Comparative analgesic and mental effects of increasing plasma concentrations of dexmedetomidine and alfentanil in humans.
BACKGROUND
In animals, systemic and intrathecal administration of the alpha2 -adrenergic receptor agonist dexmedetomidine results in robust antinociceptive effects in models of heat pain. In humans, systemically administered dexmedetomidine is approved for sedating patients in the intensive care unit. However, whether systemic administration of dexmedetomidine in humans produces significant analgesia at doses causing sedation but not unconsciousness remains controversial.


METHODS
This study in human volunteers used a placebo-controlled, double-blind, and randomized design to examine whether dexmedetomidine at doses causing mild to severe sedation produces analgesia in experimental models of heat and electrical pain. Results were compared to the effects of the mu-opioid receptor agonist alfentanil. A computer-controlled infusion provided four median step-up plasma concentrations of dexmedetomidine (0.09, 0.24, 0.54, and 1.23 ng/ml) and alfentanil (13.4, 33.8, 67.8, and 126.1 ng/ml).


RESULTS
Sedative and cognitive effects of dexmedetomidine were dose-dependent, resulting in a median sedation score of 95 of 100 and slowing of cognitive speed (reaction time, trail-making test) by a factor of about two at the highest plasma concentration. Dexmedetomidine did not attenuate heat or electrical pain. Alfentanil caused severe sedation (median sedation score 88 of 100) and slowed cognitive speed by a factor of approximately 1.4 at the highest plasma concentration. Alfentanil attenuated heat and electrical pain dose dependently.


CONCLUSIONS
This study documents that systemic dexmedetomidine lacks analgesic efficacy for heat and electrical pain at doses causing mild to severe sedation. These results provide further evidence suggesting that systemic administration of dexmedetomidine lacks broad analgesic activity in models of acute pain at doses not rendering humans unconscious.
Angst
Martin S
MS
Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305-5117, USA. ang@stanford.edu
Ramaswamy
Bhamini
B
Davies
M Frances
MF
Maze
Mervyn
M
D000316:Adrenergic alpha-Agonists / Q000097:blood* / Q000494:pharmacology*; D000328:Adult; D015760:Alfentanil / Q000097:blood* / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000097:blood* / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000097:blood* / Q000494:pharmacology*; D020927:Dexmedetomidine / Q000097:blood* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006439:Hemodynamics / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D008606:Mental Processes / Q000187:drug effects*; D009483:Neuropsychological Tests; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D015760:Alfentanil; D020927:Dexmedetomidine