Atracurium

How to use atracurium in theatre/ICU

• Typical intubating dose: 0.5 mg/kg IV (range 0.4–0.6 mg/kg). Onset ~2–3 min; clinical duration ~20–35 min.
  • Lower dose (e.g. 0.3 mg/kg) gives slower onset and shorter/less intense block; useful if concern about histamine-mediated effects.
• Maintenance: 0.1–0.2 mg/kg boluses or infusion ~5–10 micrograms/kg/min (titrate to TOF).
  • Infusion requirement may increase with enzyme-inducing drugs and decrease with volatile agents, hypothermia, and magnesium.
• Reversal: neostigmine + antimuscarinic when TOF count ≥2 (or preferably TOF ratio improving); sugammadex has no role.
  • Allow adequate spontaneous recovery; deep block reversal is slower than with aminosteroids because sugammadex is ineffective.
• Monitoring: quantitative neuromuscular monitoring recommended (TOF ratio ≥0.9 before extubation).
  • Atracurium can have variable recovery in ICU (temperature/pH effects); avoid relying on clinical tests alone.

When to choose atracurium

• Useful when organ-independent elimination is desirable: renal failure, hepatic failure, multi-organ failure.
  • Cisatracurium is often preferred in ICU due to less histamine release and less laudanosine production, but atracurium remains acceptable with monitoring.
• Avoid/Use caution: severe asthma, haemodynamic instability, raised ICP/seizure risk (theoretical via laudanosine), situations where histamine release would be problematic.
  • Histamine-related effects are dose- and rate-dependent; slow injection and smaller doses reduce risk.

Drug class and mechanism

• Non-depolarising neuromuscular blocker; benzylisoquinolinium compound; competitive antagonist at nicotinic acetylcholine receptors at the neuromuscular junction.
• Produces skeletal muscle paralysis without analgesia or hypnosis; requires sedation/anaesthesia and ventilation support.

Pharmacokinetics (PK)

• Elimination is largely organ-independent: Hofmann elimination (temperature- and pH-dependent) + non-specific ester hydrolysis (plasma/tissue esterases).
  • Hofmann elimination increases with higher temperature and higher pH (alkalosis); decreases with hypothermia and acidosis → prolonged block.
• Metabolites: laudanosine (CNS stimulant; theoretical seizure risk) and a quaternary acrylate; metabolites are more dependent on hepatic/renal clearance than parent drug.
  • Clinically significant seizures are rare at standard anaesthetic doses; risk discussed mainly with prolonged high-dose infusions, especially in ICU.
• Onset/duration: intermediate-acting; onset slower than rocuronium; recovery relatively predictable but affected by temperature/pH and concomitant drugs.

Pharmacodynamics (PD) and clinical effects

• Histamine release: can cause flushing, bronchospasm, hypotension, tachycardia; most likely with rapid injection or higher doses.
  • Management: slow administration, reduce dose, treat with fluids/vasopressors; consider alternative NMBD (e.g. cisatracurium) in high-risk patients.
• No significant vagolytic effect (contrast: pancuronium). Cardiovascular stability generally good at standard doses but histamine can dominate.
• Does not trigger malignant hyperthermia; does not cause hyperkalaemia (unlike suxamethonium).

Dose, preparation, and administration

• Common preparation: 10 mg/mL (check local formulation). Store refrigerated (2–8°C) to reduce degradation; protect from prolonged room temperature storage.
  • Atracurium undergoes spontaneous degradation; potency decreases more rapidly at higher temperatures.
• Give IV; avoid mixing in alkaline solutions (e.g. thiopentone) due to incompatibility/precipitation risk; flush line between drugs.

Interactions and factors altering block

• Potentiation: volatile anaesthetics, aminoglycosides, magnesium, lithium, local anaesthetics (systemic), some antiarrhythmics, tetracyclines.
  • ICU: corticosteroid + NMBD exposure associated with ICU-acquired weakness/myopathy; minimise dose/duration and monitor closely.
• Resistance: chronic anticonvulsants (enzyme induction), burns (after ~24–48 h), upper motor neuron lesions (upregulation of receptors) — may increase dose requirements.
• Acid–base/temperature: acidosis and hypothermia prolong effect by reducing Hofmann elimination; alkalosis and hyperthermia shorten effect.

Use in special populations

• Renal failure: parent drug clearance largely unaffected; metabolites (incl. laudanosine) may accumulate—clinical relevance usually low at standard doses; monitor recovery.
• Hepatic failure: parent drug clearance largely preserved; metabolites may accumulate; consider cisatracurium if prolonged infusion anticipated.
• Pregnancy: crosses placenta minimally (quaternary ammonium); can be used for RSI alternative when suxamethonium contraindicated, but onset slower than rocuronium.
• Elderly: sensitivity may increase and clearance may be reduced; titrate to effect with monitoring.

Adverse effects and complications

• Histamine-mediated: hypotension, flushing, bronchospasm; risk increased with rapid bolus and larger doses.
• Anaphylaxis: possible with any NMBD; manage per anaphylaxis guidelines and document/arrange investigation.
• Prolonged paralysis: hypothermia, acidosis, drug interactions, critical illness; ensure quantitative monitoring and appropriate reversal.
• Laudanosine: theoretical CNS excitation/seizures, mainly with prolonged infusions; more relevant historically with atracurium than cisatracurium.

Comparison: atracurium vs cisatracurium vs rocuronium (high yield)

• Atracurium: intermediate; Hofmann + ester hydrolysis; more histamine release; more laudanosine than cisatracurium.
• Cisatracurium: stereoisomer; less histamine; less laudanosine; often preferred in ICU for infusions.
• Rocuronium: aminosteroid; hepatic/biliary clearance; rapid onset at higher dose; reversible with sugammadex.