Epinephrine and its Use in Anaphylaxis: Current Issues

Keith J. Simons; F. Estelle R. Simons

Disclosures

Curr Opin Allergy Clin Immunol. 2010;10(4):354-361. 

In This Article

Practical Pharmacology of Epinephrine

The pharmacology of epinephrine is summarized in Table 1.[1,2,8•,12]

Beneficial Effects

In patients with anaphylaxis, epinephrine has potent life-saving alpha-1 adrenergic vasoconstrictor effects on the small arterioles and precapillary sphincters in most body organ systems.[1] Through vasoconstriction, it decreases mucosal edema, thereby preventing and relieving upper airway obstruction and increases blood pressure, thereby preventing and relieving shock. Its beta-1 adrenergic effects lead to increased rate and force of cardiac contractions. Its beta-2 effects lead to increased bronchodilation and decreased release of histamine, tryptase, and other mediators of inflammation from mast cells and basophils.[1]

Routes of Administration

The pros and cons of epinephrine administration through various routes are summarized in Table 2.[1,8•,12–18,19•,20•] Intramuscular injection into the mid-anterolateral aspect of the thigh is recommended as the initial route of choice in most[4,5] but not all[6] anaphylaxis guidelines. Epinephrine has a vasodilator effect in skeletal muscle,[1] which facilitates rapid absorption into the central circulation and prompt pharmacologic effects.[12–16]

In contrast, the powerful vasoconstrictor effect of epinephrine injected into subcutaneous tissue potentially delays epinephrine absorption from this site and onset of pharmacologic effects.[1] This delay may be clinically relevant in anaphylaxis.[17]

Intravenous infusion of epinephrine is occasionally needed in the community, for example, when a patient with anaphylaxis in a physician's office does not respond to intramuscular epinephrine or experiences profound hypotension or shock. An intravenous bolus dose is needed if cardiorespiratory arrest has occurred. In such patients, paradoxically, venous access might be difficult. Iatrogenic overdosing through the intravenous route is not uncommon, contributing to the perception that epinephrine has a narrower benefit-to-risk ratio when injected intravenously than when given by other routes in anaphylaxis.[16,20•]

Intrinsic Limitations

Soon after epinephrine was introduced for clinical use, its intrinsic pharmacologic limitations became apparent (Table 1). It cannot be given orally, as swallowed epinephrine is metabolized by catechol-o-methyltransferase in the wall of the gastrointestinal tract and by monoamine oxidase in the gastrointestinal tract wall and in the liver.[1] Regardless of the route of administration, epinephrine has a short duration of action and a narrow therapeutic index; that is, its benefits cannot be separated from its adverse effects.[8•,12,15] It also has biphasic pharmacologic effects; for example, a low dose might have the opposite effect to that which is intended and might lead to vasodilation and increased release of mediators of inflammation.[1,12] In addition, epinephrine formulations in solution for injection have a short shelf-life (typically 12–18 months) and epinephrine degradation products are inactive.[12]

Adverse Effects

Mild transient pharmacologic effects such as pallor, tremor, anxiety, palpitations, headache, and dizziness occur within minutes after epinephrine injection.[12–15] These effects confirm that a therapeutic dose has been given (Table 1). Serious adverse effects such as pulmonary edema or hypertension potentially occur when epinephrine is given in overdose by any route, most commonly after an intravenous bolus injection, an overly rapid intravenous infusion, or an erroneous intravenous injection of a 1 mg/ml (1 : 1000) epinephrine solution instead of an appropriately diluted 0.1 mg/ml (1 : 10 000) epinephrine solution.[4,5,16,20•]

Epinephrine and the Heart

The heart is underrecognized as a target organ in anaphylaxis. Mast cells are present throughout the myocardium, between muscle fibers, around blood vessels, and in the coronary artery intima. In patients with coronary artery disease, mast cells are also present in the atherosclerotic plaques, where they contribute to atherogenesis.[21] Histamine, leukotrienes, platelet-activating factor, and other mediators of inflammation released after mast cell stimulation potentially lead to coronary artery spasm.[21] Patients of any age, including children, with anaphylaxis can present with angina or myocardial infarction due to vasospasm.[22,23•] In middle-aged or elderly patients, these acute coronary syndromes potentially occur either through vasospasm or through acute plaque rupture and thrombus formation.[22,23•]

Some patients taking beta-adrenergic blockers or angiotensin-converting enzyme (ACE) inhibitors are at increased risk of severe or fatal anaphylaxis.[24,25•] In an observational study of 962 patients with stinging insect venom allergy, 21% of whom developed severe systemic allergic reactions defined as shock, loss of consciousness, or cardiopulmonary arrest, ACE inhibitors were identified as one of the significant risk factors for severe anaphylaxis.[25•]

In middle-aged or elderly patients who might have sub-clinical coronary artery disease and in patients with diagnosed coronary artery disease, concerns about the potential cardiac effects of epinephrine should be weighed against the cardiac risks of untreated anaphylaxis. In these patients, it is important to remember that epinephrine injection usually enhances blood flow in the coronary arteries through its beta-2 adrenergic actions, which leads to increased myocardial contractility and increased duration of diastole compared with systole (Table 1).[1,8•] There are no absolute contraindications to epinephrine use in anaphylaxis.

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