Adrenaline (Epinephrine)

Epinephrine (Adrenaline): The Anesthesiologist's Double-Edged Sword

Introduction

Adrenaline AmpouleEpinephrine, commonly known by its trade name Adrenaline, is an endogenous catecholamine and one of the most potent, rapid-acting, and essential drugs in the anesthesiologist's arsenal. It is the prototypical non-selective adrenergic agonist. Its ability to dramatically increase heart rate, contractility, and blood pressure makes it a life-saving rescue drug. However, these same properties render it extremely dangerous if used inappropriately or in the wrong dose. A deep understanding of its pharmacology is non-negotiable for every anesthesia provider.

1. Chemical Structure

Epinephrine is a catecholamine. Its structure consists of:

  1. A catechol ring (a benzene ring with two hydroxyl groups).
  2. An ethylamine side chain.

This catechol structure is key to its pharmacology. It makes the molecule highly polar, which prevents it from crossing the blood-brain barrier easily and makes it rapidly metabolized by enzymes like Catechol-O-Methyltransferase (COMT) and Monoamine Oxidase (MAO).

Adrenaline_chemical_structure

2. Mechanism of Action (MOA)

Epinephrine is a direct-acting, non-selective adrenergic agonist. It stimulates all four major adrenergic receptor subtypes:

  • α1 Receptors: Located on vascular smooth muscle (especially in skin, mucosa, kidney, and splanchnic beds). Stimulation causes potent vasoconstriction.
  • α2 Receptors: Located presynaptically on nerve endings and on platelets. Stimulation inhibits further norepinephrine release and promotes platelet aggregation.
  • β1 Receptors: Located primarily in the heart. Stimulation causes:
    • Increased Heart Rate (Positive Chronotropy)
    • Increased Contractility (Positive Inotropy)
    • Increased Conduction Velocity (Positive Dromotropy)
  • β2 Receptors: Located on bronchial and vascular smooth muscle (in skeletal muscle), the uterus, and in the liver. Stimulation causes:
    • Bronchodilation
    • Vasodilation (in skeletal muscle)
    • Uterine Relaxation
    • Increased Glycogenolysis and Gluconeogenesis (leading to hyperglycemia)

3. Pharmacokinetics

  • Onset: Immediate (< 1 minute) with IV administration. Slower with IM (5-10 min) and SC (10-20 min).
  • Distribution: Widely distributed throughout the body.
  • Metabolism: Rapidly metabolized in the liver and other tissues by MAO and COMT. This is why its duration of action is extremely short when given as an IV bolus.
  • Duration of Action: Very short with IV bolus (1-5 minutes). Longer with IM/SC (up to 4 hours).
  • Excretion: Metabolites (e.g., Metanephrine, VMA) are excreted in the urine.

4. Pharmacodynamics (Dose-Dependent Effects)

The clinical effects of epinephrine are critically dependent on the dose, as different receptor populations have different affinities for the drug.

Dose Range
Dominant Receptor Effect
Hemodynamic Consequence
Clinical Scenario
Low Dose (e.g., 0.5-2 mcg/min) β2 > β1 > α1 Vasodilation (β2) is more prominent than vasoconstriction (α1). HR and contractility increase (β1). Net Effect: Slight decrease in diastolic pressure, slight increase in systolic pressure. Used for low-dose inotropy.
Moderate Dose (e.g., 2-10 mcg/min) β1 > α1 > β2 Strong increase in HR and contractility (β1). Noticeable vasoconstriction (α1). Net Effect: Increased systolic, diastolic, and mean arterial pressure (MAP). The classic "pressor" effect.
High Dose (e.g., >10 mcg/min) α1 >> β1 Intense vasoconstriction (α1) dominates. Net Effect: Profound hypertension. The intense vasoconstriction can trigger a baroreceptor-mediated reflex bradycardia, which can be counterintuitive and dangerous.

 

5. Clinical Uses in Anesthesia

  1. Hemodynamic Support: First-line vasopressor/inotrope for most forms of shock (e.g., septic, anaphylactic, cardiogenic) after adequate fluid resuscitation.
  2. Cardiac Arrest: The cornerstone of ACLS algorithms for pulseless electrical activity (PEA), asystole, and ventricular fibrillation.
  3. Adjunct to Local Anesthetics:
    • Vasoconstriction (α1) decreases systemic absorption of the local anesthetic, prolonging its duration and reducing the risk of systemic toxicity.
    • Improves the quality of the block by decreasing bleeding in the surgical field.
  4. Treatment of Anaphylaxis: Drug of choice. Reverses bronchoconstriction (β2), vasodilation, and urticaria (α1).
  5. Treatment of Severe Bronchospasm: Potent bronchodilator (β2) when other treatments (e.g., albuterol) are insufficient.
  6. Control of Local Bleeding: Used topically or via infiltration (e.g., in ENT, plastic surgery) for its hemostatic properties.

6. Dosage

Indication
Route
Dose
Cardiac Arrest IV 1 mg (10 ml of 1:10,000 solution) every 3-5 minutes.
Anaphylaxis IM/SC 0.3 - 0.5 mg (0.3-0.5 ml of 1:1000 solution). May repeat.
Hypotension/Shock IV Infusion 2 - 10 mcg/min. Titrate to effect (MAP > 65 mmHg).
Local Anesthetic Adjunct Infiltration/Block 1:100,000 or 1:200,000 concentration.

 

7. Adverse Effects & Complications

These are direct extensions of its pharmacology and are often dose-related.

  • Cardiovascular:
    • Tachyarrhythmias: Sinus tachycardia, PVCs, VTach, VFib.
    • Hypertension: Can lead to angina, myocardial ischemia, and intracerebral hemorrhage.
    • Reflex Bradycardia: Seen with very high doses causing intense vasoconstriction.
  • Metabolic:
    • Hyperglycemia: Can be problematic in diabetic patients.
    • Hypokalemia: β2 stimulation drives potassium intracellularly. Can precipitate arrhythmias.
  • Local:
    • Tissue Necrosis/Ischemia: If extravasation occurs from an IV line, intense α1-mediated vasoconstriction can cut off blood supply. Treatment: Infiltrate the area with phentolamine (an α-blocker).
  • Drug Interactions:
    • MAO Inhibitors: Can lead to severe, unpredictable hypertension.
    • β-Blockers: Non-selective β-blockers (e.g., propranolol) block the vasodilatory (β2) effects of epinephrine, leaving the vasoconstrictive (α1) effects unopposed. This can cause paradoxical hypertension and bradycardia. Use a cardioselective β-blocker (e.g., esmolol) if needed.

8. Special Section: Concentrations, Preparation, and Indications

Medication errors with epinephrine are common and can be fatal. Always double-check the concentration and label clearly.

The standard ampule in most operating rooms is 1 mg in 1 ml (a 1:1000 solution). All other concentrations are prepared from this.

Concentration
Ratio
Strength (mg/ml)
How to Prepare (from 1 mg/ml stock)
Primary Indication
Key Clinical Pearl
Stock Solution 1:1,000 1 mg/ml This is the ampule you receive. IM/SC injection for anaphylaxis; Subcutaneous infiltration for hemostasis. NEVER give this concentration undiluted as an IV bolus.
"Code Dose" 1:10,000 0.1 mg/ml Add 1 ml of 1:1,000 to 9 ml of Normal Saline. IV Bolus for Cardiac Arrest. This is the concentration used in ACLS. 1 mg = 10 ml.
"Local Anesthetic" 1:100,000 10 mcg/ml Add 1 ml of 1:1,000 to 9 ml of Saline. Then add 1 ml of that solution to 9 ml of local anesthetic. Adjunct for nerve blocks, epidurals, local infiltration. Final concentration is 10 mcg/ml. For a 50 ml block, add 0.5 ml of 1:1,000 stock.
Infusion Bag Varies e.g., 4 mcg/ml Add 4 mg (4 ml of 1:1,000) to a 250 ml bag of saline OR 8 mg to a 500 ml bag. Continuous IV infusion for hemodynamic support. Clearly label the bag with the concentration (e.g., "Epinephrine 4 mcg/ml").

 

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