Introduction

Relatively selective α₂-adrenergic agonist with sedative properties.

Uses for Dexmedetomidine

Sedation in Critical Care Settings

Sedation of initially intubated and mechanically ventilated patients in an intensive care setting (i.e., ICU).

May be used to provide mild to moderate levels of sedation, but not considered suitable for deep sedation.

FDA-labeled for use only for short-term (<24 hours) sedation; however, has been used for prolonged sedation^{† [off-label]} in the intensive care setting. (See Tolerance and Tachyphylaxis under Cautions.)

Produces sedation, anxiolysis, and analgesia without causing significant respiratory depression.

Appears to be as effective as propofol and benzodiazepines (e.g., midazolam, lorazepam) for sedation in critically ill mechanically ventilated adults; however, because of some modest clinical benefits (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium), nonbenzodiazepine sedatives (dexmedetomidine or propofol) are generally preferred to benzodiazepines.

When selecting an appropriate sedative agent, consider patient's individual sedation goals in addition to specific drug-related (e.g., pharmacology, pharmacokinetics, adverse effects, availability, costs) and patient-related (e.g., comorbid conditions such as anxiety, seizures, or alcohol or benzodiazepine withdrawal) factors.

Patients receiving dexmedetomidine are more arousable than those receiving other sedatives, which may be particularly useful for daily awakening trials.

Because dexmedetomidine does not have a substantial respiratory depressant effect, infusions of the drug can be continued following extubation, if needed.

Procedural Sedation

Sedation of nonintubated patients prior to and/or during surgical or other procedures.

Comparative efficacy with other sedative agents not established. May be preferred in certain patients (e.g., those in whom respiratory compromise with benzodiazepines is a concern); however, consider risks versus benefits.

Dexmedetomidine Dosage and Administration

General

• Administer only by individuals experienced in the management of patients in an intensive care or surgical setting.

• Individualize dosage and titrate to desired level of sedation.

• Monitor patient continuously.

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.

May adsorb to some types of natural rubber; use administration components made with synthetic or coated natural rubber gaskets.

Commercially available as an injection concentrate that must be diluted prior to IV infusion or as a premixed ready-to-use solution (dexmedetomidine hydrochloride in 0.9% sodium chloride injection).

Dilution

Must dilute the injection concentrate in 0.9% sodium chloride injection prior to administration. To prepare the 4-mcg/mL concentration used for loading and maintenance infusions, one method of dilution is to add 2 mL of the concentrate (100 mcg/mL) to 48 mL of 0.9% sodium chloride injection.

Rate of Administration

Administer by slow IV infusion via a controlled-infusion device.

Rapid IV infusion associated with loss of α₂-adrenergic selectivity and adverse cardiovascular effects. (See Actions and also see Cardiovascular Effects under Cautions.)

Dosage

Available as dexmedetomidine hydrochloride; dosage is expressed in terms of dexmedetomidine.

Adults

Sedation in Critical Care Settings

IV

Initiation of sedation: 1 mcg/kg as a loading infusion over 10 minutes. Because of risk of adverse hemodynamic effects, many clinicians do not recommend a loading dose; if a loading dose is used, caution is advised, particularly in patients with bradycardia, heart block, or hemodynamic instability. Manufacturer states loading dose may not be required in patients converting from an alternative sedative agent.

Maintenance of sedation: Continuous IV infusion at a rate of 0.2–0.7 mcg/kg per hour recommended. Adjust infusion rate to desired level of sedation; in most cases, a light rather than deep level of sedation is recommended in critically ill, mechanically ventilated patients. Assess depth and quality of sedation using a validated and reliable assessment tool. Adjust dosage slowly to reduce risk of hypotension and other adverse effects.

Evidence from clinical studies supports use of infusion rates up to 1.5 mcg/kg per hour.

Manufacturer states that continuous IV infusion of dexmedetomidine should not exceed 24 hours. However, the drug has been used for prolonged (>24 hours) sedation in the ICU.

Procedural Sedation

IV

Initiation of sedation: 1 mcg/kg as a loading infusion over 10 minutes. A loading infusion of 0.5 mcg/kg over 10 minutes may be suitable for less invasive procedures (e.g., ophthalmic surgery). For awake fiberoptic intubation, a loading infusion of 1 mcg/kg over 10 minutes is recommended.

Maintenance of sedation: Initiate maintenance infusion at a rate of 0.6 mcg/kg per hour; adjust rate within range of 0.2–1 mcg/kg per hour to achieve desired level of sedation. For awake fiberoptic intubation in adults, a maintenance infusion of 0.7 mcg/kg per hour is recommended until endotracheal tube is secured.

Special Populations

Hepatic Impairment

Consider dosage reduction.

Renal Impairment

Manufacturer makes no special dosage recommendations.

Geriatric Patients

For initiation and maintenance of ICU sedation in geriatric patients >65 years of age, consider dosage reduction.

For procedural sedation in geriatric patients >65 years of age, reduce loading dose to 0.5 mcg/kg over 10 minutes; consider dosage reduction for maintenance of procedural sedation.

Contraindications

• None.

Warnings/Precautions

Administration Precautions

To minimize risk of adverse effects, follow recommendations for administration and monitoring of dexmedetomidine therapy. (See General under Dosage and Administration.)

Cardiovascular Effects

Bradycardia and sinus arrest reported in young, healthy adults with high vagal tone; also associated with other methods of administration, including rapid IV administration.

Hypotension and/or bradycardia reported frequently; although intervention rarely required, some cases resulted in fatality. May be more pronounced in geriatric patients or those with hypovolemia, diabetes mellitus, or chronic hypertension. If treatment is required, consider slowing or stopping dexmedetomidine infusion, increasing IV fluids, elevating lower extremities, and/or use of vasopressors; consider IV anticholinergic agents (e.g., atropine sulfate, glycopyrrolate) to modify vagal tone. More advanced resuscitative measures may be necessary in patients with significant cardiovascular dysfunction.

Transient hypertension reported with loading dose; treatment generally not required, although reduction in the loading dose infusion rate may be desirable.

Supraventricular and ventricular tachycardia, atrial fibrillation, extrasystoles, and cardiac arrest reported during postmarketing experience.

Use with caution in patients with (or at risk of) advanced heart block and/or severe ventricular dysfunction, and in patients receiving concomitant drugs that slow cardiac conduction.

Withdrawal Effects

Abrupt withdrawal of dexmedetomidine may result in clonidine-like withdrawal symptoms. Withdrawal-related events (e.g., nausea, vomiting, agitation, tachycardia, hypertension) reported following discontinuance of therapy in some patients after prolonged (up to 7 days) infusion for ICU sedation. Withdrawal symptoms not reported with short-term (<6 hours) infusions for procedural sedation.

If tachycardia and/or hypertension occurs after discontinuance of dexmedetomidine, institute supportive therapy.

Arousability

Some patients observed to be arousable and alert when stimulated; should not be considered as evidence of lack of efficacy in the absence of other signs and symptoms.

Tolerance and Tachyphylaxis

Use of dexmedetomidine for durations >24 hours associated with tolerance, tachyphylaxis, and dose-related increase in adverse effects.

Specific Populations

Pregnancy

Category C.

No adequate and well-controlled studies in pregnant women. No evidence of teratogenicity in animal studies; however, fetal toxicity (e.g., postimplantation loss, reduced pup viability, reduced pup weight) observed.

Use during pregnancy only when potential benefits justify potential risks to fetus.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Caution if used in nursing women.

Pediatric Use

Manufacturer states safety and efficacy not established in pediatric patients <18 years of age. However, the drug has been used in pediatric patients undergoing sedation in the ICU or other settings to facilitate mechanical ventilation or other procedures (e.g., radiologic imaging). Additional study is needed to evaluate the drug's safety in this population.

Geriatric Use

Hypotension and/or bradycardia may be more pronounced. Consider dosage reduction. (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Pharmacokinetics in patients with severe renal impairment (Cl_cr <30 mL/minute) and healthy individuals are similar.

Hepatic Impairment

Clearance may be reduced. Consider dosage reduction. (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Short-term (<24 hours) infusions for ICU sedation: Hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypovolemia, atelectasis, atrial fibrillation, hypoxia, tachycardia, hemorrhage, anemia, dry mouth.

Long-term (>24 hours) infusions for ICU sedation: Hypotension, bradycardia, hypertension, tachycardia, hypokalemia, agitation, hyperglycemia, constipation, hypoglycemia, respiratory failure.

Procedural sedation: Hypotension, respiratory depression, bradycardia, hypertension, tachycardia, nausea, dry mouth.

General

• Administer only by individuals experienced in the management of patients in an intensive care or surgical setting.

• Individualize dosage and titrate to desired level of sedation.

• Monitor patient continuously.

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.

May adsorb to some types of natural rubber; use administration components made with synthetic or coated natural rubber gaskets.

Commercially available as an injection concentrate that must be diluted prior to IV infusion or as a premixed ready-to-use solution (dexmedetomidine hydrochloride in 0.9% sodium chloride injection).

Dilution

Must dilute the injection concentrate in 0.9% sodium chloride injection prior to administration. To prepare the 4-mcg/mL concentration used for loading and maintenance infusions, one method of dilution is to add 2 mL of the concentrate (100 mcg/mL) to 48 mL of 0.9% sodium chloride injection.

Rate of Administration

Administer by slow IV infusion via a controlled-infusion device.

Rapid IV infusion associated with loss of α₂-adrenergic selectivity and adverse cardiovascular effects. (See Actions and also see Cardiovascular Effects under Cautions.)

Dosage

Available as dexmedetomidine hydrochloride; dosage is expressed in terms of dexmedetomidine.

Adults

Sedation in Critical Care Settings

IV

Initiation of sedation: 1 mcg/kg as a loading infusion over 10 minutes. Because of risk of adverse hemodynamic effects, many clinicians do not recommend a loading dose; if a loading dose is used, caution is advised, particularly in patients with bradycardia, heart block, or hemodynamic instability. Manufacturer states loading dose may not be required in patients converting from an alternative sedative agent.

Maintenance of sedation: Continuous IV infusion at a rate of 0.2–0.7 mcg/kg per hour recommended. Adjust infusion rate to desired level of sedation; in most cases, a light rather than deep level of sedation is recommended in critically ill, mechanically ventilated patients. Assess depth and quality of sedation using a validated and reliable assessment tool. Adjust dosage slowly to reduce risk of hypotension and other adverse effects.

Evidence from clinical studies supports use of infusion rates up to 1.5 mcg/kg per hour.

Manufacturer states that continuous IV infusion of dexmedetomidine should not exceed 24 hours. However, the drug has been used for prolonged (>24 hours) sedation in the ICU.

Procedural Sedation

IV

Initiation of sedation: 1 mcg/kg as a loading infusion over 10 minutes. A loading infusion of 0.5 mcg/kg over 10 minutes may be suitable for less invasive procedures (e.g., ophthalmic surgery). For awake fiberoptic intubation, a loading infusion of 1 mcg/kg over 10 minutes is recommended.

Maintenance of sedation: Initiate maintenance infusion at a rate of 0.6 mcg/kg per hour; adjust rate within range of 0.2–1 mcg/kg per hour to achieve desired level of sedation. For awake fiberoptic intubation in adults, a maintenance infusion of 0.7 mcg/kg per hour is recommended until endotracheal tube is secured.

Special Populations

Hepatic Impairment

Consider dosage reduction.

Renal Impairment

Manufacturer makes no special dosage recommendations.

Geriatric Patients

For initiation and maintenance of ICU sedation in geriatric patients >65 years of age, consider dosage reduction.

For procedural sedation in geriatric patients >65 years of age, reduce loading dose to 0.5 mcg/kg over 10 minutes; consider dosage reduction for maintenance of procedural sedation.

Metabolized by CYP isoenzymes, principally CYP2A6. However, no evidence of clinically important CYP-mediated drug interactions in vitro.

Drugs with Negative Chronotropic Effects

Potential pharmacodynamic interaction (additive pharmacodynamic effects). Use with caution.

Protein-bound Drugs

Pharmacokinetic interaction unlikely.

Specific Drugs