Atracurium

Usage

• Atracurium besylate is a non-depolarizing neuromuscular blocking agent (NMBA) used as an adjunct to general anesthesia to facilitate endotracheal intubation, provide skeletal muscle relaxation during surgery or controlled ventilation, and to facilitate mechanical ventilation in intensive care unit (ICU) patients. It is classified as a neuromuscular blocker within the broader category of peripheral skeletal muscle relaxants.

• Pharmacological Classification: Neuromuscular blocking agent, Skeletal muscle relaxant.

• Mechanism of Action: Atracurium competitively binds to nicotinic acetylcholine receptors at the neuromuscular junction, antagonizing the action of acetylcholine. This prevents depolarization of the muscle cell membrane, leading to skeletal muscle paralysis. It is metabolized primarily through ester hydrolysis and Hofmann elimination.

Alternate Names

• Tracrium, Atracurium besilate.

• Brand Names: Tracrium, BFS-Atracu (and various generic versions).

How It Works

• Pharmacodynamics: Atracurium causes dose-dependent skeletal muscle relaxation by blocking neuromuscular transmission. It does not possess hormonal activity or analgesic properties. Onset of action is rapid, typically within 2-3 minutes after intravenous bolus administration. Duration of action is intermediate, generally lasting 20-35 minutes.

• Pharmacokinetics:

  • Absorption: Administered intravenously.
  • Metabolism: Atracurium undergoes spontaneous non-enzymatic degradation in plasma and tissues via Hofmann elimination and ester hydrolysis. This unique metabolism makes it suitable for patients with hepatic or renal impairment, as it does not rely on these organs for elimination. Laudanosine, a metabolite, may accumulate in ICU patients with prolonged infusions.
  • Elimination: Atracurium and its metabolites are primarily excreted in the urine and bile.

• Mode of Action: Atracurium competitively blocks the binding of acetylcholine to nicotinic cholinergic receptors at the motor endplate of the neuromuscular junction, inhibiting ion channel opening and subsequent depolarization.

• Receptor Binding: Nicotinic cholinergic receptors at the neuromuscular junction.

Dosage

Standard Dosage

Adults:

• Intubation: 0.4-0.5 mg/kg IV bolus.
• Surgical Relaxation: 0.4-0.5 mg/kg IV bolus followed by a continuous infusion of 0.005-0.01 mg/kg/min or intermittent boluses of 0.1-0.2 mg/kg every 15-25 minutes.

Children:

• <1 month: Safety and efficacy not established.
• 1 month - 2 years: 0.3-0.4 mg/kg IV bolus (under halothane anesthesia).

• 2 years: Same as adult dose. Children may require more frequent maintenance doses.

Special Cases:

• Elderly Patients: Initial dose at the lower end of the range, administered slowly.
• Patients with Renal Impairment: No dose adjustment necessary.
• Patients with Hepatic Dysfunction: No dose adjustment necessary.
• Patients with Cardiovascular Disease: Initial dose of 0.3-0.4 mg/kg administered slowly over 60 seconds.

Clinical Use Cases

• Intubation: 0.5-0.6 mg/kg IV bolus.
• Surgical Procedures: Initial bolus of 0.4-0.5 mg/kg followed by maintenance doses as needed.
• Mechanical Ventilation: Initial bolus followed by continuous infusion. Rates ranging from 0.0045-0.0295 mg/kg/min (0.27-1.77 mg/kg/hour).
• Intensive Care Unit (ICU) Use: Continuous infusion of 0.000011-0.000013 mg/kg/min (0.65-0.78 mcg/kg/min), titrated to effect.
• Emergency Situations: Rapid sequence intubation: 0.5-0.6 mg/kg IV bolus.

Side Effects

Common Side Effects

• Skin flushing, redness, itching, hives, injection site reaction, transient hypotension, and changes in heart rate (tachycardia or bradycardia).

Rare but Serious Side Effects

• Prolonged neuromuscular blockade, inadequate block, severe allergic reactions (anaphylaxis), bronchospasm, laryngospasm, and cardiac arrest (rare).

Adverse Drug Reactions (ADR)

• Anaphylaxis, prolonged neuromuscular blockade requiring mechanical ventilation.

Contraindications

• Hypersensitivity to atracurium, cisatracurium, or benzenesulfonic acid.

Drug Interactions

• Antibiotics: Aminoglycosides, polymyxins, clindamycin.
• Anesthetics: Inhalational agents (e.g., isoflurane, enflurane, halothane) may potentiate neuromuscular blockade.
• Other: Magnesium salts, procainamide, quinidine, lithium, anticholinesterases (e.g., donepezil).

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C

• Atracurium crosses the placenta but is generally considered safe for use during cesarean section in appropriate doses. Use in other stages of pregnancy should be carefully weighed against potential risks to the fetus.

• Breastfeeding: It is unknown whether atracurium is excreted in breast milk. Caution is advised.

Drug Profile Summary

• Mechanism of Action: Competitive neuromuscular blocking agent.
• Side Effects: Flushing, hypotension, tachycardia/bradycardia, allergic reactions.
• Contraindications: Hypersensitivity.
• Drug Interactions: Aminoglycosides, inhalational anesthetics, magnesium.
• Pregnancy & Breastfeeding: Category C; caution advised.
• Dosage: 0.4-0.5 mg/kg IV bolus; continuous infusion titrated to effect.
• Monitoring Parameters: Train-of-four (TOF) monitoring, vital signs, oxygen saturation.

Popular Combinations

• Atracurium is commonly used with inhalational anesthetics and opioid analgesics during surgical procedures.

Precautions

• General Precautions: Neuromuscular monitoring is essential. Ensure adequate ventilation is available. Caution in patients with myasthenia gravis, Eaton-Lambert syndrome, or other neuromuscular diseases.
• Specific Populations: Use with caution in pregnancy, especially the first trimester. Caution with breastfeeding.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Atracurium?

A: Intubation: 0.4-0.5 mg/kg IV. Surgical relaxation: 0.4-0.5 mg/kg IV followed by maintenance doses. ICU: Continuous infusion titrated to effect.

Q2: How does Atracurium work?

A: It competitively blocks nicotinic acetylcholine receptors at the neuromuscular junction, preventing muscle contraction.

Q3: What are the common side effects of Atracurium?

A: Flushing, hypotension, tachycardia or bradycardia, allergic reactions.

Q4: What are the contraindications for Atracurium?

A: Hypersensitivity to atracurium, cisatracurium, or benzenesulfonic acid.

Q5: Can Atracurium be used in patients with renal or hepatic impairment?

A: Yes, no dosage adjustments are necessary due to its unique metabolic pathway.

Q6: What are the important drug interactions with Atracurium?

A: Aminoglycosides, inhalational anesthetics, magnesium salts.

Q7: Can Atracurium be used during pregnancy?

A: Use with caution, especially in the first trimester. Generally safe during cesarean section with proper dosage.

Q8: How is neuromuscular blockade monitored during Atracurium administration?

A: Primarily through train-of-four (TOF) monitoring.

Q9: What is the duration of action of Atracurium?

A: Approximately 20-35 minutes after a single bolus dose.

Q10: What is the antidote for Atracurium overdose?

A: Neostigmine or edrophonium, along with atropine to prevent bradycardia.