Why is epinephrine (adrenaline) administered intramuscularly (IM) while other medications are given intravenously (IV) in the treatment of anaphylaxis?

From the Guidelines

Epinephrine is administered intramuscularly (IM) in the treatment of anaphylaxis because it provides a more rapid increase in plasma and tissue concentrations of epinephrine compared to subcutaneous injection, and it is the recommended route by strong international consensus, as stated in the 2024 American Heart Association and American Red Cross guidelines for first aid 1.

Key Points

• The intramuscular route is preferred over subcutaneous injection because it allows for faster absorption of epinephrine into the bloodstream, which is critical in the treatment of anaphylaxis 1.
• The recommended dose of epinephrine for anaphylaxis is 0.01 mg/kg, up to a maximum of 0.3 mg, and it should be administered into the lateral thigh muscle (vastus lateralis) 1.
• Epinephrine autoinjectors are available in fixed doses of 0.15 mg and 0.30 mg, and the choice of dose depends on the patient's weight, with 0.15 mg recommended for children weighing 10-25 kg and 0.30 mg for those weighing 25 kg or more 1.
• The administration of epinephrine via the intramuscular route is crucial in the first-aid treatment of anaphylaxis, as it allows for prompt and effective treatment, which can be life-saving in severe cases 1.

Administration Considerations

• Epinephrine should be administered as soon as possible after the onset of anaphylaxis symptoms, and repeated doses may be necessary every 5-15 minutes if symptoms persist or worsen 1.
• The use of epinephrine autoinjectors can facilitate prompt treatment, especially in community settings, and education on their use is essential for effective management of anaphylaxis 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action Epinephrine acts on both alpha and beta-adrenergic receptors. 12. 2 Pharmacodynamics Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid [see Warnings and Precautions 5-(5.3)]. Epinephrine causes mydriasis when administered parenterally. 12.3 Pharmacokinetics When administered parenterally, epinephrine has a rapid onset and short duration of action.

The reason epinephrine is administered intramuscularly (IM) in the treatment of anaphylaxis is not explicitly stated in the provided drug labels. However, it can be inferred that the rapid onset of action when administered parenterally, as mentioned in the pharmacokinetics section, may be a factor in the choice of administration route.

• Key points:
  • Rapid onset of action when administered parenterally
  • Short duration of action However, without direct information on why IM is preferred over IV, no conclusion can be drawn regarding the specific reason for this choice 2.

From the Research

Administration of Epinephrine in Anaphylaxis

• Epinephrine is administered intramuscularly (IM) in the treatment of anaphylaxis, as it is the first-line treatment and has no absolute contraindications to its use 3.
• The intramuscular route is preferred over subcutaneous injection, with the lateral aspect of the thigh being the site of choice, as it allows for faster absorption of epinephrine into the bloodstream 4, 5.
• The reasons for administering epinephrine IM rather than intravenously (IV) are not explicitly stated in the provided studies, but it can be inferred that IM administration is preferred due to its faster absorption and higher peak plasma concentrations compared to subcutaneous injection 4, 6.
• Alternative routes of administration, such as intranasal, sublingual, and inhaled, are being investigated, but currently, IM epinephrine remains the standard of care for anaphylaxis treatment 3, 7.

Pharmacokinetics of Epinephrine

• The pharmacokinetics of epinephrine autoinjectors have been studied, and the results show that intramuscular injection leads to faster peak plasma concentrations (Cmax) and higher area-under-curve (AUC) values compared to subcutaneous injection 6.
• The dose of epinephrine also affects its pharmacokinetics, with higher doses leading to higher Cmax and AUC values 6.
• The time to reach peak epinephrine concentrations (Tmax) is typically around 5-10 minutes and 30-50 minutes for the two discernable Cmax's identified in most studies 6.