Atracurium Besilate

Approved Indications:

• Adjunct to general anesthesia: To facilitate endotracheal intubation and skeletal muscle relaxation during surgical procedures.
• Facilitation of mechanical ventilation: Used in intensive care units (ICUs) for patients requiring prolonged respiratory support.

Clinically Accepted Off-label Uses:

• Status asthmaticus (refractory cases): As a paralytic agent to assist mechanical ventilation when standard treatments fail.
• Electroconvulsive therapy (ECT): Occasionally used to reduce muscular convulsions during ECT sessions.

Route of Administration: Intravenous (IV) injection or continuous infusion only.

Adult Dosage:

• Initial (intubation): 0.4–0.5 mg/kg IV over 60 seconds.
• Maintenance (intermittent bolus): 0.08–0.1 mg/kg IV every 20–45 minutes as needed.
• Continuous infusion: 5–9 mcg/kg/min, adjusted based on neuromuscular monitoring.

Pediatric Dosage:

• Children >1 month: 0.3–0.6 mg/kg IV (intubation); maintenance doses or infusion as per adult protocol.
• Neonates: Use with caution; reduced doses required; close neuromuscular monitoring essential.

Elderly Patients:

• No dosage adjustment generally required. However, due to possible increased sensitivity, titration should be cautious.

Renal Impairment:

• No dose adjustment necessary. Atracurium is primarily metabolized by Hofmann elimination, which is independent of renal function.

Hepatic Impairment:

• No dose adjustment typically needed. Elimination is not dependent on liver enzymes.

ICU Sedation (Prolonged Ventilation):

• Continuous infusion of 0.3–0.6 mg/kg/hr is commonly used; requires frequent monitoring with Train-of-Four (TOF) neuromuscular assessment.

Administration Notes:

• Avoid rapid IV bolus (can cause histamine release).
• Always use peripheral nerve stimulator to guide dosing.
• Reversal of blockade: Anticholinesterases (e.g., neostigmine + atropine) may be used when recovery is desired.

Atracurium Besilate is a non-depolarizing neuromuscular blocking agent of the benzylisoquinolinium class. It works by competitively binding to nicotinic acetylcholine receptors at the neuromuscular junction, thereby blocking acetylcholine from activating these receptors and preventing depolarization of skeletal muscle fibers. This leads to reversible paralysis of skeletal muscles. Atracurium does not depolarize the muscle membrane, thus avoiding fasciculations seen with depolarizing agents. The drug’s activity is terminated by spontaneous degradation through Hofmann elimination and plasma ester hydrolysis rather than by organ-dependent metabolism.

• Absorption: Administered IV; 100% bioavailability.
• Onset of Action: Within 2–3 minutes after bolus injection.
• Duration of Action: 20–35 minutes after a single dose.
• Distribution: Volume of distribution ~0.2–0.5 L/kg.
• Metabolism:
• Hofmann elimination: Non-enzymatic, pH- and temperature-dependent degradation.
• Ester hydrolysis: By nonspecific plasma esterases.
• Half-life (Terminal): Approximately 20 minutes.
• Excretion: Inactive metabolites excreted via urine and bile. Clearance is largely independent of hepatic and renal function.
• Active Metabolites: Produces laudanosine, which has CNS excitatory properties but is clinically insignificant at standard doses.

Pregnancy:

• FDA Pregnancy Category C (historical): No adequate human studies; animal studies showed some adverse effects.
• Should be used during pregnancy only if clearly necessary (e.g., during surgery or critical care).
• May cause transient neonatal muscle weakness if administered before delivery.

Lactation:

• Unknown whether excreted in human breast milk.
• Due to its short half-life and poor oral bioavailability, adverse effects in nursing infants are unlikely.
• Use with caution; temporary suspension of breastfeeding may be considered after administration.

• Primary Class: Skeletal Muscle Relaxant
• Subclass: Non-depolarizing neuromuscular blocker
• Chemical Class: Benzylisoquinolinium derivative
• Duration: Intermediate-acting

• Hypersensitivity to atracurium or any component of the formulation.
• History of anaphylaxis to other non-depolarizing neuromuscular blocking agents.
• Known severe allergic reaction to benzylisoquinoline compounds.

• Anaphylaxis: Life-threatening allergic reactions can occur; cross-sensitivity among neuromuscular blockers exists.
• Histamine Release: Rapid injection can cause hypotension, flushing, or bronchospasm; administer over 60 seconds.
• Prolonged Paralysis: Prolonged infusion or corticosteroid co-administration may lead to extended neuromuscular blockade.
• Laudanosine Accumulation: Especially with prolonged infusion; may increase risk of CNS excitation or seizures.
• Acidosis and Hypothermia: May prolong drug activity due to effects on Hofmann elimination.
• Myasthenia Gravis or Neuromuscular Disease: Enhanced sensitivity; use lower doses with caution.
• Monitoring: Continuous neuromuscular function monitoring is essential during administration.

Common (≥1%):

• Cardiovascular: Hypotension, flushing
• Respiratory: Bronchospasm
• Injection site reactions: Pain, irritation

Less Common (<1%):

• Allergic Reactions: Urticaria, rash, pruritus
• Neurological: Seizures (from laudanosine metabolite; rare and dose-related)
• Prolonged paralysis: Especially with high doses or extended ICU use

Serious Side Effects:

• Anaphylaxis
• Severe bronchospasm
• Seizures (rare)

Timing & Dose-dependence:

• Onset within minutes; duration depends on dose and patient condition.
• Higher doses and prolonged infusion increase risk of adverse effects.

Potentiating Interactions:

• Inhalation anesthetics: (e.g., halothane, isoflurane) enhance neuromuscular block.
• Antibiotics: (e.g., aminoglycosides, polymyxins, tetracyclines) may increase effect.
• Magnesium sulfate and lithium: Enhance blockade.
• Corticosteroids (prolonged): Increase risk of persistent neuromuscular weakness.

Antagonizing Agents:

• Acetylcholinesterase inhibitors: (e.g., neostigmine, edrophonium) reverse blockade.

Metabolic Interactions:

• Not metabolized by CYP450 enzymes; minimal risk of hepatic drug interactions.

Food/Alcohol Interactions: No clinically significant food or alcohol interactions reported.

• No major updates in FDA, WHO, or EMA guidelines regarding new indications or warnings.
• Critical care guidelines (e.g., for ventilated patients) emphasize the importance of limiting prolonged infusion and neuromuscular monitoring to prevent complications.
• Recent post-COVID ICU protocols continue to support its use with tight monitoring of neuromuscular blockade.

• Temperature: Store at 2°C to 8°C (refrigerated).
• Do not freeze.
• Light Protection: Keep protected from direct light.
• Handling:
• Once removed from refrigeration, stable for up to 24 hours at room temperature.
• Discard any unused solution.
• For IV infusion, use immediately after dilution.
• Compatibility: Compatible with sodium chloride 0.9% or dextrose 5% for dilution.