Dexmedetomidine

Article Author:
Bradley Reel
Article Editor:
Christopher Maani
Updated:
10/27/2018 12:31:32 PM
PubMed Link:
Dexmedetomidine

Indications

The FDA-approved indications for dexmedetomidine are sedation of intubated and mechanically ventilated patients in the intensive care unit (ICU), and peri-procedural (or peri-operative) sedation of non-intubated patients. Over time, usage has expanded to off-label uses including treatment and prevention of delirium, adjunctive analgesia, therapy for insomnia in the ICU, and treatment of alcohol withdraw. This is because it commonly produces a sedated state allowing patients to be both comfortable and cooperative during mechanical ventilation. Additionally, it does not require stoppage to accomplish extubation and is safe to use in non-intubated patients. This is because it does not produce significant respiratory depression. Given inherent analgesic properties which are rare to most sedatives, dexmedetomidine produces an opioid-sparing effect.

ICU sedation with dexmedetomidine has been shown to decrease the incidence and duration of delirium, as well as delay the onset of delirium when compared with other sedatives. Evidence also exists that in patients with delirium, the time to extubation and the number of ventilator-dependent hours is reduced. This may be related to the ability of dexmedetomidine to reduce the need for other medications (for examples, propofol, benzodiazepines, opioids) to promote a comfortable/cooperative patient. This effect has been particularly useful in the treatment of elderly post-cardiac surgery patients. The beneficial effects in this particular patient population extend into longer outcomes, including survival at 2 years and improved cognitive function and quality of life. It has also become common to treat poor sleep in the ICU with dexmedetomidine infusions at doses as high as 1.5 mcg/kg per hr. This practice is supported by research showing dexmedetomidine often yields sleep quality closely related to stage 2 non-REM sleep. However, it is also important to note that there is data showing that normal sleep patterns are altered, and no restorative rapid-eye-movement or slow-wave sleep is achieved. Additionally, studies demonstrating benefit in clinical outcomes related to improved sleep generated by dexmedetomidine are sparse.

Dexmedetomidine is commonly used in anesthesia practice as well. It is used for procedural sedation for a variety of operations. It is also used frequently for sedation during the performance of awake intubation. It is ideally suited for this indication for the reasons stated above. Dexmedetomidine is also used as an adjunct infusion during general anesthesia. There is evidence that dexmedetomidine decreases postoperative pain, postoperative opioid usage, and nausea. This effect has also been shown to be present when dexmedetomidine is used for sedation during procedures performed under spinal anesthesia. However, at least one recent study has called into question this opioid-sparing effect for a cohort of patients undergoing major spine surgery. There has been interest in using dexmedetomidine as an adjunct to prevent emergence agitation, post-operative delirium, and postoperative cognitive dysfunction. There is evidence for prevention of emergence agitation in both children and adults. Because of enthusiasm over apparent prevention/treatment of delirium with dexmedetomidine when used for ICU sedation, it was hoped this benefit would be reproduced for postoperative delirium if an intraoperative infusion of dexmedetomidine was used; however, a recent randomized trial did not show a statistically significant benefit in this post-operative population. Dexmedetomidine has also been used in peripheral nerve blocks to prolong the duration of analgesia. Research suggests the dexmedetomidine may prolong the duration of a peripheral nerve block for approximately 3 hours.

Mechanism of Action

Dexmedetomidine is an alpha agonist having sedative, anxiolytic, hypnotic, analgesic, and sympatholytic properties. It produces these effects by inhibition of central sympathetic outflow by blocking the alpha receptors in the brainstem, thereby inhibiting the release of norepinephrine. It has a selectivity of 1600:1 for the alpha2 receptor as compared to alpha1. This is especially significant when comparing this to another alpha agonist, clonidine, with a selectivity of 220:1. The mechanism by which dexmedetomidine may increase the duration of a peripheral nerve block is not fully understood but is believed to most likely be a perineural mechanism rather than a systemic or central mechanism. It is thought to prolong the duration by blocking the cation current.

Administration

For ICU sedation, the typical dosage range is 0.2 to 0.7 mcg/kg per hour. However, the dose can be increased to 1.5 mcg/kg per hour to achieve the desired sedation level. Doses as high as 2.5 mcg/kg per hour have been described, but it is unlikely that doses higher than 1.5 mcg/kg per hour achieve any further therapeutic benefit in the absence of increased side effects. Dosage adjustments for renal or hepatic impairment are not required but should be considered, especially for hepatic impairment. The manufacturer does not recommend durations longer than 24 hours; however, longer durations have been shown to be safe and effective. A loading dose of 0.5 to 1.0 mcg/kg can be administered. It is usually avoided if the medication is to be used for labile critically ill patients or those with tenuous hemodynamics.

When used in anesthesia, a loading dose of 0.5 to 1.0 mcg/kg is usually followed by continuous infusion of 0.2 to 0.7 mcg/kg per hour titrated to desired sedation goals. As mentioned, higher infusion doses can be used to achieve the desired effect.

When used as an adjunct for peripheral nerve block the dose of dexmedetomidine is usually 1 mcg/kg to achieve the desired prolongation.

Adverse Effects

The most common adverse effects of dexmedetomidine are hypotension, bradycardia, and hypertension. Hypertension is produced by stimulation of alpha subtypes of receptors in vascular smooth muscles. Hypertension usually does not require treatment and can be avoided by the slow administration or omission of the loading dose. Hypotension and bradycardia are produced by stimulation of presynaptic alpha receptors, which leads to a decreased release of norepinephrine; this is in addition to the decrease in the central sympathetic outflow. These are concerns regardless of the route of administration.

Contraindications

There are no absolute contraindications to use of dexmedetomidine. However, it should be used cautiously in patients with bradycardia and hypotension as the medication may exacerbate these findings. Additionally, it should be used cautiously in patients with known heart failure as there is level B evidence showing dexmedetomidine can potentially exacerbate myocardial dysfunction.

Monitoring

There are no specific drug monitoring requirements. The level of sedation, heart rate/rhythm, blood pressure, and pulse oximetry should be monitored closely.

Toxicity

At present, there is no chemical reversal or antidote for dexmedetomidine. Supportive care and close monitoring are the staples of treatment for overdose.