What is the effect of epinephrine (adrenaline) on cardiac inotropy during anaphylaxis?

From the Guidelines

Adrenaline (epinephrine) at anaphylaxis doses has a significant positive inotropic effect on the heart, increasing cardiac contractility and output by binding to beta-1 adrenergic receptors in the myocardium, as supported by the most recent guidelines 1.

Key Points

• The recommended dose for anaphylaxis is 0.2 to 0.5 mg (1:1000) intramuscularly, to be repeated every 5 to 15 min as needed, according to the 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care 1.
• Epinephrine increases cardiac contractility by stimulating beta-1 adrenergic receptors, which enhances the force of cardiac contraction and cardiac output.
• The positive inotropic effect begins within minutes of administration and is relatively short-lived (approximately 15-20 minutes), which is why repeated doses may be necessary every 5-15 minutes in severe anaphylaxis if symptoms persist.
• Healthcare providers should be aware that higher doses or intravenous administration carries increased risk of adverse cardiac effects, including arrhythmias, myocardial ischemia, and potential cardiac injury, particularly in elderly patients or those with pre-existing cardiovascular disease.

Administration and Monitoring

• Epinephrine should be administered early by intramuscular injection (or autoinjector) to all patients with signs of a systemic allergic reaction, especially hypotension, airway swelling, or difficulty breathing 1.
• Close hemodynamic monitoring is recommended in patients with anaphylactic shock.
• Immediate referral to a health professional with expertise in advanced airway placement, including surgical airway management, is recommended in cases of potential airway compromise.

Special Considerations

• There is no absolute contraindication to epinephrine use in the treatment of anaphylaxis, but potential epinephrine-related adverse events must be balanced in high-risk patients, such as elderly patients with multiple comorbidities and patients with complex congenital heart disease, pulmonary hypertension, or prior epinephrine-associated cardiomyopathy 1.
• Providers should be aware of the need to appropriately counsel patients when using epinephrine, including technique of administration and the need to restrain young children and infants to avoid inadvertent epinephrine needle injuries.

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

The effect of epinephrine on cardiac inotropy during anaphylaxis is not directly stated in the provided drug label. However, it is known that beta-adrenergic receptors are present in the heart, and stimulation of these receptors can increase heart rate and contractility.

• Key points:
  • Epinephrine acts on both alpha and beta-adrenergic receptors.
  • Beta-adrenergic receptors are involved in increasing heart rate and contractility. However, the label does not explicitly state the effect of epinephrine on cardiac inotropy during anaphylaxis. 2

From the Research

Effect of Epinephrine on Cardiac Inotropy

• Epinephrine (adrenaline) is universally recommended as the initial drug of choice for the treatment of anaphylaxis, and it has life-saving pharmacologic effects in multiple organ systems, including the cardiovascular system 3.
• The use of epinephrine can help prevent and relieve shock, which is a critical aspect of anaphylaxis treatment, and its effects on cardiac inotropy are essential in this context 4.
• However, the evidence in support of epinephrine's therapeutic approach is modest, mainly due to the lack of well-designed trials, and serious adverse effects are commonly reported following its use, especially when given intravenously 4.
• The administration of epinephrine can increase cardiac contractility and heart rate, which can be beneficial in treating anaphylaxis, but it can also lead to adverse effects such as hypertension, ventricular arrhythmias, and myocardial infarction 5.
• The risk of serious cardiac adverse effects is lower when epinephrine is administered intramuscularly, which is the recommended route of administration for anaphylaxis treatment, rather than intravenously 6.

Administration and Dosage

• The initial recommended adult dose of epinephrine for anaphylaxis treatment is 0.3-0.5 mg, injected intramuscularly in the anterolateral aspect of the mid-thigh 3.
• The dose to be administered is 300-600 µg for an adult or 10 µg/kg for a child, and the injection can be repeated every 10-15 minutes until there is a response 6.
• Junior doctors may be unsure about the dose and route of administration of epinephrine, highlighting the need for improved education and access to appropriate drugs 7.

Safety and Efficacy

• Side effects occur in approximately 21.64% of patients who receive epinephrine for an anaphylactic reaction, but they are usually mild and transient 5.
• Potentially severe adverse effects, such as high blood pressure, chest discomfort, or ECG alterations, occur in less than 3% of cases, and are more commonly associated with intravenous administration 5.
• The use of an autoinjector for epinephrine administration can help eliminate all manifestations of anaphylaxis, and its use should be specially practiced in advance 6.