Dexmedetomidine

Mechanism of Action:

-It is an imidazole derivative and is a specific alpha-2 adrenoceptor agonist that acts via post-synaptic alpha-2 receptors primarily in the locus ceruleus to increase conductance through K+ channels.

Uses and Dose:

-Its main actions are sedation, anxiolysis, and analgesia

-It is a clear, colorless isotonic solution containing 100 g/ml of dexmedetomidine base and 9 mg/ml of sodium chloride in water. The solution is preservative-free and contains no additives.

-Dexmedetomidine can be administered intravenously, intramuscularly, and transdermally.

1. ICU Sedation:

-Used for sedation of initially intubated and mechanically ventilated patients in ICU.

-Loading: 1 mcg/kg IV over 10 minutes; loading dose may not be required for adults converted from other sedative therapy.

-Maintenance 0.2-0.7 mcg/kg/h. continuous IV infusion; not to exceed 24 h.

-The duration of use should not exceed 24 hours.

-Dexmedetomidine has been infused in mechanically ventilated patients before, during, and after extubation; it is not necessary to discontinue dexmedetomidine before extubation.

2. Procedural Sedation:

Indicated for sedation of non-intubated patients before and/or during surgical and other procedures.

Loading: 1 mcg/kg IV over 10 minutes.

Maintenance 0.6 mcg/kg/h. IV titrate to effect (usually 0.2-1 mcg/kg/h.).

3. Awake Fiberoptic Intubation:

Loading: 1 mcg/kg IV over 10 minutes.

Maintenance 0.7 mcg/kg/hr IV until endotracheal tube secured.

Dosage Modifications:

-Dose reduction may be required if co-administered with other concomitant anesthetics, sedatives, hypnotics, or opioids.

-Consider dose reduction in patients with hepatic impairment or aged ≥ 65 y.; clearance decreases with increasing severity of hepatic impairment.

-Renal impairment: No dosage adjustment required.

Pharmacokinetics

Distribution: It is 94% protein-bound in the plasma; the volume of distribution is 1.33 l/kg. The distribution half-life is 6 minutes.

Metabolism: The drug undergoes extensive hepatic metabolism to methyl and glucuronide conjugates.

Excretion: 95% of the metabolites are excreted in the urine. The elimination half-life is 2 hours, and the clearance is 39 l/hour.

Pharmacodynamics:

1. Cardiovascular System: It causes a predictable decrease in the mean arterial pressure and heart rate.

2. Respiratory System: It causes a slight increase in PaCO₂ and a decrease in minute ventilation, with minimal change in the respiratory rate—these effects are not clinically significant.

3. Central Nervous System: The drug is sedative and anxiolytic—ventilated patients remain easily arousable and cooperative during treatment. Reversible memory impairment is an additional feature.

4. Metabolic / Other: It causes a decrease in plasma epinephrine and norepinephrine concentrations. It does not impair adrenal steroidogenesis when used in the short term.

Side Effects:

Hypotension, bradycardia, nausea, and a dry mouth are the most commonly reported side effects of the drug.

Categories: Anesthetic drugs