly, most EMS educational materials teach that for an adult, the needle for an intramuscular injection should be at least 25 mm, or 1–1½ inches long.

The generally accepted shelf life of epinephrine if appropriately stored is around 18 months, at which point the solution should be replaced. This holds true for epinephrine auto-injectors such as the EpiPen.12 After 18 months medically significant amounts of epinephrine may be present, but the exact amount is less certain.13 The expiration date on a medication is not a suggestion, it is concrete. Medical directors or chiefs cannot authorize medications to be used past their manufacturer-approved date of expiration. It is likely that the expired auto-injectors no longer contained enough epinephrine to reverse the symptoms of anaphylaxis.

The majority of BLS ambulance services that choose to stock epinephrine for anaphylaxis use auto-injectors, either because they are easy to use and require minimal training or to minimize dosing errors.16,17 Unfortunately, ease of use is not without its drawbacks. Although the epinephrine contained within each auto-injector is cheap and generic, the auto-injector mechanism has been patented and is proprietary. Three of the most common auto-injector brands include EpiPen (Mylan Inc., Canonsburg, PA), Adrenaclick (Amedra Pharmaceuticals, Horsham, PA) and Auvi-Q (Sanofi-Aventis U.S., Bridgewater, NJ).

The price tag has increased steadily each year without much variance between brands. A review of pharmaceutical retailers in 2016 reveals the cost of an EpiPen two-pack is now over $900. In 2001 the price was under $35 per unit. With that price increase and a shelf life of less than 18 months, it becomes easier to understand why an EMS department may make the poor decision to forgo replenishing auto-injectors. This price also makes it less likely for auto-injectors to be used even when indicated.18

History and Cost of Epinephrine

The catecholamine epinephrine was discovered and purified from the adrenal gland before the term hormone existed and was first synthesized in a laboratory by 1904.14 It has a long history of pharmaceutical use. It has been generic for decades, meaning its formula is no longer proprietary.

Epinephrine is a relatively unstable molecule, and heat and oxygen exposure will degrade it rather quickly, even stored in a relatively stable environment, and likely more quickly in an ambulance or EMS bag. Though shelf life is limited, a generic solution of epinephrine is easily and cheaply manufactured. According to the International Drug Price Indicator Guide, the cost of wholesale epinephrine ranges from $0.15 to $0.95 per milliliter.15 At appropriate concentration (1:1,000, or 1 mg/mL), the 0.3 mg of epinephrine in an adult EpiPen is contained in approximately 0.3 mL of solution. Although cost can vary considerably by manufacturer, this indicates the cost of epinephrine contained in each adult auto-injector is considerably less than $1. With this theoretically low cost, the decision by our hypothetical EMS department to discontinue EpiPen replacement sounds unreasonable.

Alternatives to the Auto-Injector

The high and steadily rising price of auto-injectors does not mean the need for IM epinephrine administration is falling. More recent bodies of literature suggest quite the opposite. The World Allergy Organization’s estimate of anaphylaxis (between 0.05% and 2%) may be lower than actual lifetime prevalence.19–21 With possible increases in both prevalence and cost of treatment, there has been rising interest in less expensive treatment.

Healthcare professionals with adequate training can draw epinephrine from a vial or ampule using a needle and syringe. This has historically been limited to paramedics, nurses and physicians. Basic emergency medical technicians (EMT-Bs), with fewer training hours than paramedics, are more often restricted.

While an auto-injector is a simple device to deploy, it may not be as simple to deploy correctly. Multiple studies have demonstrated errors in administration, including risk to the person deploying the device. If the auto-injector is accidentally reversed, the needle can strike the thumb of the deployer, piercing as deep as the bone or joint.22,23 While this would seem counterintuitive, the spring-loaded mechanism and the inherent “pop” it makes as it deploys may also contribute to a fear of using these devices.

An alternative is a syringe-access epinephrine program. One example is called “Check and Inject.” This pilot program began in King County, WA. Success there has led to expansion within Washington and emulation in other states, including New York. Such checklist-based alternative programs attempt to mimic the benefits of auto-injectors (ease of use, minimizing chance of dosing error) by supplying everything needed for epinephrine administration in a ready-made kit: clear checklist instructions, a vial of epinephrine at the appropriate concentration, a 1-mL syringe and a packaged safety needle. The New York program even includes a custom “Epi Safe” syringe with clear labeling of adult vs. pediatric volumes. In many of these programs, rather than replacing the entire kit when the epinephrine expires, the vial can be easily removed and exchanged. In King County, the kit costs about $10 without epinephrine, and each vial of epinephrine can be replaced for about $2.50.24 Many states have reported a variety of other ways to deal with rising costs of proprietary methods of administration. Most still rely on auto-injectors for BLS ambulances.

EMS providers and fire departments are the natural targets for pilot training programs like Check and Inject. They are first responders, making them first-line in administration of lifesaving therapies like epinephrine in the face of anaphylaxis. Paramedics are already trained to use needle, syringe and vial. For this reason, much of the potential economic gain in the use of alternatives depends on EMTs and the BLS ambulances they staff.

The appropriate place for the use of less-expensive alternatives is currently in the hands of those with adequate training—not in the hands of the lay public. The purpose of programs like “Check and Inject” is to balance economic benefit and safety, creating something between the proprietary auto-injector and generic syringe and vial. As has been shown in the pilot programs across the country, the risk of dosing and administration error can be minimized by creating a specialized kit.

The general public also spends a great deal on auto-injectors because standard guidelines suggest they be prescribed to anyone who has experienced an anaphylactic reaction.1 Appropriately, most programs aimed to supply alternatives require some experience in the healthcare field. Appreciation for treatment side effects and minimizing the possibility of dosing error are very important for epinephrine. Unfortunately, that has not deterred some members of the general public from acquiring their own needles, syringes and epinephrine solution.22

It is important for people who follow this route to ensure they have both proper training and potent epinephrine. If they choose to prefill syringes, these must be changed out frequently because of loss of potency over time. Some estimates suggest a prefilled syringe is clinically potent for only three months.25 The fact that the price of auto-injectors has driven those untrained to seek out potentially dangerous alternatives is strong indication of the need for other options.

Some people have also resorted to purchasing auto-injectors from Canada and bringing them into the U.S. Currently an EpiPen there costs $100 (Canadian) and may be purchased across the counter at any pharmacy. However, while these are the same devices sold in the U.S., the Canadian devices may not be stocked on ambulances in the U.S.

In addition to raw economic savings, the pilot program in King County has seen a dramatic increase in appropriate use of epinephrine. With an EpiPen, it appeared EMTs were occasionally hesitant to administer in cases where epinephrine would have been beneficial. Per the professional standards manager for King County EMS, James Duren, appropriate usage under the Check and Inject program increased from 40% to 98%.24 It is not possible to tell whether this increase is due to the decreased cost, comfort with the syringes, fear of the auto-injector or additional training.

Syringe-access epinephrine programs like the one in King County are not unique. At least 13 states currently train some EMT-Bs in methods of epinephrine administration other than the auto-injector. Some used prefilled syringes, some vials, and some ampules. Some programs are in pilot phases, not yet not statewide. This interest in operationally and fiscally prudent, medically driven intervention is a clear demonstration of the professionalism of EMS—finding a financial problem and developing an operationally sound training program to overcome it, while assuring patient care is not jeopardized.

Alternate Reality

Consider an alternative sequence of events in our anaphylactic 5-year-old. Instead of an EMT reaching for an expired auto-injector, they grab a plastic box. The contents of the box include a syringe with custom markings specific to pediatric vs. adult dosing, a needle and a vial of epinephrine replaced just a few months prior. While it takes a few seconds longer for the first dose of epinephrine to be administered, the dose and location are correct. The EMT has received extra training and uses an instructive checklist. The additional time for administration does not matter except in the most extreme cases.24 Within minutes the child’s respirations become less labored, and her blood pressure rises. During transport to the ED, her condition continues to improve. After additional medications and a few hours of observation in the ED, she and her mother are sent home with a new auto-injector prescription.

As the EMTs drive away, they discuss their department’s switch from the auto-injector to the epinephrine kits a couple years back. The additional training seemed easy at the time. They didn’t have to worry about which end of the auto-injector to use, or about having a spring release with a “pop.” Drawing up the medication went without a hitch, and giving the injection in the lateral thigh was just as easy as it was in training. Saving nearly $2,000 per ambulance seemed like a good idea when they first discussed it and made even more sense today.

Medical Director Reminders

  • Always check medications on board your ambulance for expiration dates and replace per policy.
  • Follow your local, regional and state protocols and work within your scope of practice.
  • If you believe your agency would benefit from a syringe-access program, share this article with your training officers and medical directors.

Conclusion

All EMS providers must be able to treat anaphylaxis. This means immediate access to epinephrine that can be given IM. The lack of reasonably priced generic alternatives to expensive treatments has long been a problem in more areas of medicine than just emergency medical services.

Epinephrine for the treatment of an anaphylactic reaction is relatively unique in that only the auto-injection method of administration is proprietary. While auto-injectors are a perfect solution for the lay public, EMS professionals, both paid and unpaid, are able to learn to use syringes safely. This opens the doors for creative solutions, of which Check and Inject is one example. Syringe-access epinephrine programs can alleviate the problem of EMS reliance on auto-injectors and are a much more financially reasonable option. Easing the financial burden of supplying epinephrine will ensure it is more widely available on ambulances. With widespread availability and additional training for EMS providers, patient care can only improve.

References

1. Simons FE, et al. World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis. WAO Journal, 2011; 4: 13–37.

2. Kemp SF, Lockey RF. Anaphylaxis: A review of causes and mechanisms. J Allergy Clin Immunol, 2002; 110(3): 341–8.

3. Campbell RL, et al. Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients. J Allergy Clin Immunol, 2012; 129(3): 748–52.

4. Mitsuhata H, Shimizu R, Yokoyama M. Role of nitric oxide in aphaphylactic shock. J Clin Immunol, 1995; 15(6): 277–83.

5. Lee S, Bellilio MF, Hess EP, et al. Time of onset and predictors of biphasic anaphylactic reactions: a systematic review and meta-analysis. J Allergy Clin Immunol Pract, 2015 May–Jun; 3(3): 408–16.

6. Lieberman P, Camargo CA Jr., Bohlke K, et al. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol, 2006 Nov; 97(5): 596–602.

7. Wood RA, et al. Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol, 2014; 133(2): 461–7.

8. American Cancer Society. Key statistics for colorectal cancer, http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics.

9. Simons KJ, Simons FE. Epinephrine and its uses in anaphylaxis: current issues. Curr Opin Allergy Clin Immunol, 2010 Aug; 10(4): 354–61.

10. Johnson S, Henderson S. Myth: the Trendelenburg position improves circulation in cases of shock. CJEM, 2004; 6(1): 48–9.

11. Song T, et al. Subcutaneous tissue depth differences between males and females: The need for gender based epinephrine needle. J Allergy Clin Immunol, 2004; 113(2): S241.

12. Electronic Medicines Compendium. EpiPen Adrenaline (Epinephrine) Auto-Injector 0.3mg, https://www.medicines.org.uk/emc/medicine/26974.

13. Simons FE, Gu X, Simons KJ. Outdated EpiPen and EpiPen Jr. autoinjectors: past their prime? J Allergy Clin Immunol, 2000 May; 105(5): 1,025–30.

14. Henderson J. Ernest Starling and ‘Hormones’: an historical commentary. J Endocrinol, 2005; 184(1): 5–10.

15. International Drug Price Indicator Guide. Epinephrine, https://www.msh.org/resources/international-drug-price-indicator-guide.

16. Stecher D, et al. Epinephrine auto-injectors: Is needle length adequate for delivery of epinephrine intramuscularly? Pediatrics, 2009; 124(1): 65–70.

17. Lippert WC, Wall EJ. Optimal intramuscular needle-penetration depth. Pediatrics, 2008; 122(3): e556–63.

18. Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis: a statement of the World Allergy Organization. WAO Journal, 2008; Suppl 2: S18–S26.

19. Clark S, et al. Frequency of U.S. emergency department visits for food-related acute allergic reactions. J Allergy Clin Immunol, 2011; 127(3): 682–3.

20. Nowak RM, Macias CG. Anaphylaxis on the other front line: perspectives from the emergency department Am J Med, 2014; 127(1 Suppl): S34–S44.

21. Dudley LS, Mansour MR, Merlin MA. Epinephrine for anaphylaxis: underutilized and unavailable. Western J Emerg Med, 2015; 16(3): 385–7.

22. Simons FE, Lieberman PL, Read EJ Jr., Edwards ES. Hazards of unintentional injection of epinephrine from autoinjectors: a systematic review. Ann Allergy Asthma Immunol, 2009 Apr; 102(4): 282–7.

23. Simons FE, et al. Voluntarily reported unintentional injections from epinephrine auto-injectors. J Allergy Clin Immunol, 2010; 125(2): 419–23.

24. Aleccia J. King County drops EpiPen for cheaper kit with same drug. Seattle Times, http://www.seattletimes.com/seattle-news/king-county-drops-epipen-for-cheaper-kit-with-same-drug/.

25. Swetlitz I. High price of EpiPens spurs consumers, EMTs to resort to syringes for allergic reactions. Stat, https://www.statnews.com/2016/07/06/epipen-prices-allergies/.

26. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy andAnaphylaxis Network symposium. J Allergy Clin Immunol, 2006 Feb; 117(2): 391–7.

After he completed an undergraduate degree at Oregon State University, an interest in medicine drew Ian D. Brasted, BS, to Albany Medical College, where he is now a third-year medical student.  

Matthew C. Ruppel, DO, is an emergency medicine resident at Albany Medical Center in Albany, NY. His medical interests include airway management, resuscitation and EMS.

 

 

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