Does equipoise exist amongst experts regarding the role of hyperbaric oxygen treatment for necrotising soft tissue infection?
Does equipoise exist amongst experts regarding the role of hyperbaric oxygen treatment for necrotising soft tissue infection?
复制标题
对于高压氧治疗坏死性软组织感染的作用，专家们是否存在平衡？
DOI：
10.1111/ans.16337
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发表时间：
2021
影响因子：
1.7
通讯作者：
J. Watterson
中科院分区：
文献类型：
--
作者：
Bridget Devaney;D. Pilcher;B. Mitra;J. Watterson
坏死性软组织感染 (NSTI) 包括坏死性筋膜炎、肌炎和蜂窝组织炎，是可能危及生命的感染，通常需要重症监护级别的治疗、广泛的手术清创、广谱抗生素以及多专业和多学科的护理方法。 NSTI 的估计发病率为每 10 万人中有 3.5 例，NSTI 的死亡率差异很大，但据报道一般在 20-30% 范围内。自 20 世纪 60 年代 Brummelkamp 首次提出高压氧治疗 (HBOT) 可以治疗厌氧菌感染以来，一些中心就将高压氧治疗 (HBOT) 作为 NSTI 的辅助治疗。支持在 NSTI 中使用 HBOT 的生理机制很有吸引力——增加组织氧张力（既通过渗透效应减少组织水肿，又挽救严重缺血区域）、增强抗生素效率、提高白细胞杀伤功效和抗炎作用。许多非随机观察性研究表明 HBOT 可能有益于 NSTI 的治疗，而其他研究报告 HBOT 的死亡率没有变化。截至撰写本文时，尚无随机对照试验 (RCT) 评估此问题；然而，2014 年 Cochrane 综述的建议是，随机对照试验将是评估 HBOT 对 NSTI 有效性的最佳行动方案。在规划 NSTI 的 HBOT 随机对照试验时，需要考虑多种因素。鉴于 NSTI 的发病率较低，需要进行多中心或多国研究以获得足够的效力。手术和抗生素方法需要标准化。考虑到病情的异质性（严重程度和受影响的解剖区域），多重分层方法是必要的，并且会进一步增加所需的参与者数量。所有利益相关者的参与对于任何未来随机对照试验的成功至关重要。同样重要的是，必须考虑试验的道德规范，特别是随机分组患者不接受治疗的道德规范，这在许多中心是常规做法。本杰明·弗里德曼 (Benjamin Freedman) 于 1987 年提出了集体或临床均衡的概念；这一概念要求专家医学界对治疗具有真正的不确定性，以便临床试验中患者的随机化被认为是合乎道德的。 2011 年，这一定义进一步明确为“医学专家界对所研究病症的网络首选医学既定程序存在真正的不可知论或冲突状态”。 Johnson 等人的伦理学研究旨在量化临床平衡以及研究可能被视为道德或不道德的阈值。他们得出的结论是，当平衡被扰乱超过 70:30 时，试验被认为是不道德的，例如，如果 70% 的专家赞成某种治疗方法，那么 50% 的受试者宁愿使用该治疗方法，也不愿在试验中进行测试。约翰逊建议，如果专家们完全不可知论，或者各自持平，那么他们的选票应该平均分配给每一方。为了评估关于在 NSTI 中使用 HBOT 的临床平衡，并了解准备参加对此进行研究的随机对照试验的专家组比例，我们开展了一项匿名调查，并将其分发给我们组织中负责 NSTI 患者护理的主要利益相关者。 Alfred Health 比澳大利亚任何其他中心更频繁地使用 HBOT 来管理 NSTI（表 S1）。使用 Alfred Health 托管的研究电子数据捕获工具开展调查并收集和管理研究数据。它通过电子邮件分发给 Alfred Health 的专家人员：34 名整形外科和普通外科医生、33 名重症医生、41 名传染病医生和 5 名高压氧医生。参与者被要求提供以下信息：他们的专业、他们对 HBOT 在 NSTI 患者中发挥作用的说法的反应以及他们是否准备参加随机对照试验来调查这一点。该调查保持简短，以提高回复率。调查方案经阿尔弗雷德医院研究和伦理委员会审查并批准（项目编号 307/20）。
Necrotising soft-tissue infections (NSTIs) include necrotising forms of fasciitis, myositis and cellulitis and are potentially lifethreatening infections that frequently require intensive care level treatment, extensive surgical debridement, broad spectrum antibiotics and a multispecialty and multidisciplinary approach to care. The estimated incidence of NSTI is 3.5 cases per 100 000 persons and the mortality rate for NSTI varies widely, but is generally reported to be in the range of 20–30%. Hyperbaric oxygen treatment (HBOT) is offered as an adjunctive treatment for NSTI in some centres and has been since the 1960s when Brummelkamp first proposed it could treat anaerobic infections. The proposed physiologic mechanisms supporting the use of HBOT in NSTI are attractive – increased tissue oxygen tension (which both reduce tissue oedema via an osmotic effect and also salvage critically ischaemic areas), potentiation of antibiotic efficiency, improved white cell killing efficacy and anti-inflammatory effects. A number of non-randomized observational studies suggest that HBOT may be beneficial in the treatment of NSTI while other studies report no change in mortality with HBOT. There are no randomized controlled trials (RCTs) evaluating this question at the time of writing; however, the recommendation from a 2014 Cochrane review was that an RCT would be the best course of action to evaluate the effectiveness of HBOT for NSTI. In planning for an RCT of HBOT for NSTI, there are multiple considerations to be taken into account. Given the low incidence of NSTI, a multi-centre or multi-national study is required for adequate power. Surgical and antibiotic approaches would need to be standardized. Given the heterogeneity of the condition (both in severity and anatomical area affected), a multiple stratification approach would be necessary and would further increase the number of participants required. Engagement from all stakeholders would be essential for the success of any future RCT. Also importantly, the ethics of the trial must be considered and in particular, the ethics of randomizing patients away from a treatment, which is routine practice in many centres. The idea of collective or clinical equipoise was argued by Benjamin Freedman in 1987; a concept requiring genuine uncertainty about a treatment within the expert medical community in order for the randomization of patients within a clinical trial to be considered ethical. This definition was further sharpened in 2011 to ‘a state of genuine agnosticism or conflict in the expert medical community about the net preferred medically established procedure for the condition under study’. Johnson, et al.’s ethometric study was an effort to quantify clinical equipoise and the thresholds at which a study may be considered ethical or unethical. They concluded that trials are perceived to be unethical when equipoise is disturbed beyond 70:30, for example if 70% of experts favour a treatment, then 50% of subjects would prefer that the treatment is used rather than be tested in a trial. Johnson suggests that if experts are completely agnostic, or individually equipoised, their votes should be divided and added equally to each side. In order to assess clinical equipoise regarding the use of HBOT in NSTI and to gauge what proportion of an expert group would be prepared to participate in an RCT examining this, we developed an anonymous survey that was distributed to key stakeholders in the care of patients with NSTI at our organization. HBOT is used more frequently for management of NSTI at Alfred Health than any other centre in Australasia (Table S1). The survey was developed and study data were collected and managed using research electronic data capturetools hosted at Alfred Health. It was distributed via email to specialist staff at Alfred Health: 34 plastic and reconstructive and general surgeons, 33 intensivists, 41 infectious disease physicians and five hyperbaric physicians. Participants were asked to provide the following: their specialty, their response to the statement that HBOT has a role in patients with NSTI and whether or not they would be prepared to participate in an RCT to investigate this. The survey was kept brief to aid response rates. Protocol for the survey was reviewed and approved by The Alfred Hospital Research and Ethics Committee (project number 307/20).