Sen Indrani, Agarwal Sunil, Tharyan Prathap, Forster Rachel
Vascular Surgery, Christian Medical College, Vellore, Tamil Nadu, India, 632004.
Cochrane Database Syst Rev. 2018 Apr 16;4(4):CD009366. doi: 10.1002/14651858.CD009366.pub2.
BACKGROUND: Peripheral arterial disease (PAD) is a common circulatory problem that can lead to reduced blood flow to the limbs, which may result in critical limb ischaemia (CLI), a painful manifestation that occurs when a person is at rest. The mainstay of treatment for CLI is surgical or endovascular repair. However, when these means of treatment are not suitable, due to anatomical reasons or comorbidities, treatment for pain is limited. Lumbar sympathectomy and prostanoids have both been shown to reduce pain from CLI in people who suffer from non-reconstructable PAD, but there is currently insufficient evidence to determine if one treatment is superior. Due to the severity of the rest pain caused by CLI, and its impact on quality of life, it is important that people are receiving the best pain relief treatment available, therefore interest in this area of research is high. OBJECTIVES: To compare the efficacy of lumbar sympathectomy with prostanoid infusion in improving symptoms and function and avoiding amputation in people with critical limb ischaemia (CLI) due to non-reconstructable peripheral arterial disease (PAD). SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 29 March 2017) and CENTRAL (2017, Issue 2). The CIS also searched clinical trials databases for ongoing or unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), with parallel treatment groups, that compared lumbar sympathectomy (surgical or chemical) with prostanoids (any type and dosage) in people with CLI due to non-reconstructable PAD. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials, extracted data and assessed risk of bias. Any disagreements were resolved by discussion. We performed fixed-effect model meta-analyses, when there was no overt sign of heterogeneity, with risk ratios (RRs) and 95% confidence intervals (CIs). We graded the quality of evidence according to GRADE. MAIN RESULTS: We included a single study in this review comparing lumbar sympathectomy with prostanoids for the treatment of CLI in people with non-reconstructable PAD. The single study included 200 participants with Buerger's disease, a form of PAD, 100 in each treatment group, but only 162 were actually included in the analyses. The study compared an open surgical technique for lumbar sympathectomy with the prostanoid, iloprost, and followed participants for 24 weeks.Risk of bias was low for most evaluated domains. Due to the nature of the treatment, blinding of the participants and those providing the treatment would be impossible as a surgical procedure was compared with intravenous injections. It was not mentioned if blinded assessors evaluated the study outcomes, therefore, we judged subjective outcomes (i.e. pain reduction) to be at unclear risk of detection bias and objective outcomes (i.e. ulcer healing, amputation and mortality) at low risk of detection bias. We also rated the risk of attrition bias as unclear; 38 out of 200 (19%) participants were not included in the analysis without clear explanation (16 of 100 in the iloprost arm and 22 of 100 in the sympathectomy arm). The quality of evidence was low due to serious imprecision because the study numbers were low and there was only one study included.The single included study reported on the outcome of complete healing without pain or major amputation, which fell under three separate outcomes for our review: relief of rest pain, complete ulcer healing and avoidance of major amputation. We chose to keep the outcome as a singularly reported outcome in order to not introduce bias into the outcomes, which may have been the case if reported separately. The limited evidence suggests participants who received prostaglandins had improved complete ulcer healing without rest pain or major amputation when compared with those who received lumbar sympathectomy (RR 1.63, 95% CI 1.30 to 2.05), but as it was the only included study, we rated the data as low-quality and could not draw any overall conclusions. The study authors stated that more participants who received prostaglandins reported adverse effects, such as headache, flushing, nausea and abdominal discomfort, but only one participant experienced severe enough adverse effects to drop out. Five participants who underwent lumbar sympathectomy reported minor wound infection (low-quality evidence). There was no reported mortality in either of the treatment groups (low-quality evidence).The included study did not report on claudication distances, quality of life or functional status, ankle brachial pressure index (ABPI), tissue oxygenation or toe pressures, or progression to minor amputation, complications or provide any cost-effectiveness data. AUTHORS' CONCLUSIONS: Low-quality evidence from a single study in a select group of participants (people with Buerger's disease) suggests that prostaglandins are superior to open surgical lumbar sympathectomy for complete ulcer healing without rest pain or major amputation, but possibly incur more adverse effects. Further studies are needed to better understand if prostaglandins truly are more efficacious than open surgical lumbar sympathectomy and if there are any concerns with adverse effects. It would be of great importance for future studies to include other forms of PAD (as Buerger's disease is a select type of PAD), other methods of sympathectomy as well as data on quality of life, complications and cost-effectiveness.
背景:外周动脉疾病(PAD)是一种常见的循环系统问题,可导致肢体血流减少,进而可能引发严重肢体缺血(CLI),这是一种在患者休息时出现的疼痛症状。CLI的主要治疗方法是手术或血管腔内修复。然而,当由于解剖学原因或合并症而不适合这些治疗手段时,疼痛治疗就会受到限制。腰交感神经切除术和前列腺素类药物都已被证明可减轻患有不可重建性PAD的患者的CLI疼痛,但目前尚无足够证据确定哪种治疗方法更具优势。由于CLI引起的静息痛严重,且对生活质量有影响,因此让患者接受最佳的疼痛缓解治疗非常重要,因此该研究领域受到高度关注。 目的:比较腰交感神经切除术与前列腺素输注在改善因不可重建性外周动脉疾病(PAD)导致严重肢体缺血(CLI)患者的症状和功能以及避免截肢方面的疗效。 检索方法:Cochrane血管信息专家(CIS)检索了专业注册库(最后检索时间为2017年3月29日)和CENTRAL(2017年第2期)。CIS还检索了临床试验数据库以查找正在进行或未发表的研究。 入选标准:随机对照试验(RCT),采用平行治疗组,比较因不可重建性PAD导致CLI的患者接受腰交感神经切除术(手术或化学方法)与前列腺素类药物(任何类型和剂量)的疗效。 数据收集与分析:三位综述作者独立选择试验、提取数据并评估偏倚风险。如有分歧,通过讨论解决。当没有明显的异质性迹象时,我们使用风险比(RR)和95%置信区间(CI)进行固定效应模型荟萃分析。我们根据GRADE对证据质量进行分级。 主要结果:本综述纳入了一项单一研究,该研究比较了腰交感神经切除术与前列腺素类药物治疗不可重建性PAD患者的CLI的疗效。该单一研究纳入了200例血栓闭塞性脉管炎(一种PAD形式)患者,每个治疗组100例,但实际纳入分析的只有162例。该研究比较了开放性手术腰交感神经切除术与前列腺素类药物伊洛前列素,并对参与者进行了24周的随访。在大多数评估领域,偏倚风险较低。由于治疗的性质,参与者和提供治疗者无法进行盲法,因为手术治疗与静脉注射进行了比较。未提及是否有盲法评估者评估研究结果,因此,我们判断主观结果(即疼痛减轻)存在检测偏倚的风险不明确,而客观结果(即溃疡愈合、截肢和死亡率)存在检测偏倚的风险较低。我们还将失访偏倚的风险评为不明确;200例参与者中有38例(19%)未纳入分析,且没有明确解释(伊洛前列素组100例中有16例,腰交感神经切除术组100例中有22例)。由于研究数量少且仅纳入了一项研究,证据质量较低。纳入的单一研究报告了无疼痛或大截肢的完全愈合结果,在我们的综述中该结果属于三个单独的结果:静息痛缓解、溃疡完全愈合和避免大截肢。我们选择将该结果作为单一报告结果,以免在结果中引入偏倚,如果分别报告可能会出现这种情况。有限的证据表明,与接受腰交感神经切除术的参与者相比,接受前列腺素类药物治疗的参与者在无静息痛或大截肢的情况下溃疡完全愈合情况有所改善(RR 1.63,95%CI 1.30至2.05),但由于这是唯一纳入的研究,我们将数据评为低质量,无法得出任何总体结论。研究作者指出,接受前列腺素类药物治疗的更多参与者报告了不良反应,如头痛、潮红、恶心和腹部不适,但只有一名参与者因不良反应严重而退出。接受腰交感神经切除术的五名参与者报告了轻微伤口感染(低质量证据)。两个治疗组均未报告死亡情况(低质量证据)。纳入的研究未报告跛行距离、生活质量或功能状态、踝臂压力指数(ABPI)、组织氧合或趾压,或小截肢进展、并发症情况,也未提供任何成本效益数据。 作者结论:来自一项针对特定参与者群体(血栓闭塞性脉管炎患者)的单一研究的低质量证据表明,对于无静息痛或大截肢的溃疡完全愈合,前列腺素类药物优于开放性手术腰交感神经切除术,但可能会引发更多不良反应。需要进一步研究以更好地了解前列腺素类药物是否真的比开放性手术腰交感神经切除术更有效,以及是否存在不良反应问题。对于未来的研究来说,纳入其他形式的PAD(因为血栓闭塞性脉管炎是PAD的一种特定类型)、其他腰交感神经切除术方法以及生活质量、并发症和成本效益数据非常重要。
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