Acute Respiratory Distress Syndrome
...DS. Development of ARDS is slightly more common with salt-water aspiration than with fresh-water aspiration. Infiltrates and hypoxia develop within 12-24 hours of the initial accident. Patients who are symptomatic after 6 hours of observation generally do well. Aspiration is particularly damaging to lung tissue, leading to an osmotic gradient that favors movement of water into airspaces of the lung. Aspiration may be visible with chest radiography, although the chest radiograph may be normal early in the course of the disease. SMOKE INHALATION Smoke inhalation causes lung tissue damage from direct heat, toxic chemicals, and particulate matter carried into the lower lung. Patients with smoke inhalation initially may be asymptomatic. Patients with airway burns and/or exposure to carbon monoxide or toxic fumes should be monitored closely for development of ARDS, even if symptoms initially are absent OVERDOSES Overdoses of narcotics (eg, heroin), salicylates, tricyclic antidepressants, and other sedatives have been associated with development of ARDS. (Overdoses of tricyclic antidepressants are the most common.) This risk is independent of the risk from concurrent aspiration. Other implicated toxins and drugs include tocolytic agents, hydrochlorothiazide, protamine, and interleukin-2 (IL-2). III. PATHOLOGY ARDS is associated with diffuse damage to the alveoli and lung capillary endothelium. The early phase is described as being exudative, whereas the later phase is fibroproliferative in character. Early ARDS is characterized by an increase in the permeability of the alveolar-capillary barrier leading to an influx of fluid into the alveoli. The alveolar-capillary barrier is formed by the microvascular endothelium and the epithelial lining of the alveoli. Hence, a variety of insults resulting in damage either to the vascular endothelium or to the alveolar epithelium could result in ARDS. The main site of injury may be focused on either the vascular endothelium (eg, sepsis) or the alveolar epithelium (eg, aspiration of gastric contents).# Injury to the endothelium results in increased capillary permeability and the influx of protein-rich fluid into the alveolar space. Injury to the alveolar lining cells also promotes pulmonary edema formation. Two types of alveolar epithelial cells exist. Type I cells, comprising 90% of the alveolar epithelium, are injured easily. Damage to type I cells allows both increased entry of fluid into the alveoli and decreased clearance of fluid from the alveolar space. Type II cells are relatively more resistant to injury. However, type II cells have several important functions, including the production of surfactant, ion transport, and proliferation and differentiation into type l cells after cellular injury. Damage to type II cells results in decreased production of surfactant with resultant decreased compliance and alveolar collapse. Interference with the normal repair processes in the lung may lead to the development of fibrosis.# Neutrophils are thought to play an important role in the pathogenesis of ARDS. Evidence for this comes from studies of bronchoalveolar lavage (BAL) and lung biopsy specimens in early ARDS. Despite the apparent importance of neutrophils in ARDS, the syndrome may develop in profoundly neutropenic patients, and infusion of granulocyte colony-stimulating factor (GCSF) in patients with ventilator-associated pneumonia does not promote the development of ARDS. This and other evidence suggest to some that the neutrophils observed in ARDS may be reactive rather than causative. Cytokines, such as tumor necrosis factor (TNF), leukotrienes, macrophage inhibitory factor, and numerous others, along with platelet sequestration and activation, also are important in the development of ARDS. An imbalance of proinflammatory and anti-inflammatory cytokines is thought to occur after an inciting event, such as sepsis. Evidence from animal studies suggests that the development of ARDS may be promoted by the positive airway pressure delivered to the lung by mechanical ventilation. This is termed ventilator-associated lung injury. ARDS is an inhomogeneous process. Relatively normal alveoli, more compliant than affected alveoli, may become overdistended by the delivered tidal volume, resulting in barotrauma (pneumothorax and interstitial air). Alveoli already damaged by ARDS may experience further injury by the shear forces exerted by the cycle of collapse at end expiration and reexpansion by positive pressure at the next inspiration (so called volutrauma). In addition to the mechanical effects on alveoli, these forces promote the secretion of proinflammatory cytokines with resultant worsening inflammation and pulmonary edema. The use of positive end-expiratory pressure (PEEP) to diminish alveolar collapse and the use of low tidal volumes and limited levels of inspiratory filling pressures appear to be beneficial in diminishing the observed ventilator-associated lung injury. ARDS is associated with severe hypoxemia; therefore, high inspired oxygen concentrations are required to maintain adequate tissue oxygenation and life. Unfortunately, oxygen toxicity may promote further lung injury. Generally, oxygen concentrations greater than 65% for prolonged periods (days) result in diffuse alveolar damage, hyaline membrane formation, and, eventually, fibrosis. ARDS is uniformly associated with pulmonary hypertension. Pulmonary artery vasoconstriction likely contributes to ventilation-perfusion mismatch and is one of the mechanisms of hypoxemia in ARDS. Normalization of pulmonary artery pressures occurs as the syndrome resolves. The development of progressive pulmonary hypertension is associated with a poor prognosis. The acute phase of ARDS usually resolves completely. Less commonly, residual pulmonary fibrosis occurs, in which the alveolar spaces are filled with mesenchymal cells and new blood vessels. This process seems to be facilitated by interleukin (IL)-1. Progression to fibrosis may be predicted early in the course by the finding of increased levels of procollagen peptide III (PCP-III) in the fluid obtained by BAL. This and the finding of fibrosis on biopsy correlate with an increased mortality rate. IV. SYMPTOMOLOGY Symptoms of ARDS can vary, depending on the cause, but they usually develop within 1 to 3 days after a trauma or infection damages the lungs. Shortness of breath occurs first, followed in most cases by rapid, shallow breathing. Patients initially have tachypnea, dyspnea, and normal auscultatory findings in the chest. Some elderly patients may present with an unexplained altered mental status. Patients then become tachycardic with mild cyanosis and later develop coarse rales. They progress to respiratory distress with diffuse rhonchi and signs of consolidation, often requiring positive pressure ventilatory support. Even with significant hypoxemia, these clinical findings may not be obvious, so an arterial blood gas is warranted early in patients at risk. Initial oxygenation ratios and ventilatory parameters do not reliably predict the ultimate outcome in individual patients. The oxygen deprivation caused by ARDS and the leakage into the bloodstream of certain proteins (cytokines) produced by lung cells and white blood cells can lead to inflammation and complications in other organs; failure of several organs (a condition called multiple organ system failure) may also result.# Organ failure can begin soon after the onset of ARDS or days or weeks later. Additionally, people with ARDS are less able to fight lung infections, and they tend to develop bacterial pneumonia. V. EXPECTED DIAGNOSTIC TEST RESULTS Doctors diagnose ARDS when a person suffering from severe infection or injury develops breathing problems or a chest x-ray shows fluid in the air sacs of both lungs. Doctors should do blood tests to show a low level of oxygen in the blood indicating the onset of ARDS. Other conditions that could cause breathing problems should also have been ruled out before making the diagnosis. ARDS can be confused with other illnesses that have similar symptoms. The most important is congestive heart failure. In congestive heart failure, fluid backs up into the lungs because the heart is weak and cannot pump well. However, there is no injury to the lungs in congestive heart failure. Since a chest x-ray is abnormal for both ARDS and congestive heart failure, it is sometimes very difficult to tell them apart. Chest auscultation reveals abnormal breath sounds, such as crackles that suggest fluid in the lungs. Often the blood pressure is low. Cyanosis is also commonly seen. Table II. TESTS USED IN the DIAGNOSIS of ARDS chest X-ray arterial blood gas CBC and blood chemistries Evaluation for possible infections Cultures and analysis of sputum specimens Occasionally an echocardiogram or Swan-Ganz catheterization may need to be done to exclude congestive heart failure which can have a similar chest X-ray appearance to ARDS. VI. CURRENT ACCEPTED MEDICAL TREATMENT A trial was conducted using lower tidal volume ventilation versus a higher tidal volume in the treatment of patients with lung injury early in their course. This trial was undertaken because of the important, unanswered question of the role of lung stretch in the outcome of patients with lung injury. Prior trials have demonstrated conflicting results, leaving clinicians in a quandary. Should larger tidal volumes, which have long been recommended and were in widespread clinical use, be used? Such larger tidal volumes more effectively remove carbon dioxide and maintain acid base balance. The alternative, lower tidal volumes, are less effective for these purposes and may be more uncomfortable for the patient. This landmark randomized controlled trial, which enrolled 861 subjects, answered this question clearly showing for the first time that lower tidal volumes result in improved survival, with a similar need for sedatives for patient comfort. # Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome and if the results are applied to the care of patients across the country, tens of thousands of deaths per year will be prevented.# The objective and accepted treatment is to provide enough support for the failing respiratory system (and other systems) until these systems have time to heal. Treatment of the underlying condition that caused ARDS is essential. The main supportive treatment of the failing respiratory system in ARDS is mechanical ventilation (a breathing machine) to deliver high doses of oxygen and a continuous level of pressure called PEEP (positive end-expiratory pressure) to the damaged lungs. The high pressures and other breathing machine settings required to treat ARDS often require that the patient be deeply sedated with medications. This treatment is continued until the patient is well enough to breathe on his or her own. Medications may be needed to treat infections, reduce inflammation, and eliminate fluid from the lungs. No drug has proved beneficial in the prevention or management of ARDS. The early administration of corticosteroids in septic patients does not prevent the development of ARDS. Numerous pharmacologic therapies, including the use of inhaled synthetic surfactant, intravenous antibody to endotoxin, ketoconazole, and ibuprofen, have been tried and are not effective. Small sepsis trials suggest a potential role for antibody to TNF and recombinant IL-1 receptor antagonist. Inhaled nitric oxide (NO), a potent pulmonary vasodilator seemed promising in early trials but, in larger controlled trials, did not change mortality rates in adults with ARDS. A potential role exists for corticosteroids in patients with late ARDS (fibroproliferative phase) because they decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. This may be considered rescue therapy in selected patients, but widespread use is not recommended pending the results of an ARDS Network trial now underway.# VII. PROGNOSIS The prognosis of ARDS depends not only upon the degree of respiratory failure, but also upon infection and the failure of other organs, particularly the liver, kidney, and central nervous system. As previously noted, the prognosis of ARDS has improved over the last 20 years. Sixty to 70% of patients surv...