Stubhaug A, Breivik H, Eide P K, Kreunen M, Foss A
Department of Anaesthesiology, National Hospital, Oslo, Norway.
Acta Anaesthesiol Scand. 1997 Oct;41(9):1124-32. doi: 10.1111/j.1399-6576.1997.tb04854.x.
Tissue injury induces central sensitization in the spinal cord dorsal horn neurons via mechanisms involving N-methyl-D-aspartate (NMDA) receptors, leading to secondary hyperalgesia. Using punctuate mechanical hyperalgesia as a measure of central sensitization, we examined whether induction and maintenance of central sensitization after surgery could be prevented by a low-dose infusion of the NMDA-receptor antagonist ketamine.
Twenty living kidney donors were included in a randomized, double-blind, parallel, two-group study. Before start of surgery 10 patients received an i.v. bolus of racemic ketamine 0.5 mg.kg-1, followed by a continuous i.v. infusion of ketamine 2 micrograms.kg-1.min-1 for 24 h, thereafter 1 microgram.kg-1.min-1 for another 48 h. The control group received placebo bolus and infusion. A standard general anaesthesia including fentanyl was used. Patient-controlled (PCA) i.v. morphine was used for postoperative analgesia. Punctuate mechanical hyperalgesia and temporal summation of mechanical stimuli causing "wind-up pain" were measured using von Frey filaments.
The area of punctuate mechanical hyperalgesia was significantly reduced in the ketamine group 1, 3 and 7 d after the operation (P < 0.01-0.001). "Wind-up pain" was also reduced by ketamine (P < 0.05). PCA morphine consumption and pain intensity (visual analogue scale) differed between groups only during the first hours after surgery, in favour of ketamine. The ketamine patients scored significantly higher on a global satisfaction score. Side-effects were most frequent in the placebo group.
Low-dose i.v. infusion of ketamine during and after surgery reduces mechanical punctuate hyperalgesia surrounding the surgical incision. These results indicate that blockade of NMDA receptors prevents the central sensitization caused by nociceptive input during and after surgery.
组织损伤通过涉及N-甲基-D-天冬氨酸（NMDA）受体的机制诱导脊髓背角神经元中枢敏化，导致继发性痛觉过敏。我们以点状机械性痛觉过敏作为中枢敏化的指标，研究了手术中及术后给予低剂量NMDA受体拮抗剂氯胺酮能否预防中枢敏化的诱导和维持。
20名活体肾供者纳入一项随机、双盲、平行两组研究。手术开始前，10名患者静脉注射消旋氯胺酮0.5 mg·kg-1，随后静脉持续输注氯胺酮2 μg·kg-1·min-1，共24小时，之后以1 μg·kg-1·min-1再输注48小时。对照组接受安慰剂推注和输注。采用包括芬太尼在内的标准全身麻醉。术后镇痛采用患者自控静脉注射吗啡。使用von Frey细丝测量点状机械性痛觉过敏区域以及引起“卷绕痛”的机械刺激的时间总和。
氯胺酮组术后1天、3天和7天的点状机械性痛觉过敏区域显著减小（P<0.01-0.001）。氯胺酮也减轻了“卷绕痛”（P<0.05）。仅在术后最初数小时内，两组间患者自控静脉注射吗啡的用量和疼痛强度（视觉模拟评分）存在差异，氯胺酮组更具优势。氯胺酮组患者的总体满意度评分显著更高。安慰剂组的副作用最为常见。
手术中及术后静脉输注低剂量氯胺酮可减轻手术切口周围的点状机械性痛觉过敏。这些结果表明，阻断NMDA受体可预防手术中及术后伤害性输入引起的中枢敏化。
