Dexmedetomidine
Highly selective alpha-2 adrenoceptor agonistFor exam revision only — verify all doses against the current BNF, the SmPC and your local formulary before clinical use. Disclaimer
Summary
IV alpha-2 agonist with sedative and analgesic effects and minimal respiratory depression; less hypotension and a more predictable haemodynamic profile than clonidine; IV infusion only.
Indications & Dosing
- Critical-care sedation
IV loading 0.5-1.0 micrograms/kg (avoid if unstable); infusion 0.2-0.7 micrograms/kg/hr (up to 1.5). May reduce ventilation days and delirium; wean gradually.
- Adjunct to anaesthesia
IV loading 0.5-1.0 micrograms/kg; infusion 0.2-0.7 micrograms/kg/hr. Reduces MAC, opioid-sparing, reduces PONV and emergence delirium.
- Procedural / regional
Procedural sedation (e.g. awake intubation); prolongs regional/neuraxial blocks.
Contraindications
- Extreme caution in heart block, bradycardia, hypotension/hypovolaemia, severe LV dysfunction, PVD; and with beta-blockers/digoxin, TCAs, haloperidol (QT).
- Bolus dosing not recommended (vasoconstriction, hypertension, reflex bradycardia); avoid sudden withdrawal (rebound hypertension).
Formulations
- Injection (vials)
200 micrograms/2 mL, 400 micrograms/4 mL, 1000 micrograms/10 mL.
- Infusion
Dilute to 4 or 8 micrograms/mL in 0.9% saline or 5% glucose.
Structure & Chemical Properties
- Imidazoline derivative; dextroisomer of medetomidine; formula C13H16N2.
- Basic molecule, pKa 7.1; freely water-soluble with excellent fat solubility.
Effect Timings
- Onset / peak
<5 min / within 15 min.
- Context-sensitive half-time
Up to 4 hr after prolonged infusion.
Absorption
- Oral bioavailability
16% (extensive first-pass); primarily IV, can be intranasal.
Distribution
- Protein binding
94% (albumin and alpha-1-glycoprotein).
- Volume of distribution
1.31-2.46 L/kg; crosses blood-brain and placental barriers.
Metabolism
- Site
Primarily hepatic (glucuronidation + CYP450).
- Metabolites
Inactive; excreted renally (95%) and faecally (4%).
Elimination
- Distribution half-life
6 min.
- Terminal half-life
2 hr; does not accumulate in renal failure.
- Clearance
30-60 mL/min/kg.
Mechanism of Action
- Highly selective presynaptic alpha-2 agonist (alpha-1:alpha-2 1:1,620) acting on the locus coeruleus - more potent, more predictable sedation than clonidine.
- Limited alpha-1 and imidazoline activity (less than clonidine).
Systemic Effects
- CNS
Sedation/anxiolysis resembling natural sleep (rousable); decreases cerebral blood flow (not ICP); decreases IOP.
- CVS
Bolus: vasoconstriction, hypertension, reflex bradycardia (avoid). Therapeutic: bradycardia (~20%), vasodilation/hypotension (more predictable than clonidine); CO maintained.
- Respiratory
Minimal depression; no change in RR or PaCO2 at therapeutic doses.
- GI / Renal
Reduces gut motility, antisialogogue; diuresis (inhibits ADH).
Side Effects & Toxicity
- Excessive sedation, confusion, hallucinations; hypotension (transient hypertension on injection); bradycardia/heart block; dry mouth; constipation.