The use of α-2 adrenergic receptor agonist dexmedetomidine in cardiac surgery
By Shanna C. Ten Clay, MD and Hong Liu, MD
University of California Davis Health System, Sacramento, CA
Dexmedetomidine, a highly selective α-2 adrenergic receptor agonist, has been used successfully in both the operating room (OR) and the intensive care unit (ICU) to provide sedation and analgesia since its approval in the US in 19991. In October 2008, the Food and Drug Administration approved the expansion of its use to sedation for surgery or other procedures2.
The properties of this agent are produced by stimulation of α-2 receptors on presynaptic neurons. The net effect is a decrease in norepinephrine release from presynaptic neurons with inhibition of postsynaptic activation, which attenuates central nervous system excitation, especially in the locus coeruleus. Uniquely, its actions are not mediated by the γ-aminobutyric (GABA)-mimetic system. Thus it does not depress the respiratory drive and has sedative, analgesic, and anti-shivering properties. In producing a state of “cooperative sedation,” dexmedetomidine allows the patient to interact with healthcare providers. While patient cooperation can be achieved with other properly dosed sedatives, dexmedetomidine maintains this property throughout the usual dosage range. It has been advocated as an adjunctive agent for use intraoperatively since it blunts the stress response to surgery via sympatholysis, decreases opioid requirements, causes sedation, and does not produce respiratory depression3. Dexmedetomidine can be administered as a 1 μg/kg loading infusion over 10 minutes, followed by a continuous intravenous infusion between 0.2 and 0.7 μg/kg/h2.
Dexmedetomidine also has a significant effect on the cardiovascular system. Through its effects on the central nervous system, dexmedetomidine produces sympatholysis and a reduction in blood pressure which can be potentially beneficial in preventing myocardial ischemia4. Although dexmedetomidine has been used extensively in most surgical procedures, its use in cardiac surgery has been limited mainly to pediatric cardiac surgery and it provides an adequate level of sedation/analgesia either alone or in combination with low-dose conventional agents for these patients5-7. In adult cardiac surgery, dexmedetomidine has demonstrated the ability to lower opioid requirements in patients postoperatively versus those receiving propofol. In a recent meta-analysis Chalikonda and colleagues found that α-2 agonists reduce the incidence of myocardial ischemic episodes in patients with known or suspected coronary artery disease undergoing noncardiac surgery8. In the same study there was a reduction in mortality in noncardiac surgical patients with use of α-2 agonists8. In another retrospective study, the authors compared the perioperative use of dexmedetomidine on the outcomes in cardiac surgical patients and found an associated decrease in the incidence of postoperative cardiovascular complications and postoperative mortality up to 30 days in patients undergoing coronary artery bypass grafting9. Because dexmedetomidine use can provide sedation without respiratory depression, it can be used to assist in weaning from mechanical ventilation even in patients who failed previous extubation trials.10,11
In summary, dexmedetomidine is a highly selective α-2 agonist with the ability to provide sedation, analgesia, and sympatholysis. These properties can potentially be beneficial in myocardial protection, lowing narcotic usage, facilitating earlier extubation, and reducing postoperative delirium after cardiac surgery12,13.
References
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2. Product information. Precedex (dexmedetomidine) Lake Forest, IL; Hospira, October 2008.
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