What is the likelihood of adverse effects if 1 milligram of intramuscular (IM) epinephrine (adrenaline) 1:1,000 is administered instead of 0.5 milligrams?

From the Guidelines

The likelihood of adverse effects is high if 1 mg of intramuscular epinephrine 1:1,000 is given instead of 0.5 mg, as this represents a significant overdose. The recommended adult dose for anaphylaxis is 0.3-0.5 mg of 1:1,000 epinephrine administered intramuscularly, as stated in the 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (GRADE) analysis 1. Doubling this dose to 1 mg substantially increases the risk of serious cardiovascular side effects including severe hypertension, tachycardia, arrhythmias, myocardial ischemia, and potentially stroke. Some key points to consider include:

• Patients may experience intense anxiety, tremors, headache, and dizziness.
• The elderly and those with pre-existing cardiovascular disease, hypertension, hyperthyroidism, or those taking certain medications like beta-blockers are at particularly high risk for adverse outcomes.
• Epinephrine has a narrow therapeutic window, and its potent alpha and beta-adrenergic effects become dangerous at higher doses.
• Healthcare providers should always verify epinephrine concentration and dosing before administration, as the difference between therapeutic and toxic doses is relatively small, as noted in the anaphylaxis-a 2020 practice parameter update 1. Additionally, the clinical practice guideline: immunotherapy for inhalant allergy also emphasizes the importance of proper epinephrine dosing, recommending 0.01 mg/kg of 1 mg/mL (1:1000), up to 0.5 mg in adults and 0.3 mg in children and teenagers 1. It is crucial to follow these guidelines to minimize the risk of adverse effects and ensure the best possible outcomes for patients.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Anaphylaxis: Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 to 0. 5 mL) intramuscularly or subcutaneously into anterolateral aspect of the thigh every 5 to 10 minutes as necessary ADVERSE REACTIONS Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory difficulties Arrhythmias, including fatal ventricular fibrillation, rapid rises in blood pressure producing cerebral hemorrhage, and angina have occurred

The likelihood of adverse effects may be increased if 1 mg of intramuscular epinephrine 1:1,000 is given rather than 0.5 mg, as the recommended dose is 0.3 to 0.5 mg. Higher doses may lead to a greater risk of adverse reactions, including cardiovascular effects such as arrhythmias, rapid rises in blood pressure, and angina. Key points to consider:

• The dose of 1 mg is twice the upper limit of the recommended dose.
• Increased risk of adverse reactions, particularly cardiovascular effects, may occur with higher doses.
• Patients with underlying heart disease or other conditions, such as hyperthyroidism, Parkinson's disease, diabetes, and pheochromocytoma, may be at greater risk of having adverse reactions 2.

From the Research

Adverse Effects of Epinephrine

The likelihood of adverse effects when administering 1 mg of intramuscular epinephrine 1:1,000 instead of 0.5 mg is a concern. Key points to consider include:

• The recommended dose of epinephrine for anaphylaxis is 300-600 µg for an adult or 10 µg/kg for a child 3
• Administering epinephrine intramuscularly is considered safer than intravenous administration, with a lower risk of cardiovascular adverse effects 4, 3, 5
• The risk of overdose and adverse cardiovascular events is significantly higher with intravenous bolus epinephrine administration compared to intramuscular administration 4
• There is no direct evidence in the provided studies comparing the adverse effects of 1 mg versus 0.5 mg of intramuscular epinephrine 1:1,000

Considerations for Administration

When administering epinephrine, consider the following:

• The method of choice for administration is by intramuscular injection with an autoinjector, mainly for reactions of intermediate severity 3
• The injection should be given in the lateral portion of the thigh and can be repeated every 10-15 minutes until there is a response 3
• Training may still be necessary in emergency care settings to minimize drug dosing and administration errors and to allay concerns about the safety of epinephrine 5