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Table 7 Epinephrine (Adrenaline): First-Line Medication for Anaphylaxis Treatment

From: World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis

Strength of Recommendationsa B-C (As Defined in Footnote)a
Pharmacologic effects when given by injectionb At alpha-1 adrenergic receptor
  Increases vasoconstriction and increases vascular resistance (in most body organ systems)c
  Increases blood pressure
  Decreases mucosal edema in the airways
  At beta-1 adrenergic receptor
  Increases cardiac contraction force
  Increases heart rate
  At beta-2 adrenergic receptor
  Decreases mediator release
  Increases bronchodilation
Clinical relevance Increases blood pressure and prevents and relieves hypotension and shock
  Decreases upper airway obstruction, eg. in larynx
  Decreases urticaria and angioedema
  Decreases wheezing
Potential adverse effects after the usual epinephrine dose of 0.01 mg/kg of a 1:1,000 (1 mg/mL) solution intramuscularlyd (to a maximum of 0.5 mg [adult] or 0.3 mg [child]) Pallor, tremor, anxiety, palpitations, dizziness, headache; these symptoms indicate that a pharmacologic dose has been injected
Potential adverse effects after epinephrine overdose (eg. overly rapid intravenous infusion, intravenous bolus dose, or dosing error, eg. intravenous administration of an undiluted 1:1,000 (1 mg/mL) solutione) Ventricular arrhythmias, hypertension, pulmonary edema; note that the heart itself is a potential target organ in anaphylaxis; therefore, acute coronary syndromes (angina, myocardial infarction, arrhythmias) can also occur in untreated anaphylaxis in patients with known coronary artery disease, in those in whom subclinical coronary artery disease is unmasked, and even in patients (including children) without coronary artery disease in whom the symptoms are due to transient vasospasm
Reasons why the intramuscular route is preferred over the subcutaneous route for initial treatment of anaphylaxis Epinephrine has a vasodilator effect in skeletal musclec; skeletal muscle is well-vascularized; after intramuscular injection into the vastus lateralis (mid-anterolateral thigh), absorption is rapid and epinephrine reaches the central circulation rapidly; rapid absorption is important in anaphylaxis, in which the median times to cardiorespiratory arrest are reported as 5 minutes (iatrogenic, eg. injected medication), 15 minutes (stinging insect venom), 30 minutes (food)
Reasons for apparent lack of response to epinephrine Error in diagnosis, patient suddenly stands or sits (or is placed in the upright position) after epinephrine injection; rapid anaphylaxis progression; patient taking a beta-adrenergic blocker or other medication that interferes with epinephrine effect; epinephrine injected too late; dose too low on mg/kg basis; dose too low because epinephrine is past expiry datef; not enough injection force used; route not optimal; injection site not optimal; other
  1. aLevels of evidence are defined as: A: directly based on meta-analysis of randomized controlled trials or evidence from at least one randomized controlled trial; B: directly based on at least one controlled study without randomization or one other type of quasi-experimental study, or extrapolated from such studies; C: directly based on evidence from non-experimental descriptive studies such as comparative studies, or extrapolated from randomized controlled trials or quasi-experimental studies.
  2. bIntramuscular epinephrine injection is preferred in the initial treatment of anaphylaxis for the reasons listed above. Subcutaneous epinephrine injection causes local vasoconstriction that potentially leads to delayed absorption. If epinephrine is given by metered-dose inhaler, it is difficult to inhale the 20-30 puffs needed to achieve high plasma/tissue epinephrine concentrations and systemic effects. Epinephrine is occasionally administered through an endotracheal tube, or by face mask and compressor, or topically for mucosal edema and obstruction in the oropharynx and larynx. Epinephrine given orally is ineffective because of rapid metabolism in the gastrointestinal tract.
  3. cEpinephrine has a vasodilator effect in skeletal muscle. It also enhances blood flow in coronary arteries due to increased myocardial contractility and increased duration of diastole. These actions are well-recognized effects of endogenous epinephrine in the "fight or flight" response.
  4. dThe maximum initial intramuscular dose of epinephrine in anaphylaxis (0.3-0.5 mg) of a 1:1,000 (1 mg/mL) solution is lower than the 1 mg dose recommended for initial use in cardiopulmonary resuscitation. The intramuscular dose is unlikely to be effective if anaphylaxis has progressed to shock or cardiac arrest.
  5. eIdeally, epinephrine should be administered intravenously only by physicians who are trained, experienced and equipped to give vasopressors through infusion pump and titrate the dose frequently, based on continuous monitoring of blood pressure and cardiac rate and function.
  6. fEpinephrine in solution potentially degrades rapidly if exposed to heat and light.
  7. Adapted from references [2, 3, 13, 14, 22, 23, 3032, 3941, 88, 89, 9799, 104, 116].