Comparative analgesic and mental effects of increasing plasma concentrations of dexmedetomidine and alfentanil in humans
Comparative analgesic and mental effects of increasing plasma concentrations of dexmedetomidine and alfentanil in humans
复制标题
DOI：
10.1097/00000542-200409000-00024
复制
发表时间：
2004-09-01
期刊：
影响因子：
8.8
通讯作者：
Maze, M
中科院分区：
文献类型：
--
作者：
Angst, MS;Ramaswamy, B;Maze, M
背景资料：在动物中，全身和鞘内给予α（2）-肾上腺素能受体激动剂右美托咪定在热痛模型中产生了强烈的抗伤害效应。在人类中，全身给药的右旋美托咪啶被批准用于使重症监护室中的患者镇静。然而，是否在人体全身给药右美托咪定产生显着的镇痛剂量引起镇静，但不是unconsciousness仍然存在争议。方法：本研究在人类志愿者使用安慰剂对照，双盲，随机设计，以检查是否右美托咪定的剂量引起轻度至严重的镇静产生镇痛的热和电疼痛的实验模型。结果与μ阿片受体激动剂阿芬太尼的作用进行了比较。计算机控制的输注提供了4个中位右旋地托咪定血药浓度递增（0.09、0.24、0.54和1.23 ng/ml）和阿芬太尼（13.4、33.8、67.8和126.1 ng/ml）。右美托咪定的镇静和认知作用具有剂量依赖性，在最高血浆浓度下，导致镇静评分中值为95/100，认知速度（反应时间，跟踪测试）减慢约2倍。右美托咪定不能减轻热痛或电痛。阿芬太尼引起严重的镇静（镇静评分中位数为88/100），并在最高血浆浓度下使认知速度减慢约1.4倍。Alfentanil衰减热和电pain dose dependented.Conclusion：本研究记录了全身性右美托咪定在引起轻度至重度镇静的剂量下对热和电疼痛缺乏镇痛效果。这些结果提供了进一步的证据，表明在急性疼痛模型中，右旋地托咪定的全身给药在不使人失去意识的剂量下缺乏广泛的镇痛活性。
Background: In animals, systemic and intrathecal administration of the alpha(2)-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 dexinedetomidine 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 dexinedetomidine (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, trailmaking 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.Conclusion: 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 dexinedetomidine lacks broad analgesic activity in models of acute pain at doses not rendering humans unconscious.