Acute Lung Injury and Acute Respiratory Distress Syndrome

Chapter 24 Acute Lung Injury and Acute Respiratory Distress Syndrome



Elizabeth A. Rozanski, DVM, DACVIM, DACVECC, Daniel L. Chan, DVM, DACVECC, DACVN, MRCVS



KEY POINTS



• Acute lung injury (ALI) is a severe complication of critical illness or injury. Acute respiratory distress syndrome (ARDS) is a more severe form of ALI.

• Inflammation and alterations in the alveolar-capillary membrane lead to the influx of inflammatory cells and proteinaceous fluid, causing alveolar flooding and resulting in severe hypoxemia.

• ALI and ARDS are clinical diagnoses.

• The relative clinical importance of ALI in animals is likely growing, but uncertain.


INTRODUCTION


Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent life-threatening complications of critical illness in people. These complications reflect the advances in critical care that have occurred in human medicine during the last 40 years. As a result of these advances most patients now survive beyond the initial injury and illness, but they are at risk of developing complications such as multiple organ failure, ALI, and ARDS.


Early pathologic and clinical reports from World War I describe findings consistent with the modern definitions of ALI, although it was not recognized as a clinical entity.1 During the 1960s it was recognized that although previously healthy, young soldiers injured in combat could be resuscitated in the field, they would often die days to weeks later from progressive multiple organ failure. Ashbaugh and colleagues are credited with the first modern description of adult respiratory distress syndrome in 1967.2 Since its recognition, ARDS has remained a devastating complication of critical illness, with survival rates now only slightly better than they were 40 years ago. Adult respiratory distress syndrome was reclassified as acute respiratory distress syndrome in 1994 to include pediatric patients.3



HUMAN PERSPECTIVE


Acute lung injury–acute respiratory distress syndrome (ALI-ARDS) has been defined by the American-European Consensus Conference of 1994 as severe respiratory failure following a catastrophic event.3 The catastrophic event may be pulmonary (e.g., aspiration pneumonia or pulmonary contusion) or extrapulmonary (e.g., abdominal sepsis).


More recently, other inciting events have been recognized to result in a specific form of ALI. For example blood transfusions can be associated with pulmonary injury, a syndrome that is termed transfusion-related acute lung injury (TRALI). ALI-ARDS is further defined by a low oxygenation index (PaO2-to-FiO2 ratio). Patients with ALI have an oxygenation index of less than 300, and those with the more severe category of ARDS have an index of less than 200.3 Additional diagnostic criteria include bilateral pulmonary infiltrates on thoracic radiographs, exclusion of cardiogenic pulmonary edema, and decreased lung compliance.


The most consistent histologic pattern appreciated with ARDS is diffuse alveolar damage.4,5 However, this pattern is considered rather nonspecific and may be associated with a variety of clinical syndromes in addition to ARDS, including other pulmonary conditions such as acute interstitial pneumonia, inhalation of toxic substances, or prior treatment with amiodarone.6-8


In cases of suspected ARDS, stages of lung injury include exudative, proliferative, and, ultimately, fibrotic phases. During the initial insult, hemorrhage and protein-rich pulmonary edema accumulate in the alveoli. The initial exudative phase (days 0 to 6) is characterized by protein-rich edema, the influx of neutrophils, and eosinophilic hyaline membranes in the walls of the alveolar ducts. This is followed by the proliferative phase (days 4 to 10) characterized by a decrease in edema and hyaline membranes and an increase in interstitial fibrosis. The final fibrotic phase (day 8 onward) is characterized by pronounced fibrosis that ultimately may obliterate areas of the lung. Histopathologic criteria are useful in understanding the pathophysiology and evaluating patients with ARDS, although this syndrome should be considered a clinical diagnosis; a lung biopsy or autopsy is not required for diagnosis.


The arterial hypoxemia observed in ALI-ARDS develops from a variety of factors including ventilation-perfusion (V/Q) mismatch, shunting of venous blood into the arterial circulation, and low alveolar partial pressure of oxygen (PAO2). Diffusion limitation is rarely a major contributor to hypoxemia in people with ARDS. V/Q mismatch is the most clinically relevant cause of hypoxemia in people with ARDS. Regions with low V/Q are a result of partial alveolar collapse or obstruction caused by factors such as accumulation of exudate and loss of surfactant. When complete alveolar collapse or obstruction occurs it creates a physiologic shunt.


Physiologic shunt will permit deoxygenated venous blood to flow directly into the arterial circulation without exposure to functional gas exchange units. The result is a reduction in the arterial partial pressure of oxygen (PaO2). This cause of hypoxemia is not responsive to oxygen therapy; mechanical ventilation may allow recruitment of previously collapsed alveoli, reducing the degree of physiologic shunt. Importantly, venous oxygen desaturation will magnify abnormalities associated with shunting, and efforts to improve venous oxygenation by improving perfusion and decreasing oxygen consumption will improve arterial oxygenation in those with a significant physiologic shunt.


Decreased PAO2 may be caused by hypoventilation associated with low pulmonary compliance. This type of hypoxemia generally improves with supplemental oxygen.


In people with ALI-ARDS, pulmonary functional abnormalities noted in addition to hypoxemia include decreased functional residual capacity, mild to moderate reductions in the forced expiratory volume in 1 second and forced vital capacity, decreased diffusing capacity, decreased compliance, and increased resistance. Alterations in surfactant production and composition may also contribute to alveolar collapse, and pulmonary arterial hypertension may result from increased pulmonary vascular resistance. Limited pulmonary function testing has been performed in veterinary patients with ALI-ARDS.


The underlying cause for ALI and ARDS is often unknown. These syndromes should be considered the final end points of a variety of pathophysiologic insults that can be infectious, traumatic, inflammatory, or immune mediated in origin. Common features of massive injury include pronounced microvascular permeability, leukocyte activation, and alterations in cytokine production. Inflammatory mediators are responsible at least in part for the development and propagation of ALI-ARDS. Overzealous response on the part of the host may magnify the initially appropriate inflammatory response and result in perpetuation of injury. Major humoral mediators of ALI-ARDS include the proinflammatory cytokines interleukin-1 and tumor necrosis factor-α, and cellular mediators include neutrophils and macrophages.


Therapy for ALI-ARDS is primarily supportive, and no specific pharmacologic therapy is associated with an improved outcome. Inhaled nitric oxide and surfactant therapy have been shown to improve oxygenation, but positive survival benefits are not observed.9 Surfactant therapy can be lifesaving in infants with respiratory distress syndrome, and modification of surfactant composition and administration technique trials are ongoing.10,11 Cytokine blocking agents have not been effective despite initial early promise. Intravenous β2-agonists have been shown to effectively lower lung water in the β-Agonist Lung Injury Trial (BALTI),12 and both positive fluid balance and high tidal volumes have been associated with a worse outcome.13 A major breakthrough in the treatment of patients with ARDS is the use of lower tidal volumes in mechanical ventilation, which have been associated with less ventilator-induced lung injury and improved patient outcomes.14 Most guidelines include limiting fluid balance to prevent overhydration, limiting ventilator-induced lung injury by limiting tidal volumes, using appropriate positive end-expiratory pressure (PEEP), and preventing other complications of critical illness.15,16


Treatment with activated protein C, which has been effective in sepsis, is being evaluated for ARDS in a phase II clinical trial. The Prospective, Randomized Phase II Clinical Trial of Activated Protein C (Xigris) Versus Placebo for the Treatment of Acute Lung Injury is sponsored by the National Heart, Lung, and Blood Institute with an expected completion date of 2008. A variety of other trials evaluating other pharmacologic and ventilatory maneuvers including surfactant, inhaled nitric oxide, and granulocyte-macrophage colony-stimulating factor are recruiting patients, and further information can be found at www.clinicaltrials.gov.


Resolution of ARDS occurs in an orderly fashion, similar to repair in any other tissue. First, excessive fluid and proteins (soluble and insoluble) are removed from the airways and alveoli. Next the type II alveolar epithelial cells must repopulate the epithelial lining, and the abnormal interstitium must restore its normal matrix. Finally, the damaged endothelium must be repaired to restore blood flow, and unnecessary or residual cellular components must be removed.4,17


If recovery is incomplete, persistent deficiencies in lung function may remain. Most recovery occurs over the first 3 months following extubation, with some additional recovery over the first year.18 Quality of life of survivors is typically good, although depending on the concurrent critical illness or injury, there may be persistent abnormalities.18 Some long-term human survivors of critical illness develop psychologic sequelae and may require ongoing therapy to regain their predisease state.

Related posts:

  1. Deteriorating Mental Status
  2. Hyperthermia and Fever
  3. Thoracentesis
  4. Pulmonary Contusions and Hemorrhage

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Acute Lung Injury and Acute Respiratory Distress Syndrome

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