Introduction
Accidental intravenous (IV) epinephrine administration is a rare but serious medical event that can occur in various healthcare settings. Epinephrine, commonly known as adrenaline, is a hormone and medication used to treat severe allergic reactions (anaphylaxis), cardiac arrest, and other life-threatening emergencies. While epinephrine is a life-saving intervention, unintentional IV administration can lead to adverse effects and complications. This article highlights the causes, risks, and preventive measures associated with accidental intravenous epinephrine administration.
What Is Epinephrine?
Epinephrine, also known as adrenaline, serves dual roles as a hormone and a neurotransmitter in the body. Produced and released by the adrenal glands, situated atop the kidneys, it functions as a hormone. As a neurotransmitter in the central nervous system, epinephrine acts as a chemical messenger, facilitating the transmission of nerve signals between nerve cells, muscle cells, or gland cells. Playing a crucial role in the sympathetic nervous system, part of the body's emergency response to danger, epinephrine is associated with the well-known "fight-or-flight" response. This physiological reaction is medically termed the acute stress response.
Epinephrine belongs to compounds known as catecholamines, including norepinephrine and dopamine. The name is derived from a specific molecule in their structure. In its hormonal role, epinephrine is synthesized from norepinephrine within the adrenal gland.
How Is the Dosage of Epinephrine Calculated?
Epinephrine, administered through injection, comes in two concentrations: 1:1,000 for intramuscular use and 1:10,000 for intravenous use. The labeling of epinephrine is unique, expressing the concentration in a non-traditional ratio format, such as parts per 1,000 (1 gram per 1,000 milliliters, or 1 mg/mL), rather than the more common percentage concentration (grams per 100 milliliters). Epinephrine does not adhere to current FDA labeling requirements due to its use predating the 1938 Food, Drug, and Cosmetic Act. Consequently, the formulation for intramuscular use (1 mg/mL) is ten times more concentrated than that for intravenous administration (0.1 mg/mL). To enhance clarity, it is recommended to explicitly state on the label the precise amount in conventional units (such as mg/mL) present in the solution.
What Are the Recommended Uses and Doses for Administering Epinephrine?
As per guidelines from the American Heart Association and a joint task force practice parameter published in the Journal of Allergy and Clinical Immunology, the recommended treatment for anaphylaxis involves administering epinephrine (1:1,000) at a dose of 0.3 to 0.5 mg intramuscularly (IM) in adults (0.3 to 0.5 mL) and 0.01 mg/kg IM (up to 0.3 mg) in children. This dosage can be repeated every five to ten minutes until clinical improvement is evident. Subcutaneous administration of epinephrine is no longer advised, as intramuscular administration in the thigh achieves faster peak plasma concentrations. Prefilled autoinjectors are available for convenient use, delivering 0.3 mg for adults and 0.15 mg for children weighing 15 to 30 kg directly into the thigh.
For patients showing signs of anaphylactic shock with severe hypotension and hypoperfusion, intravenous administration of epinephrine (1:10,000) may be necessary. The recommended intravenous doses are 0.1 mg in adults and 0.01 mg/kg in children (up to the adult dose), administered slowly over five minutes. In some cases, an intravenous infusion at rates of 1 to 4 µg/min in adults may be initiated to avoid the need for repeated epinephrine injections.
During cardiac arrest, epinephrine (1:10,000) is administered intravenously as a bolus at a dose of 1 mg in adults and 0.01 mg/kg in children (up to 1 mg), with repetition every three to five minutes.
What Factors Contribute to Mistakes in Dosing or Other Errors When Administering Epinephrine?
Several factors contribute to errors in dosing or administering epinephrine. Confusion often arises about the correct dose, formulation, and method of giving epinephrine. Some hospital "crash carts" mistakenly stock the intravenous formulation meant for cardiac arrest, causing delays when a patient with anaphylaxis needs the more concentrated intramuscular version. Many doctors find calculating and converting doses accurately challenging, especially in stressful situations. In a survey, half of 150 hospital physicians struggled to convert epinephrine doses correctly.
Physicians may lack sufficient knowledge about the right dose and concentration for anaphylaxis. Another survey of 253 radiologists found that none could provide the correct dose, concentration, and administration route for epinephrine. Some would have given an overdose. Miscommunication among team members caring for a critically ill patient can lead to the wrong administration route (intravenous instead of intramuscular). A review of anaphylaxis cases revealed a 2.4 percent incidence of life-threatening complications due to improper epinephrine administration, including cases of inadvertent intravenous use.
These errors result from various factors, including insufficient physician knowledge, a lack of intramuscular doses in emergency carts, complicated dose calculations, and poor communication between physicians and nurses. Additionally, some hospitals need prefilled syringes with intramuscular epinephrine, which contributes to mistakes. Malfunctions in infusion pumps during continuous infusion can also lead to inappropriate intravenous epinephrine administration.
What Are the Negative Effects Associated With Accidentally Administering Too Much Epinephrine?
When intravenous doses of epinephrine are too high, it can lead to increased heart rate (tachycardia) and elevated blood pressure (hypertension). In cases of short-term exposure, these effects may resolve on their own without causing harm to organs. The body quickly breaks down epinephrine and has a short duration of action (around two minutes). However, if exposure is prolonged through continuous infusion, both adults and children may experience prolonged cardiovascular toxicity.
What Are the Treatment Considerations for an Unintentional Overdose of Epinephrine?
In managing patients who have taken too much epinephrine, as with any critically ill individual, the primary focus is to ensure control of the airway, breathing, and circulation. Continuous monitoring of the heart and regular blood pressure checks are crucial. An electrocardiogram (ECG) should be performed to detect any signs of heart muscle ischemia.
For patients displaying evidence of heart muscle ischemia, inadequate blood flow to organs, heart failure, fluid accumulation in the lungs (pulmonary edema), or persistent severe high blood pressure or rapid heartbeat, the consideration of administering an antidote becomes important. Phentolamine, a nonselective alpha-blocker, can be given intravenously at doses of 5 mg for adults and 1 mg for children to counteract constriction in peripheral and coronary arteries. In cases of persistent rapid heartbeat, a short-acting, heart-specific beta-blocker like Esmolol may be an option, but this should be used sparingly. It is essential to avoid beta-blockade without simultaneously administering Phentolamine or another vasodilator to prevent the risks associated with unopposed alpha-adrenergic stimulation.
Conclusion
In conclusion, accidental intravenous (IV) administration of epinephrine poses a rare but serious risk in healthcare settings. The unique concentration labeling and potential for confusion contribute to dosing errors, emphasizing the need for clear communication and labeling practices. While guidelines exist for proper epinephrine administration, surveys reveal challenges among healthcare professionals, such as inaccurate dosing calculations and appropriate routes. Unintentional overdose can lead to adverse effects, especially in prolonged exposures. In the event of an overdose, immediate management involves maintaining the airway, breathing, and circulation, with considerations for antidote administration such as Phentolamine.
