Dexmedetomidine is a highly selective α₂ adrenoreceptor agonist approved by the US FDA for short-term postoperative sedation. Alpha₂ adrenoreceptors have been found in the peripheral and central nervous systems and in the liver, pancreas, kidneys, and eyes. Stimulation of α₂ receptors in the brain inhibits neuronal firing, which leads to decreases in blood pressure and heart rate and increase in sedation. Stimulation of α₂ receptors in the spinal cord produces an analgesic effect. The physiologic responses elicited by activation of α₂ receptors in other organs include decreased salivation and insulin secretion from the pancreas, increased glomerular filtration and secretion of sodium and water, inhibited rennin secretion from the kidneys and decreased intraocular pressure.¹ Apart from its well-known sedative, anxiolytic and analgesic properties, dexmedetomidine appears to have potential applications in many other clinical scenarios, including neuroprotection, cardioprotection,² and renoprotection.

From recent publications, dexmedetomidine can be used off label in a variety of clinical settings,³ including functional neurosurgery,⁴ pediatric procedural sedation, awake fiberoptic intubation, endoscopic examination, cardiac surgery, and bariatric surgery.⁵ It is particularly useful in the surgical management of epilepsy and surgery near Broca’s and Wernicke’s speech areas because such procedures require the patient to be awake during the operation to test neurocognitive function. Dexmedetomidine does not interfere with electrophysiologic monitoring or microelectrode recording during implantation of deep-brain stimulators. It has been used as a sole agent during awake fiberoptic intubation in patients with a difficult airway. Its advantage over other more commonly used sedative-hypnotic agents in selective, high-risk populations such as those with compromised airway and morbid obesity is that it produces less respiratory depression. The anesthesiologist can easily maintain a patient’s airway with spontaneous ventilation to avoid desaturation or pulmonary aspiration during fiberoptic intubation or endoscopic examination. Dexmedetomidine can also provide a dry field for oral procedures as it is an antisialogogue. The use of dexmedetomidine in lieu of opioids for laparoscopic Roux-en-Y gastric bypass surgery to treat morbid obesity has gained popularity in the United States.⁶ Such management not only provides a hemodynamically stable course but also reduces the need for opioids and volatile anesthetics.

Dexmedetomidine reduces the stress response. It was shown in Venn et al’s study that postoperative infusion of dexmedetomidine reduced inflammatory response without interfering with adrenocortical function in postoperative patients who needed sedation and mechanical ventilation in the intensive care unit after complex major abdominal or pelvic surgery.⁷ In their study, the patients who received dexmedetomidine showed a continuing decline in interleukin 6 (IL-6) concentrations. IL-6 is the principal cytokine released after surgery, and circulating IL-6 concentrations reflect the magnitude of the inflammatory response to surgical trauma. The effects of dexmedetomidine on inflammatory response in critically ill patients had similar results.⁸ The levels of TNF-α, IL-1β and IL-6 were significantly decreased after 24 hours of dexmedetomidine infusion. In contrast, midazolam infusion did not affect cytokine production in septic patients in their study. The anti-inflammatory effects of dexmedetomidine were further verified in an animal model. Dexmedetomidine dose-dependently attenuated high mortality rate in rats after endotoxin-induced septic shock.⁹ Dexmedetomidine administration also inhibited increases in plasma cytokine concentrations after endotoxin injection.¹⁰

However, the anti-inflammatory effects of dexmedetomidine cannot be reproduced in every animal model. The study reported by Yang and colleagues¹¹ in this issue of the journal tested the effects of dexmedetomidine in ventilator-induced lung injury (VILI) in a rat model. They found that dexmedetomidine at clinically relevant dosages had no significant effects on attenuating VILI, but dexmedetomidine at a dosage approximately 10 times higher than the clinical dosage significantly attenuated VILI. Such results are perplexing. The mechanisms of VILI are complicated^12,13 and involvement of inflammatory cytokines in VILI has not been unequivocally demonstrated experimentally and clinically.¹⁴ The negative results of dexmedetomidine in attenuation of inflammatory mediator activation in VILI do not necessarily mean that it does not have an effect on other aspects of VILI. The results in this report can also be interpreted in the light of other possibilities: the anti-inflammatory effects of dexmedetomidine cannot be induced in this model; involvement of inflammatory mediators is not evident; only a few α₂ receptors exist so there was failure to acquire a full response upon dexmedetomidine treatment in lung parenchyma. Further studies are needed to test the anti-inflammatory and other pharmacologic effects of dexmedetomidine in rat models and different animal models.

Michael J. Sheen, MD
Attending Anesthesiologist
Tri-Service General Hospital/
National Defense Medical Center
Executive Editor, Acta Anaesthesiologica Taiwanica

Shung-Tai Ho, MD, MS
Professor of Anesthesiology
Tri-Service General Hospital/
National Defense Medical Center
Editor-in-Chief, Acta Anaesthesiologica Taiwanica