When time is of the essence: Recognizing and treating anaphylaxis

Early administration of epinephrine is the BLS and ALS treatment for an anaphylactic reaction to an allergen


Anaphylaxis is a life-threatening allergic reaction to specific triggers such as foods, medications, insect venom, or latex. As many as 40.9 million people in the United States suffer from severe allergies that may put them at risk for anaphylaxis [1].

The number of reported anaphylaxis cases in the U.S. rose from 5,700 in 1999, to 7,700 in 2009 [2]. While death from anaphylaxis is relatively rare, about 60-80 cases are reported annually. Many of these occur in hospitals and are a result of medication reactions.

Since an allergic reaction can become an anaphylactic reaction in only a few minutes, it is essential that EMS providers understand the basic pathophysiology behind such a reaction, recognize its signs and symptoms quickly, and initiate appropriate treatment that will benefit the patient and not cause harm.

An anaphylactic reaction to a bee sting. (Image Greg Friese)
An anaphylactic reaction to a bee sting. (Image Greg Friese)

The immune system response to an allergen

The immune system is responsible for detecting potentially infectious agents and clearing them from the body. It consists of several highly specialized tissues and organs, such as the thymus gland, spleen, appendix, tonsils, bone marrow and adenoids, as well as a circulatory system that is separate from the cardiovascular system.

There is also a circulation system that is separate from the cardovascular system. Lymphatic vessels and lymph nodes carry lymph, a clear fluid containing white blood cells. Lymph circulates throughout body tissues. The lymphatic vessels collect and direct lymph back into the blood circulation. Lymph nodes are located throughout the lymphatic vessels and are the site of the initial attack of the immune system against infectious agents.

Bone marrow located within the hollows of large bones produces specialized cells called lymphocytes that circulate within the lymph. The two major types of lymphocytes are B cells, which originate in the bone marrow, and T cells, which begin in the thymus.

B cells produce antibodies that circulate in the blood and lymph streams and attach to foreign antigens to mark them for destruction by other immune cells. They make up what is known as antibody-mediated or humoral immunity. The antibodies that B cells produce are specialized proteins that are highly specific to target a given antigen, or foreign protein.

T cells, also found in blood and lymph, mark and attack diseased cells they recognize as foreign. They are responsible for cell-mediated or cellular immunity. T cells regulate and coordinate the overall immune response.

Antibodies belong to a class of proteins called immunoglobulin. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM.

Of these, the IgE antibody is the one responsible for the majority of allergic reactions. Researchers have found that allergy sufferers have 10 times as much IgE in their blood as people without allergies [3]. This hypersensitivity to allergens (antigens that elicit an allergic response) can lead to a potentially devastating series of events.

Anaphylaxis: When anitbodies go wild

When IgE is released, it circulates through the blood and lymph. Other specialized cells of the immune system called mast cells and basophils are located in specific parts of the body, such as the respiratory and gastrointestinal (GI) tract. When IgE contacts these cells, they release a variety of chemicals that include histamine.

Normally, histamine stimulates two receptors found within the body. H1 receptors cause bronchoconstriction and increases movement through the GI tract. H2 receptors cause peripheral vasodilation and the release of gastric acid. Combined, these reactions reduce the chances of more antigens entering the body, and remove them from the body more quickly. Histamine also causes the body to release its water into the interstitial space, to help bring more white blood cells to the site of infection.

This process goes into overdrive during an allergic reaction. People with allergies appear to release a much larger amount of histamine than normal. The H1 and H2 receptor sites are overstimulated, causing such reactions as runny or stuffy nose, sneezing, wheezing, and watery and itchy eyes.

If the reaction worsens, multiple body systems are affected, including the cardiovascular, respiratory, gastrointestinal and skin. Patients can develop hives or urticaria, which can be very itchy as fluid shifts into the sublayers of the skin.

There is also the release of a chemical called slow-reacting substance of anaphylaxis, or SRS-A. SRS-A greatly increases histamine effects and causes bronchial spasms, resulting in wheezing and difficulty breathing during severe allergic reactions.

Signs of an anaphylactic reaction

In a severe allergic reaction or anaphylaxis, the body is overwhelmed by its own immune response which leads to:

  • Hypotention
  • Hypoxia
  • Altered mental status

The allergen usually reaches the bloodstream very quickly, and circulates widely throughout the body. This is why intravenous medications and chemicals are often the cause of severe anaphylaxis, as well as hymenoptera – the class of insects that includes sawflies, wasps, bees, and ants – stings.

During an anaphylactic reaction massive amounts of fluid shift out of the vasculature and into the interstitial space. The relative volume loss from the shift, along with massive peripheral vasodilation cause blood pressure to drop quickly. The patient's heart attempts to compensate for the decreasing blood pressure and increasing hypoxia by increasing its rate and contractility.

Major swelling can occur in the patient's facial, neck and upper and lower airway tissues, compromising the airway and making it harder to breathe. The GI system is overstimulated as well, causing nausea and possibly vomiting to occur.

Anaphylaxis treatment by EMTs and paramedics

As in other disease processes, the faster anaphylaxis sets in, the less likely the body can compensate and the more likely it will be fatal. Treatment must occur quickly in the form of rapid, aggressive support of the airway, breathing and circulatory status of the patient, and administering epinephrine as early as possible.

The body produces epinephrine naturally through the adrenal glands. Epinephrine increases heart rate (chronotropy) and contractility (inotropy). It also constricts the peripheral vascular system. These effects combine to raise blood pressure. Epinephrine also causes the bronchioles to dilate, improving airflow to the alveoli.

EMS providers should weigh the benefits and risks of epinephrine, as they do for any medication, before administration. Side effects of epinephrine include: 

  • myocardial irritability
  • increased myocardial oxygen consumption and
  • an increased risk of infarction.

However, for a patient with life-threatening signs of anaphylaxis (hypotension, hypoxia, altered mental status), epinephrine’s benefits to improving cardiac output and bronchodilate far outweighs its risk. In a position paper, the National Association of EMS Physicians (NAEMSP) indicates that EMS personnel must have the capability to administer epinephrine in a timely manner [4].

Epinephrine is administered as 0.3 – 0.5 mg of 1:1,000 dose intramuscularly. Epinephrine may be given intravenously, using a 1:10,000 concentration. Follow your local protocols to administer additional doses of epinephrine if the patient's anaphylaxis symptoms return – a rebound reaction – or vasodilation and bronchoconstriction are not improved three to five minutes after the initial dose.

Antihistamines, such as diphenhydramine (Benedryl), block the effects of histamine on the receptor sites. Diphenhydramine blocks both H1 and H2 receptor sites. Administer 25 – 50 mg of diphenhydramine either intramuscularly or intravenously.

In addition to epinephrine and antihistamines, a patient with signs of hypotension should be given volume replacement. Several boluses of 250 – 500 mL of normal saline or lactated ringers may be needed to help preserve circulating volume.

Auscultate lung sounds frequently for possible fluid overload. An inhaled beta agonist such as albuterol will also help reverse the bronchospasm associated with the allergic reaction.

Corticosteroids can help during the recovery from an anaphylactic reaction by reducing the inflammatory response. This class of drug includes methylprednisone, hydrocortisone and dexamethasone.

Reassess and transport

It's important to note that the beneficial effects of epinephrine, while quick, are short lived. Epinephrine is rapidly broken down by the body; ongoing assessment of vital signs, oxygenation and ventilation must be continuous. EMS providers may need to administer a second dose of epinephrine while waiting for the longer-lasting effects of diphenhydramine or corticosteroids to begin.

In very severe cases of anaphylaxis, massive swelling of the airway's soft tissue may require immediate transport by basic level EMS providers to the closest receiving facility for surgical intervention. Paramedics may perform a needle or surgical cricothyrotomy to preserve the airway if pharmacologic interventions are not successful.

References

1. Neugut AI et al. Anaphylaxis in the United States: An investigation into its epidemiology. Arch Intern Med. 2001;161(1):15-21.

2. Ma L et al. Case fatality and population mortality associated with anaphylaxis in the United States. J Allergy Clin Immunol 2014 Apr; 133:1075.

3. Kay AB. Allergy and allergic diseases: first of two parts. N Engl J Med 2001;344:30-37

4. Jacobson RC and MIllin MG. The use of epinephrine for out-of-hospital treatment of anaphylaxis: resource document for the national association of ems physicians position statement. Prehosp Emerg Care. 2011 Oct-Dec;15(4):570-6.

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