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M53.doc 1 10/2/20075:25:01 PM
Comparative clinical pharmacology of dexmedetomidine
Akira Asada, MD
Professor and Chair
Department of Anesthesiology and Intensive Care Medicine
Osaka City University Medical School
Drugs used for sedation include analgesics such as opioids, sedatives such
as propofol and midazolam, or neuroleptics. All of these agents have
adverse consequences, such as respiratory depression, delirium, lack of
orientation and cooperation, hypotension, tolerance and abuse potential. A
new agent, dexmedetomidine was approved for sedation in the intensive
care unit in Japan in 2004. Dexmedetomidine is an alpha-2 agonist that acts
on the locus ceruleus/norepinephrine axis, providing non-REM sleep,
sedation, anxiolysis without respiratory depression. The agent produces
both sedative and analgesic properties through the effects on the alpha-2
receptors in the brain and spinal cord.
Many papers have been published to show the neuroprotective role of the
agent to improve neurological outcome. The agent produced a
dose-dependent reduction in neuronal injury provoked by oxygen-glucose
deprivation in glial-neuronal cultures derived from rats. The agent usually
causes a decrease in heart rate, and blood pressure as a result of a centrally
mediated reduction in sympathetic tone. The reduction may have a
beneficial effect on the heart.
The agent can facilitate the extubation process by attenuating the
hemodynamic responses without respiratory depression. Another novel
advantage of the agent is to make a sedated patient aroused easily to
demonstrate normal cognitive ability. Therefore, a neurological assessment
could be done whenever required. The duration for mechanical ventilation
and days for hospital stay would be reduced by the agent.
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