经皮尼古丁用于耻骨后前列腺根治术术后镇痛

背景既住动物实验和人类研究表明尼古丁可能具有抗伤害效应。本研究假设手术前7nag尼古丁缓释贴可能降低全麻下耻骨后前列腺根治术（radicalretropubic prostatectomy，RRP）患者的术后镇痛药物使用剂量。方法全麻下行RRP的非吸烟患者纳入此项前瞻性、双盲、安慰剂对照研究。患者于麻醉诱导前30～60分钟随机接受7mg尼古丁缓释贴或安慰剂，麻醉采用标准化流程，手术后镇痛采用标准的吗啡患者自控镇痛（PCA）方案和酮洛酸15nag，每6小时静脉注射。收集麻醉后恢复室（PACu）及手术后4、6、12、24小时的数据。结果90例患者数据纳入分析，尼古丁组44例，安慰剂组46例。两组相比，在年龄、身高、体重、AsA分级、手术时程、手术中芬太尼使用剂量上差异没有统计学意义。吗啡24小时累积使用剂量，尼古丁组明显低于安慰剂组（均数±标准差）：33．3±30．8mg对44．7±26．4mg（P=0．0059，时间与干预措施的交互效应P=0.0031）。然而，重复测量分析发现，静息及咳嗽时疼痛的干预措施以及与时间的交互作用差异均没有统计学意义。Posf而DC分析显示，静息及咳嗽时疼痛在任何两个时间点间差异均无统计学意义。手术后，,5。2心、呕吐及是否需要止吐药物，两组之间比较差异没有统计学意义。尼古丁组患者恶心口述评分的最大值高于安慰剂组（中位数，25％～75％的可信区闻分别为4、0～6对0、0～6，P=0.0158）。24小时尼古丁血浆浓度-tPACU中（P=0．049）、手术后6、12、24小时（均为P=0．002）的吗啡累积使用剂量明显负相关。结论虽然没有降低手术后疼痛评分及恶心、呕吐发生率，但手术前给予7mg尼古丁缓释贴显著降低了全麻下RRP患者手术后吗啡累积使用剂量。

BACKGROUND： Previous animal and human studies suggested that nicotine might have an antinociceptive effect. We hypothesized that the preoperative application of a 7 mg nicotine patch would result in reduced postoperative analgesic requirements in patients undergoing radical retropubic prostatectomy （RRP） under general anesthesia. METHODS： Nonsmokers undergoing RRP under general anesthesia were enrolled in this prospective, double-blind, placebo-controlled study. Patients were randomly assigned to receive a patch of 7 mg nicotine or placebo applied behind the ear 30 - 60 rain before induction of anesthesia. The anesthetic technique was standardized. Postoperative analgesia was provided with a standardized morphine patient-controlled analgesia and 6 hourly ketorolac 15 mg IV. Data were collected in the postanesthesia care unit and at 6, 12, and 24 h after surgery. RESULTS： Ninety patients were included in the analysis： 44 in the nicotine group and 46 in the placebo group. The groups did not differ significantly with respect to age, height, weight, ASA class, length of surgery, or amounts of intraoperative fentanyl received. The nicotine group showed significantly lower cumulative morphine consumption at 24h （mean±SD）：33.3 ±30.8 mgvs 44.7±26.4 mg （P =0.0059, time × treatment P = 0. 0031）. However, the repeated measures tests found no difference in amount of pain reported on coughing or at rest, either as treatment effects or in interaction with time. In post hoc comparisons, there was no significant difference in amount of pain reported on coughing or at rest at any of the times assessed. There were also no significant differ- ences between the groups in the incidence of postoperative nausea and vomiting or the need for rescue antiemetics. However, the maximum nausea verbal rating scale score was higher in the nicotine than in the placebo group （median, 25th to 75th percentiles --4, 0-6 vs 0, 0-6, P = 0.0158）. There was a significant negative correlation between the 24 h plasma nicotine levels and postoperative morphine consumption in the postanesthesia care unit （P = 0.049）, as well as at 6, 12, and 24 h （P = 0.002）. CONCLUSIONS： The preoperative application of a 7 mg nicotine patch resulted in a significant reduction in opioid consumption in patients undergoing RRP under general anesthesia. Despite this reduction in opioid use, there was no reduction in pain scores or postoperative nausea and vomiting with the use of transdermal nicotine.