Gajjar Ketan, Martin-Hirsch Pierre P L, Bryant Andrew, Owens Gemma L
Gynaecological Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, UK, CB2 0QQ.
Cochrane Database Syst Rev. 2016 Jul 18;7(7):CD006120. doi: 10.1002/14651858.CD006120.pub4.
BACKGROUND: Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. OBJECTIVES: To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. MAIN RESULTS: We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral analgesics (non-steroidal anti-inflammatory drugs (NSAIDs)), inhalation analgesia (gas mixture of isoflurane and desflurane), lignocaine spray, cocaine spray, local application of benzocaine gel, lignocaine-prilocaine cream (EMLA cream) and transcutaneous electrical nerve stimulation (TENS).Most comparisons were restricted to single trial analyses and were under-powered to detect differences in pain scores between treatments that may or may not have been present. There was no difference in pain relief between women who received local anaesthetic infiltration (lignocaine 2%; administered as a paracervical or direct cervical injection) and a saline placebo (mean difference (MD) -13.74; 95% CI -34.32 to 6.83; 2 trials; 130 women; low quality evidence). However, when local anaesthetic was combined with a vasoconstrictor agent (one trial used lignocaine plus adrenaline while the second trial used prilocaine plus felypressin), there was less pain (on visual analogue scale (VAS)) compared with no treatment (MD -23.73; 95% CI -37.53 to -9.93; 2 trials; 95 women; low quality evidence). Comparing two preparations of local anaesthetic combined with vasoconstrictor, prilocaine plus felypressin did not differ from lignocaine plus adrenaline for its effect on pain control (MD -0.05; 95% CI -0.26 to 0.16; 1 trial; 200 women). Although the mean (± standard deviation (SD)) observed blood loss score was less with lignocaine plus adrenaline (1.33 ± 1.05) compared with prilocaine plus felypressin (1.74 ± 0.98), the difference was not clinically as the overall scores in both groups were low (MD 0.41; 95% CI 0.13 to 0.69; 1 trial; 200 women). Inhalation of gas mixture (isoflurane and desflurane) in addition to standard cervical injection with prilocaine plus felypressin resulted in less pain during the LLETZ (loop excision of the transformation zone) procedure (MD -7.20; 95% CI -12.45 to -1.95; 1 trial; 389 women). Lignocaine plus ornipressin resulted in less measured blood loss (MD -8.75 ml; 95% CI -10.43 to -7.07; 1 trial; 100 women) and a shorter duration of treatment (MD -7.72 minutes; 95% CI -8.49 to -6.95; 1 trial; 100 women) than cervical infiltration with lignocaine alone. Buffered solution (sodium bicarbonate buffer mixed with lignocaine plus adrenaline) was not superior to non-buffered solution of lignocaine plus adrenaline in relieving pain during the procedure (MD -8.00; 95% CI -17.57 to 1.57; 1 trial; 52 women).One meta-analysis found no difference in pain using VAS between women who received oral analgesic and women who received placebo (MD -3.51; 95% CI -10.03 to 3.01; 2 trials; 129 women; low quality evidence).Cocaine spray was associated with less pain (MD -28.00; 95% CI -37.86 to -18.14; 1 trial; 50 women) and blood loss (MD 0.04; 95% CI 0 to 0.70; 1 trial; 50 women) than placebo.None of the trials reported serious adverse events and majority of trials were at moderate or high risk of bias (13 trials). AUTHORS' CONCLUSIONS: Based on two small trials, there was no difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (MD -3.51; 95% CI -10.03 to 3.01; 129 women). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.
背景:子宫颈癌前病变(宫颈上皮内瘤变,CIN)通常采用切除或消融手术治疗。在英国,国民医疗服务体系(NHS)的子宫颈癌筛查指南建议,超过80%的治疗应在门诊环境(阴道镜诊所)进行。此外,这些指南建议在激光或切除治疗前应始终给予镇痛。目前采用了各种疼痛缓解策略,这些策略可能会减轻这些手术过程中的疼痛。 目的:评估疼痛缓解(镇痛)措施是否能减轻阴道镜检查治疗期间及术后的疼痛。 检索方法:我们检索了Cochrane对照试验中心注册库(CENTRAL 2016年第2期)、MEDLINE(1950年至2016年3月第3周)和Embase(1980年至2016年第12周),以查找与阴道镜检查管理镇痛相关的任何设计的研究。我们还检索了临床试验注册库、科学会议摘要、纳入研究的参考文献列表,并联系了该领域的专家。 选择标准:随机对照试验(RCT),比较在门诊阴道镜诊所环境中接受环形切除、激光消融、激光切除或冷冻手术的CIN女性患者在门诊治疗前、治疗期间或治疗后的所有类型疼痛缓解措施。 数据收集与分析:我们独立评估研究的纳入资格、提取数据并评估偏倚风险。我们将数据录入Review Manager 5并进行准确性的二次核对。在可能的情况下,我们将结果表示为平均疼痛评分和平均标准误差,并带有95%置信区间(CI),并在荟萃分析中综合数据。 主要结果:我们在综述中纳入了19项方法学质量各异的RCT(1720名女性)。这些试验比较了多种旨在减轻接受CIN治疗女性疼痛的干预措施,包括单独注射利多卡因、利多卡因加肾上腺素、缓冲利多卡因加肾上腺素、丙胺卡因加非那根、口服镇痛药(非甾体抗炎药,NSAIDs)、吸入镇痛(异氟烷和地氟烷混合气体)、利多卡因喷雾、可卡因喷雾、局部应用苯佐卡因凝胶、利多卡因-丙胺卡因乳膏(EMLA乳膏)和经皮电刺激神经疗法(TENS)。大多数比较仅限于单项试验分析,且检测治疗之间疼痛评分差异的能力不足,这些差异可能存在也可能不存在。接受局部麻醉浸润(2%利多卡因;作为宫颈旁或直接宫颈注射给药)的女性与生理盐水安慰剂相比,疼痛缓解没有差异(平均差异(MD)-13.74;95% CI -34.32至6.83;2项试验;130名女性;低质量证据)。然而,当局部麻醉与血管收缩剂联合使用时(一项试验使用利多卡因加肾上腺素,另一项试验使用丙胺卡因加非那根),与未治疗相比,疼痛(视觉模拟评分法(VAS))较轻(MD -23.73;95% CI -37.53至-9.93;2项试验;95名女性;低质量证据)。比较两种联合血管收缩剂的局部麻醉制剂,丙胺卡因加非那根在疼痛控制效果上与利多卡因加肾上腺素没有差异(MD -0.05;95% CI -0.26至0.16;1项试验;200名女性)。尽管与丙胺卡因加非那根(1.74±0.98)相比,利多卡因加肾上腺素观察到的平均(±标准差(SD))失血量评分较低(1.33±1.05),但差异在临床上不显著,因为两组的总体评分都较低(MD 0.41;95% CI 0.13至0.69;1项试验;200名女性)。除了标准的丙胺卡因加非那根宫颈注射外,吸入混合气体(异氟烷和地氟烷)在大环形切除术(转化区环形切除)过程中疼痛较轻(MD -7.20;95% CI -12.45至-1.95;1项试验;389名女性)。与单独宫颈浸润利多卡因相比,利多卡因加去甲加压素导致测量的失血量较少(MD -8.75 ml;95% CI -10.43至-7.07;1项试验;100名女性)且治疗持续时间较短(MD -7.72分钟;95% CI -8.49至-6.95;1项试验;100名女性)。缓冲溶液(碳酸氢钠缓冲液与利多卡因加肾上腺素混合)在手术过程中缓解疼痛方面并不优于未缓冲的利多卡因加肾上腺素溶液(MD -8.00;95% CI -17.57至1.57;1项试验;52名女性)。一项荟萃分析发现,接受口服镇痛药的女性与接受安慰剂的女性在使用VAS评估的疼痛方面没有差异(MD -3.51;95% CI -10.03至3.01;2项试验;129名女性;低质量证据)。与安慰剂相比,可卡因喷雾导致的疼痛较轻(MD -28.00;95% CI -37.86至-18.14;1项试验;50名女性)且失血量较少(MD 0.04;95% CI从0至0.70;1项试验;50名女性)。没有试验报告严重不良事件,大多数试验存在中度或高度偏倚风险(13项试验)。 作者结论:基于两项小型试验,接受口服镇痛药的女性与接受安慰剂或未治疗的女性在疼痛缓解方面没有差异(MD -3.51;95% CI -10.03至3.01;129名女性)。我们认为该证据质量低至中等。在常规临床实践中,宫颈内注射局部麻醉药并加用血管收缩剂(利多卡因加肾上腺素或丙胺卡因加非那根)似乎是治疗的最佳镇痛方法。然而,应进行进一步的高质量、足够样本量的试验,以提供估计口服镇痛药疗效、局部麻醉药最佳给药途径和剂量所需的数据。
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