Dexmedetomidine

Dexmedetomidine is a highly selective alpha-2 adrenergic agonist producing sedation, anxiolysis and analgesia with little respiratory depression, and a sedation from which the patient can be roused easily. It is used for intensive care sedation, awake procedures such as fibreoptic intubation, and as an anaesthetic adjunct. It causes bradycardia and hypotension, and withdrawal after prolonged use.

Class. Alpha-2 adrenergic agonist (sedative).

Mechanism. Activates presynaptic and postsynaptic alpha-2 receptors in the locus coeruleus and spinal cord, reducing noradrenaline release and producing sedation similar to natural sleep and analgesia.

Pharmacokinetics. Intravenous onset 5 to 10 minutes (after a loading dose) and peak effect at 15 to 30 minutes. Distribution half-life about 6 minutes; elimination half-life about 2 hours. Protein binding about 94%. Extensive hepatic metabolism by glucuronidation and CYP2A6, with inactive metabolites excreted in urine and faeces. Clearance is reduced in liver impairment.

Indications are sedation of ventilated patients in intensive care, procedural sedation (fibreoptic intubation, imaging, minor surgery), and as an adjunct to anaesthesia.

Adults

• Intensive care sedation: optional loading dose of 1 microgram/kg over 10 minutes (omit in unstable patients), then maintenance 0.2 to 0.7 micrograms/kg/hour, titrated every 30 minutes (maximum 1.4 micrograms/kg/hour).
• Procedural sedation (non-intubated): loading dose 1 microgram/kg over 10 minutes (0.5 microgram/kg for less invasive procedures), then maintenance 0.2 to 1 microgram/kg/hour (usually 0.6 microgram/kg/hour).
• Fibreoptic intubation: loading dose 1 microgram/kg over 10 minutes, then 0.7 micrograms/kg/hour until the tube is placed.
• Older adults (over 65 years): reduce the loading dose to 0.5 microgram/kg and the maintenance rate.
• Liver impairment: reduce doses.
• Do not give a loading dose to unstable patients.

Children (specialist, often off-label)

• Intensive care: loading dose 0.5 to 1 microgram/kg over 10 minutes, then 0.2 to 1.4 micrograms/kg/hour.
• Intranasal premedication or sedation: 2 to 3 micrograms/kg, onset about 30 to 45 minutes.
• Emergence agitation after sevoflurane: 0.3 to 0.5 microgram/kg.

Contraindications. Advanced heart block (grade 2 or 3) without a pacemaker; uncontrolled hypotension; acute cerebrovascular conditions; hypersensitivity.

Boxed-warning-level risks. Bradycardia, sinus arrest and hypotension (particularly with a loading dose or rapid bolus); transient hypertension with a bolus; withdrawal syndrome (agitation, tachycardia, hypertension) after more than 24 hours of infusion.

Adverse effects. Common: bradycardia, hypotension, dry mouth, nausea. Serious: sinus arrest, severe hypotension, hypertension, atrial fibrillation, withdrawal agitation, fever.

Interactions. Sedatives, opioids, propofol and volatile agents add sedation and may need dose reduction by 30 to 50%. Beta blockers, digoxin, verapamil and diltiazem add bradycardia and block. Antihypertensives add hypotension.

Common prescribing errors. Giving a loading dose to an unstable or older patient; expecting amnesia; stopping an infusion after several days abruptly; using it as a sole drug in agitated delirium; failing to dilute correctly.

Special groups

• Pregnancy: limited data; use only when benefit outweighs risk.
• Breastfeeding: small amounts enter milk; avoid prolonged use.
• Older adults: reduce dose, and monitor for bradycardia and hypotension.
• Kidney impairment: no adjustment.
• Liver impairment: reduce the maintenance dose.
• Regional: availability and cost limit use; where it is available, prepare dilutions in labelled syringes to avoid errors with the concentrate.

Formulations. Concentrate 100 micrograms/mL (200 micrograms in 2 mL), and ready-to-use bags or vials at 4 micrograms/mL or 8 micrograms/mL.

Administration. Dilute the concentrate to 4 micrograms/mL (200 micrograms in 48 mL of 0.9% sodium chloride) or 8 micrograms/mL for infusion. Give the loading dose over at least 10 minutes. Use an infusion pump.

Baseline. Heart rate and rhythm, blood pressure, conduction disease, volume status, liver function, current sedatives and rate-slowing drugs.

Monitoring. Continuous electrocardiogram and blood pressure, oxygen saturation and capnography, with sedation scoring. After long infusion, observe for withdrawal.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Reduce the dose or stop for heart rate under 50 beats/minute, systolic blood pressure under 90 mmHg, or new heart block. After more than 24 hours of infusion, reduce stepwise over 24 hours or more.

Referral and escalation. Symptomatic bradycardia needs atropine 0.5 to 1 mg intravenously and stopping the infusion. Severe hypotension needs fluids and a vasopressor. Sinus arrest needs advanced life support.