In a critical care nurse's utopia, drugs would be easily titrated with no adverse effects. Drugs would automatically modulate their desired effects as needed, and work uniformly on all patients. Drug researchers are working relentlessly toward those goals. One step in that direction is dexmedetomidine HCl (Precedex), a versatile, relatively selective alpha2-receptor agonist with sedative properties. Dexmedetomidine is gaining popularity in critical care settings because of its ease of use in maintaining hemodynamic and respiratory stability. This drug doesn't cause respiratory depression, so it's useful in weaning patients from mechanical ventilation. A patient on a continuous dexmedetomidine infusion during weaning remains calm and relaxed, but can be aroused by voice and obey commands. In the absence of verbal stimulation, the patient easily returns to a resting state without further intervention.
When it can and can't be used
Approved by the Food and Drug Administration (FDA) in 1999, dexmedetomidine is indicated for short-term sedation of endotracheally intubated, mechanically ventilated patients during treatment in a critical care setting. Infusions should be no more than 24 hours, and the drug needn't be discontinued before extubation, as long as the infusion time doesn't exceed 24 hours.
Dexmedetomidine is contraindicated in patients hypersensitive to the drug. Research data is limited regarding the use of dexmedetomidine in pregnancy, labor and delivery, and lactation. The FDA has classified this agent as a pregnancy risk category C, so it should be used in pregnant women only when the benefits of the drug outweigh the risk to the fetus.
Don't use dexmedetomidine in patients with advanced heart block and severe ventricular dysfunction. Decreased doses may be needed for patients with impaired renal function, diabetes, or chronic hypertension.1 Dose reduction should be considered in patients with impaired hepatic function because of the risk of decreased drug clearance. Monitor older adults closely, as the dosage may need to be reduced for them as well.
Use caution in administering dexmedetomidine to patients with high vagal tone because of the risk of clinically significant bradycardia and sinus arrest. In clinical trials, anticholinergics such as atropine were effective in treating most episodes of dexmedetomidine-induced bradycardia.1 Use precautions for patients showing signs of hypovolemia. Blood volume replacement may be necessary before initial dosing to increase the efficacy of the drug.
If a patient is on vasodilators, monitor hemodynamics closely while using dexmedetomidine. If he becomes hypotensive, decrease or stop the infusion or administer vasopressors as needed to increase blood pressure (BP). Monitor for transient hypertension during the loading dose, and if necessary, decrease the rate of the loading dose or stop it.1 Typically, the hypertension will resolve without intervention.
How it works
Dexmedetomidine's selectivity depends on the infusion rate and drug dosage. Alpha1- and alpha2-agonist activity can occur with slow intravenous (I.V.) infusions of high doses (1,000 mcg/kg or more) and with rapid I.V. administration.
In the blood vessels, alpha1 activity causes vasoconstriction. Blood vessels with alpha1 receptors are present in the integumentary and gastrointestinal systems. When these receptors are stimulated, blood flow to these organs decreases. In contrast, the alpha2-adrenoreceptor agonists cause sedation by stimulation of the locus caeruleus, a part of the brainstem involved in the sleep-wake cycle. Sedation is caused by the inhibition of the sympathetic vasomotor center of the brain. Dexmedetomidine works presynaptically by inhibiting the release of norepinephrine while postsynaptically causing sedation.2
Dexmedetomidine is approved for use in adults at a loading dose infusion of 1 mcg/kg over 10 minutes, followed by a maintenance infusion of 0.2 to 0.7 mcg/kg/hour. The maintenance infusion is adjusted to the desired level of sedation.1 The drug should be administered using a controlled infusion device. To prepare the infusion, withdraw 2 mL of the drug and add it to 48 mL of 0.9% sodium chloride solution for injection, for a total volume of 50 mL. Shake gently to mix the solution well.
In one trial, six subjects with impaired renal function were compared with six with normal renal function. Investigators noted that although sedative effects were more pronounced in those with renal impairment, the pharmacokinetic and hemodynamic profiles weren't clinically significant.3
According to the FDA, patients may experience withdrawal symptoms upon abrupt cessation of the drug, including nervousness, agitation, and headaches, followed by a rapid increase in BP.1 Monitor and treat these signs and symptoms carefully.
Nurses in neuroscience intensive care units have found dexmedetomidine to be helpful in many nursing interventions. During neurological assessments, patients on dexmedetomidine frequently take less time to arouse and return to a rested state with little to no titration. Other interventions become easier to perform on a calm, cooperative patient, such as range-of-motion exercises, pain assessment, and body position and alignment changes. Note that a patient on dexmedetomidine is arousable and sometimes alert, so don't assume that his dosage isn't adequate. Assess for other signs and symptoms of distress, pain, or discomfort.1
Unlike other sedatives, dexmedetomidine causes less change in BP, making the balance between adequate sedation and hemodynamic stability more manageable. But you'll still want to maintain tight BP parameters. In some cases, patients have developed bradycardia and hypotension with dexmedetomidine use. These changes may be related to hypovolemia, age-related changes, or decreased cardiac function.
Sometimes, dexmedetomidine alone isn't enough to sedate the patient. Helpful adjuncts include small doses of propofol, lorazepam, midazolam, or morphine. In trials, patients who were treated with dexmedetomidine as the primary sedative (compared with a propofol infusion) showed a decreased need for pain management drugs or further supplementation after extubation.2 These patients verbalized less pain and discomfort, even while remaining intubated. Be sure to monitor the patient for any enhanced effects while giving supplemental drugs because many can augment the effects of the other medications.
The most common adverse reactions to dexmedetomidine are hypertension, hypotension, nausea, bradycardia, hypoxia, and anemia.1 Overdoses of dexmedetomidine can lead to second- and third-degree heart block, which generally resolves spontaneously.
Stepping into the future
Dexmedetomidine is a strong step into the future of sedation in critical care. However, more research is needed on the drug's cost-effectiveness in critical care settings, use for longer periods than 24 hours, use in pediatric patients, toxicology in special populations, and comparison to other sedatives.