Atracurium: Uses, Dosage, Side Effects and Interactions

Atracurium besylate is a widely used non-depolarizing neuromuscular blocking agent, primarily utilized in anesthesia to facilitate muscle relaxation during surgical procedures and mechanical ventilation. Its unique metabolism—independent of liver and kidney function—makes it especially valuable for patients with compromised organ function. This article provides a comprehensive, evidence-based overview of atracurium’s clinical applications, recommended dosages, potential side effects, and drug interactions, synthesizing findings from peer-reviewed studies and clinical experience.

Uses of Atracurium

Atracurium serves as a cornerstone in modern anesthesia practice, thanks to its reliable muscle-relaxing properties and predictable pharmacokinetics. It is particularly valued when organ-independent elimination is advantageous.

Indication	Patient Population	Use Setting	Source(s)
Muscle relaxation	Adults, pediatrics	Surgery, ICU ventilation	2 6 8 9
Endotracheal intubation	All ages	Induction of anesthesia	2 8 11
Cardiac surgery	Patients with/without renal dysfunction	Cardiopulmonary bypass	3 4
Electroconvulsive therapy	Psychiatric patients	ECT modification	11

Table 1: Clinical Uses of Atracurium

General Anesthesia and Surgery

Atracurium is most commonly used to induce skeletal muscle relaxation during surgical procedures that require general anesthesia. It allows for controlled muscle paralysis, optimizing surgical conditions and facilitating endotracheal intubation. Its intermediate duration of action and reliable onset make it a preferred choice for a wide range of operations, including those of moderate to extended length 2 6 7 9.

Endotracheal Intubation

A key use of atracurium is to facilitate endotracheal intubation—essential for securing the airway during anesthesia or mechanical ventilation. Doses of 0.3–0.6 mg/kg IV produce suitable intubating conditions within 1–2 minutes, providing quick and effective muscle relaxation 2 6 8 11.

Use in Patients with Renal or Hepatic Dysfunction

Unlike many muscle relaxants, atracurium is not dependent on hepatic or renal elimination. It undergoes Hofmann elimination (a temperature- and pH-dependent chemical breakdown) and ester hydrolysis, allowing for safe use in patients with impaired kidney or liver function. This feature is particularly relevant in cardiac surgery, ICU settings, and among patients with end-stage renal failure 3 4 13 14.

Pediatric and Special Populations

Atracurium is effective in neonates, infants, and children. Pediatric patients require lower doses for the same degree of neuromuscular blockade, and recovery tends to be prompt across all age groups 8.

Electroconvulsive Therapy (ECT)

Atracurium is also employed during ECT to modify tonic-clonic convulsions, minimizing muscle injury while allowing for therapeutic seizures. Doses between 0.3 and 0.5 mg/kg have been studied, with higher doses providing more complete suppression of peripheral convulsions 11.

Dosage of Atracurium

Selecting the correct atracurium dose is crucial for ensuring effective muscle relaxation while minimizing risks. Dosage varies based on age, clinical scenario, and patient-specific factors.

Dose (mg/kg)	Indication/Population	Onset (min)	Source(s)
0.3–0.6	Intubation, surgery (adult)	1–2	2 6 7
0.5	Pediatric intubation	0.9–1.4	8
0.6 (bolus)	Cardiac surgery (initial dose)	1–2	4
0.006–0.0066/min	Infusion (maintenance)	—	4 5
0.3–0.5	Electroconvulsive therapy	—	11

Table 2: Atracurium Dosage and Administration

Adult and Pediatric Dosing

• Intubation and Surgical Relaxation: Recommended IV bolus dose is typically 0.3–0.6 mg/kg for adults, achieving profound muscle relaxation within 1–2 minutes 2 6. For children, 0.5 mg/kg provides rapid and effective blockade, though neonates and infants require less per kilogram due to increased sensitivity 8.
• Maintenance: During longer procedures, atracurium can be administered by continuous infusion at 0.006–0.0066 mg/kg/min (approx. 0.4 mg/kg/h), allowing for steady neuromuscular blockade 4 5.

Special Populations

• Renal or Hepatic Impairment: No dose adjustment is necessary, as elimination is independent of organ function 3 13 14.
• Cardiac Surgery & Hypothermia: Lower infusion rates are required during hypothermia, as the breakdown of atracurium slows with reduced temperature 4.
• Pediatrics: Neonates and infants require lower doses; recovery time is generally shorter compared to older children 8.

Reversal of Blockade

• Antagonism: Spontaneous recovery is possible, but reversal can be accelerated with neostigmine or edrophonium, typically preceded by atropine to prevent bradycardia 2 5 9.

Practical Considerations

• Administration Speed: Rapid bolus injection (e.g., 5 seconds) can cause transient histamine release; slower administration (over 75 seconds) reduces this risk 1.
• Cumulative Effects: Atracurium does not accumulate even with repeated doses or prolonged infusion, supporting its safety profile for lengthy procedures 2 3 5 6 9.

Side Effects of Atracurium

While generally well-tolerated, atracurium can cause several side effects, most notably related to histamine release and, rarely, allergic reactions.

Side Effect	Frequency/Severity	Risk Factors	Source(s)
Histamine release	Mild-moderate, transient	High/rapid doses	1 9
Hypotension	Mild, dose-dependent	Rapid/high doses	1 6
Tachycardia	Mild, dose-dependent	Rapid/high doses	1 6 7
Allergic reactions	Rare	Allergic diathesis	9 12
Seizure risk (rare)	Uncommon, metabolite-related	High doses/ICU	15

Table 3: Common Side Effects of Atracurium

Histamine Release and Cardiovascular Effects

• Histamine Release: Rapid IV bolus dosing can lead to transient histamine release, manifesting as flushing, hypotension, and tachycardia. This effect is minimized by slower administration or pretreatment with H1 and H2 antihistamines 1 9.
• Cardiovascular Effects: At clinically relevant doses, atracurium typically does not cause significant changes in blood pressure or heart rate. Mild decreases in arterial pressure and increases in heart rate can occur at higher doses, but these are rarely clinically significant in healthy patients 6 7 10.

Allergic and Hypersensitivity Reactions

• Anaphylaxis: Large post-marketing studies have not demonstrated an increased risk of anaphylaxis with atracurium compared to other neuromuscular blockers 12. Nonetheless, caution is advised in patients with a history of allergic diathesis 9.
• Other Reactions: No unique or previously unreported adverse effects were observed in large-scale surveillance 12.

Central Nervous System Effects

• Seizures: Atracurium’s metabolite, laudanosine, may lower seizure threshold, but clinically significant seizures are rare and usually associated with prolonged, high-dose infusions in ICU settings 15.

Pediatric and Special Populations

• Tolerance: Children and infants generally tolerate atracurium well, with a safety profile comparable to adults 8 9.

Interactions of Atracurium

Understanding drug interactions is essential for safe clinical use, especially in complex surgical or critical care settings.

Interacting Agent	Effect on Atracurium	Clinical Relevance	Source(s)
Halothane	Potentiates blockade	Increased effect	2
Neostigmine, Edrophonium	Reverses blockade	Antagonism	2 5 9
Other NM blockers	Additive effects	Monitor closely	17
Cyclosporin (Sandimmun)	Mild potentiation (animal studies)	Possibly relevant	16
Azathioprine	Slight antagonism	Negligible	14
Isoflurane	No significant change	Safe to use	10

Table 4: Drug Interactions with Atracurium

Anesthetic Drug Interactions

• Volatile Anesthetics: Agents like halothane potentiate the neuromuscular blockade of atracurium, prolonging its effect 2. Isoflurane does not significantly alter atracurium’s cardiovascular profile or intensity of block 10.
• Reversal Agents: Cholinesterase inhibitors such as neostigmine and edrophonium effectively reverse atracurium-induced blockade. Atropine is often given beforehand to counteract bradycardia 2 5 9.

Other Neuromuscular Blockers

• Combination Therapy: When combined with other neuromuscular blocking agents (e.g., cisatracurium, vecuronium, rocuronium), effects may be additive or synergistic. For example, the interaction between cisatracurium and atracurium is additive, while synergy is observed with vecuronium or rocuronium 17. Dose adjustments and close monitoring are necessary.

Immunosuppressants

• Cyclosporin: In animal studies, cyclosporin (particularly when formulated with Cremophor) mildly potentiated the effect of atracurium, though the clinical significance in humans is uncertain 16.
• Azathioprine: Only a minor, transient antagonism of neuromuscular block was noted, likely of little clinical importance 14.

Special Considerations

• Renal and Hepatic Function: Because atracurium is eliminated independently of these organs, interactions with drugs affecting renal or hepatic metabolism are minimal 3 13 14.
• Metabolite Effects: Laudanosine, atracurium’s metabolite, can interact with neuronal acetylcholine receptors, but clinical effects are usually negligible barring overdose or prolonged infusion 15.

Conclusion

Atracurium besylate stands out as a versatile, reliable neuromuscular blocking agent for surgical anesthesia and critical care, with unique advantages in patients with compromised organ function. Its predictable action, minimal accumulation, and favorable interaction profile underpin its widespread use. However, clinicians must be vigilant regarding histamine-mediated side effects, potential drug interactions, and rare but serious reactions.

Key Takeaways:

• Atracurium is valuable for muscle relaxation in surgery, ICU, and ECT settings, especially where hepatic or renal impairment is present 2 3 4 6 8 11 13.
• Standard dosing ranges from 0.3–0.6 mg/kg IV bolus for adults, with lower requirements in children and special populations; continuous infusion is suitable for prolonged procedures 2 4 5 6 8.
• Side effects are generally mild, with histamine release (flushing, hypotension, tachycardia) being the most notable; slow administration reduces this risk 1 6 9.
• Atracurium interacts predictably with other anesthetic agents and neuromuscular blockers; cholinesterase inhibitors effectively reverse its effects 2 5 9 17.
• Ongoing monitoring and patient-specific assessment ensure safe and effective use of atracurium across a broad range of clinical scenarios.

By understanding atracurium’s pharmacology, dosing, safety, and interactions, clinicians can maximize its benefits while minimizing risks—leading to better outcomes for patients requiring surgical anesthesia or mechanical ventilation.