Pancuronium

Pancuronium is a long-acting aminosteroid non-depolarising neuromuscular blocking drug with vagolytic and sympathomimetic effects, causing tachycardia and a rise in blood pressure. It is inexpensive and remains in use for long procedures, cardiac surgery and ventilation in intensive care in some settings. The long duration and renal elimination make residual block a particular concern.

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

Mechanism. Competitive antagonism of acetylcholine at the nicotinic receptor of the motor end plate, with blockade of cardiac muscarinic receptors.

Pharmacokinetics. Onset 2 to 3 minutes at 0.08 to 0.1 mg/kg. Clinical duration 60 to 100 minutes. Elimination half-life about 2 hours, prolonged in kidney and liver impairment and in older adults. About 40 to 60% is excreted unchanged in urine; the rest is metabolised in the liver to less active metabolites and excreted in bile.

Indications are tracheal intubation, maintenance of relaxation in long procedures, and ventilation in intensive care when a long-acting relaxant and a modest rise in heart rate are acceptable.

Adults

• Intubation: 0.08 to 0.1 mg/kg intravenously .
• Maintenance: 0.01 to 0.02 mg/kg (usually 1 to 2 mg) every 30 to 60 minutes as needed.
• Intensive care: intubating dose, then intermittent boluses of 0.01 to 0.02 mg/kg, adjusted by train-of-four monitoring.
• Older adults, kidney impairment, liver impairment: reduce doses by 25 to 50% and extend intervals.
• No fixed maximum dose; titrate to effect.

Children

• Over 1 month: 0.08 to 0.1 mg/kg intravenously; maintenance 0.01 to 0.02 mg/kg.
• Neonates: more sensitive; use a test dose of 0.02 mg/kg, then titrate.

Reversal. Neostigmine 50 micrograms/kg with glycopyrronium 10 micrograms/kg when the train-of-four count is at least 2, or sugammadex 4 mg/kg at a deep block (effect is less predictable and the dose may need repeating).

Contraindications. Hypersensitivity to pancuronium or bromide; ischaemic heart disease and tachyarrhythmias (relative); hypertension that is uncontrolled (relative); severe kidney failure with a creatinine clearance under 10 mL/minute (relative); absence of airway skills and ventilation equipment.

Boxed-warning-level risks. Residual paralysis from the long duration; tachycardia and hypertension in patients with ischaemic heart disease; anaphylaxis.

Adverse effects. Common: tachycardia, hypertension, mild increase in cardiac output, salivation. Serious: arrhythmias, myocardial ischaemia, prolonged paralysis, residual block with aspiration, anaphylaxis, intensive care acquired weakness.

Interactions. Volatile anaesthetics, aminoglycosides, clindamycin, magnesium, lithium and calcium channel blockers prolong the block. Tricyclic antidepressants, halothane and sympathomimetics increase arrhythmia risk. Long term antiepileptics shorten the block.

Common prescribing errors. Using in patients with coronary disease or arrhythmia; failing to reverse a long block; repeated doses in kidney failure; not monitoring the train-of-four count during long cases.

Special groups

• Pregnancy: limited use; crosses the placenta modestly. Prefer shorter-acting agents.
• Breastfeeding: compatible after recovery.
• Older adults: prolonged duration; use lower doses.
• Kidney impairment: prolonged action; reduce doses and extend intervals.
• Liver impairment: prolonged action; reduce doses.
• Regional: inexpensive and heat stable enough for storage at room temperature for up to 6 months in many labels, so it may be the only long-acting relaxant available; plan for the long duration and keep ventilation until full recovery.

Formulations. Injection 2 mg/mL (4 mg in 2 mL ampoules).

Administration. Give as an intravenous bolus followed by a flush. Store at 2 to 8 degrees Celsius; check the label for the allowed time at room temperature.

Baseline. Cardiovascular status, heart rate, kidney and liver function, neuromuscular disease, allergy history, current medicines.

Monitoring. Continuous electrocardiogram, blood pressure, oxygen saturation and capnography. Train-of-four monitoring, with a ratio of at least 0.9 before extubation. Heart rate and blood pressure after each dose.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Stop repeating doses when the train-of-four count remains 1 to 2. Stop and treat for heart rate over 120 beats/minute with ischaemia, or arrhythmia.

Referral and escalation. Persistent block needs ventilation with sedation until recovery, reversal when the train-of-four count permits, and correction of electrolytes. Tachycardia with chest pain needs a 12-lead electrocardiogram and cardiology review. Anaphylaxis needs intramuscular adrenaline.