Hood D D, Mallak K A, Eisenach J C, Tong C
Department of Anesthesia, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157-1009, USA.
Anesthesiology. 1996 Aug;85(2):315-25. doi: 10.1097/00000542-199608000-00013.
alpha 2-Adrenergic agonists are thought to produce analgesia, in part, by activating spinal acetylcholine release. The purpose of the current study was to examine the interaction between intrathecal neostigmine and epidural clonidine for analgesia and side effects in humans.
A total of 58 volunteers received an intrathecal injection of 5% dextrose in normal saline (D5NS) or neostigmine (50, 100, or 200 micrograms in D5NS), followed in 1 h by epidural saline or clonidine (computer-controlled infusion targeted to 50, 100, 200, or 400 ng/ml in cerebrospinal fluid) using an isobolographic design. Visual analog scale pain to a noxious cold stimulus, nausea, weakness, sedation, and other safety variables was measured before and at specified intervals after drug administration.
The first 21 volunteers randomized to receive intrathecal hyperbaric neostigmine rather than D5NS received the drug while in the sitting position, and had none-to-minimal analgesia 1 h later. The remaining volunteers received the drug while in the lateral position, and demonstrated dose-dependent analgesia in the foot 1 h later. Epidural clonidine also caused dose-dependent analgesia. The combination of neostigmine and clonidine resulted in an additive enhancement for analgesia, but no enhancement of each drug's side effects, and a reduction in clonidine-induced hypotension. Neostigmine injected into subjects in the lateral position diminished clonidine-induced reductions in blood pressure and plasma norepinephrine.
These results support enhancement of alpha 2-adrenergic analgesia by intrathecal neostigmine, but do not demonstrate synergy, as observed in animals. Lack of enhancement of side effects suggests this combination may be clinically useful.
α2肾上腺素能激动剂被认为部分通过激活脊髓乙酰胆碱释放来产生镇痛作用。本研究的目的是探讨鞘内注射新斯的明与硬膜外注射可乐定在人体镇痛及副作用方面的相互作用。
58名志愿者接受鞘内注射生理盐水（D5NS）或新斯的明（50、100或200微克溶于D5NS），1小时后采用等效应线图设计硬膜外注射生理盐水或可乐定（计算机控制输注，目标脑脊液浓度为50、100、200或400纳克/毫升）。在给药前及给药后特定时间间隔测量对有害冷刺激的视觉模拟评分疼痛、恶心、虚弱、镇静及其他安全变量。
最初随机接受鞘内高压新斯的明而非D5NS的21名志愿者在坐位时接受药物，1小时后镇痛作用无至轻微。其余志愿者在侧卧位时接受药物，1小时后足部出现剂量依赖性镇痛。硬膜外可乐定也引起剂量依赖性镇痛。新斯的明与可乐定联合使用导致镇痛作用相加增强，但未增强每种药物的副作用，且可乐定引起的低血压有所减轻。向侧卧位受试者注射新斯的明可减轻可乐定引起的血压和血浆去甲肾上腺素降低。
这些结果支持鞘内注射新斯的明增强α2肾上腺素能镇痛作用，但未显示出如在动物中观察到的协同作用。副作用未增强表明这种联合用药可能具有临床实用性。
