Uses

Unlike the other drugs described in this chapter, dexmedetomidine is not indicated for induction or maintenance of anesthesia. Its role at present is largely limited to brief (<24 hours) postoperative sedation. It has, however, been described as an adjuvant during anesthesia to reduce the hypnotic and opioid requirements for conscious sedation and may possibly be considered perioperatively in patients at high risk for myocardial ischemia.

Sedation

As a premedicant at intravenous doses of 0.33 to 0.67 µg/kg given 15 minutes before surgery, dexmedetomidine appears to be efficacious while minimizing the cardiovascular side effects of hypotension and bradycardia.^[691] Within this dosage range, dexmedetomidine reduces thiopental requirements (by ≅30%) for short procedures,^{[691] [692]} reduces the requirements of volatile anesthetics (by ≅25%), and when compared with 2 µg/kg fentanyl, more effectively attenuates the hemodynamic response to endotracheal intubation.^[693] Dexmedetomidine has also been evaluated as an intramuscular injection (2.5 µg/kg) with or without fentanyl administered 45 to 90 minutes before surgery. This regimen was compared with intramuscular midazolam plus fentanyl and was found to provide equal anxiolysis, a reduced response to intubation, lower volatile anesthetic requirements, and a lower incidence of postoperative shivering but a higher incidence of bradycardia. Atipamezole, a selective α₂ -antagonist, was effective at a dose of 50 µg/kg in reversing the sedation of dexmedetomidine, 2 µg/kg intramuscularly, when used to provide sedation for brief operative procedures.^[667] This reversal of effects resulted in a more rapid recovery than occurred after equisedative doses of midazolam.

In several studies dexmedetomidine has demonstrated advantages over propofol for sedation in mechanically ventilated postoperative patients. When both drugs were titrated to equal sedation as assessed by the BIS index (approximately 50) and Ramsay sedation score (5), dexmedetomidine required significantly less alfentanil (2.5 versus 0.8 mg/hr). Heart rates were slower in the dexmedetomidine group, whereas mean arterial pressures were similar. Interestingly, the PaO₂ /FIO₂ ratio was significantly higher in the dexmedetomidine group. Time to extubation after discontinuation of the infusion was similar: 28 minutes. Patients receiving dexmedetomidine appeared to have greater recall of their stay in the ICU, but all described it as pleasant overall.^[694] Several other studies have confirmed the decreased requirement for opioids (over 50%) when dexmedetomidine is used for sedation versus propofol or benzodiazepines. Most studies also describe more stable hemodynamics during weaning when dexmedetomidine is used for sedation.^[695] This finding is of obvious benefit in patients at high risk for myocardial ischemia. For sedation in the ICU, loading doses of 2.5 to 6.0 µg/kg/hr delivered over a 10-minute period have been used. The lower infusion rate has been associated with fewer episodes of severe bradycardia and other hemodynamic perturbations. This dose is followed by infusion rates of 0.1 to 1 µg/kg/hr, which are generally needed to maintain adequate sedation.

When used for intraoperative sedation, dexmedetomidine (1 µg/kg over a 10-minute period) results in a slower onset than propofol (75 µg/kg/min over a 10-minute period) does but similar cardiorespiratory effects when titrated to equal sedation. The average infusion rate of dexmedetomidine intraoperatively to maintain a BIS index value of 70 to 80 was 0.7 µg/kg/hr. Sedation was more prolonged after termination of the infusion, as was recovery of blood pressure. However, lower doses of opioid were needed in the first hour.^[685]

Clonidine in doses of 3 to 5 µg/kg orally, usually given 30 to 90 minutes before surgery, similarly reduces the MAC of the potent volatile anesthetics (by 30% to 50%), reduces opioid requirements, attenuates the hemodynamic response to intubation, and generally provides a more stable hemodynamic profile intraoperatively,^{[659] [696] [697]} although significant bradycardia and hypotension during and immediately after induction have been observed. This reduction in anesthetic requirements also translates into more rapid awakening after surgery.^[698] Clonidine also reduces intraocular pressure, perioperative catecholamines, and postoperative analgesic requirements and prevents the usual deterioration in renal function after aortocoronary bypass.^{[659] [698] [699] [700]} As with clonidine, intraocular pressure is decreased (33%), catecholamine secretion is reduced, perioperative analgesic requirements are less, and recovery is more rapid after dexmedetomidine. ^{[701] [702]}

Maintenance of Anesthesia

Dexmedetomidine has also been used as a maintenance infusion starting with a loading dose of 170 ng/kg/min for 10 minutes and then followed by an infusion of 10 ng/kg/min. This regimen resulted in a plasma concentration of slightly less than 1 ng/mL. After induction with

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α₂ -Adrenergic agonists possess many important characteristics that are valuable for anesthesia. It would appear, however, that at anesthetic concentrations in humans, the cardiovascular effects (hypotension, brady-cardia) of these drugs may be the major drawback that prevents them from being used as the primary anesthetic, and their role is therefore limited to use as an adjuvant for other anesthetic drugs. The exact role of dexmedetomidine either as a premedicant or as an intravenous anesthetic adjuvant is still to be determined. However, dexmedetomidine appears to be a very effective sedative for patients in the ICU, where it may provide advantages over other available sedatives because of its minimal effect on respiration, its analgesic efficacy, and its hemodynamic profile. The use of dexmedetomidine for long-term sedation needs further investigation.