Dexmedetomidine (Precedex)

Matt Green, MD October 09; updated April 2014

Page Index:

Introduction/Indications
Description of the Drug
Manufacturer's Package Insert
Administration
Pharmacy Notes

Introduction/ Indications

Dexmedetomidine (Precedex) is a selective α-2 adrenoreceptor agonist. It has combined sedative, analgesic, anxiolytic and sympatholytic properties. Furthermore, DEX does not significantly depress the ventilatory drive or produce respiratory depression.
Dexmedetomidine is available in the OR pyxis for use in the main OR. At this point we anticipate using Dexmedetomidine only in cases where its unique properties will be useful.

Awake Craniotomies
** Awake Fiberoptic Intubations
** Bariatric surgery
** Pediatric MRI
** Any case where ventilatory/respiratory compromise is of concern and need to limit opiates
** Sedation for MAC cases in Interventional Radiology
Emergence
Delerium in Children

Description

Mechanism of Action

Dexmedetomidine is 
-an α-2 receptor agonist, with a 
-high ratio of specificity for the α-2 vs. the α -1 receptor of 1600:1 (versus Clonidine's profile of 200:1) thereby making DEX a complete agonist at the α-2 adrenergic receptor. 
-Pre and Post synaptic α-2-adrenoreceptors are located in the central and peripheral nervous system, vascular smooth muscle, heart and other organs.
** Presynaptic α-2 receptor activation reduces norepinephrine release
** Postsynaptic activation of α-2 receptors hyperpolarizes neural membranes, acting as a feedback loop, further reducing norepinephrine release
** Exerts hypnotic / anxiolytic action by post synaptic activation of α-2 receptors in locus ceruleus of brain stem
** Analgesic properties are exerted at pre-synaptic sites in spinal cord

Physiologic Effects of DEX

** Cardiovascular and Hemodynamic: Hypotension & Bradycardia have been reported especially in the presence of comorbid disease, administration with other medications with negative inotropic effects, or following large rapid bolus doses. In healthy adult volunteers, there is a biphasic effect following dexmedetomidine with an initial increase in systolic BP, and a reflex decrease in HR, followed by stabilization of sBP and HR values below baseline.
** Respiratory: Preserved ventilation, even at high doses. 
Airway reactivity: In dogs, IV DEX has been shown to prevent histamine- induced bronchoconstriction.
** CNS: Sedative effects, unreliable amnesia, anxiolysis. 
Sedative properties unique in such way to parallel natural sleep. 
No effect on ICP. CPP reduced by virtue of lowering MAP. Seizure threshold results in literature are mixed, with very high doses of DEX 100-500 mcg/kg favoring lowering the seizure threshold, and lower doses increasing the seizure threshold in cocaine induced seizure model. May have neuroprotective effects. 
Miscellaneous CNS effects of mention were prevention of opioid induced muscle rigidity and attenuation of shivering.
** GI motility: Decreased, but much less than morphine.
** Adrenalcortical function: In concentrations that are used clinically, there is no evidence to suggest that DEX depressed adrenocortical function to the same extent that occurs with etomidate.

Pharmacokinetics/Metabolism

** In healthy adult volunteers, dexmedetomidine's pharmacokinetic profile includes a rapid distribution phase of 6 minutes, an elimination half life of 2 hours, and a steady state volume of distribution of 118L. It is highly protein bound at 94%. 
** It undergoes hepatic metabolism with limited unchanged drug excreted in the urine or stool. Caution should be used in patients with severe hepatic failure as elimination half life is more than doubled. 

Manufacturer's Package Insert

The complete manufacturer's Package Insert is available for downloading in  pdf format by clicking here.

Administration

Dose
** Initial loading dose of 1mcg/kg IV over 10 minutes. Avoid in patients with hypovolemia, hypotension, or pre-existing bradycardia
** Infusion: 0.2-2.0 mcg/kg/hr, however, reports in literature of using as much as 10mcg/kg/hr as sole anesthetic without any adverse outcomes.

Guidelines for Use in Awake Fiberoptic Intubation
are available from the manufacturer in pdf format by clicking here.

For Emergence Delerium Treatment in Children:

Bramhall and SSC have Dexmedetomidine syringes in the Anesthesia Workroom refrigerator (4 mcg/ml 1 ml in a 3 ml syringe). 
The usual dose to prevent post-op delerium is 1 mcg/kg in children administered slowly. It has pretty significant cardiac effects (bradycardia and hypotension); concurrent treatment with Digoxin is considered a contraindication. 

For sedation in Interventional Radiology, follow these suggested guidelines

Pharmacy Notes

Dexmedetomidine is available in the MMC Pyxis as 200mcg, 2ml (100mcg/ml) single use vials. The cost of each vial is approximately $60. Please be mindful of the expense and use this drug only in situations in which it is specifically indicated.

To mix the drug, obtain a 60 cc syringe, then add 48 ml of normal saline, 2ml Dexmedetomidine single dose vial (100mcg/ml) = a concentration of Dexmedetomidine 4mcg/ml (DEX 200mcg in 50cc).

Alternatively, dilute 200mcg to 20cc (10 mcg/ml) and run in a MedFusion pump at 0.7-1.0 mcg/kg/hr, or about 7-10 cc/hr for a normal adult.

Return excess drug as you do now, fitting the syringe into an envelope, remember to check the box "other" in QA form under analgesics.