Wallace Mark S, Dyck Barry J, Rossi Steve S, Yaksh Tony L
Department of Anesthesiology, 0818, University of California, San Diego School of Medicine,San Diego, CA 92103,USA.
Pain. 1996 Jul;66(1):69-77. doi: 10.1016/0304-3959(96)02980-6.
Systemic lidocaine has been reported to be effective in treating several neuropathic pain syndromes. Few reports relate plasma lidocaine concentration to analgesia and the available studies have been complicated by labile plasma lidocaine concentrations. We used a computer-controlled infusion pump (CCIP) to target and maintain stable plasma lidocaine concentrations and study the effect of intravenous lidocaine on (1) pain scores, (2) current perception thresholds, (3) side effects, and (4) pain distribution in patients suffering from peripheral nerve injury pain.
This study used a randomized double-blind placebo-controlled design. Eleven patients suffering from neuropathic pain after peripheral nerve injury received both a lidocaine and saline infusion in separate study sessions. The order of the study sessions was randomized and separated from each other by 1 week. The CCIP was programmed to target plasma lidocaine concentrations of 0.5, 1, 1.5, 2, and 2.5 micrograms/ml, each held for 10 min. Pain scores and pain distribution were assessed in the painful area, and electrical current perception thresholds (CPT) of the ring finger were measured using a cutaneous perception threshold neurometer (Neurometer CPT, Neurotron, Baltimore, MD). Side effects were recorded at fixed intervals. Plasma lidocaine concentrations were measured at 4 and 9 min after each step increase in infusion and correlated with the observed effects.
Saline infusion had no effect. However, with lidocaine there was a significant plasma concentration-dependent decrease in pain scores starting at 1.5 micrograms/ml. This effect typically corresponded with a decrease in the size of the receptive field to which the pain was referred. For the electrical stimulus, there was no significant effect on cutaneous perception at 2000-Hz stimulation at the highest concentration examined; however, there was a significant increase in thresholds at 250-Hz (starting at 1.5 micrograms/ml) and 5-Hz (starting at 1.0 micrograms/ml) stimulation. There were no serious side effects. In all, 54.5% of patients reported lightheadedness (average plasma lidocaine concentration: 1.5 micrograms/ml) and one patient reported nausea (2.3 micrograms/ml).
The computer-controlled delivery of intravenous lidocaine results in relatively stable plasma concentrations which allows a more thorough evaluation of the relationship between plasma concentration and patient response. This administration methodology for intravenous lidocaine may prove to be a valuable clinical and research tool.
据报道,全身性利多卡因对治疗多种神经性疼痛综合征有效。很少有报告将血浆利多卡因浓度与镇痛效果相关联,并且现有的研究因血浆利多卡因浓度不稳定而变得复杂。我们使用计算机控制输注泵(CCIP)来靶向并维持稳定的血浆利多卡因浓度,并研究静脉注射利多卡因对周围神经损伤性疼痛患者的(1)疼痛评分、(2)电流感觉阈值、(3)副作用以及(4)疼痛分布的影响。
本研究采用随机双盲安慰剂对照设计。11名周围神经损伤后患有神经性疼痛的患者在不同的研究阶段分别接受了利多卡因和生理盐水输注。研究阶段的顺序是随机的,且彼此间隔1周。CCIP被编程为将血浆利多卡因浓度靶向至0.5、1、1.5、2和2.5微克/毫升,每个浓度维持10分钟。在疼痛区域评估疼痛评分和疼痛分布,并使用皮肤感觉阈值神经仪(Neurometer CPT,Neurotron,巴尔的摩,马里兰州)测量无名指的电流感觉阈值(CPT)。定期记录副作用。在每次输注增加步骤后4分钟和9分钟测量血浆利多卡因浓度,并将其与观察到的效果相关联。
输注生理盐水没有效果。然而,使用利多卡因时,从1.5微克/毫升开始,疼痛评分出现了显著的血浆浓度依赖性降低。这种效果通常对应于疼痛所涉及的感受野大小的减小。对于电刺激,在最高检测浓度下,2000赫兹刺激时对皮肤感觉没有显著影响;然而,在250赫兹(从1.5微克/毫升开始)和5赫兹(从1.0微克/毫升开始)刺激时阈值有显著增加。没有严重的副作用。总体而言,54.5%的患者报告有头晕(平均血浆利多卡因浓度:1.5微克/毫升),一名患者报告有恶心(2.3微克/毫升)。
计算机控制的静脉注射利多卡因给药可导致相对稳定的血浆浓度,这使得能够更全面地评估血浆浓度与患者反应之间的关系。这种静脉注射利多卡因的给药方法可能被证明是一种有价值的临床和研究工具。