46: Pharmacologic treatments for anaphylaxis

In this episode I’ll review the pharmacologic treatments for anaphylaxis.
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Definition

Anaphylaxis is a potentially fatal allergic reaction with a rapid onset. Immunoglobulin E (IgE)-mediated allergic reactions to food, insect stings and medications are the most common triggers for anaphylaxis. As a result of the IgE reaction, mast cells release histamine and other mediators of anaphylaxis. If not properly treated, it will progress to respiratory arrest and cardiovascular collapse.

Diagnostic criteria

According to World Allergy Organization guidelines, anaphylaxis is highly likely when any one of the following three criteria is fulfilled:

1. Acute onset of an illness (within minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized urticaria, itching or flushing, swollen lips-tongue-uvula) AND AT LEAST ONE OF THE FOLLOWING: A) Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) B) Reduced blood pressure or associated symptoms of end-organ dysfunction (eg. hypotonia [collapse], syncope, incontinence)

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (within minutes to several hours) A) Involvement of the skin-mucosal tissue (eg, generalized urticaria, itch-flush, swollen lips-tongue-uvula) B) Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) C) Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) D) Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

3. Reduced blood pressure after exposure to known allergen for that patient (within minutes to several hours) A) Infants and children: low systolic blood pressure (age-specific) or greater than 30% decrease in systolic blood pressure B) Adults: systolic blood pressure of less than 90 mm Hg or greater than 30% decrease from that person’s baseline

Treatment of anaphylaxis

Epinephrine, IV fluids, and airway management are the main treatments for anaphylaxis.

Epinephrine

Epinephrine is the drug of choice for anaphylaxis.  Epinephrine has no absolute contraindications to use in the treatment of anaphylaxis. Epinephrine stabilizes mast cells, prevents or reverses obstruction to airflow in the upper and lower respiratory tracts and prevents or reverses cardiovascular collapse. Intramuscular (IM) injection is the preferred route of administration for the treatment of anaphylaxis.

Several different preparations of epinephrine are available – take care to select the correct one!   The epinephrine preparation for intramuscular injection contains 1 mg per mL and will also be labeled as epinephrine 1:1000.

The recommended adult dose of epinephrine (1 mg per mL) is 0.3 to 0.5 mg per single dose, injected IM into the mid-outer thigh. If needed, this dose may be repeated every 5 to 15 minutes. Occasionally patients with extreme anaphylactic reactions do not adequately perfuse muscle tissue and therefore do not respond well to IM injection of epinephrine.  If this occurs, administer epinephrine via an infusion pump at a rate of 2 to 10 mcg /minute (or 0.1 mcg / kg / minute).

Glucagon

For patients who are receiving beta-blockers, epinephrine’s effectiveness will be blunted, and hypotension and bradycardia may persist despite administration of epinephrine. If this occurs, glucagon is an attractive option due to it’s inotropic and chronotropic effects that are not mediated through beta-receptors.  A dose of 1 to 5 mg in adults given IV over five minutes followed by an infusion of 5 to 15 micrograms per minute is recommended.  Overly rapid administration of glucagon will induce emesis.

Adjunctive treatment

Treatment of anaphylaxis with medications other than epinephrine is not supported by evidence. Rationale for adjunctive treatments are extrapolated from other disease states such as urticaria or asthma.  The following four adjunctive treatments are commonly used despite lack of evidence for their benefit:

H1 antihistamines

H1 antihistamines such as diphenhydramine or cetirizine relieve itching and urticaria. They have no effect on any of the life-threatening symptoms of anaphylaxis.

H2 antihistamines

H2 antihistamines such as famotidine or ranitidine given with an H1 antihistamine may provide some additional relief of hives.  They have no effect on any of the life-threatening symptoms of anaphylaxis.

Glucocorticoids

Glucocorticoids have an onset of action that is measured in hours and are therefore not helpful in the acute treatment of anaphylaxis.  They have been routinely given to patients with anaphylaxis with the hope of preventing biphasic, late phase, or protracted anaphylaxis but evidence of effect is lacking.

Bronchodilators

Albuterol may be used to treat bronchospasm that persists despite administration of epinephrine.  Remember that mucosal edema is not reversed by albuterol – the alpha-1 adrenergic effects of epinephrine are required for this.

Drug disease interactions

As a pharmacist, I find fascinating the idea that medications may interact with the disease state of anaphylaxis.

Angiotensin converting enzyme (ACE) inhibitors

Angiotensin II production is a normal compensatory response to anaphylaxis.  Expect patients who develop anaphylaxis while on ACE inhibitors to have particularly profound hypotension.

Beta-blockers

Beta-adrenergic blockers may make anaphylaxis more resistant to treatment by blocking the bronchodilator and cardiovascular effects of epinephrine.  Glucagon (discussed above) is recommended in this scenario.

Pitfalls in anaphylaxis treatment

The successful treatment of anaphylaxis revolves around timely administration of an adequate dose of epinephrine.  Here are 3 pitfalls to watch out for:

1. Any delay in administration of epinephrine.

2. Thinking that medications other than epinephrine are adequate to treat anaphylaxis.

3. Errors in epinephrine administration due to multiple/confusing dosage forms. The Pharmacy Nation Slack group is a free group with other pharmacists from around the world collaborating with each other using real-time messaging to help better care for patients. I invite you to join me and the over 120 other Pharmacy Nation members there. You can sign up at pharmacynation.org.

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If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.

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