Dexmedetomidine (trade names Precedex [US market], Dexdor [European market], Dexdomitor) is a sedative medication used by intensive care units and anesthesiologists. It is relatively unusual in its ability to provide sedation without causing respiratory depression. Like clonidine, it is an agonist of α2-adrenergic receptors in certain parts of the brain. It is the S-enantiomer of medetomidine, used in veterinary medicine. Dexmedetomidine hydrochloride is also used in veterinary medicine for dogs and cats. The drug was developed by Orion Pharma.
Indications
Dexmedetomidine is indicated for sedation of critically ill or injured patients in an intensive care unit setting. Its indication in the US was recently expanded to include nonintubated patient requiring sedation for surgery or procedures short-term. It is also useful as an adjunct for sedation and general anesthesia in the setting of certain operations and invasive medical procedures, such as colonoscopy. There are no absolute contraindications to the use of dexmedetomidine. Limiting its usefulness is the caution that the drug cannot be bolused due to concerns about peripheral α2-receptor stimulation with resulting hypotension and bradycardia, combined with its current high cost relative to generic medications such as propofol, fentanyl and midazolam which can achieve similar clinical effects.
Intensive care unit sedation
Compared to midazolam, dexmedetomidine was similarly effective for sedation, but shortened the time to extubation. It was associated with less delirium, tachycardia and hypotension, but more bradycardia. It also seemed to be superior to lorazepam for ventilated patients in the intensive care unit. Compared to midazolam, dexmedetomidine is superior due to reduced intensive care costs. The reduced costs are due to a reduction in intensive care unit stay as well as reduced mechanical ventilation.
Procedural sedation
Dexmedetomidine has sedative, analgesic, sympatholytic, and anxiolytic effects that blunt many of the cardiovascular responses in the perioperative period. It reduces the requirements for volatile anesthetics, sedatives and analgesics without causing significant respiratory depression. Dexmedetomidine has also been used for procedural sedation in children.
Other
Dexmedetomidine may be useful for the treatment of the deleterious cardiovascular effects of acute amphetamines and cocaine intoxication and overdose. Dexmedetomidine may also offer a new paradigm in the pharmacologic treatment of symptoms of distress (intractable pain, agitation, or delirium) at the end of life. Recently, an investigator initiated IND was approved by the FDA to examine the use of dexmedetomidine in treating cancer patients at the end of life who are suffering from intractable pain, agitation, or delirium.
Dosage and administration
Intravenous infusion of dexmedetomidine is commonly initiated with a 1 µg/kg loading dose, administered over 10 minutes, followed by a maintenance infusion of 0.2â€"1.0 µg/kg/hour. There may be great individual variability in the hemodynamic effects (especially on heart rate and blood pressure), as well as the sedative effects of this drug. For this reason, the dose must be carefully adjusted to achieve the desired clinical effect.
Veterinary use
Dexmedetomidine (trade name Dexdomitor) is commonly used as a sedative, anxiolytic, and anesthetic adjunct in dogs and cats. It is formulated in a much higher concentration (500 µg/ml) and given at a much higher dose in small animals than in humans. As a stand alone agent, it is labeled at 375 µg/m2 IV or 500 µg/m2 IM in dogs (10-20x higher than human loading dose, depending on weight of dog). The effective dose can be markedly decreased with the concurrent administration of an opioid (2-10 µg/kg given with morphine equivalent of 0.2-1 mg/kg when given IV). It can also be used combined with an equal volume (0.05 to 0.3 ml total of each, depending on level of sedation desired and weight of cat) of ketamine and opioid (butorphanol, buprenorphine, morphine, or hydromorphone) to provide profound sedation as an IM injection in cats (known in veterinary circles as "Kitty Magic"). As an anxiolytic agent, it is typically given at a 0.5-2 µg/kg bolus followed by a continuous infusion at 0.5-2 µg/kg/h. It is most often used for this purpose post-operatively. It is also used at this dose for maintenance of sedation in patients being mechanically ventilated.
Unlike in human patients, dexmedetomidine tends to cause initial hypertension in small animals. It is considered contra-indicated in dogs with mitral-insufficiency and dilated cardiomyopathy due to concerns over its transient increase in afterload and bradycardia both of which could contribute to acute decompensation. In cats with hypertrophic cardiomyopathy, however, it is considered by some to be particularly useful when sedation is required as the resultant bradycardia may be of benefit in states where diastolic function is compromised. Dexmedetomidine is also considered to be contraindicated in hypotensive and/or hypovolemic patients, hyperkalemic patients (such as cats who have had prolonged urethral obstruction or other conditions causing acute renal failure) and should be used with extreme caution in geriatric patients.
Also unlike in human patients, a reversal agent, atipamazole (trade name Antisedan) is commonly used to reverse the effects of dexmedtomidine after sedation is no longer needed. It is given IM in an equal volume to the Dexdomitor solution used. This makes dexmeditomine particularly useful for outpatient procedures as sedative effects can be completely (or almost completely) resolved within 30 minutes of the end of a procedure (especially if a short acting opioid such as fentanyl is used as part of the sedative protocol).
Pricing and patent life
Dexmedetomidine is currently more expensive than off-patent sedatives, such as propofol and midazolam (median per-patient drug acquisition cost was reported as $75 for dexmedetomidine vs $60 for midazolam in one study). Dexmedetomidine is expected to lose patent protection in the United States in 2013 at which time the acquisition cost of this drug will likely decrease.
See also
- Xylazine, another α2-receptor agonist used in veterinary anesthesia.
- Medetomidine, the racemic mixture of S-medetomidine (dexmedetomidine) and R-medetomidine, used in small animal anesthesia.
- Detomidine, a similar compound widely used in large animal anesthesia.
References
External links
- Website of Precedex