Cisatracurium

Cisatracurium is the single active isomer (1R-cis 1’R-cis) of atracurium. It has about four times the potency of atracurium, a similar organ-independent Hofmann elimination, no histamine release at clinical doses, and produces much less laudanosine. It is the preferred relaxant in many intensive care units and in patients with kidney or liver failure.

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 at 0.15 mg/kg and 1.5 to 2 minutes at 0.4 mg/kg. Clinical duration 40 to 60 minutes at 0.15 mg/kg. Elimination half-life about 25 minutes. About 77% is eliminated by Hofmann elimination, which depends on pH and temperature, with the remainder by renal excretion and a small proportion by esterases. Laudanosine is produced in much smaller amounts than with atracurium.

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

Adults

• Intubation: 0.15 mg/kg intravenously (range 0.1 to 0.2 mg/kg).
• Maintenance: 0.03 mg/kg every 20 minutes, or infusion 1 to 2 micrograms/kg/minute (0.06 to 0.12 mg/kg/hour) after early recovery.
• Intensive care infusion: 3 micrograms/kg/minute (0.18 mg/kg/hour), with a range of 0.5 to 10.2 micrograms/kg/minute, titrated by train-of-four monitoring.
• Obesity: dose by ideal body weight.
• No fixed maximum dose; titrate to effect.

Children

• Ages 2 to 12 years: 0.1 mg/kg intravenously over 5 to 10 seconds.
• Infants 1 to 23 months: 0.15 mg/kg intravenously.
• Maintenance: 0.02 mg/kg every 10 to 15 minutes or infusion 1 to 2 micrograms/kg/minute.

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 cisatracurium, atracurium or benzenesulfonic acid; absence of airway skills and ventilation equipment.

Boxed-warning-level risks. Anaphylaxis; residual paralysis; intensive care acquired weakness with prolonged infusion, especially with corticosteroids.

Adverse effects. Common: few at clinical doses; occasional bradycardia and hypotension. Serious: anaphylaxis, prolonged weakness after long infusions, residual block.

Interactions. Volatile anaesthetics reduce the dose by 15 to 40%. Aminoglycosides, clindamycin, magnesium, lithium and calcium channel blockers prolong the block. Long term antiepileptics shorten it. Acidosis and hypothermia prolong it. Alkaline solutions including Ringer’s lactate cause precipitation.

Common prescribing errors. Mixing with alkaline fluids; leaving a long infusion at fixed rate without train-of-four monitoring; assuming that organ failure requires dose reduction; expecting sugammadex to reverse it.

Special groups

• Pregnancy: low placental transfer; used for caesarean section.
• Breastfeeding: compatible after recovery.
• Older adults: slightly longer onset; usual dose.
• Kidney impairment: no dose adjustment.
• Liver impairment: no dose adjustment.
• Regional: store at 2 to 8 degrees Celsius; most labels allow storage at room temperature for up to 21 days; keep the date on the vial.

Formulations. Injection 2 mg/mL (5 mg in 2.5 mL, 10 mg in 5 mL and 20 mg in 10 mL) and 5 mg/mL (200 mg in 20 mL, for intensive care).

Administration. Give as an intravenous bolus with a flush. Dilute for infusion in 0.9% sodium chloride or 5% glucose to 0.1 to 2 mg/mL. Do not mix with alkaline solutions.

Baseline. Allergy history, neuromuscular disease, weight, temperature, acid-base status.

Monitoring. Continuous electrocardiogram, oxygen saturation and capnography. Train-of-four monitoring, with a ratio of at least 0.9 before extubation. In intensive care, daily review of the need for paralysis and the train-of-four count.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Reduce the infusion when the train-of-four count is 1 to 2. Stop as soon as paralysis is no longer needed. Avoid combining with high-dose corticosteroids for long periods.

Referral and escalation. Persistent weakness needs review for critical illness myopathy and neuropathy, electrolyte correction and rehabilitation. Anaphylaxis needs intramuscular adrenaline.