尼古丁透皮贴剂用于手术后镇痛：一项剂量-范围的初步研究

背景一些动物研究已证实尼古丁在手术后有镇痛作用。然而，尼古丁经鼻喷雾剂在临床试验中得到的结果却好坏参半，这可能与其药代动力学的差异有关，或者受试者中有接触过尼古丁的吸烟者。本初步研究在手术前对非吸烟患者应用尼古丁透皮贴剂，旨在观察其镇痛作用。方法40例接受普外科手术的受试者参加此项随机、双盲、安慰剂对照的前瞻性研究，患者手术后需留院一晚并采用患者自控镇痛。手术前即刻分别给予受试者剂量为0、5、10或15mg的尼古丁透皮贴剂。本研究观察的主要指标为手术后第1小时及此后5天的疼痛程度，使用数字评价量表（NRS）进行评分。次要指标为镇痛药的用量、血流动力学数据、恶心及镇静情况。结果应用尼古丁透皮贴剂的治疗组在手术后第1小时及手术后5天中，疼痛评分均低于使用安慰剂的对照组，手术后第1小时：P=0．003，NRS均值下降1．4，95％CI=0．3～2．6；手术后5天：P=0．03，NRS均值下降1．0，95％CI=0．1-1．9。尼古丁剂量超过5mg时镇痛效果没有明显的提升。治疗组中有镇痛药的使用量减少、恶心增加、心动过速减少和收缩期血压轻度下降的趋势，但无统计学意义。结论剂量为5—15mg的尼古丁透皮贴剂可降低普外科手术后的疼痛评分，但是不能减少阿片类镇痛药的需求及其产生的副作用。

BACKGROUND： Nicotine has been shown to be anfinociceptive in the postoperative period in animal studies. Human studies with nasal nicotine sprays have had mixed results, possibly due to variability in pharmacokinetics and potential patient variables such as exposure to nicotine in tobacco smokers. In this pilot study, we examined the analgesic effect of a transdermal nicotine patch applied before surgery in nonsmokers. METHODS： We conducted a randomized, doubleblind, prospective placebo-controlled trial of 40 subjects, undergoing general surgery that required postoperative patient-controlled analgesia and an overnight hospital admission. Immediately before surgery, a transdermal nicotine patch containing 0, 5, 10, or 15 mg was applied. The primary outcome variable was pain report using a numerical rating scale （NRS） in the first hour after surgery and over the next 5 days. Secondary outcomes were pain medication use, hemodynamic values, nausea, and sedation. RESULTS： Patients treated with nicotine reported lower pain scores when compared with those treated with place- bo during the first hour after surgery （P = 0. 003, average NRS decrease = 1.4, 95% CI = 0.3 - 2.6） and for 5 days after surgery （P = 0. 03, average NRS decrease = 1.0, 95% CI = 0. 1 - 1. 9）. There was no increased benefit of nicotine with doses