Can fainting and hypotension be a reaction to epinephrine (adrenaline)?

Fainting and Low Blood Pressure Are NOT Typical Reactions to Epinephrine—They Are the Conditions Epinephrine Treats

Epinephrine is the primary treatment for hypotension and impending syncope in anaphylaxis, not a cause of these symptoms. However, in rare circumstances involving overdose or paradoxical responses in patients on beta-blockers, epinephrine can theoretically worsen hypotension through unopposed alpha-adrenergic effects 1.

Understanding the Normal Physiological Response

Epinephrine's mechanism of action directly counteracts hypotension and prevents syncope:

• Alpha-adrenergic effects cause vasoconstriction, increasing peripheral vascular resistance and blood pressure 2
• Beta-1 adrenergic effects increase cardiac inotropy and chronotropy, supporting cardiovascular function and cardiac output 2
• Beta-2 adrenergic effects cause bronchodilation and inhibit further mediator release from mast cells 2

These combined effects make epinephrine the cornerstone treatment for anaphylactic shock, where hypotension and potential syncope are the primary life-threatening manifestations 1, 3.

When Hypotension Can Paradoxically Occur With Epinephrine

Beta-Blocker Interactions (Most Important Clinical Scenario)

In patients taking beta-blockers, epinephrine can paradoxically worsen hypotension and bradycardia through unopposed alpha-adrenergic and reflex vagotonic effects 1. This occurs because:

• Beta-blockade prevents epinephrine's beneficial cardiac effects (increased contractility and heart rate) 1
• Unopposed alpha-adrenergic stimulation can cause excessive vasoconstriction with reflex bradycardia 1
• These patients may experience decreased cardiac contractility with perpetuation of hypotension 1

Critical management point: Even patients on beta-blockers should still receive epinephrine for anaphylaxis, as there are no absolute contraindications 2. However, they may require glucagon as adjunctive therapy if refractory to epinephrine 1, 2.

Epinephrine Overdose

Excessive epinephrine dosing can cause severe hypertension followed by hypotension 4:

• Overdosage may produce extremely elevated arterial pressure, potentially causing cerebrovascular hemorrhage 4
• This can be followed by cardiac arrhythmias, myocardial ischemia, and subsequent hypotension 4
• Transient bradycardia followed by tachycardia may occur 4
• Prolonged hypotension may follow after initial hypertensive crisis 4

In a critical care transport study, only 1 episode of transient extreme hypertension occurred among 100 doses of push-dose epinephrine, with no patient harm 5. Major adverse events occurred in only 3.6% of cases when IV epinephrine was used for severe asthma 6.

Endogenous Epinephrine During Vasovagal Syncope

Interestingly, endogenous epinephrine release may contribute to vasodilation during vasovagal syncope 7:

• During syncopal episodes, plasma adrenaline (epinephrine) concentrations increase before the faint 7
• This endogenous epinephrine may contribute to the vasodilation and hypotension that occur during syncope 7
• However, this represents a pathophysiologic response to impending syncope, not a reaction to administered epinephrine 7

Key distinction: Vasovagal syncope lacks pruritus and occurs with bradycardia and hypotension, helping distinguish it from anaphylaxis 3.

Clinical Implications for Epinephrine Administration

Proper Dosing Prevents Adverse Events

Appropriate dosing is critical to avoid complications:

• Adults and children ≥30 kg: 0.3-0.5 mg (1:1000 solution) intramuscularly 1, 3, 2
• Children <30 kg: 0.01 mg/kg (maximum 0.3 mg) intramuscularly 1, 2
• IV epinephrine for anaphylactic shock: 0.05-0.1 mg (1:10,000 solution) with close hemodynamic monitoring 1

Route of Administration Matters

Intramuscular administration into the anterolateral thigh is preferred for first-line treatment 1, 2:

• Produces rapid peak plasma concentrations 1
• Safer than IV route for initial management 1
• Epinephrine inhalers cannot achieve plasma concentrations needed for hemodynamic stabilization and should not be relied upon for hypotension 8

When Hypotension Persists Despite Epinephrine

If hypotension continues after appropriate epinephrine administration, consider:

• Fluid resuscitation: Anaphylaxis can shift 50% of intravascular fluid into extravascular space within 10 minutes 1
• Additional vasopressors: Norepinephrine, vasopressin, or dopamine may be needed for refractory hypotension 1
• Glucagon: Specifically for patients on beta-blockers (1-5 mg IV over 5 minutes) 1

Common Pitfalls to Avoid

1. Delaying epinephrine due to fear of adverse effects: Delayed administration is directly associated with increased hospitalization, hypoxic-ischemic encephalopathy, and death 2. The risk of withholding epinephrine far exceeds the risk of administration 3, 2.

2. Using antihistamines instead of epinephrine as first-line treatment: This is a dangerous practice that increases morbidity and mortality 2.

3. Assuming hypotension after epinephrine means the drug caused it: More likely, the hypotension represents inadequate treatment of the underlying anaphylaxis requiring additional epinephrine, fluids, or vasopressors 1.

4. Withholding epinephrine in patients on beta-blockers: While these patients may have a blunted response, epinephrine should still be administered with glucagon available as backup 1, 2.