The Adult Respiratory Distress Syndrome

Symposium on Respiratory Failure

The Adult Respiratory Distress Syndrome MD.,** and Roger C. Bone, MD.t Robert Balk, M.D., M.D.t

The adult respiratory syndrome (ARDS) is a common cause of acute respiratory failure. It has been called many different names over the decades, but all reflect the acute lung injury that results from a variety of insults (Table 1). These insults can either directly or indirectly involve the 15 , 66 All the processes lead to a clinical picture of respiratory distress, lungs. 15, diffuse pulmonary infiltrates on chest x-ray, decreased pulmonary compliance, and impaired oxygen transport. 88 The adult respiratory distress syndrome can be defined as a diffuse lung injury resulting in noncardiogenic (nonhydrostatic) pulmonary edema and acute respiratory failure. It can affect patients of all age groups and is 37 Strict particularly tragic since healthy young people are often afflicted. 37 2), Since criteria have been developed to diagnose this syndrome (Table 2). fronl a variety of unrelated insults, it is ARDS is a syndrome resulting from important to adhere to strict criteria and eliminate patients with underlying chronic lung disease and lung disease resulting from left heart failure. Pulmonary collapse was known to occur even on the battlefields of 88 With the advent of blood banking in World War 11, pap8 World War 1. tients with massive blood loss became salvageable, and renal failure 22 Buford emerged as the major cause of late mortality in these patients. 22 and Burbank described a traumatic wet lung that appeared after a pene20 Mallory described pulmonary lesions in each trating injury to the chest. 20 necropsy case that he reviewed from World War 11. 79 In 1950, Jenkins 11.79 et al. described congestive atelectasis, which is the syndrome known as "shock lung. "72 Interestingly, there were no reports documenting aware-

*Assistant

Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas tProfessor of Medicine, and Chief, Division of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas Supported in part by NIH Academic Career Award 1K07 HL00518-01 and a Pulmonary Chair Association, from the Arkansas Lung Association.

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Synonyms for Adult Respiratory Distress Syndrome Acute respiratory distress in adults Adult hyaline membrane disease Bronchopulmonary dysplasia Congestive atelectasis DaNang lung Hemorrhagic atelectasis Hemorrhagic lung syndrome Hypoxic hyperventilation Noncardiogenic pulmonary edema Oxygen toxicity Post-perfusion lung Post -transfusion lung Post-transfusion Post-traumatic atelectasis Post-traumatic pulmonary insufficiency Progressive respiratory distress Pulmonary contusion Pulmonary microembolism Pump lung Respiratory insufficiency syndrome Respiratory lung Shock lung Stiff lung syndrome Transplant lung Traumatic wet lung Wet lung White lung syndrome

Table 2.

Criteria for Diagnosing Adult Respiratory Distress Syndrome*

Clinical Setting Catastrophic event Pulmonary Nonpulmonary Exclusions Chronic pulmonary disease Left heart abnormalities Respiratory distress Uudged 0udged clinically) Tachypnea> > 20 beats per min, usually greater Tachypnea Labored breathing Diffuse Pulmonary Infiltrates on X-ray Film Interstitial (initially) Alveolar (later) Physiologic Fr02 > 0.. 0.66 Pa0 2 < 50 mm Hg with FI0 Overall compliance < 50 ml per cm, usually 20 to 30 ml per cm VDlVT Increased shunt fraction QS/QT and deadspace ventilation VD/VT Pathologic > 1000 gm Heavy lungs, usually usually> Congestive atelectasis Hyaline membranes Fibrosis

*From Petty, T. C.: Adult respiratory distress syndrome: Definition and historical perspective. Clin. Chest Med., 3:3--7, 1982, with permission.

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ness of respiratory failure after trauma or shock during the Korean War in the early 1950s. 8 The Vietnam War in the 1960s brought a redescription of "shock Hshock lung." This was in part due to rapid helicopter evacuation, vigorous field resuscitation, and improved diagnostic methods. Ashbaugh, Bigelow, and Petty were the first to describe this syndrome after civilian trauma. 33 Because of the similarities to infant respiratory distress syndrome, they coined the term adult respiratory distress syndrome. 3 Originally it was thought that lack of surfactant played an etiologic role, but later the defect in surfactant was found to be a result of the acute lung injury.88 They were also the first group to describe the beneficial effects of positive end-expiratory pressure (PEEP) in the treatment of this syndrome. 3 The adult respiratory distress syndrome is a common disorder and is associated with high mortality. It is estimated that ARDS develops in 84 More than 75 per cent of patients requiring 150,000 patients each year. 84 greater than 50 per cent inspired oxygen concentration to maintain ade84 quate oxygenation will die. 84

CLINICAL STAGES OF ARDS A variety of clinical conditions can give rise to the adult respiratory distress syndrome (Table 3). Sepsis, aspiration, near drowning, drug overdose, pancreatitis, inhalation of smoke and other inhaled gases, shock, trauma, consumptive coagulopathy, and high inspired oxygen fractions are

Table 3.

Causes of Adult Respiratory Distress Syndrome

Aspiration Gastric acid Near-drowning Drug-related Chlordiazepoxide (Librium) Colchicine Dextran 40 Ethchlorvynol (Placidyl) Fluorescein Heroin Leukagglutinin reaction Methadone Propoxyphene (Darvon) Salicylates Thiazides Infectious Causes Bacterial pneumonia Fungal and Pneumocystis carinii pneumonia Gram-negative sepsis Tuberculosis Viral pneumonia

Metabolic Disorders Diabetic ketoacidosis Uremia Physiochemical (N0 2 , NH 33,, Cl" C12 , cadmium, Inhaled toxin (NO" phosgene, smoke, oxygen) Pancreatitis Smoke inhalation Trauma Burns Fat embolism Fractures Head trauma Lung contusion Nonthoracic trauma Shock of any etiology Miscellaneous Amniotic fluid embolism Bowel infarction Carcinomatosis Dead fetus Eclampsia

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13, 15, 15, 16, 16, 21, 21, 25, 25, 26, 26, 28, 28, 33, 33, 37, 37, 43, 43, 47, 47, 52, 56, 59, 59, 63, 64, 66, 66, 68, 68, 73, 73, 80, 80, 81, 81, among the causes. 6,6, 11, 13, 52, 56, 63, 64, 83,88,89,92,94,102 No matter what the cause, four stages characterize the clinical course: (1) injury, (2) apparent stability, (3) respiratory insufficiency, stage,88 During initial injury there are usually no evident and (4) terminal stage. clinical signs, and the chest roentgenogram may be clear. This phase may last as long as six hours. Hyperventilation and abnormalities of the chest roentgenogram and physical examination occur during the phase of apparent stability. Approximately 12 to 24 hours after the injury the chest roentgenogram exhibits fine reticular infiltrates representing perivascular fluid accumulation and interstitial edema. A diffuse, 5-lobed alveolar and interstitial infiltrate is present during the phase of respiratory insufficiency which occurs during the next 12 to 24 hours (Fig. 1). Tachypnea and crackles are noted on physical examination. There is a severe reduction in arterial oxygen tension even when high inspired oxygen concentrations are given. The terminal stage is characterized by persistent severe hypoxemia despite administration of 100 per cent oxygen and carbon dioxide retention. A number of investigators have tried to find the key to detecting early ARDS. Weigell et al. prospectively studied 73 patients with ARDS to idenARDS.1l3 tify those factors that would predict the onset of ARDS .113 They found that serial determinations de terminations of arterial oxygen tensions were the best indicator.

83,88,89,92,94,102

PHYSIOLOGY OF ARDS

A maldistribution of ventilation, intrapulmonary shunting, is the major cause of hypoxemia in ARDS. ARDS.4,4, 29, 29. 30, 30, 57 57 Shunting results when the alveolus is perfused and not ventilated. Many alveoli are ventilated, but not perfused, which results in increased physiologic deadspace. There is an in-

Figure 1. A chest roentgenogram shows a diffuse alveolar and interstitial infiltrate in a patient with the adult respiratory distress syndrome, syndrome.

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crease in physiologic deadspace and right to left shunting in ARDS. In severe ARDS, these abnormalities may exceed 50 per cent. There are changes in lung compliance resulting from fluid accumulation in the interstitium and alveoli, and resultant collapse of the terminal air spaces. These factors produce the maldistribution of ventilation and right to left shunting. An increase in pulmonary vascular resistance may result from hypoxia, vasoconstriction, increased interstitial fluid pressure, or intravascular clot94 Non-uniform increases in pulmonary vascular resistance can poting. 37, 94 tentiate the ventilation perfusion abnormalities. The pulmonary hypertension sign,l17 that is produced is an unfavorable prognostic sign. 117 The functional residual capacity is decreased in ARDS secondary to the microatelectasis and edema. There is also a decrease in lung compliance or a stiffening of the lung. All of these changes result in a widening of the alveolar-arterial oxygen tension gradient and produce profound hypoxemia which is resistant to high inspired oxygen concentrations. In the late stages, there is no longer a sufficient number of functional respiratory units to maintain adequate ventilation, and carbon dioxide retention occurs. Hypoxemia results in a decreased oxygen delivery to the tissues and their cellular mitochondria. This produces a reduction in oxidative metabolism and results in the production of lactate. Accumulation of lactic acid adds to the respiratory acidosis and may further depress tissue metabolism. 7

MECHANISMS OF LUNG INJURY The mechanism of the acute lung injury in ARDS is unknown. A large number of potential mediators have been shown to be able to produce or sustain the intense inflammatory response that is characteristic of the adult respiratory distress syndrome. These mediators include arachidonic acid and its metabolites (prostaglandins, leukotrienes, thromboxane A2), serol3-endorphin, fibrin and fibrin degradation products, tonin, histamine, ~-endorphin, complement, superoxides, polymorp,1lOnuclear polymorpponuclear leukocytes, platelets, free fatty acids, bradykinins, proteolytic enzymes, and lysosomes. 1, 15,40,45,55,65, 15, 40, 45, 55, 65, 68, 71, 73, 87, 95, 108 68. 108 ARDS is marked by increased lung vascular perlueability permeability which leads to the noncardiogenic pulmonary edema. A variety of insults produce increased pulmonary vascular permeability. Included in this list are gram-negative bacterial infusions, oxygen toxicity, gram-negative endotoxin infusion, increased intracranial pressure, oleic acid infusion, gastric acid 1s,27,42,54, 66, 82, 86, 96,102,103 aspiration, and extensive pulmonary microembolization. 15,27,42,54,66,82,86,96,102,103 Studies by Brigham et al. showed no correlation between the amount of pulmonary edema and the severity of the gas exchange abnormality.15 abnormality,l5 The abnormal distribution of ventilation and perfusion may be exacerbated IS Experimental by loss of the normal hypoxic pulmonary vasoconstriction. 15 studies have shown that early after the infusion of endotoxin there is an increase in airway resistance and a decrease in lung compliance. With time the airway resistance decreases toward normal and pulmonary edema develops. The products of arachidonic acid metabolism and arachidonic acid have received increasing attention as potential mediators of the lung injury

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.14. 17. 46. 48, 48. 53, 61, 61. 93, Ill, Ill. 115, 115. 116 Arachidonic acid infusion proof ARDS .14, 17, 23, 34, 35, 44, 46, permeability,86 duces pulmonary vasoconstriction but does not increase permeability. 86 The cyclo-oxygenase metabolites may mediate the pulmonary vasoconstriction, airway constriction, and loss of hypoxic vasoconstriction that are seen in experimental studies of ARDS.15 ARDS .15 Prostacyclin is a potent vasodilator and I5 The lipoxygenase pathway A22 is a potent vasoconstrictor. 15 thromboxane A produces hydroxy fatty acid and leukotrienes. These products may be responsible for granulocyte chemotaxis, bronchoconstriction, and possibly increased vascular permeability. 15 A number of investigators have demonstrated possible roles for prostaglandins and thromboxane in the acute lung injury of endotoxin shock. Our laboratory has demonstrated an increase in both 6-keto prostaglandin Flu la and thromboxane B2 F 2 ,, the stable end products of prostacyclin and thromA22 metabolism in endotoxin shock in sheep.69 Using ibuprofen, a boxane A prostaglandin synthetase inhibitor, there was an improvement in the 69 When ibuprofen was hemodynamic alterations of canine endotoxin shock. 69 combined with aminoglycoside therapy, there was also an improvement in survival in sheep given infusions of live Escherichia coli. 70 coli,1° Activated polymorphonuclear leukocytes have been shown to damage I5, 57, 71 71 These granulocytes produce superoxides and endothelial surfaces. 15, other free radicals which may be important mediators of lung injury. Brigham et al. have produced noncardiogenic pulmonary edema in sheep with histamine infusions and have blocked this reaction with diphenhydra18 Complement may also play a role in the mine, an HI receptor blocker. I8 development of acute lung injury by generating superoxide radicals, enhancing the stickiness of cells, and promoting release of lysosomal proI5, 54, 65, 71, 71. 73 Platelets also release vasoactive mediators, lysosomes, tease. 15 108 We reported that patients with ARDS and disseminated heparin.los and heparin. intravascular coagulation (DIe) (DIC) have more hypoxemia and lower compliDIC.lI Clearly, further investigation ance than patients with ARDS but no DIC.ll is still required before we totally unravel the role of each potential mediator in the production of acute lung injury.

PATHOPHYSIOLOGY OF ARDS

The alveolar-capillary membrane is the primary site of injury in the adult respiratory distress syndrome. In many experimental models of ARDS, there are swelling and retraction of the capillary endothelial cells. This results in a larger in~racellular intracellular gap that leads to increased alveolar permeability and interstitial edema. Increased interstitial fluid produces stiffer noncompliant lungs. As the process continues, alveolar edema results and alveolar collapse occurs. There is microatelectasis, and eventually alveolar disruption and hemorrhagic edema result. In the normal state, the intracellular junctions of the alveolar epithelium are tight and the membrane has low permeability to lipid insoluble substances other than water. The normal loose junctions separating capillary endothelial cells allow small molecules (less than 10,000 MW) to pass. The first leak occurs

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through the capillary endothelium in the adult respiratory distress syndrome.5, 78, 92, 103 II pneumoSurfactant, a phospholipoprotein produced by the type 11 cyte, has decreased activity in ARDS. Its normal function is to reduce alveolar surface tension. In its absence the alveolar surface tension is high 51 and alveoli tend to collapse. 51 The terminal bronchiole may also be a site of increased permeability. Histamine has been shown to produce leakage of proteins and fluid from the bronchiolar venous plexus at the terminal bronchiole level prior to the development of alveolar edema. 88 A similar leakage has also been described in endotoxin shock. 88 Staub has suggested that fluid movement across the 106 terminal bronchioles may be important in pulmonary edema. 106

PATHOLOGIC CHANGES IN ARDS Despite the diverse causes of ARDS, the pathologic changes are uniform and nonspecific. 55 Both acute and chronic stages are described. 55 The lungs may appear grossly normal during the first few hours after the initial insult. The acute stage reveals interstitial and alveolar edema that is secondary to the damage to the epithelial and endothelial cell layers. 55 The alveolar spaces are inhomogenously filled with a proteinaceous and often a hemorrhagic fluid. 55 White blood cells, macrophages, cell fragments, amorphous material, protein, fibrin strands, and remnants of surfactant are also present along with an occasional hyaline membrane. 55 While light microscopy reveals little interstitial change, electron microscopy shows widening of the interstitial space with fluid accumulation, blood cells, and occasional fibrin strands. 5,5, 98 98 Endothelial cells appear to have better preservation than the epithelial cells, which may indicate a greater reparative capacity of the endothelial cells. 55 When antecedent DIe is present, there may be free intravascular fibrin. 55 The chronic stage is marked by a proliferative tissue reaction with epithelial transformation, distinct alveolar septal thickening by cell proliferation, and infiltration with a variety of interstitial cells. 55 These changes may occur within a few days of the initial insult. There is an increase in II pneumocytes that line the the number of cuboidal cells resembling type 11 Evans has shown that these cells alveolus during the reparative process. 55 ·Evans 41 The are able to transform into type I cells in approximately 48 hours. 41 protein-rich fluid in the alveolar space may become organized and create a pattern of intra-alveolar fibrosis. 55 This can lead to an additional reduction in the gas exchanging surface area. 55

TREATMENT There is no specific therapy for ARDS. The treatment is directed toward maintaining adequate tissue oxygenation of vital organs, particularly the brain and heart, through respiratory and circulatory support. If possi-

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ble, treatment of the underlying cause of lung damage should also be instituted. Once the alveolar-capillary membrane is damaged, the clinical problem is essentially the same regardless of the inciting event. 67 This supportive therapy should continue until the integrity of the alveolar-capillary membrane is re-established. The critical factors in treatment include: (1) optimal distention of alveoli to increase functional residual capacity, (2) careful attention to fluid balance and maintenance of adequate tissue perfusion, and (3) control of the primary problem. One of the major objectives of therapy is to obtain optimal distention of alveoli and reverse alveolar collapse. Positive end-expiratory pressure (PEEP) is used to increase the functional residual capacity (FRC) and correct the progressive atelectasis. 44., 9,9. 37, 51,114 51, 114 The use of PEEP creates a distending pressure that is sufficient to overcome the elastic forces in the alveolar walls and to maintain the functional residual capacity. The use of PEEP allows maintenance of adequate oxygenation with a decrease in required oxygen concentration. This helps to minimize the potential toxic effects of high oxygen tension to the lung and yet maintain adequate arte51. 114 rial oxygenation. 4, 51, A number of excellent reviews deal with the use of PEEP.4, 12,32,39,49,58,67,74,77,105,107,110,114 12,32.39,49,58.67,74,77,105,107,110,114 PEEP has been an integral part of the treatment of ARDS for almost 15 years. 114 PEEP allows the airway and alveolar pressures to increase at the end of expiration to levels greater than pressure. 4. 51, 51. 114 This produces a continuous positive distendatmospheric pressure,4, ing pressure across the walls of the airways and alveoli and maintains the patency of many closed or atelectatic gas exchange units. 44,• 51,114 51, 114 The result is improved ventilation of alveoli that were previously sites of shunting or low ventilation in relation to perfusion. This recruitment increases the Pa0 22 ,4, • 4. 51, 114 The use of PEEP may also stabilize flUid-filled fluid-filled alveoli and allow the fluid to occupy a relatively flattened layer on the alveolar wall that would permit gas exchange. 51 There is no evidence that the use of PEEP decreases extravascular lung water. 4,4, 51, 114 In fact, with high lung volumes 36 there may be an increase in extravascular lung water. 36 . Improved compliance results from the increase in functional residual PEEP.51 This results from a shift of the capacity produced by the use of PEEP,51 end expiration point to a steeper portion of the pressure-volume curve of the lung and chest wall. 51 It is important to note that there is not a linear relationship between improved compliance and increased PEEP. \;Vith high PEEP, alveoli Inay may become overdistended and may be underperfused as a result of high intra-alveolar pressure and a reduction in cardiac output. 51 mav be attributed to the use of PEEP Other beneficial effects that may include conservation of alveolar surfactant surfa~tant and a reduction in alveolar surface tension. 4,4. 51 It has been shown that ventilation with high tidal volumes lowcan cause surfactant to aggregate and thus diminish its effectiveness in lowering alveolar surface tension, tension. There are also several reports, primarily in the surgical literature, which suggest that early use of PEEP may prevent the development of ARDS.58, 97, 97, 109, 112 112 The selection of the optimal level of PEEP has been a controversial 51. 114 Most agree that PEEP should be increased in small increments, issue. 51,

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and the cardiac output requirements of the patient should be monitored during these changes. If the cardiac output falls, it should be supported with volume infusions and inotropic drugs. 51. 51, 114 The goal of PEEP is to Fr022 to 50 per cent or less. 51 51,, 114 Suter has defined allow a reduction in the FI0 "optimal PEEP" as the level of PEEP that produces maximal pulmonary ID7 Gallagher et al. defined "best PEEP" as the level of PEEP compliance. 107 that reduces the intrapulmonary shunt fraction to less than 15 per cent of the cardiac output. 49 Which, if either, of these levels is the ideal is still a matter of debate. At present the level of PEEP should be guided by the ability to reduce the inspired oxygen concentration and maintain adequate tissue oxygen delivery. 51, 51, 114 The use of PEEP has a variety of hemodynamic effects including impaired venous return, increased pulmonary vascular resistance, reduced left ventricular afterload, and altered right and left ventricular geometry and compliance. 4, 51, 51. 77,118 77, 118 A majority of patients with ARDS require ventilatory assistance. If the arterial oxygen tension is less than 60 mm Hg on room air in a patient with previously normal lungs, the patient is a candidate for supplemental oxygen. Ventilatory assistance becomes necessary if the arterial oxygen tension does not reach adequate levels despite administration of high oxygen concentrations. 4, 67 67 Volume-cycled ventilators are preferred, and the suggested tidal volume is between 10 and 13 ml per kg. If the patient requires the use of PEEP, the tidal volume may need to be reduced to avoid pul37 monary barotrauma. 24, 37 PEEP can be used to maintain adequate arterial oxygen tension when inspired oxygen concentrations are above 50 per cent. Oxygen toxicity usually occurs after two to three days of an FI0 73 Fr022 that exceeds 60 per cent. cent.73 With an inspired oxygen concentration of 40 per cent or less, there have been no reports of oxygen toxicity. It is well documented that there are a number of potential complications associated with assisted ventilations, 1l9 and it is important to carefully monitor the patient. 1l9 Sepsis is one of the most frequent causes of the ARDS, and its early recognition is important in order that effective treatment may be insti75 Proper bacterial cultures and immunologic techniques should tuted. 22, 25, 26, 75 present, There guide the choice of appropriate antibiotics when infection is present. have also been reports of improved survival in patients with sepsis who are treated early with pharmacologic doses of corticosteroids (methylprednisolone sodium succinate, 30 mg per kg). 85, 85, 99, 101, 10!, 104 It is also vitally important to maintain proper fluid balance. balance, This helps to ensure adequate perfusion and oxygen delivery to vital organs such as the brain, heart, and kidneys. This is guided by the physical examination, hemodynamic information, and laboratory data. data, The use of the flowdirected balloon-tipped Swan-Ganz catheter has greatly aided this evaluation by allowing ready access to pulmonary capillary wedge pressure, mixed venous oxygen tension, and thermodilution cardiac output determinations. nations, A mixed venous oxygen tension below 30 mm Hg is an indicator of severe tissue hypoxia. 88 Unfortunately, the mixed venous oxygen tension sepsis, 8 is not as reliable a prognosticator in the presence of sepsis. Correction and proper treatment of the underlying disorder is also a

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necessity in the proper care of these seriously ill patients. This therapy must be individualized as a variety of causes may produce this syndrome. It is important to remember that more than one cause may be present in a given patient. Adequate patient support in an intensive care unit is required to allow the lung to recover. Proper nursing care with strict attention to detail is invaluable. Table 4 summarizes the goals of treatment of ARDS.

COMPLICA nONS COMPLICATIONS With improvements in treatment and supportive therapy, patients 9o Unfortunately, multiorgan failure and other complinow survive longer. 9o 9o Table 5 lists a number of comcations develop in some of these patients. 9o plications that are prone to occur in these seriously ill patients. Among the pulmonary complications is pulmonary embolic disease, which is difficult to diagnose in these patients without a pulmonary angiogram. Pingleton et al. have shown that the use of prophylactic low-dose heparin decreases the incidence of documented pulmonary emboli in a respiratory intensive care 91 Low-dose heparin was found unit from eight cases to one case per year. 91 to be safe and should be routinely used unless there is a specific contraindication, such as bleeding diathesis or lesion, head injury, malignant hypertension, or severe liver disease. Pulmonary barotrauma includes pneumothorax, pneumomediastinum, and subcutaneous emphysema. The predisposing factors for the development of pulmonary barotrauma include the use of volume ventilators, high inflation pressures in the presence of decreased compliance, high levels of PEEP, high tidal volumes, a complication of intravascular catheter placement, necrotizing pneumonias, and bronchoscopy during mechanical ventilation. 10, 24, 90 Table 4.

Treatment of Acute Respiratory Failure

Good nursing care Frequent position changes Elevation of head and chest Chest physiotherapy Frequent deep breaths and cough Prevention and control of infection Adequate fluid balance with maintenance of tissue perfusion Bronchodilators if signs of increased airway resistance Pharmacologic doses of steroids if sepsis is a cause for acute respiratory failure Ventilatory assistance if indicated U se volume-cycled ventilators Use Use tidal volumes 10 to 13 ml per kg (to maintain optimum compliance) Keep inspired oxygen concentration as low as possible consistent with adequate arterial 2: 60 mm Hg) and mixed venous oxygenation (Pv0 (PvO,2 2: (PaO,2 ~ ~ 30 mm Hg) oxygenation (Pa0 Keep inflation pressure as low as possible Provide adequate humidification Use 2: 50 per cent U se positive end-expiratory pressure if an inspired oxygen concentration of ~,50 is required for more than 24 hours

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Complications Associated with the Adult Respiratory Distress Syndrome

Pulmonary Pulmonary emboli Pulmonary barotrauma Pulmonary fibrosis Pulmonary complications of ventilatory and monitoring procedures Mechanical ventilation right main stem intubation alveolar hypoventilation Swan-Ganz catheterization pulmonary infarction pulmonary hemorrhage Gastrointestinal Gastrointestinal hemorrhage Ileus Gastric distention Pneumoperitoneum Renal Renal failure Fluid retention Cardiac Arrhythmia Hypotension Low cardiac output Infection Sepsis Nosocomial pneumonia Hematologic Anemia Thrombocytopenia Disseminated intravascular coagulation Other Hepatic Endocrine Neurologic Psychiatric

The gastrointestinal complications include gastrointestinal hemorCastrointestinal rhage, ileus, gastric distention, and pneumoperitoneum. 9o Gastrointestinal hemorrhage has the greatest impact on survival, and current recommendations include prophylaxis with antacids. 76, 90, 106 Recent literature has shown that antacids may have better acid neutralizing capacity and may better protect against stress ulceration. 76, 106 The importance of monitoring the adequacy of therapy with determinations of gastric pH has been stressed. 76, 106 Cardiovascular complications include arrhythmias, hypotension, and 90 Almost all patients have flow-directed balloondecreased cardiac output. 90 Swan-Canz catheters which allow determination of pulmonary captipped Swan-Ganz illary wedge pressure, cardiac output, and mixed venous oxygen tension. Unfortunately, such catheterization may also be arrhythmogenic, espe90 cially when coupled with acidosis, alkalosis, or hypoxemia. 90 Other complications include renal failure, which is associated with a

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60 per cent mortality in ARDS.50 Nosocomial infections are important causes of late morbidity and mortality.90 It is also important to maintain the nutritional status of the patient and to prevent the development of protein calorie starvation. 90 90 An aggressive approach toward these potential complications is vital for patient management. Exquisite attention to detail, the use of prophylactic measures, and keen anticipation are the cornerstones of good management. When a complication develops, prompt recognition and treatment are essential.

PROGNOSIS 50 per Most authors continue to report a mortality rate of greater than 50 cent for patients with the adult respiratory distress syndrome. 37, 75 This high mortality persists despite advances in our understanding of the physiologic and pathologic alterations and despite improvements in monitoring and forms of treatment. It is important to note that in those patients who do recover from ARDS there is a return to almost normal pulmonary 38,100 function.38, 100 function.

REFERENCES 1. Adams, T., Jr., and Traker, D. C.: The effects of prostaglandin synthetase inhibitor, ibuprofen, on the cardiopulmonary response to endotoxin in sheep. Circ. Shock, 9:481-489, 1982. 2. Anderson, R. R., Holliday, R. L., and Driedger, A. A.: Documentation of pulmonary capillary permeability pern1eability in the adult respiratory distress syndrome accompanying human sepsis. Am. Rev. Respir. Dis., 119:869, 1979. 3. Ashbaugh, D. G., Bigelow, D. B., Petty, T. L., et al.: a!.: Acute respiratory distress in adults. Lancet, 2:319, 1967. 4. Ayres, S. M.: Mechanisms and consequences of pulmonary edema: Cardiac lung, shock Am. lung and principles of ventilatory therapy in adult respiratory distress syndrome. AIn. Heart J., 103:97-112, 1982. IIeart . oflung lung parenchyma in the adult 5. Bachafen, M., and Weibel, E. R.: Structural alterations of respiratory distress syndrome. Clin. Chest Med., 3:35-56, 1982. 6. Bartlett, R. H.: Pulmonary pathophysiology in surgical patients. Surg. Clin. North Am., 60: 1323-1338, 1980. 60:1323-1338, J. C., and Vleeming, W.; The effect of compensation of acidosis on survival in 7. Bastrians, J. endotoxin shock. Adv. Shock Res., 6:163-174, 1981. 8. Bone, R. C.: The adult respiratory distress syndrome: Diagnosis and treatment. Proc. Cardio!., 5:4~6, 5:4~66, 1979. Cardiol., 9. Bone, R. C.: Treatment of adult respiratory distress syndrome with diuretics, dialysis 6:136--139, 1978. and positive end expiratory pressure. Crit. Care Med., 6:136-139, Francis, P. B., and Pierce, A. K.; Pulmonary barotrauma complicating 10. Bone, R. C., Frands, positive end expiratory pressure. Am. Rev. Respir. Dis., 1135:921, 1976. 11. Bone, R. C., Francis, P. B., and Pierce, A. K.: Intravascular coagulation associated with the adult respiratory distress syndrome. Am. J. Med., 61 :585-589, 1976. a!.: Changes in hepatic flow induced by contin12. Bonnet, F., Richard, C., Glaser, P., et al.: uous positive pressure ventilation in critically ill patients. Crit. Care Med., 10:703705, 1982. J.: Salicylate pulmonary edema: The 13. Bowers, R. E., Brigham, K. L., and Owens, P. J.: mechanism in sheep and review of the clinical literature. Am. Rev. Respir. Dis., 11.5:261, . 115:261, 1977.

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