>> Identify the different types of anaphylaxis.
>> Learn the pathophysiology and the leading causes of anaphylactic reactions.
>> List methods of treatment for anaphylactic incidents.
Allergen: An environmental substance that can produce a hypersensitive allergic reaction in the body but may not be intrinsically harmful.
Anaphylactic reaction: An acute allergic responses triggered by IgE-mediated antigen-stimulated mast cell activation resulting in histamine release.
Anaphylactic shock: A severe and sometimes fatal systemic allergic reaction to a sensitizing substance, such as a drug, vaccine, specific food, serum, insect venom or chemical.
Anaphylaxis: An exaggerated, life-threatening hypersensitivity reaction to a previously encountered antigen.
Basophil: A granulocytic white blood cell that represent 1% or less of the total white blood cell count. The relative number of basophils increases in severe allergic reactions.
Bronchodilation: A widening of the lumen of the bronchi, allowing increased airflow to and from the lungs.
Mast cells: A constituent of connective tissue containing large basophilic granules that contain heparin, serotonin, bradykinin and histamine.
Paramedics responding to a school cafeteria for a respiratory distress call encounter a 7-year-old male patient with a known allergy to peanuts, who lapsed into acute respiratory distress after he had nibbled on a snack bar that contained peanuts.
His chief complaint to the school nurse was tightening in the throat, which quickly progressed to a chief complaint of shortness of breath. He was only able to speak three or four word phrases, and his respiratory rate climbed to 44 by the time the EMS crew arrived on scene.
The young patient soon became unresponsive, apneic and grossly cyanotic. Paramedics introduced bag-valve-mask (BVM) rescue breathing. Because the patient’s allergy history was known, he was also quickly administered epinephrine via the intramuscular (IM) route while peripheral IV access was obtained. Because of his shock state, it was difficult to gain peripheral vein access, so an EZ-IO needle was placed via the intraosseous (IO) route in his left proximal tibia. Diphenhydramine was then given via IO, and BVM assistance was continued.
His initial oxygen saturation measured 33%. After approximately one minute of BVM oxygenation, oxygen saturation improved to 80%. Nebulized albuterol and ipratroprium bromide were then introduced to the BVM circuit and delivered to the patient. Paramedics consulted with a base hospital physician, and an order for epinephrine via IO was given. Shortly after the IO epi was administered, the patient’s oxygen saturation increased to 92%, and transport was initiated.
Anaphylaxis refers to a rapidly developing allergic reaction that can affect a number of the body’s systems at once. Severe anaphylactic reactions can be fatal and happen within minutes. Anaphylactic reactions can happen so suddenly and become severe so rapidly that there have been examples of hospital inpatient deaths.
Many patients can suffer minor allergy symptoms; however, some can react in a more rapid and accelerated manner that can result in severe shock and, often, death. Substances injected into, or ingested by, an individual gain access into the bloodstream and can trigger anaphylaxis. A reaction involving the skin, lungs, nose, throat and gastrointestinal tract can then result.
Severe cases of anaphylaxis can occur within seconds or minutes of exposure and be fatal if untreated or not treated fast enough. Most anaphylactic reactions are less severe and can be ended with prompt medical attention or EMS and ALS interventions.
Approximately 1,500 deaths are reported annually from anaphylaxis. Causes for anaphylaxis can be divided into four major subtypes: food, drugs, latex reaction and insect stings. Largely depending on the substance, the chance of anaphylaxis after exposure to a substance has been from less than 1% to up to 10%.
The physiology of anaphylaxis and its leading causes can be divided into two major groups. The first group is commonly related to the production of Immunoglobulin E (IgE). The body produces IgE when it’s exposed to an allergen. The production of IgE causes the body to become sensitized to the allergen. Further exposures to the allergen by a sensitized individual may result in anaphylaxis. The severity of the anaphylactic reaction is difficult to predict. This group is referred to as IgE-mediated anaphylaxis.
IgE-mediated anaphylaxis results when basophils and mast cells in tissue and blood become coated with IgE. Basophils and mast cells release substances, known as mediators (largely histamines), which can cause allergic reactions. Subsequent reexposure to allergens can cause an explosive release of these mediators and IgE, resulting in an anaphylactic reaction.
Common IgE-mediated causes include medications, such as penicillin, cephlosporins and anesthetics. Insect stings, including fire ants, wasps, honey bees and hornets, are common causes. Other common causes are foods, such as peanuts, shellfish, eggs, milk and wheat. Vaccines, hormones, latex and animal proteins round out other common causes of IgE-mediated anaphylaxis.
The second group, called non-IgE-mediated anaphylaxis, or anaphylactoid reactions, are similar to IgE-mediated reactions, except they don’t require an IgE-immune reaction.
These types of reactions are thought to result in the commonly unexpected anaphylactic reactions that require 9-1-1 services because of the sudden development of anaphylactic shock. In these cases, no previous sensitivity is required, and the signs and symptoms are no different from IgE-mediated anaphylaxis. It’s difficult to distinguish the difference between the two groups. They are usually most easily differentiated by the attainment of the patient’s history. However, treatment is no different for either group. Common non-IgE-mediated causes of anaphylaxis include non-steroidal anti-inflammatories, narcotics, muscle relaxants and gamma gobulin, X-ray dyes, preservatives, sulfites, and physical exercise.
These reactions occur during intense, prolonged and strenuous exercise and often after eating prior to exertion. In some cases, the cause can be idiopathic. Up to 25% of non-IgE mediated anaphylactic reactions can be idiopathic. Often, IgE-mediated anaphylaxis can be confused with non-IgE-mediated anaphylaxis because the victim most likely was unwittingly sensitized to previous exposures, (i.e., they had previously been bitten or stung by an insect or eaten food with hidden allergens).
Because anaphylaxis affects almost all human systems, reactions of this type are almost always categorized as severe. The severity of the reaction will vary from person to person. The more rapidly the signs and symptoms of anaphylaxis develop, the more likely a severe reaction will result. Subsequent reactions to the same trigger often result in similar reactions; however, this doesn’t necessarily incline the person to a non-IgE-mediated reaction.
Signs & Symptoms
An underlying history of asthma or any type of allergic disease, such as eczema, rhinitis or multiple environmental allergies, doesn’t increase the risk of IgE-medicated anaphylaxis, but it does increase the risk of non-IgE-mediated anaphylaxis and can be more difficult to treat. The risks of anaphylaxis may decrease over time, but a person who’s known to be at risk should always be prepared for the worst. Many patients usually have refillable prescriptions from their doctors for such products as EpiPen Auto-Injectors and usually have oral diphenhydramine nearby.
The symptoms of anaphylaxis can occur within seconds of exposure or can take an hour or more. The earliest symptoms are often related to changes in the skin, including hives and itching—especially in the groin and armpits. Flushing of the skin, often with a patchy appearance, coupled with a complaint of warmth is common. These symptoms are often accompanied by a feeling of impending doom, rapid and often irregular pulses, and increased anxiety. Continued symptoms include swelling of the throat and tongue, resulting in hoarseness, as well as difficulty breathing and swallowing. Sneezing, wheezing and runny nose all increase difficulty breathing. Vomiting, diarrhea and abdominal cramping may also develop.
In more severe cases—about 25% of all anaphylactic reactions—the mediators flood the bloodstream and cause gross capillary vasodilatation and a subsequent drop in blood pressure, lightheadedness and loss of consciousness, resulting in anaphylactic shock. The speed and severity of the reaction indicate the treatment needed to mitigate the anaphylaxis. The effects of the treatment often lead to the three following outcomes:
>> Signs and symptoms are sometimes mild enough and recognized early enough, and they often fade when self-treated;
>> Signs and symptoms don’t subsequently recur from this type of exposure; and
>> Treatment is rendered, and improvement of the signs and symptoms is seen; however, symptoms may recur in four to 12 hours. This late phase reaction requires further treatment and close observation, and it can occur in about 10% of the cases. About 20% of anaphylactic reactions are severe enough and persistent enough to require intense EMS treatment and hospitalization. Let’s take a look at a few more cases.
Case Presentation No. 2
While visiting a remotely located zoological garden, a 23-year-old man was stung by an insect, presumed to be some type of bee or wasp. Although the insect wasn’t seen, the man found the stinger and removed it quickly after being stung. The man rapidly developed hives, experienced difficulty breathing and complained of his throat feeling tight and swollen. Nearby zookeepers summoned onsite first-aid personnel, who administered oxygen and called 9-1-1.
On arrival, paramedics find the patient supine on a park bench being cared for by park first-aid personnel. They tell the crew that the patient has had no previous history of allergic reactions, and no knowledge of having been stung by a bee before. The patient is observed by the crew to be flushed (red faced) and lethargic. Audible and auscultated wheezing is heard.
The patient’s initial blood pressure taken by the first-aid crew was 100/60. Paramedics recheck the blood pressure and find it to now be 80/40. His pulses are thready with a rate of 130 bpm corresponding with an ECG rhythm of sinus tachycardia, and his oxygen saturation is measured at 70%.
The paramedic crew quickly administers 0.3 mg of epinephrine 1:1,000 IM while they prepare for IV access. The patient becomes unresponsive, and his blood pressure is no longer obtainable. The ECG rhythm remains sinus tachycardia at a rate of 150 bpm. No pulses can be now felt. IO vascular access is quickly obtained, and the paramedic’s base hospital physician quickly orders epinephrine 1:10,000 (0.1 mg) via IO. Chest compressions and BVM ventilations are initiated.
The patient is placed on a spine board, and advanced airway equipment is readied. After two minutes of chest compressions and ventilations, pulses can now be felt at the carotid artery. An ECG shows a sinus tachycardia with a heart rate of 130 bpm and blood pressure of 100/64. The patient remains unresponsive; however, respiratory effort is spontaneous and wheezing is clearing, with oxygen saturation at 88%. While the crew prepares for transport, the patient regains consciousness but remains disoriented.
Treatment for anaphylactic reactions includes oxygenation, airway support, and medications, such as nebulized albuterol or ipratroprium. Additional medications, including epinephrine, diphenhydramine, dopamine and dosed fluid boluses, may also be required. CPR is often necessary. Maintenance of a patient’s oxygenation levels and airway support are of primary concern. Maintaining oxygen levels is often the key to successful resuscitation efforts, although it may present one of the largest challenges.
All patients suffering from anaphylaxis should be placed on supplemental oxygen as soon as possible, and maintenance of oxygen saturation should be monitored. Development of severe wheezing, increased bronchial secretions, and swollen or inflamed respiratory anatomy, increases the need for supplemental oxygenation. Management of the airway with advanced airway devices may initially present a challenge. Basic management may be required until the actions of delivered medications have a chance to reduce the airway obstacles.
The focus of the resuscitative efforts for anaphylactic reactions should be largely directed at mitigating the anaphylactic process. It’s important to provide inline nebulized medications, including albuterol and ipratroprium, via a device that will ensure proper delivery, such as handheld oxygen-powered nebulizer devices, nebulizer mask configurations or devices placed within the BVM circuit.
Careful consideration should be given to the use of fluid boluses or aggressive fluid infusions to treat the hypotensive effects of anaphylaxis. The presence of clear lungs may be an indication to use fluid to help increase volume and preload to aid in the resuscitation of hypotension and also dilute the histamine boluses within the bloodstream. Normal saline solution is ordinarily preferred; however, it’s important to be wary of fluid shifts because they may have medical implications. Selecting an alternative fluid may be more helpful. Epinephrine, a sympathomimetic with both alpha and beta effects, has actions that include bronchodilation (beta-2) and vasoconstriction (alpha). Actions on the heart include increased heart rate (beta-1, chronotropic), contractility (inotropic), atrial-ventricular conduction and automaticity (dromotropic).
Onset of actions usually occurs when administered via IV or when IM is one to two minutes with duration of action of five to 10 minutes. IM route action occurs in about five to 10 minutes, with a duration of action of one to four hours. Dosages for IM routes are usually 0.3 mg of a 1:1,000 concentration and 0.1mg of 1:10,000 concentration for IV or IM routes. These dosages are common for anaphylactic reactions.
Many people with a known history of allergic or anaphylactic reactions carry an EpiPen Auto-Injector. Most EpiPens deliver a 0.3 mg dosage of epinephrine via the IM route when the device is pressed against the injection site. Devices often carried by children deliver an IM dosage of 0.15 mg of epinephrine. First responders should consider the dosage administered and an estimation of the time when it was injected when assessing patients with anaphylactic reactions.
Another primary prehospital medication that’s helpful with resuscitation of anaphylactic reactions is diphenhydramine hydrachloride. A common brand name, Benadryl, is a potent antihistamine. The action of diphenhydramine results when it binds to histamine receptor sites, blocking the effects of histamines.
Notable onset of action is 15–30 minutes and can last from six to 12 hours. Preferable routes during an anaphylactic emergency include IM, IV and IO. It should be noted that the subcutaneous route has been abandoned in the prehospital setting for the delivery of injectable medications for anaphylactic reactions where capillary stability in the dermis during an anaphylactic reaction is often compromised and uptake of medications is delayed. Corticosteroidal and steroidal medications are also used in the prehospital setting; however, these medications aren’t considered resuscitative. Onset of action for these medications is considered outside the resuscitative window; however, it’s believed to reduce the chances of recurrence or late phase reactions.
Use of these medications for anaphylactic reactions is typically considered during a post resuscitative, planned therapeutic regimen to aid in recovery and prevention of anaphylactic reactions. Corticosteroid, often referred to as the “sooner the better” therapy deployed in the prehospital setting, has seen positive outcomes for patients who have suffered an anaphylactic reaction. However, it’s not clearly known whether the administration of the drug in the prehospital setting is more beneficial than delivery of the drug after emergency department (ED) admission.
Albuterol (Proventil and Ventolin) is a potent sympathomimetic bronchodilator (beta-2 specific). Albuterol works by relaxing bronchial smooth muscles by stimulating beta-2 adrenergic receptors, producing bronchodilation, relieving bronchospasm and decreasing airway resistance. Onset of action occurs in about five minutes, peaks in about an hour and lasts up to five hours. Initial dosage (usually in combination with ipratroprium) is 6 mL (0.083%) via nebulizer.
Ipratroprium bromide (Atrovent) is an anticholinergic bronchodilator. It works as an antagonist on the actions of acetylcholine. It prevents the interaction of acetylcholine with muscarinic receptors in bronchial smooth muscle, causing bronchodilation. The effects also cause drying of respiratory tract secretions with an onset of action within 15–30 minutes, peaking in one to two hours and lasting about four to five hours. Adult dosage (usually in combination with albuterol) is 2.5 mL (0.02%) via nebulizer. Dopamine hydrocholoride (Intropin) is a sympathomimetic vasopressor with both alpha and beta properties. In low and medium dosages, it selectively dilates blood vessels supplying the brain, kidneys, heart and gastrointestinal tract. At medium to high doses, it can increase cardiac output by improving contractility and stroke volume, with a resulting increase in blood pressure.
At high dosages it causes vasoconstriction and an increase in heart rate. Onset of action occurs in less than five minutes and duration is approximately 10 minutes after drug administration has stopped. First responders should quickly assess patients suffering from anaphylactic reactions and institute appropriate interventions as the needs are identified. Information about the history of the situation is extremely helpful in these situations, so seek out anyone who witnessed the event or who was able to discuss the problem with the patient before the patient became incapacitated.
Often, as in the first case presentation, the patient has a known allergy and felt the risk of exposure was less than they actually experienced. In this case, the wrapper from the snack food was retained, and first responders were able to quickly identify the allergen. Treatment focused on the mitigation of the anaphylactic reaction with emergency interventions for the symptoms that required them.
Timing is important, especially when there are delays from the time of exposure to the time 9-1-1 is summoned and first responders encounter the patient with anaphylaxis. Many people, not knowing they have been exposed or being exposed with no previous history of problems, dismiss the initial signs and symptoms. Unfortunately, the signs and symptoms progress so rapidly that help may be out of reach for a period of time, which could be detrimental to their chances of survival.
Case Presentation No. 3
A 53-year-old female with previous exposures to bee stings with no reactions was meeting friends for a horseback ride. She stopped to clear a small tree that had fallen across her path. As she moved toward the obstruction, she was stung by a wasp near her left temple. She quickly brushed the wasp away and cleared the tree from the trail.
While she was returning to her horse, she remarked to her friends that she felt dizzy. She dismissed the feeling, took three more steps toward her horse and collapsed. Her friends realized she lapsed into an unconscious state and was not breathing well, so they placed her in a supine position in the bed of a pickup truck and called 9-1-1 to request an EMS unit meet them at the nearest rendezvous location. The responding EMS crew was BLS and there were no nearby first responder services. Because of the remote location, 20 minutes elapsed from the time of the exposure to the arrival of the BLS ambulance.
On arrival, the EMS crew finds the female without a pulse and not breathing. CPR is initiated and an immediate transport to the nearest hospital, approximately 30 minutes away, is initiated. An ALS ambulance is dispatched to intercept the BLS ambulance near the halfway point to the destination hospital. Cardiac arrest algorithms are followed for asystole by the ALS crew during transport. The patient was delivered to the hospital approximately 50 minutes after the sting, where a return of spontaneous circulation was achieved.
The patient in this case had an expired prescription for an EpiPen Auto-Injector. The patient’s friends had no knowledge of the patient’s previous exposures or risk factors. The situation was further compounded by the lack of available ALS services and the remote location. People with known exposures or allergies are usually counseled for preparedness, uses of medications and availability of special kits to carry with them. They’re also usually counseled about best practices to avoid exposures, including sharing information with others to help decrease the risks
Patient No. 1 was admitted to the hospital for observation and completely recovered. He was discharged home 24 hours later with his parents and with appropriate education and direction including carrying use of an Epi Pen. Patient No. 2 was admitted to the hospital for observation and recovery of anoxic brain syndrome. He was released after three days of care without any significant or noticeable effects and direction to have an Epi Pen available at all times. Patient No. 3 was admitted to the Medical Intensive Care Unit and subsequently succumbed after absence of brain function was discovered and life support terminated by her family. The family has since made Epi Pen products available in and around their ranch and vehicles.
EMS should educate the public that it’s always better to contact them when an exposure is identified rather than allow the signs and symptoms to progress untreated. Everyone should take precautions should the unexpected anaphylactic reaction occur.
1. Tintinalli J, ed. Tintinalli’s Emergency Medicine: A comprehensive study guide 4th edition. McGraw-Hill: New York, (209–211), 2011.
2. Neumar R, Otto C, Link M, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;11(122):S729–S767.
3. San Diego County Paramedic Association: Protocol and Medication Guide. 2011–2012 ed. SDCPA: La Mesa, Calif.