Angst Martin S, Ramaswamy Bhamini, Davies M Frances, Maze Mervyn
Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305-5117, USA.
Anesthesiology. 2004 Sep;101(3):744-52. doi: 10.1097/00000542-200409000-00024.
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.
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).
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.
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.
在动物中，α2 -肾上腺素能受体激动剂右美托咪定的全身给药和鞘内给药在热痛模型中产生强大的镇痛作用。在人类中，全身给药的右美托咪定被批准用于重症监护病房患者的镇静。然而，在人类中全身给药右美托咪定在引起镇静但未导致昏迷的剂量下是否产生显著镇痛作用仍存在争议。
这项针对人类志愿者的研究采用安慰剂对照、双盲和随机设计，以检查在热痛和电痛实验模型中，引起轻度至重度镇静的右美托咪定剂量是否产生镇痛作用。将结果与μ-阿片受体激动剂阿芬太尼的作用进行比较。通过计算机控制输注提供右美托咪定（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）的四个中位递增血浆浓度。
右美托咪定的镇静和认知作用呈剂量依赖性，在最高血浆浓度下，中位镇静评分为100分中的95分，认知速度（反应时间、连线测验）减慢约两倍。右美托咪定未减轻热痛或电痛。阿芬太尼引起严重镇静（中位镇静评分为100分中的88分），在最高血浆浓度下认知速度减慢约1.4倍。阿芬太尼剂量依赖性地减轻热痛和电痛。
本研究证明，全身应用右美托咪定在引起轻度至重度镇静的剂量下对热痛和电痛缺乏镇痛效果。这些结果提供了进一步的证据，表明在不使人类昏迷的剂量下，全身应用右美托咪定在急性疼痛模型中缺乏广泛的镇痛活性。
