腰椎间盘突出症治疗的循证医学综述.doc

Treatment of Lumbar Disc Herniation: An Evidence-Based Review 腰椎间盘突出症治疗的循证医学综述Wayne Moschetti, MD, Adam M. Pearson, MD, MS, and William A. Abdu, MD, MS Several randomized controlled trials (RCTs) and prospective observational cohort studies have compared surgical to conservative treatment for patients with sciatica caused by lumbar disc herniation. Whereas no RCT has been able to compare surgery with nonoperative treatment without substantial crossover between treatment groups, multiple RCTs and observational studies have suggested that surgery resulted in faster improvement and a greater degree of improvement compared with nonoperative treatment. However, many patients in these studies also experienced improvement with nonoperative care without adverse sequelae. This paper critically reviews the literature comparing surgery with nonoperative treatment for lumbar disc herniation. Semin Spine Surg 21:223-229 2009 Elsevier Inc. All rights reserved. KEYWORDS Maine lumbar spine study, Spine Patient Outcomes Research Trial, sciatica, intervertebral disc herniation, low back pain, lumbar disc herniation 对于腰椎间盘突出导致的坐骨神经痛，有几项随机对照试验（RCTs）和前瞻性的观察队列研究对手术和保守治疗进行了比较。尽管目前还没有RCT能对手术和非手术治疗进行没有任何组间交叉的比较，多项RCT和观察研究都认为与非手术治疗相比，手术可以获得更快、更大程度的改善。然而，在这些研究中很多患者通过非手术治疗也获得了改善，并且没有导致不良的后果。本文对文献进行审慎的综述，以对腰椎间盘突出症的手术和非手术治疗进行比较。关键词 缅因州腰椎研究；脊柱患者治疗结果研究试验；坐骨神经痛；椎间盘突出；腰痛；腰椎间盘突出ciatica is dened as pain radiating in an area of the leg that is served by a single nerve root in the lumbar or sacral spine and may be associated with motor or sensory decits. A lumbar intervertebral disc herniation (IDH) is the most common cause of sciatica in working adults, with an estimated annual incidence of 5 per 1000 adults.1,2 Diskectomy is the most common lumbar spine surgery, and more than 250,000 elective lumbar spine surgeries occur each year in the USA.3 Many patients with sciatica will improve over time, yet surgery is frequently considered for patients with severe symptoms or symptoms that persist. Most spine surgeons agree that surgery should be offered only after a course of nonoperative treatment for sciatica has failed. The most effective type and duration of conservative treatment has not been determined and varies substantially.4 In the USA, the rate of back surgery was found to be approximately 40% higher when compared with 11 other countries and was more than ve times the rate in England and Scotland.1 There is also signicant regional variation in the rate of diskectomy in the USA and internationally, suggesting that the indications for surgery are also variable.3,5 Given this substantial variation in the rate of surgery, it is clear that the appropriate timing of and indications for surgery are inconsistent. The economic impact of back pain and sciatica is well known as demonstrated by a Dutch study concluding that low back pain was responsible for more time off work and disability than any other medical condition.6 In light of the uncertainty surrounding the outcomes of surgical and nonoperative treatment for lumbar IDH, this article aims to review the pertinent literature to assist spine care professionals in providing evidence-based recommendations to their patients. 坐骨神经痛是指小腿的放射性疼痛，该区域由起源于腰骶部的单一神经支配，并可伴有运动或感觉障碍。腰椎间盘突出（IDH）是导致成年劳动者坐骨神经痛最常见的原因，据估计成人每年的发生率约为51,2。椎间盘切除术是最常用的腰椎手术，在美国每年要实施超过250000例选择性的腰椎手术3。随着时间过去，很多患者的坐骨神经痛也可自行缓解，然而，对于症状持续或症状严重的患者，通常考虑手术治疗。大多数脊柱外科医生都认为，坐骨神经痛的患者只有经过系统的非手术治疗失败后，方可选择手术治疗。至于最有效的类型和合适的保守治疗期限，目前并没有统一的意见，且各种观点差异很大4。在美国，脊柱手术的比率高出其他11个国家约40%，是英格兰和苏格兰的5倍余1。美国和国际上椎间盘切除术的比率也都存在着明显的地区差异，这提示各地手术适应证上的差异也很大3,5。考虑到手术率上明显的差异，很显然，要确定适当的手术时机和手术适应证是不太现实的。众所周知，背痛与坐骨神经痛可对经济产生明显的影响，荷兰学者的研究也证实了这一点，其结论认为腰痛导致的工作时间缺失以及劳动能力的丧失比任何其他疾病都要多6。考虑到腰椎间盘突出症手术和非手术治疗相关结果的不确定性，本文旨在综述相关文献，帮助脊柱外科医生向他们的患者提供循证医学建议。Webers Classic Randomized Control Trial In 1983, from a single referral center in Norway, Weber7 published the rst randomized control trial (RCT) comparing surgery and nonoperative treatment for patients with a herniated lumbar disc and radicular symptoms. Excluding patients with “intolerable” pain and those with “no indication” for operative intervention, this paper looked at 126 patients with “uncertain” indications for surgical treatment. These patients were randomized to surgical or nonoperative treatment. Follow-up examination was performed at 1, 4, and 10 years. Those undergoing surgery improved signicantly more on a descriptive outcome scale (good, fair, poor, bad) compared with those treated nonoperative at the 1-year follow-up examination. Sixty-ve percent of surgical patients had a “good” outcome compared with 36% in the nonoperative group. At the 4-year follow up, the surgical patients still showed better results (70% “good” outcome vs 51% for nonoperative patients), but the difference was no longer statistically signicant. Only minor changes took place during the last 6 years of the study. Weber经典随机对照试验1983年，来自挪威一个转诊中心的Weber7发表了比较手术和非手术治疗伴有根性症状的腰椎间盘突出的研究，这是针对该问题发表的第一个随机对照试验（RCT）。研究排除了伴有“无法忍受”的疼痛的患者，以及没有手术干预指征的患者，文章共纳入了126例“指征不明确的”患者。这些患者随机进行手术和非手术治疗，1、4、10年是进行随访复查。在1年随访时，按照疗效评价标准（好、一般、较差、差），与非手术治疗的患者相比，进行手术的患者改善更明显。手术治疗的患者65%治疗结果为“好”，而非手术治疗者仅为36%。4年随访时，手术患者仍然显示出更好的治疗结果（70%为“好”，非手术治疗者为51%），但此后两组的差异不再具有统计学意义。在该研究的最后6年中只发生了很微小的改变。Webers study represented the rst effort to perform a prospective RCT comparing surgery with nonoperative treatment for IDH. Similar to subsequent RCTs, this study was affected by a substantial number of patients crossing over from nonoperative treatment to surgery. In the rst year after randomization, 17 of the 66 patients (26%) assigned to non-operative treatment underwent surgery while 1 patient assigned to surgery refused and was treated nonoperatively. Weber performed both an intention to treat (ITT) and an as-treated analysis, with similar results for the 2 analyses. By todays standards, this study would seem limited by vague inclusion criteria, antiquated imaging techniques (magnetic resonance imaging (MRI) was not routinely obtained in the assessment of patients), and a lack of validated outcomes and power analysis. However, 10-year follow-up for a similar RCT has not been accomplished by any subsequent study, and its ndings are similar to more modern studies. Weber的研究第一次对IDH的手术和非手术治疗进行了前瞻性的RCT，与后来的RCT类似，该研究由于较多患者从非手术治疗改为手术治疗，而受到了一些影响。在随机化后的第一年内，66例安排进行非手术治疗的患者中，17例（26%）患者进行了手术治疗，同时也有1例分配到手术组的患者拒绝手术也进行了非手术治疗。Weber进行了意向治疗分析（ITT）和接受治疗分析，这两个分析的结果类似。按照现在的标准，这一研究还是存在一些局限性，主要由于其纳入标准较含糊、影像学方法较陈旧（接受评估的患者并没有常规进行MRI检查），且缺乏有效的效力分析。然而，后来的任何研究也没有对一个类似的RCT进行10年的随访，并且其研究结果与很多现代的研究都很相似。译者注：意向治疗分析（intention to treat analysis， ITT）、接受治疗分析（as-treated analysis）和效力分析都是RCT相关的三种重要的分析方法。详见/download/da4e58d0ac2b470d59dde5420946-3149709012011.pdfWeber 1983年发表在Spine上的经典文献：/bbs/user/download/15391877/ospective%20Study%20with%20Ten%20Years%20of%20Observation.pdfModern RCTs In a smaller, more recent, RCT with shorter follow-up, Osterman et al8 attempted to assess the effectiveness of microdiskectomy for lumbar disc herniation. Fifty-six patients with a lumbar disc herniation, clinical ndings of nerve root compression, and radicular pain lasting 6-12 weeks were randomized to microdiskectomy or an isometric physical therapy program. In this study, no clinically or statistically signicant differences between the groups in leg or back pain, Oswestry disability index (ODI), or quality of life were noted at the 2-year follow-up. Compared with the nonoperative patients, the surgery group improved signicantly more on the leg pain visual analog scale (VAS) at 6 weeks and was more likely to be satised with their treatment at all follow-up visits other than at 1 year. In a subgroup analysis, patients with an L4-L5 disc herniation (n = 28) improved more with surgery than with nonoperative treatment on all outcome measures. Those with an L5-S1 herniation (n = 28) improved to a similar degree with surgery and nonoperative treatment. Shortcomings of this study include the small sample size and the 36% crossover from nonoperative treatment to surgery. The authors reported that the study was powered to detect a 15 point change on the VAS, while the observed differences were 9 points on leg pain and 10 points on back pain at 2 years. These differences may have been clinically meaningful, but the study was not sufciently powered to detect them. In addition, 10 out of 28 (36%) patients in the control group crossed over to surgery and were analyzed according to the ITT principle. As such, a benecial treatment effect of surgery may have been obscured due to crossover. The authors did note that an as-treated analysis revealed no signicant differences, however, the nonoperative group included only 17 patients after the crossover occurred, limiting power even further. 现代的RCT在最近的一项短期随访的小规模RCT中,Osterman等8试图对腰椎间盘突出症微创椎间盘切除的有效性进行评价。56例腰椎间盘突出的患者，临床上有神经根受压的表现，根性疼痛持续6-12周，纳入研究后随机分配接受微创椎间盘切除术或等长理疗计划。在该研究中，从两年随访时记录的腰或腿痛、Oswestry功能障碍评分（ODI）及生活质量等数据来看，两组间没有任何明显的临床或统计学差异。与非手术治疗的患者相比，6周时手术组腿痛的视觉模拟评分（VAS）改善更为明显，与1年时不同，这一点可能使患者在整个随访过程中都对其治疗感到满意。在其亚组的分析中，L4-5椎间盘突出的患者（n=28），与非手术治疗相比，手术后治疗结果各项指标的改善都更为明显。而L5S1突出的患者（n=28）手术与非手术改善的程度类似。这一研究的不足主要包括样本含量较小，36%的患者从非手术治疗改为手术治疗。作者报告其研究中将VAS存在15点的变化视为是有意义的，两年时，观察到的差异腿痛为9点，背痛为10点。而这些差异也许是具有临床意义的，但该研究无法充分说明这一点。此外，对照组的28例患者中有10例（36%）改而行手术治疗，作者按照ITT的原则进行了分析。同样地，由于这种变换，手术治疗有利的治疗效果也被模糊化了。作者没有注意到接受治疗分析显示差异没有统计学意义，然而，这些患者变换治疗方式后非手术组仅剩下17例患者，则更进一步限制了其效力。A recent RCT by Peul et al9 compared early microdiskectomy with prolonged nonoperative treatment followed by surgery if needed (Table 1). This study randomized 283 pa tients to early surgery or prolonged nonoperative treatment. Patients were 18-65 years old, had sciatica for 6-12 weeks before enrollment and had MRI-conrmed disc herniations that correlated with their symptoms. The primary outcome measures were the Roland Disability Questionnaire for Sciatica, VAS for leg pain and 7-point Likert scale of perceived recovery, with recovery dened as complete or nearly complete disappearance of symptoms. Eighty-nine percent of patients assigned to early surgery underwent surgery at a median of 1.9 weeks. The other 16 patients initially assigned to surgery had recovered before undergoing surgery. Of the patients assigned to prolonged nonoperative care, 39% un-derwent surgery at a median of 14.6 weeks. All the patients were followed for 52 weeks.Peul等9近来的一项RCT对早期微创椎间盘切除术与延期非手术治疗后如果须要再行手术进行了比较（表1）。该研究随机对283例患者进行早期手术或延期非手术治疗。患者年龄18-65岁，纳入研究前坐骨神经痛持续6-12周，MRI证实存在与症状相对应的椎间盘突出。对治疗结果的主要评价指标包括Roland功能障碍调查问卷以评价坐骨神经痛，VAS评价腿痛，7点Likert标尺评价感觉功能恢复情况，恢复是指症状完全或几乎完全消失。被分配进行早期手术的患者中89%实施了手术，接受手术的时间其中位数为1.9周。另外16例患者最初分配进行手术，而实施手术前痊愈。在分配进行延期非手术治疗的患者中，39%进行了手术，手术时间的中位数为14.6周。所有患者均随访了52周。There were no differences in the primary outcome measures at 1 year in the ITT analysis. Not surprisingly, the early surgery group improved more rapidly than the prolonged nonoperative care group. This was quantied by comparing the areas under the curves for the Roland Disability Questionnaire and the leg pain VAS over the 52-week follow-up. This analysis revealed no signicant differences for the Roland Disability Questionnaire, whereas the results for leg pain favored early surgery. The KaplanMeier curve comparing time with recovery also showed signicantly faster recovery for the early surgery group (median recovery time 4.0 weeks for early surgery vs 12.1 weeks for prolonged nonoperative care, P 0.001), though about 95% of patients in each group had recovered by 1 year. It should be noted that about 10% of the nonoperative treatment group reached recovery between 50 and 52 weeks, so the curves were substantially different until the nal follow-up. In a subgroup analysis, a Cox proportional hazards model demonstrated that the only subgroup that did not benet from early surgery was patients whose sciatica was not provoked by sitting. 经ITT分析，1年时主要治疗结果的差异没有统计学意义。不出意料，与延期非手术治疗组相比，早期手术组改善更快。在52周的随访过程中，对Roland功能障碍调查问卷和腿痛VAS的曲线下面积进行量化比较。分析结果显示，Roland功能障碍调查问卷的差异没有统计学意义，而早期手术组腿痛的结果则更好一些。通过Kaplan-Meier曲线对恢复时间进行比较也显示，虽然各组95%的患者在1年时都恢复了，但早期手术组恢复得更快（早期手术组恢复时间的中位数4周，延期非手术组为12.1周，p0.001）。值得注意的是，非手术组大约10%的患者直到50-52周才恢复，因此在最终随访之前，曲线一直存在显著的差异。在其亚组分析中，Cox比例风险模型显示，在早期手术的患者中，唯一没有获得较好疗效的亚组，便是坐着时没有激发坐骨神经痛的患者。This study was a high quality RCT that had well-dened inclusion and exclusion criteria, validated outcomes, and very low attrition. However, rather than comparing the results of surgery and nonoperative treatment, it compared the results of early surgery vs continued conservative care followed by later surgery if necessary. This study focused on evaluating the optimal timing of surgery, not the efcacy of surgery. The study does convincingly suggest that diskectomy can be avoided in many patients who satisfy the indications for surgery without any long-term harm. By contrast, it also indicates that patients who value a quicker recovery are best treated with early diskectomy. The limitations of the study included the inability to blind patients or researchers to the treatment received, the lack of standardization of conservative care, and the high cross-over rate. 该研究是一项高质量的RCT，对纳入和排除标准都进行了明确的定义，结果有效，丢失也很小。然而，该研究并不是比较手术与非手术治疗的差异，而是比较早期手术与延期保守治疗后如果须要再行手术的治疗结果。这一研究主要评价的是最佳的手术时机，并份额手术的有效性。这一研究很有说服力，提示对于有手术指征的很多患者，椎间盘切除术都是可以避免的，并且没有任何长期损害。相反，该研究也指出，对于期望快速恢复的患者，最好的办法便是早期椎间盘切除术。该研究的局限性主要包括对于接受的治疗，无法对患者或研究者实行盲法，保守治疗缺乏统一的标准，治疗方式组间变换率较高。表1 坐骨神经痛手术与延期保守治疗的比较研究设计多中心RCT，ITT分析患者 总共283例患者（早期手术组141例，保守治疗组142例）。手术的患者平均年龄41.7岁，非手术的患者平均43.4岁（范围在18-65岁之间）。纳入标准年龄18-65岁，“导致功能障碍的腰骶神经根综合征”6-12周，MRI显示与症状相符的椎间盘突出。排除标准马尾损伤表现，肌肉麻痹，肌力下降不足以抵抗重力，既往12个月内有类似的神经根症状，脊柱手术史，骨性狭窄，腰椎滑脱，妊娠，或伴有严重的合并病症。治疗比较2周内行微创椎间盘切除术与延期保守治疗（教育、如果须要给予止痛药、对于害怕运动的患者给予理疗）失访 手术组141例中有4例失访，保守治疗组142例有3例失访结果评价主要的：Rowland功能障碍调查问卷评价坐骨神经痛，100mmVAS评估腿痛，7点Likert自我评定标尺对整体的感觉功能恢复程度进行评价。将恢复定义为完全或几乎完全恢复，2、4、8、12、26、38、52周进行评估。次要的：SF-36，焦虑指数，100mmVAS健康感知，神经系统查体，8、26、52周进行评估。研究结果初始数据没有组间差异。早期手术组接受手术的时间中位数为1.9周，早期手术组11%的患者在接受手术前恢复，而没有进行手术。延期保守治疗组39%的患者进行了手术治疗，中位数时间14.6周。52周时两组患者主要指标评价的结果没有显著的差异。早期手术组恢复的时间中位数为4.0周，而延期保守治疗组为12.1周（p0.001）。早期手术组腿痛的改善更早，早期手术组中除了坐着时不能激发坐骨神经痛的亚组以外，都显示出较好的有效性。可信度 多中心，前瞻性，应用有效结果评价的RCT。研究缺陷对手术的最佳时机进行比较，而不是评价手术的有效性。非手术治疗没有特异性，无法应用盲法，随访时间限于1年。基线 早期手术可使患者更快恢复，但1年时的结果没有差别。ITT, intention to treat，意向治疗分析; VAS, visual-analogue scale，视觉模拟评分。Maine Lumbar Spine Study Despite the RCT being considered the most valid study design, the Maine lumbar spine study (MLSS), a prospective cohort study, provides some of the best long-term data comparing surgical and nonoperative treatment of sciatica caused by lumbar disc herniation (Table 2).10-13 The MLSS enrolled 507 (235 surgical and 272 nonoperative) patients from the practices of 25 surgeons and 5 occupational medicine specialists in Maine. Patients were enrolled if they suffered from sciatica, dened as pain radiating to below the knee, though conrmatory imaging studies were not required. Given that it was an observational study, treatment was determined by the treating physician and the patient. The primary outcome measure was self-reported improvement in the predominant symptom (leg pain or back pain). The exact denition of “improvement” varied among the 3 reports (1, 5, and 10-year follow-up), with patients reporting that their predominant symptom was “much better” or “completely gone” qualifying as improved in the 1-year report, whereas those answering “better” were also included in the “improved” group at 5 and 10 years. Many other outcome measures, including back and leg pain frequency and bothersomeness, sciatica frequency and bothersomeness indexes, Roland disability scale, SF-36 scores, and work status, were also recorded. Results were reported at 1, 5, and 10 years, and statistical modeling techniques were used to control for the signicant baseline differences between the 2 groups. Substantial crossover occurred, with 15% of patients who initially chose nonoperative treatment undergoing surgery within 3 months, and 25% of the remaining nonoperative patients undergoing surgery between 3 and 120 months. The authors addressed this by assigning patients who crossed over within the rst 3 months to the surgery group, while analyzing those who subsequently crossed over after 3 months with the nonoperative group. 缅因州腰椎研究尽管RCT被认为是最为有效（可信度）的研究设计，缅因州腰椎研究（MLSS），一项前瞻性队列研究，针对腰椎间盘突出导致坐骨神经痛的患者，也为手术与非手术治疗的比较提供了一些长期随访的数据（表2）10-13。MLSS纳入了507例患者（235例手术，272例非手术），这些患者来自缅因州的25位外科医生和5为职业病学专家的门诊。如果患者存在坐骨神经痛，一般指膝部以下的放射痛，即使没有获得确切的影像学证据都纳入研究。由于这是一项观察研究，治疗方式取决于主治的医师和患者的意愿。评估结果的主要指标为主要症状（腿痛或腰痛）改善程度的自我评价。对于“改善”的确切定义在3个报告（1，5，10年随访）中存在差异，在1年随访的研究中，患者认为其主要症状“好得多”或“完全消失”则归为“改善”，而5年和10年随访的报告中，患者称其“较好”也归为“改善”。很多其他的治疗结果评价包括背痛和腿痛的频率和焦虑，坐骨神经痛的频率和焦虑指数，Roland功能障碍等级，SF-36评分，以及工作状况都记录在案。1、5、10年都报道了相关的结果，应用统计模型方法以控制两组间显著的基线差异。两组间治疗方式的变换较多，15%的患者起初选择非手术治疗3个月内进行了手术治疗，余下的非手术治疗患者25%在3-120个月之间进行了手术治疗。作者将3个月内变换治疗方式进行手术的患者直接分配到手术组，而对3个月以后非手术治疗组变换治疗方式进行手术治疗的患者进行分析。The MLSS demonstrated that surgical patients were significantly more likely to report improvement in their predominant symptom compared with the nonoperative patients at 1 and 5 years (71% vs 43%, P 0.001 at 1 year; 70% vs 56%, P 0.001 at 5 years). By 10 years, the difference on this outcome measure was no longer signicant (69% of the surgical patients reported improvement vs 61% for the nonoperative patients, P = 0.2). However, if only patients who answered that their predominant symptom was “much better” or “completely gone” were included in the improved category (as was the case for the 1-year results), the surgical group continued to have signicantly better results at 10 years compared with the nonoperative group (56% “denitely improved” with surgery vs 40% nonoperative, P = .006). The surgical group also had signicantly better results on most secondary outcome measures at all follow-up times, including low back pain improvement, leg pain improvement, sciatica