Dexmedetomidine
Brand Names: Precedex
- activation of receptors in brain and spinal cord inhibits neuronal firing (release of
norepinephrine), causing hypotension, bradycardia, sedation, and analgesia
- hypnotic and sedative effects: locus coeruleus is predominant noradrenergic
nucleus in the brain
- analgesic effects : alpha2-adrenergic receptors in the dorsal horn of the spinal cord
modulates pain transmission signals
- blood pressure and heart rate: activation of the postsynaptic alpha-2 adrenoceptors
inhibits the sympathetic activity decreases blood pressure and heart rate
Background
- alpha2 agonist with 7 to 8 times the alpha2 selectivity of clonidine
- properties: sedation, anxiolysis, sympatholysis, some analgesic properties
Dosing (adults)
ICU sedation: I.V.: Initial: Loading infusion (optional) of 1 mcg/kg over 10 minutes,
followed by a maintenance infusion of 0.2-0.7 mcg/kg/hour; adjust rate to desired
level of sedation
Procedural sedation: I.V.: Initial: Loading infusion of 0.5-1 mcg/kg over 10 minutes,
followed by a maintenance infusion of 0.6 mcg/kg/hour, titrate to desired effect; usual
range: 0.2-1 mcg/kg/hour
Fiberoptic intubation (awake): I.V. Initial: Loading infusion of 1 mcg/kg over 10
minutes, followed by a maintenance infusion of 0.7 mcg/kg/hour until endotracheal
tube is secured.
- supplied as 200 mcg/2 mL (100 mcg/mL) in a glass vial
- to prepare the infusion, withdraw 2 mL of Precedex and add to 48 mL of 0.9%
sodium chloride injection to a total of 50 mL to achieve concentration of 4 mcg/mL
- incompatible when administered with the following drugs: amphotericin B, diazepam
Indications
- FDA approved for sedation only in adults undergoing mechanical ventilation for < 24
hours
- off label uses:
- adjunctive agent for sedation and analgesia in pediatric patients in ICU
- pediatric procedural sedation
- fiberoptic intubation
- anesthesia for bariatric surgery, cardiac surgery, neurosurgical procedures
requiring intraoperative active patient participation
Advantages
- enhances the anesthetic effect of intravenous & volatile agents as well as those
used for regional block
- does not cause respiratory depression
- no evidence of cardiovascular rebound 24 h after abrupt cessation of infusion
- allows intubated patients in ICU setting to be quickly aroused and oriented upon
demand
- does not require discontinuation prior to weaning from mechanical ventilation
- ongoing sedation can be maintained with the use of dexmedetomidine during and
following extubation
- reduces the shivering in postoperative patients
- one of side effects is dry mouth, which is an advantage during fiberoptic intubation
Mechanism of Action
Dosing (pediatrics)
Loading dose: 0.5-1 mcg/kg; followed by a maintenance infusion of 0.2-0.7
mcg/kg/hour
Pharmacokinetics
- constant amount of drug eliminated per hour
- onset: rapid
- alpha2 half life: 6 minutes
- elimination half life: 2 hours
Metabolism
- biotransformation by direct glucuronidation and cytochrome P450 metabolism in
liver
- majority of metabolites excreted in urine
- no difference between healthy patients and those with renal impairment
- clearance in adult patients with mild, moderate, and severe hepatic impairment is
decreased 53%, 64%, and 74%
Side Effects
- common: hypotension, bradycardia, sinus arrest, transient hypertension, dry mouth
- effects of hypotension and bradycardia may be minimized by omitting or decreasing
the loading dose
References
1. Carollo, DS, Nossaman, BD, Ramadhyani, U. Dexmedetomidine: a review of
clinical applications. Curr Opin Aneaesthesiol. 2008;21:457-461.
2. Phan, H and Nahata, MC. Clinical Uses of Dexmedetomidine in Pediatric
Patients. Pediatr Drugs. 2008;10(1):49-69.
3. Haselman, MA. Dexmedetomidine: A Useful Adjunct to Consider in Some HighRisk Situations. AANA Journal. 2008;76(5):335-339.
4. Dexmedetomidine (drug information) on UptoDate.