Adenosine

Adenosine: The Anesthesiologist's "Chemical Defibrillator"

Introduction

Adenosine is an endogenous purine nucleoside that plays a vital role in cellular energy metabolism (as part of ATP) and neuromodulation. In pharmacology, it is a unique and powerful antiarrhythmic drug used for the rapid termination of specific supraventricular tachycardias (SVTs). Its defining characteristic is an extremely short half-life, making it a safe and effective "chemical cardioversion" agent when used correctly.

1. Chemical Structure

Adenosine is a simple molecule composed of adenine attached to a ribose sugar. It is a nucleoside, a fundamental building block of nucleic acids. Its endogenous nature is why it is so rapidly and completely metabolized by the body.

2. Mechanism of Action (MOA)

Adenosine exerts its effects by binding to specific G-protein coupled adenosine receptors (A1, A2A, A2B, A3). Its primary antiarrhythmic effect is mediated through the A1 receptor in the heart.

  • A1 Receptor Activation (AV Node): Stimulation of A1 receptors in the atrioventricular (AV) node increases potassium (K+) conductance (outward K+ current) and decreases calcium (Ca++) influx. This leads to hyperpolarization of the AV nodal cells and a dramatic slowing of conduction. The effect is so profound that it can transiently produce a complete AV block, effectively "resetting" the re-entrant circuit that causes most SVTs.

  • Other Receptor Effects:

    • A2 Receptors: Cause vasodilation (leading to flushing and hypotension) and inhibit platelet aggregation.
    • A3 Receptors: Mediate bronchoconstriction and can be involved in the release of histamine and mast cell degranulation (causing the characteristic chest pain and dyspnea).

3. Pharmacokinetics

  • Onset: Immediate (within seconds of IV bolus reaching the central circulation).
  • Distribution: Confined to the intravascular and extracellular space.
  • Metabolism: This is its most critical property. Adenosine is rapidly taken up by red blood cells and endothelial cells and is deaminated to inosine by the enzyme adenosine deaminase.
  • Half-life: Extremely short: < 10 seconds. The entire effect is over in less than a minute. This is why it must be administered as a rapid IV bolus followed by a saline flush to ensure it reaches the heart before being cleared by the lungs.

4. Pharmacodynamics

The primary effect is a transient, high-grade AV block, manifesting on the ECG as a brief period of asystole. This is the therapeutic goal. Other effects are side effects:

  • Cardiac: Brief asystole, sinus bradycardia, PVCs.
  • Vascular: Flushing, facial warmth, and a brief drop in blood pressure due to A2-mediated vasodilation.
  • Pulmonary: Bronchospasm (via A3 receptors).
  • Neurologic: A feeling of impending doom, chest pressure, and dyspnea. These symptoms are very common, transient, and often frightening to the patient if not warned beforehand.

5. Clinical Uses in Anesthesia

  1. Acute Termination of SVT: The primary indication. It is the first-line treatment for stable, narrow-complex SVT that is hemodynamically stable, including:
    • AV Nodal Re-entrant Tachycardia (AVNRT)
    • AV Re-entrant Tachycardia (AVRT) (e.g., Wolff-Parkinson-White syndrome)
  2. Diagnostic Tool: Can be used to unmask the underlying atrial rhythm in a tachycardia by transiently slowing the ventricular response. This can help differentiate SVT with aberrancy from Ventricular Tachycardia (VT). If the rhythm is SVT, adenosine will likely terminate it or reveal atrial flutter/fibrillation waves. If it's VT, adenosine will have no effect on the rhythm (though it may cause transient AV block).

6. Dosage

Indication
Route
Dose
SVT Termination IV Initial Dose: 6 mg (rapid IV bolus).<br>If unsuccessful: 12 mg (rapid IV bolus).<br>If still unsuccessful: A second 12 mg dose can be given.
Administration Technique IV CRITICAL: Must be given as a rapid bolus followed immediately by a 20 ml saline flush to ensure the drug reaches the heart before being inactivated in the lungs. Use a large, proximal IV (e.g., antecubital).

 

7. Adverse Effects

  • Common (but transient): Facial flushing, chest pressure/ discomfort, dyspnea, headache, dizziness, metallic taste.
  • Less Common: Nausea, sweating.
  • Serious (rare): Prolonged asystole, ventricular arrhythmias, severe bronchospasm. These are more likely in patients with contraindications or drug interactions.

8. Contraindications

This section is critical for patient safety.

  • Absolute Contraindications:
    • Second- or Third-Degree AV Block (without a functioning permanent pacemaker). Adenosine will completely block the only remaining conduction pathway, leading to profound, prolonged asystole.
    • Sinoatrial (SA) Node Disease (e.g., Sick Sinus Syndrome). Can cause severe sinus pauses or arrest.
  • Relative Contraindications / Use with Extreme Caution:
    • Atrial Fibrillation or Atrial Flutter: Adenosine can cause transient AV block. In atrial flutter, this may convert a stable 2:1 or 4:1 block into a dangerous 1:1 conduction, paradoxically increasing the ventricular rate dramatically.
    • Asthma or Severe COPD: Adenosine can precipitate life-threatening bronchospasm via A3 receptors.
    • Known Hypersensitivity to adenosine.
    • Long QT Syndrome: Can theoretically precipitate torsades de pointes.

9. Drug Interactions

  • Drugs that Decrease Adenosine's Effect (Require Higher Doses):
    • Methylxanthines: Caffeine, Theophylline. These are competitive antagonists at adenosine receptors. A patient who drank several cups of coffee may be resistant to a 6 mg dose.
  • Drugs that Increase Adenosine's Effect (Require Lower Doses):
    • Dipyridamole: Inhibits the cellular uptake of adenosine, potentiating its effect.
    • Carbamazepine: Can enhance AV nodal block.
    • Digoxin: Can have additive effects on AV nodal conduction.

10. Special Section:The "How-To" of Adenosine Administration for Trainees

Administering adenosine is a procedure, not just a drug order. Do it right every time.

  1. Prepare: Ensure the patient is on a continuous ECG monitor with a defibrillator available.
  2. IV Access: Confirm you have a patent, large-bore IV in a proximal vein (antecubital is ideal). A small, distal IV will not deliver the drug quickly enough.
  3. Warn the Patient: Say, "I'm going to give you a medicine now that will make your heart feel like it's stopping for a second. You may feel intense chest pressure, flushing, and shortness of breath. It will only last for a few seconds. It's a strange but normal feeling." This prevents panic and improves cooperation.
  4. Draw Up the Dose: Prepare the 6 mg dose (from a pre-filled syringe or by drawing up 6 ml from a 1 mg/ml vial).
  5. The Push and Flush: Administer the 6 mg as a rapid, forceful IV bolus. Do not push it slowly. Immediately after the push, administer a 20 ml bolus of normal saline to "flush" the drug into the central circulation.
  6. Observe: Watch the monitor. You will see a brief period of asystole (this is the goal), followed by either conversion to sinus rhythm or a return to the SVT.
  7. Re-evaluate: If the first dose fails, be prepared to immediately administer the 12 mg dose using the exact same push-and-flush technique.

Comments are closed.