Dexmedetomidine

Approved Indications:

• Sedation of Intubated and Mechanically Ventilated Patients: For sedation of adult patients in intensive care units (ICU).
• Procedural Sedation: Sedation of non-intubated patients prior to and/or during surgical and other procedures.
• Adjunct to General Anesthesia: Used to provide sedation and analgesia during anesthesia.

Off-label or Clinically Accepted Uses:

• Sedation of pediatric patients in ICU or procedural settings (limited approval in some regions).
• Sedation in monitored anesthesia care.
• Management of alcohol withdrawal syndrome.
• Adjunctive treatment in opioid or benzodiazepine withdrawal.

Adults:

• ICU Sedation:
• Loading Dose: Optional; 1 mcg/kg IV over 10 minutes.
• Maintenance Infusion: 0.2 to 0.7 mcg/kg/hour IV infusion, titrated to desired sedation level.
• Procedural Sedation:
• Loading Dose: 1 mcg/kg IV over 10 minutes.
• Maintenance Infusion: 0.2 to 1.0 mcg/kg/hour during procedure.

Pediatrics:

• Dosage must be individualized; generally lower dosing than adults.
• Limited data; use under specialist supervision.

Elderly:

• Initiate dosing at the lower end of the recommended range.
• Monitor hemodynamic response closely.

Renal Impairment:

• No specific dosage adjustment required; monitor patient response.

Hepatic Impairment:

• Use caution; reduced clearance may necessitate dose reduction.

Administration Notes:

• Administered intravenously by continuous infusion.
• Loading dose may be omitted in ICU sedation to avoid hemodynamic instability.
• Monitor vital signs and sedation level frequently.

Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist. It acts on alpha-2 receptors in the locus coeruleus of the brainstem to decrease norepinephrine release, producing sedative, anxiolytic, and analgesic effects without significant respiratory depression. Activation of alpha-2 receptors in the spinal cord also contributes to analgesia by inhibiting nociceptive neuron firing. The sedative state mimics natural sleep, allowing for easier arousability and cooperation compared to other sedatives.

• Absorption: Administered intravenously; rapid onset of action within minutes.
• Distribution: Volume of distribution approximately 118 L; highly protein bound (~94%) primarily to albumin and alpha-1 acid glycoprotein.
• Metabolism: Extensively metabolized in the liver by glucuronidation and cytochrome P450 enzymes (mainly CYP2A6).
• Half-life: Terminal elimination half-life is approximately 2 to 3 hours.
• Excretion: Metabolites excreted primarily in urine (~95%) and small amount in feces.

• Pregnancy: Classified as FDA Category C. Animal studies show adverse effects on fetus; no adequate human studies. Use only if benefits justify potential risks.
• Lactation: Unknown if excreted in human milk; use with caution and monitor infant for sedation or adverse effects if breastfeeding.

• Primary Class: Sedative and analgesic agent
• Subclass: Alpha-2 adrenergic receptor agonist

• Known hypersensitivity to dexmedetomidine or any component of the formulation.
• Advanced heart block or severe ventricular dysfunction without pacemaker support.
• Hypotension or bradycardia unresponsive to treatment.
• Concurrent use with other potent alpha-2 agonists without medical supervision.

• High-Risk Patients: Patients with cardiovascular disease, impaired hepatic function, elderly, or hypovolemia.
• Bradycardia and Hypotension: Common adverse effects; monitor heart rate and blood pressure closely. Use caution in patients with conduction abnormalities.
• Withdrawal: Abrupt discontinuation after prolonged infusion can cause withdrawal symptoms including hypertension, tachycardia, and agitation.
• Respiratory Effects: Minimal respiratory depression; still monitor respiratory function during sedation.
• Neurologic Effects: Monitor for oversedation or delirium.
• Monitoring: Continuous monitoring of cardiovascular and respiratory status is essential during administration.

Common:

• Hypotension
• Bradycardia
• Dry mouth
• Nausea
• Transient hypertension (especially during loading dose)
• Dizziness

Serious/Rare:

• Severe bradycardia requiring intervention
• Heart block
• Respiratory depression (rare)
• Withdrawal symptoms after prolonged use
• Allergic reactions including anaphylaxis (rare)

• CNS Depressants: Additive sedation with benzodiazepines, opioids, barbiturates.
• Antihypertensives and Beta-blockers: May enhance bradycardic and hypotensive effects.
• CYP2A6 inhibitors: May increase dexmedetomidine plasma levels.
• Other Alpha-2 Agonists: Additive effects; avoid concomitant use unless closely monitored.
• Alcohol: Increased sedation and hypotension risk.

• Updated ICU sedation guidelines endorse dexmedetomidine for sedation due to its minimal respiratory depression and favorable cognitive profile.
• Recommendations highlight avoidance of loading dose in hemodynamically unstable patients.
• Monitoring for bradycardia and hypotension is emphasized.
• Growing evidence supports use in pediatric sedation under specialist supervision.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light.
• Do not freeze.
• Use immediately after dilution; discard any unused portion after recommended period.
• Keep out of reach of children.