Acute lung injury and acute respiratory distress syndrome

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