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Adrenaline (Epinephrine) — Complete Emergency Drug Reference

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1. What Is Adrenaline?

• Anaphylaxis (first-line, only life-saving treatment)
• Cardiac arrest (ACLS/PALS — only vasopressor recommended)
• Symptomatic bradycardia refractory to atropine
• Septic/cardiogenic shock (vasopressor infusion)
• Severe bronchospasm

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2. Mechanism of Action

α₁-Adrenergic Effects (vasoconstriction)

α₂-Adrenergic Effects

• Pre-synaptic feedback inhibition of noradrenaline release (minor clinical relevance at therapeutic doses)

β₁-Adrenergic Effects (cardiac stimulation)

β₂-Adrenergic Effects (bronchodilation + metabolic)

Cellular Signal Transduction (β-receptor pathway)

• L-type Ca²⁺ channels → increased Ca²⁺ influx
• Ryanodine receptors on the sarcoplasmic reticulum → increased Ca²⁺ release
• Troponin I → accelerates calcium dissociation (faster relaxation)
• Phospholamban → enhances SR calcium re-uptake
• Myosin ATPase → more ATP hydrolysis → faster cross-bridge cycling

"The α-adrenergic action (vasoconstriction) increases SVR and PVR. The resultant higher aortic diastolic blood pressure improves coronary perfusion pressure and myocardial blood flow... Epinephrine also increases cerebral blood flow during good-quality CPR because peripheral vasoconstriction directs more flow to the cerebral circulation." — Miller's Anesthesia, 10e

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3. Pharmacokinetics

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4. Clinical Indications, Criteria, and Protocols

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A. ANAPHYLAXIS

Diagnostic Criteria (Table 14-1, Tintinalli's Emergency Medicine)

• Respiratory distress or hypoxia
• Hypotension or cardiovascular collapse
• Associated organ dysfunction (hypotonia, syncope, incontinence)

• Skin and/or mucosal involvement
• Respiratory compromise
• Hypotension or associated symptoms
• Persistent GI cramps or vomiting

Common Triggers

Clinical Features by System

Anaphylaxis Treatment Protocol

• Airway: examine for angioedema, stridor → intubate early if airway threatened (do not delay — progressive edema can make intubation impossible)
• Breathing: SpO₂ monitoring, O₂ to maintain saturation >90%
• Circulation: IV access, cardiac monitor, BP

• Stop the offending agent if identifiable (stop drug infusion, remove stinger)
• Do NOT perform gastric lavage for food allergens

"Epinephrine is the first-line, most effective treatment for anaphylaxis." — Tintinalli's EM

• Repeat IM dose every 5–15 minutes if no response
• IM into the anterolateral thigh gives faster and more reliable absorption than deltoid or subcutaneous routes

• α₁: Constricts blood vessels → reverses hypotension and reduces mucosal edema/angioedema
• β₁: Positive inotropy/chronotropy → supports cardiac output
• β₂: Bronchodilation → reverses bronchoconstriction; also inhibits mast cell degranulation → stops further mediator release

• Bolus 1–2 L NS (or LR) rapidly for hypotension
• Massive fluid shifts occur due to increased vascular permeability

• Occurs 3–11 hours after initial episode in 1–20% of patients
• Observe all anaphylaxis patients for minimum 4–6 hours (8–12 hours if severe)
• Discharge with prescription for ≥2 epinephrine autoinjectors, antihistamines (5 days), prednisolone (40–60 mg/day for 3–5 days), and allergy referral

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B. CARDIAC ARREST

Indications

• Ventricular fibrillation (VF) or pulseless VT — unresponsive to initial shock
• Asystole
• Pulseless electrical activity (PEA)
• Profoundly symptomatic bradycardia (when atropine fails)

Mechanism in Cardiac Arrest

"Epinephrine may provide the most benefit within the first 15 to 20 minutes of cardiac arrest during the circulatory phase, based on its alpha effects of increasing peripheral vasoconstriction and coronary and cerebral blood flow." — Tintinalli's EM

• α₁ vasoconstriction raises aortic diastolic pressure → increases coronary perfusion pressure (CPP) → critical determinant of ROSC
• β₁ stimulation increases automaticity and contractile force if any cardiac activity present
• Adverse: May worsen myocardial ischemia, increase O₂ demand, induce ventricular ectopy, and cause cerebral vasoconstriction (worsening neurologic outcomes especially after 20 min)

Cardiac Arrest Protocol (Adult — ACLS)

• Standard: 1 mg (1:10,000 concentration = 10 mL) IV or IO
• Flush with ≥20 mL NS and elevate limb after each peripheral IV dose
• Repeat every 3–5 minutes
• High-dose epinephrine (2–5 mg) — no benefit over standard dose in survival; not recommended

• Dose: 0.01 mg/kg IV/IO (1:10,000), max 1 mg per dose
• Repeat every 3–5 minutes
• Evidence for early administration in non-shockable arrest: may not be effective if given >15 minutes after EMS arrival

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C. BRADYCARDIA (Non-Arrest)

• 1 mg in 500 mL NS
• Start at 2–10 mcg/min
• Titrate upward every 3–5 minutes to effect
• Monitor: HR, BP, ECG continuously

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D. SEPTIC/CARDIOGENIC SHOCK

"The α causes vasoconstriction, while β has positive inotropic and chronotropic effects. At higher doses, epinephrine has a similar profile (at lower doses, the β effects predominate) but is associated with more adverse effects." — Harrison's Principles of Internal Medicine, 22e

• Used when noradrenaline is insufficient (second-line vasopressor in septic shock)
• Also used post-cardiac arrest for myocardial dysfunction
• Dose: Infusion titrated from 0.01–1 mcg/kg/min
• Higher doses → predominantly α effects (vasoconstriction)
• Lower doses → predominantly β effects (inotropy)

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5. Adverse Effects

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6. Contraindications and Cautions

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7. Concentration Guide — Critical for Safety

⚠️ Medication error risk: Always confirm the concentration before administration. Administering 1:1000 IV instead of 1:10,000 delivers 10× the intended dose and can cause hypertensive crisis, arrhythmia, or death.

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8. Summary — Decision Framework

EMERGENCY PRESENTATION
        │
        ├── ANAPHYLAXIS?
        │   ├── Epinephrine 0.3–0.5 mg IM (1:1000) anterolateral thigh
        │   ├── Repeat q5–15 min if needed
        │   ├── IV fluids, O₂, airway management
        │   └── Antihistamines + corticosteroids (adjunct only)
        │
        ├── CARDIAC ARREST (VF/pVT/PEA/Asystole)?
        │   ├── CPR + defibrillation (shockable rhythm)
        │   ├── Epinephrine 1 mg IV/IO (1:10,000)
        │   ├── Repeat every 3–5 min
        │   └── Amiodarone for refractory shockable rhythm
        │
        ├── BRADYCARDIA (haemodynamically unstable, atropine failed)?
        │   └── Epinephrine infusion 2–10 mcg/min IV, titrate
        │
        └── SEPTIC/CARDIOGENIC SHOCK (refractory)?
            └── Epinephrine infusion 0.01–1 mcg/kg/min, titrate

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