Atracurium

Atracurium is an intermediate-acting benzylisoquinolinium non-depolarising neuromuscular blocking drug that is broken down by spontaneous degradation (Hofmann elimination) and ester hydrolysis, independent of liver and kidney function. It is useful in organ failure. It releases histamine at higher doses, and its metabolite laudanosine can accumulate.

Class. Non-depolarising neuromuscular blocking drug (benzylisoquinolinium).

Mechanism. Competitive antagonism of acetylcholine at the nicotinic receptor of the motor end plate.

Pharmacokinetics. Onset 2 to 3 minutes. Clinical duration 20 to 45 minutes. Elimination half-life about 20 minutes. Hofmann elimination depends on pH and temperature, so acidosis and hypothermia slow it. Ester hydrolysis by plasma esterases accounts for much of the rest, with a small renal contribution. Laudanosine is excreted in urine and bile, and can cause seizures at high concentrations.

Indications are tracheal intubation, maintenance of relaxation during surgery, and mechanical ventilation in intensive care, particularly in patients with kidney or liver failure.

Adults

• Intubation: 0.5 mg/kg intravenously slowly over 60 seconds (range 0.3 to 0.6 mg/kg).
• Maintenance: 0.1 to 0.2 mg/kg every 15 to 25 minutes, or infusion 5 to 10 micrograms/kg/minute (0.3 to 0.6 mg/kg/hour).
• Intensive care infusion: 11 to 13 micrograms/kg/minute (0.65 to 0.78 mg/kg/hour), with a range of 4.5 to 29.5 micrograms/kg/minute, adjusted by train-of-four monitoring.
• Doses above 0.5 mg/kg increase the risk of histamine release; give slowly.
• Obesity: dose by ideal body weight.
• No fixed maximum dose; titrate to effect.

Children

• Over 1 month: 0.5 mg/kg intravenously, with maintenance 0.1 to 0.2 mg/kg every 15 to 25 minutes or infusion 5 to 10 micrograms/kg/minute.
• Neonates: use with caution, because Hofmann elimination is less predictable in the very young.

Reversal. Neostigmine 50 micrograms/kg with glycopyrronium 10 micrograms/kg when the train-of-four count is at least 2. Sugammadex is not effective.

Contraindications. Hypersensitivity to atracurium, cisatracurium or benzenesulfonic acid; absence of airway skills and ventilation equipment. Use with caution in severe asthma or a history of anaphylaxis.

Boxed-warning-level risks. Anaphylaxis; histamine-mediated hypotension and bronchospasm; seizures from laudanosine with prolonged high-dose infusion, particularly in liver failure; residual block.

Adverse effects. Common: skin flushing, mild hypotension, tachycardia. Serious: histamine-mediated bronchospasm and cardiovascular collapse, anaphylaxis, seizures from laudanosine, intensive care acquired weakness with long infusion, residual paralysis.

Interactions. Volatile anaesthetics reduce the dose by 25 to 50%. Aminoglycosides, clindamycin, magnesium, lithium and calcium channel blockers prolong the block. Long term antiepileptics shorten it. Acidosis and hypothermia prolong it. Do not mix with alkaline solutions such as thiopental, which cause precipitation.

Common prescribing errors. Rapid bolus of a large dose causing hypotension; using in a patient with severe asthma when cisatracurium would be safer; leaving a long infusion at a fixed rate despite recovery; assuming that organ function is irrelevant when seizures occur.

Special groups

• Pregnancy: low placental transfer; acceptable for caesarean section.
• Breastfeeding: compatible after recovery.
• Older adults: no change in elimination; usual doses.
• Kidney impairment: no change in dose.
• Liver impairment: no change in dose, but laudanosine can accumulate over days.
• Regional: the drug loses potency at room temperature (about 5% each month); keep at 2 to 8 degrees Celsius and use within 14 days once out of the refrigerator.

Formulations. Injection 10 mg/mL (25 mg in 2.5 mL and 50 mg in 5 mL ampoules).

Administration. Inject slowly over 60 seconds with a flush. For infusion dilute in 0.9% sodium chloride or 5% glucose to 0.5 to 5 mg/mL. Flush the line after thiopental or other alkaline drugs.

Baseline. Allergy history, asthma, neuromuscular disease, body weight and temperature.

Monitoring. Continuous electrocardiogram, oxygen saturation and capnography. Blood pressure after the bolus. Train-of-four monitoring, with a ratio of at least 0.9 before extubation.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Slow the injection or reduce the dose for histamine release. Reduce the infusion when the train-of-four count is 1 to 2. Avoid prolonged high-dose infusion.

Referral and escalation. Bronchospasm or hypotension from histamine needs adrenaline in small intravenous doses, fluids and treatment as anaphylaxis. New seizures during long infusions need a benzodiazepine, discontinuation of the infusion and assessment for laudanosine accumulation.