What are the uses, adverse effects, and contraindications of epinephrine (adrenaline) in a practical setting?

Epinephrine: Clinical Uses, Adverse Effects, and Contraindications

Primary Clinical Indication

Epinephrine is the first-line, life-saving medication for anaphylaxis and has no absolute contraindications in this setting. 1, 2 Delayed administration is consistently associated with fatal outcomes, making prompt injection the single most critical intervention. 1, 3

Practical Clinical Uses

Anaphylaxis Treatment (Primary Indication)

• Intramuscular injection into the anterolateral thigh (vastus lateralis) is the preferred route for first-aid treatment, providing more rapid and higher plasma concentrations than subcutaneous or arm injections. 1, 2

• Dosing for anaphylaxis:

  • Adults and children ≥30 kg: 0.3-0.5 mg (0.3-0.5 mL of 1:1000 concentration) IM 2
  • Children <30 kg: 0.01 mg/kg up to 0.3 mg IM 1, 2
  • Autoinjectors: 0.15 mg for children 10-25 kg; 0.3 mg for those ≥25 kg 1

• Repeat dosing: Administer a second dose 5-15 minutes after the first if symptoms persist or worsen. 1, 4 Between 6-19% of pediatric patients and 17% of all patients require additional doses. 1

Mechanism of Action in Anaphylaxis

Epinephrine works through multiple organ systems simultaneously: increases vasoconstriction, decreases mucosal edema, increases cardiac inotropy/chronotropy, provides bronchodilation, and downregulates further mast cell mediator release. 1 This multi-system effect is why no other medication can substitute for epinephrine in anaphylaxis. 1, 3

Other Emergency Uses

• Cardiac arrest: Higher IV doses (different from anaphylaxis dosing) 5
• Septic shock with hypotension: IV infusion 6
• Severe asthma (adjunctive): 0.3-0.5 mg subcutaneously, though selective β2-agonists are preferred 7

Administration Protocol

Immediate Management Steps

• Position patient supine or in position of comfort if respiratory distress present; elevate lower extremities. 1, 4
• Do not allow standing, walking, or running after injection. 1
• Activate emergency medical services and transport to emergency department for monitoring. 1, 4
• Monitor for 4-6 hours minimum if multiple doses required, due to biphasic reaction risk (10-35% of cases). 1, 4

Adjunctive Therapies (Never Replace Epinephrine)

• H1 antihistamines: Slow onset (≥1 hour), only relieve cutaneous symptoms, do not treat respiratory compromise or shock. 1
• Inhaled β2-agonists (albuterol): May help wheezing in patients with asthma but do not replace epinephrine. 1
• IV fluids (normal saline): Essential for persistent hypotension after epinephrine, as anaphylaxis can shift 35% of intravascular volume into extravascular space within minutes. 1
• Supplemental oxygen: For respiratory distress or hypoxia. 1
• Glucagon (1-5 mg IV): Specifically for patients on β-blockers who may be resistant to epinephrine. 1

Adverse Effects

Common Pharmacologic Effects (Not True Adverse Events)

Transient pallor, tremor, anxiety, palpitations, headache, dizziness, sweating, nausea, and restlessness are normal sympathomimetic responses similar to endogenous "fight or flight" epinephrine release. 1, 2 These symptoms are more likely in patients with heart disease, hypertension, or hyperthyroidism but do not contraindicate use in anaphylaxis. 2

Serious Adverse Effects (Rare with IM Administration)

• Cardiovascular complications: Arrhythmias (including ventricular fibrillation), myocardial ischemia/infarction, angina, hypertension, cerebral hemorrhage (particularly in elderly with cardiovascular disease), and stress cardiomyopathy. 2, 6

• Injection site complications:

  • Accidental digital/hand/foot injection causes vasoconstriction and potential tissue loss. 2
  • Buttock injection has caused gas gangrene. 2
  • Rare cases of necrotizing fasciitis and myonecrosis (Clostridial infection) following thigh injection. 1, 2

• Metabolic effects: Transient hyperglycemia in diabetics, hypokalemia, lactic acidosis. 6

Overdose Management

Iatrogenic overdose occurs when cardiac arrest doses (1:10,000 IV) are mistakenly given instead of anaphylaxis doses (1:1000 IM). 5 This potentially lethal error results from confusion about proper dosing and concentration. 5

• For severe hypertension: Consider phentolamine 5-10 mg IV (alpha-blocker) and nitrates for blood pressure control. 7
• For ventricular arrhythmias: Follow ACLS protocols with antiarrhythmic agents. 7
• Continuous cardiac monitoring with frequent vital signs every 1-2 minutes initially. 7
• Extended monitoring for 4-6 hours to detect delayed complications. 7

Contraindications

Absolute Contraindications

There are NO absolute contraindications to epinephrine use in anaphylaxis. 1, 2 The risk of death from untreated anaphylaxis always exceeds the risk of epinephrine administration. 1

Relative Considerations (Not Contraindications)

While the following conditions warrant awareness, they do not preclude epinephrine use in life-threatening anaphylaxis:

• Cardiovascular disease: Myocardial ischemia and arrhythmias can occur with epinephrine, but also occur in untreated anaphylaxis itself. 1 The benefit of epinephrine outweighs cardiac risks. 1

• β-blocker therapy: May cause resistance to epinephrine and refractory hypotension/bradycardia; glucagon should be available as rescue therapy. 1 Still administer epinephrine first. 1

• Drug interactions requiring caution:

  • MAO inhibitors and tricyclic antidepressants prolong epinephrine effects. 1, 2
  • Stimulant medications (amphetamines, methylphenidate) or cocaine abuse. 1
  • Cardiac glycosides and halogenated anesthetics increase arrhythmia risk. 2

• Pre-existing conditions: Hyperthyroidism, Parkinson's disease (may worsen temporarily), uncontrolled hypertension, recent intracranial surgery, aortic aneurysm. 1, 2

Critical Pitfalls to Avoid

Dosing and Concentration Errors

• Never confuse 1:1000 (IM/SC) with 1:10,000 (IV) concentrations. This error causes life-threatening overdose. 7, 5 Implement pre-filled syringes with clear labeling to prevent this. 7, 5

• Do not inject into buttocks, digits, hands, or feet due to risk of tissue necrosis and gas gangrene. 2

Treatment Delays

• Do not substitute antihistamines or inhaled bronchodilators for epinephrine. These are adjunctive only and do not prevent death. 1, 3

• Do not delay epinephrine while attempting IV access or waiting for antihistamines. Immediate IM injection is faster and safer. 3, 8

• Do not hesitate to give a second dose at 5-15 minutes if symptoms persist. Waiting longer increases mortality risk. 4

Post-Administration Errors

• Do not discharge patients immediately after symptom resolution. Biphasic reactions occur in 10-35% of cases requiring multiple doses; observe for minimum 4-6 hours. 1, 4

• Do not allow patients to stand or walk after injection. Position changes can precipitate cardiovascular collapse. 1

Special Populations

• Pregnancy: Pregnant women may be at higher risk for adverse effects, but epinephrine remains indicated for anaphylaxis as maternal death poses greater fetal risk. 2

• Elderly: Higher risk of cerebral hemorrhage and cardiac complications, but anaphylaxis mortality risk still exceeds treatment risk. 2

• Infants <7.5 kg: The 0.15 mg autoinjector represents a twofold overdose, but given the alternatives (dosing errors, delays, or no treatment), most physicians prescribe it anyway as the benefit-to-risk ratio remains favorable. 1