【在线速递】ICM(IF=41.787)我们从没见过ARDS的病人！

Since the initial description by Ashbaugh et al, it has been known that some forms of difuse pulmonary edema are not primarily due to increased hydrostatic lung microvasculature pressures, which characterize left heart failure and/or fuid overload, but result from alterations in alveolar-capillary permeability. Acute respiratory distress syndrome (ARDS) is the clinical expression of this acute, non-hemodynamic lung edema, and is diagnosed by hypoxemia and bilateral lung infltrates in the absence of increased capillary hydrostatic pressure (Fig. 1). ARDS is ubiquitous in the intensive care unit (ICU), representing almost a quarter of the ICU patients who require mechanical ventilation, and ubiquitous in the ICU literature. A quick search of PubMed revealed over 13,000 published articles on ARDS since 1967. Based on this, one would think that diagnosing a patient as having ARDS would really add something to improve that patient’s outcome; but does it?

Ashbaugh等人最先提出：某些弥漫性肺水肿不是由于左心衰竭和/或液体超载而导致的肺毛细血管静水压增加，而是由于肺泡—毛细血管通透性改变引起的。急性呼吸窘迫综合征(ARDS)临床表现为急性、非心源性肺水肿及低氧血症和双肺浸润，无毛细血管静水压增高。（图1）ARDS在重症监护室(ICU)中很常见，几乎占需要机械通气患者的四分之一。有关ARDS的文献也多如牛毛，PubMed的快速检索显示：自1967年以来，共发表了13,000多篇关于ARDS的文章。基于这一点，人们会认为诊断一个病人患有ARDS有助于改善病人的愈后，但事实是这样吗？ 

图1：弥漫性肺水肿的基本病理生理过程

The problem is that we generally tend to consider ARDS as a disease, forgetting that it is actually a syndrome associated with many possible pre-disposing factors ranging from pulmonary infections to heroin overdose, from intraabdominal abscess to intracranial bleeds. The attempt to distinguish between pulmonary and extrapulmonary sources–although initially promising—has not resulted in a major increase in our understanding of the disease process or in improvements in management.

问题在于我们通常倾向于将ARDS视为一种疾病，而忘记了它实际上是一种由许多病因引起的综合征，从肺部感染到吗啡过量，从腹腔脓肿到颅内出血。最初将ARDS区分为肺源性和肺外源性的尝试，尽管很有希望，但最终也没有使我们对这一疾病过程有更好的理解或改善我们对ARDS的管理。 

So, is it important to diagnose ARDS? Before answering this question, we must recognize that there is no specifc treatment for ARDS. Some years ago, we would have argued that the principal implication of an ARDS diagnosis was that it was a “prescription” for the use of small tidal volume ventilation. This recommendation followed observations from important multicenter randomized controlled trials indicating that using tidal volumes of 6 ml/kg rather than 12  ml/kg of predicted body weight (PBW) resulted in decreased mortality. Other studies supported the concept of reducing ventilator-induced lung injury (VILI) by performing so-called 'protective ventilation’, but it soon became apparent that this approach should not be limited to patients with ARDS. It is now well established that large tidal volumes should be avoided in all cases of mechanical ventilation and even during major surgery. This is similar to the concept that limiting fuid overload is a strategy applicable to all critically ill patients, not just those with ARDS.

所以，诊断ARDS真的重要吗？在回答这个问题之前，我们必须认识到ARDS没有特定的治疗方法。几年前，我们确诊ARDS主要因为它是使用小潮气量通气的“指标”。这一说法是根据一项重要的多中心随机对照试验的观察提出的，该试验表明：与使用12毫升/千克（预测体重）的潮气量相比，使用6毫升/千克潮气量的患者死亡率更低。而另有其他研究提出了通过实施所谓的“保护性通气”来减少呼吸机诱导的肺损伤(VILI)的概念。很明显，这种方法不应局限于ARDS患者，现已确定，在所有机械通气的情况下都应该避免大潮气量，甚至在大手术中也是如此。这类似于“限制液体超载”这一原则适用于所有危重患者，而不仅仅是那些患有ARDS的患者。

There is little evidence to support the use of one mode of ventilation over another in patients diagnosed with ARDS, other than for high frequency ventilation, which is not recommended. The place of recruitment maneuvers is also debated. Individual trials evaluating the efects of higher versus lower levels of positive endexpiratory pressure (PEEP) in patients with ARDS have largely been negative, although a meta-analysis demonstrated that higher PEEP was benefcial in patients with moderate or severe ARDS. Although theoretically appealing, PEEP titration based on esophageal pressure measurements has not resulted in better outcomes.

在诊断为ARDS的患者中，很少有理论支持使用某种特定通气模式，但高频通气是明确不推荐使用的。有关肺复张的方法也存在争议。尽管Meta分析表明，在中度或重度ARDS患者中，较高水平的PEEP对患者的影响较大，但高水平的PEEP与低水平PEEP患者的影响的个体试验大多无差异，虽然理论上很有吸引力，但基于食管压力测量的PEEP并没有产生更有说服力的结果。

A diagnosis of ARDS also does not suggest any specifc pharmacologic therapies. The use of muscle relaxants should be individualized, and, if efective, they almost certainly act by decreasing VILI, not by treating the underlying disease process. Even administration of corticosteroids to all patients with ARDS is controversial, despite the recent report of a benefcial efect on duration of mechanical ventilation and mortality.

诊断为ARDS并不意味着有特定的治疗药物。肌松剂的使用应该个体化，如果有效，基本上可以肯定它是通过降低呼吸机相关肺损伤，而不是通过治疗潜在的疾病过程来起作用的。不仅如此，尽管最近有报道称糖皮质激素对机械通气持续时间和死亡率有积极影响，但是否应该所有ARDS患者都使用糖皮质激素还存在争议。

Getting back to the question of whether it is important to diagnose ARDS, the LUNG SAFE study found that mild ARDS was missed by clinicians in about 50% of cases, and that severe ARDS was missed in over 20% of cases. But, given that we have no specifc treatments, does it really matter? In the LUNG SAFE study, there was a minor impact on the tidal volume chosen [very slightly lower (~0.2  ml/kg PBW)] in those patients with a clinician diagnosis of ARDS, but there was an impact on the use of adjunctive measures (from ~22% to 44%).

回到确诊ARDS是否重要的问题，肺部安全研究（LUNG SAFE study）发现：临床医生在大约50%的病例中遗漏了轻度ARDS，在超过20%的病例中遗漏了重度ARDS。但是，鉴于我们没有特定的治疗方法，这真的有关系吗？在 LUNG SAFE study中，对于那些临床医生诊断为ARDS的患者，潮气量的选择对病程的影响很小(非常略低(~0.2 ml/kg PBW)]，但是这对其他辅助措施的使用有影响（从22%到44%）。

Recent attempts to identify subgroups of patients with ARDS based on a relatively large number of clinical and laboratory variables have suggested that specifc patient populations could beneft from specifc therapies. In post hoc analyses of ARDS randomized trials, response to various treatments (level of PEEP, fuid therapy, and simvastatin) was dependent on whether the patients had a hypo- or hyper-infammatory subphenotype. Further development of parsimonious classifer models with relatively few (3 or 4) variables hopefully will help determine prospectively whether this approach will identify ARDS patients who will beneft from various therapies. And perhaps a diagnosis of ARDS will not be necessary for the utility of such a scheme. Maybe in the future we will treat patients based on a diagnosis of hypo- or hyper-infammatory lung failure [or some other Defning  phenotype(s)], rather than on the basis of having ARDS.

最近，根据较多的临床和实验室变量来区别ARDS患者亚组的尝试表明：特定的患者群体可以从特定的治疗中受益。在对ARDS随机试验的结果分析表明，对各种治疗（PEEP水平、液体治疗和辛伐他汀）的反应取决于患者是否有低炎症或高炎症。进一步开发具有相对较少变量的简约分类模型，有望前瞻性地确定该方法是否能识别出从各种治疗中受益的ARDS患者。也许ARDS的诊断对于这样一个方案的效用是不必要的。也许在未来，我们将根据低炎症或高炎症性肺衰竭（或其他定义表型）的诊断来治疗患者，而不是根据是否患有ARDS来治疗患者。

The COVID-19 pandemic has provided some interesting insights on this topic. Although COVID-19 related acute respiratory failure may often be ARDS, this is not always the case. In any event, how would a label of ARDS help these patients? Management of COVID-19 related respiratory failure is the same whether we call it ARDS or not.

新冠肺炎疫情在这个话题上提供了一些独到的见解。尽管COVID-19相关的急性呼吸衰竭常被诊断为ARDS，但并不总是如此。无论如何，ARDS的标签对新冠肺炎患者有何用处？毕竟，不管我们是否将之称为ARDS，但我们对于COVID-19相关的急性呼吸衰竭的处理是相同的。

This refects our key message: COVID-19 is a disease, and ARDS is a syndrome. ARDS usually has an underlying identifable cause, and the cause can often result in a specifc therapy, whether that is antimicrobials, surgery, corticosteroids, …. We do not need to “see” or diagnose ARDS to be able to treat it appropriately; the only beneft is that it may encourage us to search for a potentially treatable underlying condition, and it may encourage us to use lung protective ventilatory strategies.

再次强调我们想要表达的：新冠肺炎是一种疾病，ARDS是一种综合征。ARDS通常有一个潜在的可识别的病因，而这个病因往往可以对应特定的治疗，无论是抗生素，手术，激素等等。我们不需要“看到”或诊断ARDS就能适当地治疗它；唯一的好处是，它可能鼓励我们寻找潜在的可治疗的某种疾病，并可能鼓励我们使用肺保护性通气策略。

END

翻    译

 李文玉  医学硕士

     山东第一医科大学

在线速递

翻译：李文玉

编辑：宋   璇

审校：王春亭