Acute lung injury and acute respiratory distress syndrome
Acute lung injury and acute respiratory distress syndrome
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DOI：
10.1017/9781108684729.138
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发表时间：
2019-05
期刊：
影响因子：
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通讯作者：
H. Carpenter;D. Macintire;W. Tyler
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文献类型：
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作者：
H. Carpenter;D. Macintire;W. Tyler
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是严重的呼吸系统疾病，兽医学尚未对其进行充分表征。尽管过去 30 年来人类医学在这一领域进行了广泛的研究，但人们对这种复杂综合征的确切发病机制知之甚少。随着兽医重症监护设施的增加以及愿意对重症动物进行广泛治疗的主人数量的增加，识别和治疗的 ALI/ARDS 病例数量也会增加。因此，兽医不仅要认识 ALI/ARDS 的临床症状，而且还要了解可能使患者患上这些呼吸系统疾病的危险因素。预测动物状况的变化还需要了解复杂的病理生理学和发病机制。迄今为止，治疗仍然主要是对症治疗，旨在改善氧合。本文旨在为临床医生提供对风险因素、病理生理学、发病机制、临床症状和治疗的基本了解，这些可能有助于提高 ALI/ARDS 兽医患者的生存率。急性呼吸窘迫综合征（ARDS）最初被称为成人呼吸窘迫综合征，1967年首次被Ashbaugh及其同事认为是人类重症监护患者的一种临床疾病。它被定义为一种临床综合征，其特征是氧疗难治性严重低氧血症，胸片显示双侧肺泡浸润呈斑片状，肺顺应性低。人类患病率估计为每 100,000 名患者 1.5 至 75 人；但大多数专家认为，实际患病率约为每10万人中5至7人。死亡率和患病率研究中的大部分差异源于过去 30 年对 ARDS 的不同定义。 1994 年，美国-欧洲 ARDS 共识委员会通过为每种疾病建立临床诊断标准来区分急性肺损伤 (ALI) 和 ARDS。区分基于动脉氧分压与吸入氧分数的比率 (PaO2:FiO2)。值小于 300 表示 ALI，小于 200 表示 ARDS。因此，并非所有 ALI 病例都会导致 ARDS，但所有 ARDS 病例都会由 ALI 引起。尽管 ALI/ARDS 是过去 20 年来人类医学研究最多的领域之一，但人们对 ALI/ARDS 的确切病因和最佳治疗方法知之甚少。尚未发现导致 ARDS 临床症状的单一诱发事件。似乎更有可能发生多种事件，其中任何一个都可能导致 ALI/ARDS 的发展。这种假设与可能导致这种临床综合征发生的多种不相关的危险因素相一致。狗被广泛用于研究与胰腺炎、百草枯中毒、乙氯维诺中毒、创伤、油酸损伤和内毒素血症相关的 ARDS 发展的实验模型。然而，这些研究通常只关注整个综合征的一个方面，因此使得这些信息不太适用于临床兽医环境。此外，兽医文献中仅发表了孤立的病例报告和评论文章。随着更先进的急诊和重症监护设施的出现以及兽医学先进诊断能力的增加，可能会发现和治疗更多的 ALI/ARDS 病例。然而，人们对犬 ALI/ARDS 的实际患病率和死亡率知之甚少。必须假设，由于兽医的长期通气能力有限，死亡率远高于人类死亡率。需要更多信息来确定人类和犬类 ALI/ARDS 患者之间的临床差异。风险因素 人类 ALI 的公认病因有很多。这些原因通常分为两类：直接肺损伤和间接肺损伤。狗直接肺损伤的常见原因包括误吸胃内容物、钝器损伤伴肺挫伤、差点溺水、吸入有毒气体（例如烟雾吸入性损伤）、氧中毒和肺炎。这些损伤通常是进行性的，根据最初的临床参数不应低估其严重程度。人类间接肺损伤通常由全身炎症反应综合征 (SIRS) 引起，可能与脓毒症相关，也可能无关。在狗中，间接或继发性肺损伤与败血症、SIRS、休克、创伤、胰腺炎、细小病毒性肠炎、器官扭转和百草枯中毒有关。帕伦特和同事发现微生物性肺炎、败血症和吸入性肺炎是在狗身上观察到的最常见的危险因素。按发生率排序观察到的其他诱发因素包括无反应性休克、氧中毒、器官扭转、锁链勒窄继发的喉部阻塞、肺损伤和弥散性血管内凝血（DIC）。在这项研究中，58% 的狗存在不止一种危险因素，33% 的狗存在三种或更多危险因素。这与具有两种或多种诱发因素的人类患者的风险增加相当。急性呼吸窘迫综合征现在被认为是发生 SIRS 和多系统器官衰竭综合征 (MOFS) 的危险因素。事实上，一些专家认为ARDS不是单一器官衰竭综合征，而是MOFS中第一个衰竭的器官，紧随其后的是肝功能障碍。大约 20% 的 ARDS 人类患者仅因呼吸系统并发症而死亡，其余死亡则归因于其他器官衰竭。在Parent等人中。研究显示，42%的犬类死亡是由于呼吸功能障碍造成的。病理生理学 了解 ALI/ARDS 相关肺水肿病理生理学的最佳方法是 Starling 方程，它定义了液体穿过肺膜的正常运动（框 1）。正常肺组织中的平均渗透反射系数 (σ) 约为 0.7 至 0.8，描述了内皮细胞阻碍溶质（即蛋白质）从脉管系统进入间质的有效性。 Starling 力的净效应是液体和蛋白质从血管空间移动到间隙空间。肺泡上皮和间质之间的肺泡屏障可以用类似的方程来解释，其中穿过肺泡屏障的液体流量为 esCompendium August 2001 Small Animal/Exotics 713 QT = Kf[(Pmv − Pis) − σ(πmv − πis)] QT = 每单位时间过滤的液体量 Kf = 血管对液体的渗透性Pmv = 肺微血管的静水压 Pis = 肺间质的静水压 σ = 平均渗透反射系数 πmv = 肺微血管的渗透压 πis = 肺间质的渗透压 BOX 1 Starling 流体运动方程
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory diseases that have not been well characterized in veterinary medicine. Despite extensive research into this area in human medicine over the past 30 years, little is known about the exact pathogenesis of this complex syndrome. With the increase in veterinary critical care facilities and the greater number of owners who are willing to enter into extensive treatment of critically ill animals, there will also be an increase in the number of ALI/ARDS cases that are identified and treated. Therefore, it is essential for veterinarians not only to recognize the clinical signs of ALI/ARDS but also to know the risk factors that may predispose patients to developing these respiratory diseases. Knowledge of the complex pathophysiology as well as the pathogenesis is also required to anticipate changes in the animal’s condition. To date, treatment remains primarily symptomatic and is aimed at improving oxygenation. This article is intended to provide clinicians with a basic understanding of the risk factors, pathophysiology, pathogenesis, clinical signs, and treatments that may help improve the survival of veterinary patients with ALI/ARDS. Acute respiratory distress syndrome (ARDS), originally called adult respiratory distress syndrome, was first recognized as a clinical disorder in human intensive care patients by Ashbaugh and colleagues in 1967. It was defined as a clinical syndrome characterized by severe hypoxemia refractory to oxygen treatment with patchy bilateral alveolar infiltrates on chest radiographs and low pulmonary compliance. Estimates of prevalence in humans range from 1.5 to 75 per 100,000 patients; but most experts believe that the actual prevalence is about 5 to 7 per 100,000. Most of the disparity in mortality and prevalence studies has come from the varying definitions of ARDS over the past 30 years. In 1994, an American-European Consensus Committee on ARDS differentiated acute lung injury (ALI) from ARDS by establishing clinical diagnostic criteria for each condition. Differentiation is based on the ratio of partial pressure of arterial oxygen to fractional inspired oxygen (PaO2:FiO2). A value of less than 300 indicates ALI and less than 200 indicates ARDS. Consequently, all ALI cases do not result in ARDS, but all cases of ARDS will result from ALI. Despite being one of the most researched areas of human medicine in the past 20 years, little is known about the exact initiating causes and the best methods of treatment for ALI/ARDS. A single inciting event responsible for producing the clinical signs of ARDS has not been found. It appears more likely that a multitude of events occurs, and any of these can lead to the development of ALI/ARDS. This supposition would coincide with the multiple unrelated risk factors that can lead to the development of this clinical syndrome. Dogs are used extensively in experimental models for studying the development of ARDS associated with pancreatitis, paraquat poisoning, ethchlorvynol toxicosis, trauma, oleic acid injury, and endotoxemia. However, these studies often look at only a single aspect of the entire syndrome, thus making the information less applicable to the clinical veterinary setting. In addition, only isolated case reports and review articles have been published in the veterinary literature. With the advent of more advanced emergency and critical care facilities as well as an increased availability of advanced diagnostic capabilities in veterinary medicine, it is likely that more cases of ALI/ARDS will be identified and treated. However, little is known about the actual prevalence and mortality resulting from ALI/ARDS in dogs. It must be assumed that the mortality rate is much higher than is seen in human populations because of the limited long-term ventilatory capabilities in veterinary medicine. More information is needed to establish the clinical differences between human and canine patients with ALI/ARDS. RISK FACTORS There are numerous recognized causes of ALI in humans. These causes are generally placed into two categories: direct and indirect lung injury. Common causes of direct lung injury in dogs include aspiration of gastric contents, blunt force trauma with pulmonary contusions, near drowning, inhalation of noxious gases (e.g., smoke inhalation injury), oxygen toxicity, and pneumonia. These injuries are often progressive, and their severity should not be underestimated based on initial clinical parameters. Indirect lung injury in humans commonly results from systemic inflammatory response syndrome (SIRS) and may or may not be related to sepsis. In dogs, indirect or secondary lung injury has been associated with sepsis, SIRS, shock, trauma, pancreatitis, parvoviral enteritis, organ torsion, and paraquat toxicosis. Parent and colleagues identified microbial pneumonia, sepsis, and aspiration pneumonia as the most common risk factors observed in dogs. Other predisposing factors observed in order of prevalence were nonresponsive shock, oxygen toxicity, organ torsion, laryngeal obstruction secondary to strangulation with a choke chain, pulmonary trauma, and disseminated intravascular coagulation (DIC). Of the dogs in this study, 58% had more than one risk factor present and 33% had three or more risk factors. This is comparable to the increased risk seen in human patients that have two or more predisposing factors. Acute respiratory distress syndrome is now considered a risk factor for the development of SIRS and multisystem organ failure syndrome (MOFS). In fact, several experts believe that ARDS is not a single organ failure syndrome but the first organ to fail in MOFS and is closely followed by liver dysfunction. About 20% of human patients with ARDS die solely as a result of respiratory complications, and the remaining mortality is attributed to other organ failures. In the Parent et al. study, 42% of the canine deaths were attributable to respiratory dysfunction. PATHOPHYSIOLOGY The best method to understand the pathophysiology of the pulmonary edema associated with ALI/ARDS is Starling’s equation, which defines the normal movement of fluid across the pulmonary membranes (Box 1). The average osmotic reflection coefficient (σ) is about 0.7 to 0.8 in normal pulmonary tissue and describes the effectiveness of the endothelium in hindering the passage of solutes (i.e., proteins) from the vasculature into the interstitium. The net effect of Starling’s forces is that fluid and protein move from the vascular space into the interstitial space. The alveolar barrier between the epithelium of the alveolus and the interstitium can be explained with a similar equation in which the flow of fluid across the alveolar barrier is esCompendium August 2001 Small Animal/Exotics 713 QT = Kf[(Pmv − Pis) − σ(πmv − πis)] QT = Amount of fluid filtered per unit of time Kf = Permeability of vessels to fluid Pmv = Hydrostatic pressure of the pulmonary microvasculature Pis = Hydrostatic pressure of the interstitial space σ = Average osmotic reflection coefficient πmv = Osmotic pressure of the pulmonary microvasculature πis = Osmotic pressure of the interstitial space BOX 1 Starling’s Equation of Fluid Movement