From the Guidelines
Epinephrine is the first-line medication for cardiac arrest because it increases coronary and cerebral perfusion through its alpha-adrenergic vasoconstricting effects. During cardiac arrest, the standard dose is 1 mg IV/IO every 3-5 minutes. Epinephrine works by binding to alpha-1 receptors in peripheral blood vessels, causing vasoconstriction that increases aortic diastolic pressure and improves coronary perfusion pressure, which is critical for successful resuscitation. It also stimulates beta-1 receptors in the heart, potentially increasing heart rate and contractility, though this effect may be less beneficial during arrest. The drug's ability to redirect blood flow to vital organs during low-flow states makes it valuable, despite limited evidence for improved neurologically intact survival. Early administration (within 3-5 minutes of arrest onset) appears most beneficial, particularly in non-shockable rhythms like asystole and PEA.
Key Points
- The use of epinephrine in cardiac arrest is supported by the 2019 American Heart Association guidelines update, which states that it is reasonable to consider administering a 1-mg dose of intravenous/intraosseous epinephrine every 3 to 5 minutes during adult CPR 1.
- The 2019 systematic review and meta-analysis found that epinephrine increased survival to hospital discharge, survival to hospital admission, and return of spontaneous circulation (ROSC) compared to placebo 1.
- The optimal timing for epinephrine administration in patients with shockable rhythms is unknown, but it is suggested to administer epinephrine after initial defibrillation attempts have been unsuccessful 1.
- The use of vasopressin alone or in combination with epinephrine does not improve outcomes compared to epinephrine alone, and therefore, epinephrine alone is suggested 1.
Mechanism of Action
Epinephrine's mechanism of action involves binding to alpha-1 receptors in peripheral blood vessels, causing vasoconstriction, which increases aortic diastolic pressure and improves coronary perfusion pressure. It also stimulates beta-1 receptors in the heart, potentially increasing heart rate and contractility.
Clinical Evidence
The clinical evidence supporting the use of epinephrine in cardiac arrest is based on several studies, including the PARAMEDIC 2 trial, which found that epinephrine improved survival at 30 days compared to placebo 1. However, the evidence for improved neurologically intact survival is limited, and the use of epinephrine represents a balance between potential benefits and possible risks.
Recommendations
The standard dose of epinephrine for cardiac arrest is 1 mg IV/IO every 3-5 minutes, and early administration (within 3-5 minutes of arrest onset) appears most beneficial, particularly in non-shockable rhythms like asystole and PEA. The use of epinephrine should be individualized based on the patient's underlying condition and the specific circumstances of the cardiac arrest.
From the FDA Drug Label
- CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Epinephrine acts on both alpha (α)- and beta (β)-adrenergic receptors. The mechanism of the rise in blood pressure is 3-fold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), and peripheral vasoconstriction. The rationale for using epinephrine in cardiac arrest is based on its mechanism of action, which includes:
- Positive inotropic action: increasing the strength of ventricular contraction to improve cardiac output
- Positive chronotropic action: increasing heart rate to improve cardiac output
- Peripheral vasoconstriction: increasing blood pressure to improve perfusion of vital organs These effects are mediated by epinephrine's action on both alpha (α)- and beta (β)-adrenergic receptors 2.
From the Research
Rationale for Epinephrine Usage in Cardiac Arrest
The rationale for using epinephrine in cardiac arrest is based on its mechanism of action, which involves increasing coronary perfusion pressure through alpha-adrenergic properties 3. This increase in coronary perfusion pressure is crucial for restoring spontaneous circulation. The key points regarding the rationale for epinephrine usage are:
- Epinephrine's alpha-adrenergic effects are important for restoring spontaneous circulation, while its beta-adrenergic effects do not aid in this process and may even be deleterious by increasing oxygen consumption of the fibrillating myocardium 3.
- The development of adequate coronary blood flow is essential for restoring spontaneous circulation, and epinephrine helps achieve this by increasing aortic diastolic pressure 3.
- Alternative alpha-adrenergic agonists like phenylephrine and methoxamine may be considered for restoring spontaneous circulation due to their lack of significant beta-adrenergic actions 3.
Mechanism of Action and Clinical Implications
The mechanism of action of epinephrine in cardiac arrest involves:
- Increasing arterial blood pressure and coronary perfusion through alpha-1-adrenoceptor agonist effects 4.
- Potential harmful effects due to beta-adrenergic stimulation, including increased oxygen consumption of the fibrillating myocardium and reduced microvascular blood flow during and after CPR 3, 4.
- Clinical implications of epinephrine administration, including improved short-term survival (return of pulses) but uncertain or potentially harmful effects on long-term survival and functional recovery 5, 4, 6.
Optimal Usage and Future Challenges
Optimal usage of epinephrine in cardiac arrest includes:
- Standardized dosing at 1 mg per administration in adults, with higher doses potentially being harmful 6.
- Earlier administration of epinephrine being more likely to improve outcomes compared to later administration 6.
- Intravenous being the preferred route of administration, but with potential benefits of intramuscular administration being explored 6.
- The need for prospective trials to determine the correct dose, timing, and patient selection for epinephrine in cardiac arrest 4, 6.