|
Acute lung
injury (ALI) and acute respiratory distress syndrome (ARDS) are
inflammatory disorders of the lung most commonly caused by sepsis,
pneumonia, trauma, and/or aspiration. ALI and ARDS are characterized
by hypoxemia and diffuse infiltrates on chest x-ray in the absence
of elevated left atrial pressure. ALI and ARDS differ only in the
degree of hypoxemia. Diagnosis is by clinical presentation, ABGs,
and imaging studies. Treatment is with lung-protective, low tidal
volume mechanical ventilation, supportive therapy, and treatment
of underlying causes. Mortality is still high (30 to 40%) and worsens
with age and comorbidities, although overall mortality rates have
declined in the past decade.
ALI and ARDS are syndromes of widespread lung inflammation and increased pulmonary vascular permeability. ALI and ARDS are the same clinical disorder, differing only in severity of hypoxemia (see
Table 1: Acute Lung Injury and Acute Respiratory Distress Syndrome (ARDS): Consensus Definition of ALI/ARDS ). Distinguishing between these two forms is arbitrary given that Pao2 correlates poorly with lung pathology and clinical course.
|
Table 1
|
 | | |
|
Consensus
Definition of ALI/ARDS
|
|
n Acute onset of respiratory failure
|
|
n Diffuse bilateral infiltrates on chest radiograph
|
|
n Absence of left atrial hypertension (pulmonary artery occlusive pressure* [PAOP] ≤ 18 mm Hg) or no clinical evidence of left atrial hypertension
|
|
n Hypoxemia, defined as Pao2/Fio2 ≤ 300 (ALI) or ≤ 200 (ARDS)†
|
|
* If available. There is no consensus mandating pulmonary artery catheter insertion in suspected ALI/ARDS unless otherwise clinically indicated.
|
|
† Pao2 in mm Hg, Fio2 in decimal fraction (eg, 0.5).
|
|
Fio2 = fraction of inspired O2.
|
|
Etiology
and Pathophysiology
ALI/ARDS is caused by a multitude of disorders that directly or indirectly injure the lungs (see
Table 2: Acute Lung Injury and Acute Respiratory Distress Syndrome (ARDS): Clinical Disorders that Cause ARDS); sepsis and pneumonia are the most common, causing about 60% of cases. Alcoholics are at increased risk. Because definitions were only recently standardized, the incidence of ALI/ARDS is uncertain. However, recent estimates indicate that about 190,000 cases/yr occur in the US.
|
Table 2
|
| | |
|
Clinical
Disorders that Cause ARDS
|
|
Direct Lung Injury
|
Indirect Lung Injury
|
|
Common causes
|
Common causes
|
|
Less common causes
Diffuse alveolar hemorrhage
|
Less common causes
Bone marrow transplantation
Drug overdose (eg, aspirin , cocaine, opioids, phenothiazines, tricyclics)
Massive blood transfusion (>15 U)
|
|
|
Radiographic contrast (rare)
|
|
|
Stroke or seizure (neurogenic pulmonary edema)
|
|
Adapted from Ware LB and Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000; 342(18):1334–1349.
|
|
ALI/ARDS is thought to develop when pulmonary or systemic inflammation leads to systemic release of cytokines and other proinflammatory molecules. The cytokines activate alveolar macrophages and recruit neutrophils to the lungs, which in turn release leukotrienes, oxidants, platelet-activating factor, and proteases. These substances damage capillary endothelium and alveolar epithelium, disrupting the barriers between capillaries and airspaces. Edema fluid, protein, and cellular debris flood the airspaces and interstitium, causing disruption of surfactant, airspace collapse, ventilation-perfusion mismatch, shunting, stiffening of the lungs with decreased compliance, and pulmonary hypertension. The injury is distributed heterogeneously but mainly affects dependent lung zones. Histopathologically, diffuse alveolar damage results with intra-alveolar neutrophils, RBCs, and cellular debris and denuded epithelial basement membranes with formation of hyaline membranes.
ALI/ARDS resolves spontaneously for many patients through active clearance of alveolar edema, passive clearance of soluble protein, alveolar reepithelialization, and possibly neutrophilic apoptosis. Proliferation of interstitial fibroblasts and myofibroblasts with early collagen deposition may also occur at this stage without diffuse fibrosis. However, some patients later develop diffuse fibrosis and loss of normal architecture (fibrosing alveolitis, or late diffuse alveolar damage).
Symptoms and Signs
Symptoms and signs are nonspecific and typically develop within 24 to 48 h of initial injury or illness. Dyspnea is the primary symptom, occasionally accompanied by cough or chest pain. Signs invariably include tachypnea and tachycardia. Accessory muscle use, cyanotic or mottled skin, and abnormal breath sounds (crackles, rhonchi, and/or wheezes) may be present.
Diagnosis
ALI/ARDS is primarily a clinical diagnosis. Once diagnosed, testing may be required to identify a cause.
ALI/ARDS is suspected when dyspnea and respiratory insufficiency rapidly develop in settings that predispose to ARDS. A similar clinical presentation can result from acute heart failure and from pulmonary infections. All patients should have ABGs and chest x-ray; diagnosis is confirmed by demonstration of hypoxemia and widespread chest x-ray infiltrates in the absence of clinical or manometric signs of left atrial hypertension (see Table 1: Acute Lung Injury and Acute Respiratory Distress Syndrome (ARDS): Consensus Definition of ALI/ARDS).
ABGs initially show a low Pao2, a normal or low Paco2, and an elevated pH (acute uncompensated respiratory alkalosis), unless metabolic acidosis is present secondary to sepsis. The low Pao2 is only partially responsive to O2 supplementation because the pathophysiology involves shunting of blood through areas of unventilated lung.
Chest x-ray shows bilateral, symmetrical or asymmetrical, fluffy alveolar infiltrates. At the onset of illness, radiographic changes may lag behind physiologic changes, making hypoxemia seem more severe than x-ray findings would suggest. CT in the acute phase usually shows filling of airspaces in dependent lung fields (dorsal caudal in supine patients) with interlobular septal thickening, and often small pleural effusions. Late in the course, if fibrosing alveolitis develops, reticulonodular and ground-glass opacities with honeycombing and/or bullae are apparent on chest x-ray and CT.
If left atrial filling pressures are in doubt after clinical evaluation, a measurement of pulmonary artery occlusion pressure (PAOP) by right heart catheterization can clarify the diagnosis. A PAOP < 18 mm Hg in combination with the above findings is diagnostic of ALI/ARDS. A PAOP > 20 mm Hg suggests heart failure or hypervolemia.
Underlying causes:
The cause of ALI/ARDS is often obvious. When it is not, a review of drugs and recent diagnostic tests, procedures, and treatments may suggest an unrecognized cause, such as use of radiographic contrast, air embolism, or transfusion. When the cause is still uncertain, bronchoscopy with bronchoalveolar lavage (BAL) and biopsy for detection of aspiration, infection, hemorrhage, malignancy, or other disorders should be considered.
Complications:
Tachycardia, hypotension, and/or a sudden increase in the peak inspiratory pressure required for mechanical ventilation suggests possible pneumothorax; patients with such findings should have a chest x-ray immediately. Fever and an elevated WBC count with purulent tracheal aspirate suggest bacterial superinfection of the lungs (eg, hospital-acquired pneumonia); such patients should have 2 sets of blood cultures and culture of the tracheal aspirate.
Prognosis
Mortality in ALI/ARDS until recently was very high (40 to 60%) but has declined in recent years to 30 to 40%, probably because of improvements in mechanical ventilation and in treatment of sepsis. Most often, death is not caused by respiratory dysfunction but rather is related to sepsis and multiorgan dysfunction. Persistence of neutrophils and high cytokine levels in BAL fluid predict a poor prognosis. Mortality otherwise increases with age, presence of sepsis, and severity of preexisting organ insufficiency or coexisting organ dysfunction.
Pulmonary function returns close to normal in 6 to 12 mo in most ALI/ARDS patients who survive; however, patients with a protracted clinical course or severe disease may have residual pulmonary symptoms and many have persistent neuromuscular weakness.
Treatment
Treatment of ALI/ARDS includes mechanical ventilation, supportive care, and treatment of underlying causes. Treatment of underlying causes is discussed elsewhere in The Manual.
Mechanical
ventilation:
Nearly all ALI/ARDS patients require endotracheal intubation and mechanical ventilation during the acute phase of their illness. A few patients with ALI can be managed with high fractional inspired O2 (Fio2) delivered by face mask alone, or with noninvasive positive pressure ventilation (NIPPV) delivered by face mask, which effectively delivers positive end-expiratory pressure (PEEP).
Endotracheal intubation and mechanical ventilation should be considered when the respiratory rate approaches 30/min, when an Fio2 > 0.60 cannot maintain arterial O2 saturation > 90% for more than a few hours, or when the patient's breathing appears to be failing or tiring. Intubation should not be delayed until the patient is in extremis.
Mechanical ventilation carries the potential risk of O2 toxicity and may be associated with barotrauma and ventilator-induced lung injury. Recommendations for ventilator settings are designed to reduce these risks. The goal is to keep inspired O2 < 50 to 60% and plateau airway pressures < 30 cm H2O. The patient should be ventilated in assist-control mode with tidal volume set at 5 to 6 mL/kg predicted body weight. Mild to moderate respiratory acidosis is acceptable. This tidal volume–plateau pressure limited ventilator strategy reduces mortality in ARDS. (see Respiratory Failure and Mechanical Ventilation: Mechanical ventilation in ALI/ARDS.)
Prone positioning improves oxygenation in some patients, by allowing recruitment of nonventilating lung regions. However, there is no evidence for improved survival. Prone positioning is contraindicated in pregnant patients and in those with shock, spinal instability, and increased intracranial pressure.
Readiness for liberation from mechanical ventilation (see Respiratory Failure and Mechanical Ventilation: Liberation from Mechanical Ventilation), sometimes termed weaning, is based on improved lung function (ie, a decreasing need for O2 and PEEP), improvement of chest radiographic appearance, and resolution of tachypnea.
Fluid management:
There is no consensus on fluid management. A lower preload (with limited fluids and perhaps even diuretics) limits transudation of fluid in the lungs, but a higher preload optimizes cardiac output and maintains end-organ perfusion. It is not currently clear which approach maximizes survival. Pulmonary artery catheterization can be used to assess volume status and guide infusions when necessary, but the effect on mortality is unclear. Studies of the utility of pulmonary arterial catheterization and the 2 types of fluid management are underway.
In addition to intravascular volume and arterial oxygenation, O2 delivery is influenced by the amount of Hb and the cardiac output. If an anemic patient is difficult to oxygenate on a nontoxic Fio2 (eg, requires PEEP ≥ 15 cm H2O), RBCs should be transfused to a Hb of 10 to 12 g/dL. Persistent hypotension despite adequate intravascular volume should usually be managed with inotropes, not more fluid; dobutamine 2.5 to 10 μg/kg/min can raise cardiac output and improve O2 delivery. A central venous saturation ≥ 70% generally indicates adequate cardiac output.
Supportive treatment:
Supportive treatment involves prompt recognition and treatment of acquired pneumonias; management of organ system failure, especially renal failure; stress ulcer prophylaxis with H2 blockers or sucralfate ; and deep vein thrombosis prophylaxis. Nutrition must be maintained, via an enteral route if possible.
Experimental
treatments:
A definitive pharmacologic treatment for ALI/ARDS that reduces morbidity and mortality remains elusive. Inhaled nitric oxide, surfactant replacement, and many other agents directed at modulating the inflammatory response have been studied and found not to reduce morbidity or mortality. Some small studies suggest that systemic corticosteroids may be beneficial in late-stage ALI/ARDS, but a larger, prospective randomized trial found no reduction in mortality. Corticosteroids may be deleterious when given early in the course of the condition.
Last full review/revision November 2005
Content last modified November 2005
| 
