BACKGROUND Since World War I, it has been recognized that some patients with nonthoracic injuries, severe pancreatitis
, massive transfusion, sepsis, and other conditions develop respiratory distress, diffuse lung infiltrates, and respiratory failure, sometimes after a delay of hours to days. Ashbaugh et al described 12 such patients in 1967, using the term ―adult respiratory distress syndrome‖ to describe this condition. Before research into the pathogenesis and treatment of this syndrome could proceed, it was necessary to formulate a clear definition of the syndrome. Such a definition was developed in 1994 by the American-European Consensus Conference (AECC) on acute respiratory distress syndrome (ARDS). The term ―acute respiratory distress syndrome‖ was used instead of ―adult respiratory distress syndrome‖ because the syndrome occurs in both adults and children. ARDS was recognized as the most severe form of acute lung injury (ALI), a form of diffuse alveolar injury. The AECC defined ARDS as an acute condition characterized by bilateral pulmonary infiltrates and severe hypoxemia in the absence of evidence for cardiogenic pulmonary edema. According to the AECC criteria, the severity of hypoxemia necessary to make the diagnosis of ARDS is defined by the ratio of the partial pressure of oxygen in the patient’s arterial blood (PaO2) to the fraction of oxygen in the inspired air (FIO2). In ARDS, the PaO2/FIO2 ratio is less than 200, and in ALI, it is less than 300. In addition, cardiogenic pulmonary edema must be excluded either by clinical criteria or by a pulmonary capillary wedge pressure (PCWP) lower than 18 mm Hg in patients with a pulmonary artery (Swan-Ganz) catheter in place. PATHOPHYSIOLOGY ARDS is associated with diffuse alveolar damage (DAD) and lung capillary endothelial injury. 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, which make up 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 alveolar epithelial 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 a key role in the pathogenesis of ARDS, as suggested by studies of bronchoalveolar lavage (BAL) and lung biopsy specimens in early ARDS. Despite
fibrosis. The most common risk factor for ARDS is sepsis. 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 VALI. are also important in the development of ARDS. ARDS expresses itself as an inhomogeneous process. and injuries. such as sepsis. ETIOLOGY Multiple risk factors exist for ARDS. high FIO2 levels may cause DAD via oxygen free radical and related oxidative stresses. Although a high FIO2 is required to maintain adequate tissue oxygenation and life. Pulmonary artery vasoconstriction likely contributes to ventilation-perfusion mismatch and is one of the mechanisms of hypoxemia in ARDS. An imbalance of proinflammatory and anti-inflammatory cytokines is thought to occur after an inciting event. Theoretically. hyaline membrane formation. 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. aspiration of gastric contents). and. Less commonly. Generally. This process seems to be facilitated by interleukin (IL)-1. along with platelet sequestration and activation. ARDS is uniformly associated with pulmonary hypertension. and infusion of granulocyte colony-stimulating factor (G-CSF) in patients with ventilator-associated pneumonia(VAP) does not promote its development. This and other evidence suggests that the neutrophils observed in ARDS may be reactive rather than causative. may become overdistended by the delivered tidal volume.the apparent importance of neutrophils in this syndrome. which are more compliant than affected alveoli. residual pulmonary fibrosis occurs. leading to severe hypoxemia. ARDS may develop in profoundly neutropenic patients. are often required. Cytokines (tumor necrosis factor [TNF]. Alveoli already damaged by ARDS may experience further injury from the shear forces exerted by the cycle of collapse at end-expiration and reexpansion by positive pressure at the next inspiration (socalled volutrauma). This is termed ventilator-associated lung injury (VALI). The development of progressive pulmonary hypertension is associated with a poor prognosis. resulting in barotrauma (pneumothorax and interstitial air). collectively called oxygen toxicity. additional measures. Relatively normal alveoli. eventually. ARDS causes a marked increase in intrapulmonary shunting. Approximately 20% of patients with ARDS have no identified risk factor. This and the finding of fibrosis on biopsy correlate with an increased mortality rate. oxygen concentrations higher than 65% for prolonged periods (days) can result in DAD. ARDS risk factors include direct lung injury (most commonly. in which the alveolar spaces are filled with mesenchymal cells and new blood vessels. leukotrienes.
. Normalization of pulmonary artery pressures occurs as the syndrome resolves. In addition to the mechanical effects on alveoli. systemic illnesses. these forces promote the secretion of proinflammatory cytokines with resultant worsening inflammation and pulmonary edema. macrophage inhibitory factor. like lung recruitment with PEEP. and numerous others). 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. The acute phase of ARDS usually resolves completely.
000 population. partly because studies have used different definitions of the disease.000 population.
. reaching 306 per 100. Moreover. female sex (noted only in trauma cases). A prospective study using the 1994 AECC definition was performed in King County. reported much lower figures. For any underlying cause. recent data are available from the United States and international studies that may clarify the true incidence of this condition.Given the number of adult studies. and alcohol use. all cases of ARDS in a given population must be found and included. Incidence increased with age. On the basis of these statistics. a study from Utah showed an estimated incidence of 4. However. For example. increasingly severe illness as predicted by a severity scoring system such as the Acute Physiology And Chronic Health Evaluation (APACHE) increases the risk of development of ARDS. from April 1999 through July 2000 and found that the ageadjusted incidence of ALI was 86. Subsequent studies.
United States statistics
In the 1970s. The study identified associations between four single nucleotide polymorphisms and increased ALI susceptibility. Further studies are needed to examine the role of FAS in ALI.600 cases exist in the United States annually and that these cases are associated with 74. the estimated annual frequency was 75 cases per 100.000 person-years for people in aged 75-84 years. to determine an accurate estimate of its incidence.2 per 100.
A study by Glavan et al examined the association between genetic variations in the FAS gene and ALI susceptibility. cigarette smoking.8-8. several factors appear to increase the risk of ARDS after an inciting event. with or without pulmonary contusion Fractures. particularly multiple fractures and long bone fractures Burns Massive transfusion Pneumonia Aspiration Drug overdose Near drowning Postperfusion injury after cardiopulmonary bypass Pancreatitis Fat embolism General risk factors for ARDS have not been prospectively studied using the 1994 EACC criteria. major risk factors associated with the development of ARDS include the following:
Bacteremia Sepsis Trauma. Washington. EPIDEMIOLOGY The incidence of ARDS varies widely. before the development of the AECC definitions.000 population. Data obtained more recently by the NIH-sponsored ARDS Study Network suggest that the incidence of ARDS may actually be higher than the original estimate of 75 cases per 100. Although this may be problematic. it is estimated that 190. including advanced age.3 cases per 100.000 person-years. when a National Institutes of Health (NIH) study of ARDS was being planned.500 deaths.
the failure of pulmonary function to improve in the first week of treatment is a poor prognostic factor. The severity of hypoxemia at the time of diagnosis does not correlate well with survival rates. suggested much lower mortality rates. and mortality was higher in patients with higher DcR3 levels. TNF-alpha. in the range of 30-40%. Washington. especially ventilator-associated pneumonia (VAP).
Age-related differences in incidence
ARDS may occur in people of any age.
.000 population for ARDS. soluble triggering receptor expressed on myeloid cells (sTREM)-1. However. and they frequently develop nosocomial infections. Morbidity is considerable. no differences in the incidence between males and females appear to exist. in trauma patients only. Its incidence increases with advancing age.000 person-years in those between the ages of 75 and 84 years. Survivors of ARDS have significant functional impairment for years following recovery.[7. the incidence of the disease may be slightly higher among females. independently predict 28-day mortality in ARDS patients. including the PaO2/FIO2 ratio. and functional impairment may persist for months after hospital discharge. PROGNOSIS Until the 1990s. Nonsurvivors had higher DcR3 levels than survivors. plasma DcR3 levels were the only biomarker to distinguish survivors from nonsurvivors at all time points in week 1 of ARDS. although the recent success of mechanical ventilation using smaller tidal volumes may suggest a role of lung injury as a direct cause of death. However. a soluble protein with immunomodulatory effects. Patients with ARDS are likely to have prolonged hospital courses.The first study to use the 1994 AECC definitions was performed in Scandinavia. which reported annual rates of 17. Mortality in ARDS increases with advancing age. recent changes in the application of mechanical ventilation. The adverse effect of age may be related to underlying health status. regardless of APACHE II scores. The study performed in King County.000 person-years in those aged 15-19 years to 306 cases per 100.5 cases per 100. Severe disease and prolonged duration of mechanical ventilation are predictors of persistent abnormalities in pulmonary function. Note that most deaths in ARDS patients are attributable to sepsis (a poor prognostic factor) or multiorgan failure rather than to a primary pulmonary cause. and better overall supportive care of critically ill patients. one from a large county hospital in Seattle and one from the United Kingdom.
Sex-related differences in incidence
For ARDS associated with sepsis and most other causes. patients often have significant weight loss and muscle weakness. and IL-6 in ARDS patients. 8] Possible explanations for the improved survival rates may be better understanding and treatment of sepsis. In a study comparing DcR3. do not predict the outcome or risk of death. Peripheral blood levels of decoy receptor 3 (DcR3).000 population for ALI and 13. The age distribution reflects the incidence of the underlying causes. most studies reported a 40-70% mortality rate for ARDS. 2 reports in the 1990s. found mortality rates of 24% in patients between ages 15 and 19 years and 60% in patients aged 85 years and older. In addition. ranging from 16 cases per 100. However.9 cases per 100. Indices of oxygenation and ventilation.
acute abdominal findings in the case of ARDS caused by pancreatitis) are present. Carefully examine sites of intravascular lines. carefully look for signs of congestive heart failure or intravascular volume overload. decreased breath sounds over 1 lung may indicate a pneumothorax or endotracheal tube down the right main bronchus. With the onset of lung injury. tachypnea. it may take up to a few days. massive transfusion. such as trauma. Patients developing ARDS are critically ill. and only 49% had returned to work. ARDS survivors had abnormal 6-minute walking distances at 1 year. and they may not be capable of providing historical information. Check for subcutaneous air. This included lower scores in mobility. including jugular venous distention. and the need for a high fraction of inspired oxygen (FIO2) to maintain oxygen saturation. The patient may be febrile or hypothermic.
. Examination of the lungs may reveal bilateral rales. a manifestation of infection or barotrauma. although. but diffusing capacity remained mildly diminished (72%) at 1 year. A study examining health-related quality of life (HRQL) after ARDS determined that ARDS survivors had poorer overall HRQL than the general population at 6 months after recovery. and edema. 12 patients died in the first year. acute pancreatitis. drug overdose). Cyanosis of the lips and nail beds may occur. it may be harder to identify. associated hypotension and peripheral vasoconstriction with cold extremities may be present. including signs of lung consolidation or findings consistent with an acute abdomen. This rapidly progresses to severe dyspnea at rest. cardiac murmurs and gallops. in others (eg. often with multisystem organ failure. pay careful attention during the physical examination to identify potential causes of sepsis. Rales may not be present despite widespread involvement. Because the patient is often intubated and mechanically ventilated. agitation. PHYSICAL ASSESSMENT Physical findings often are nonspecific and include tachypnea. A study of this same group of patients 5 years after recovery from ARDS (9 additional patients had died and 64 were evaluated) was recently published and demonstrated continued exercise impairment and decreased quality of life related to both physical and neuropsychological factors. drain sites. the inciting event is obvious. patients initially note dyspnea with exertion.In a study of 109 survivors of ARDS. in rare instances. HISTORY Acute respiratory distress syndrome (ARDS) is characterized by the development of acute dyspnea and hypoxemia within hours to days of an inciting event. the illness develops within 12-48 hours after the inciting event. Their health-related quality of life was significantly below normal. Because ARDS often occurs in the context of sepsis. Radiographic abnormalities had also completely resolved. anxiety. Manifestations of the underlying cause (eg. and decubitus ulcers for evidence of infection. Typically. and social isolation. or aspiration. tachycardia. no patient remained oxygen dependent at 12 months. However. spirometry and lung volumes were normal at 6 months. but. In many cases. and the need for increasingly high concentrations of inspired oxygen. Because cardiogenic pulmonary edema must be distinguished from ARDS. surgical wounds. In 83 evaluable survivors. In a septic patient without an obvious source. drug overdose. energy. hepatomegaly. sepsis.
primarily related to muscle wasting and weakness. Renal failure is a frequent complication of ARDS. SUMMARY SUMMARY AND RECOMMENDATIONS
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by the acute onset of bilateral alveolar infiltrates and hypoxemia. (See "Acute respiratory distress syndrome: Clinical features and diagnosis". pneumothorax. Preventive strategies including elevation of head of the bed. If prolonged mechanical ventilation is needed. they are at risk for serious nosocomial infections. particularly in the context of sepsis. Renal failure may be related to hypotension. possibly. most notably postextubation laryngeal edema and subglottic stenosis. or both. Fluid management is complicated in this context. Patients with ARDS. use of subglottic suction endotracheal tubes. may also develop infections with drug-resistant organisms such as methicillin-resistantStaphylococcus aureus (MRSA) and vancomycinresistant Enterococcus (VRE). thus. Patients may have difficulty weaning from mechanical ventilation. barotrauma may occur. Strategies to facilitate weaning. section on 'Diagnostic criteria'. Other potential complications that may occur in these mechanically ventilated patients include accidental extubation and right mainstem intubation. Other potential infections include urinary tract infection (UTI) related to the use of urinary catheters and sinusitis related to the use of nasal feeding and drainage tubes. patients may eventually require tracheostomy. Diagnostic criteria for ARDS are provided separately. Other potential complications include ileus. including ventilator-associated pneumonia (VAP) and line sepsis. significant functional impairment was noted at 1 year. is usually the cause of death in ARDS. or underlying illness. may decrease the duration of mechanical ventilation and facilitate recovery. With prolonged intubation and tracheostomy. Patients may also develop Clostridium difficile colitis as a complication of broad-spectrum antibiotic therapy. upper airway complications may occur.)
. Corticosteroid treatment and use of neuromuscular blockade are risk factors for muscle weakness and poor functional recovery. especially if the patient is oliguric. early institution of physical therapy. attention to maintaining nutrition. stress gastritis. and anemia. In a study of survivors of ARDS. rather than respiratory failure alone. because of the extended intensive care unit (ICU) stay and treatment with multiple antibiotics. and use of weaning protocols. high mean airway pressures.COMPLICATIONS Patients with ARDS often require high-intensity mechanical ventilation. including high levels of positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) and. Stress ulcer prophylaxis is indicated for these patients. such as daily interruption of sedation. nephrotoxic drugs. The incidence of VAP in ARDS patients may be as high as 55% and appears to be higher than that in other populations requiring mechanical ventilation. Multisystem organ failure. Because patients with ARDS often require prolonged mechanical ventilation and invasive hemodynamic monitoring. Patients present with pneumomediastinum. Anemia may be prevented by the use of growth factors (epopoietin). and oral decontamination.
(See 'Mortality' above. Patients uncommonly die from respiratory failure . The underlying cause of the ARDS is the most common cause of death among patients who die early [7.
. Although it has been suggested that obesity may impact the mortality of critically ill patients with or without ARDS. Patients seldom die from respiratory failure.)
Predictors — Many studies have sought to identify factors during the acute illness that predict mortality. cognitive. (See 'Predictors' above. or treatment-related.) There are numerous factors that can be assessed during the acute illness that may predict mortality. sepsis due to nosocomial pulmonary infection is the most common cause of death among patients who die later in their clinical course. No single factor has proven to be superior to the others. an observational study of 2451 patients who had enrolled in ARDSNet randomized trials found a fall in mortality from 35 to 26 percent between 1996 and 2005 . disease-. evidence is conflicting .
MORTALITY — ARDS is associated with appreciable mortality. There is growing recognition that survivors of ARDS struggle with physical. The overall mortality rate was 41 percent. Patient-related — Older patients appear to be at an increased risk for death [5. In contrast. Likely causes include better supportive care and improved ventilatory strategies. In contrast.12]. with estimates ranging from 26 to 58 percent [4-10]. as well as reduced quality of life for at least two years following the acute illness. The improved mortality may be attributable to patients who have ARDS related to risk factors other than sepsis. the reasons are uncertain. However. and psychological disorders that may last for months or years following their acute illness. Numerous studies suggest that survival has improved over time [10.11. Although encouraging. such as trauma . (See"Mechanical ventilation in acute respiratory distress syndrome".
The underlying cause of the ARDS is the usual cause of death among patients who die early. ranging from 24 percent among patients 15 to 19 years of age to 60 percent among patients 85 years of age or older. several issues should be considered with respect to trends in ARDS-related mortality:
It is not known if mortality has decreased among patients who received their care outside of a specialized center or a clinical trial. The mortality rate increased progressively with age. such as low tidal volume ventilation [3.) Studies suggest that survival has improved for patients with ARDS. many have abnormalities in pulmonary function that are generally mild. nosocomial pneumonia and sepsis are the most common causes of death among patients who die later in their clinical course .12-14]. section on 'Low tidal volume ventilation'.15]. This was illustrated by a multicenter cohort study that followed 1113 patients with ARDS for 15 months . Among long-term survivors. As an example. To the extent that mortality has decreased.8. no single factor appears to be superior to the others.16]. Such factors can be categorized as patient-.13.
30) and there was a linear correlation between the degree of dead space ventilation and mortality. Infection – Infection and/or multiorgan dysfunction are better predictors of mortality than respiratory parameters [12. For every 0. 95% CI 1. and certain biomarkers and gene polymorphisms. However. according to an observational study of 3670 patients with ARDS that found that patients with mild. ICU-free. the odds of death increased by 45 percent. Laboratory – Routine laboratory parameters are not helpful for predicting the outcome of ARDS. failure of oxygenation to improve. the dead space fraction or Vd/Vt) determined by measuring exhaled carbon dioxide (CO2) levels . Severity of illness score – Severity of illness scores appear to correlate with mortality.58. The dead space fraction was markedly elevated (mean 0. Pulmonary vascular dysfunction – Pulmonary vascular dysfunction is indicated by an elevated transpulmonary gradient (ie. normal <0.) Underlying cause of the ARDS – Patients with trauma-related ARDS appear to have a lower likelihood of death at 90 days than patients with ARDS that is unrelated to trauma . pulmonary vascular dysfunction. 32. and 45 percent.7. As an example. moderate ARDS (PaO2/FiO2 >100 but ≤200 mmHg). respectively . Severe but not mild or moderate alcohol misuse. which is more common than death due to respiratory failure. section on 'Acute Physiologic and Chronic Health Evaluation (APACHE)'. or severe ARDS (PaO2/FiO2≤100 mmHg).78 per 25-point increase. infection.Disease-related — Disease-related predictors of mortality include severe hypoxemia. and hypotensionor vasopressor-free days .05 increase in dead space fraction. >285 dyne s/cm). This was illustrated by a series of 179 patients with early ARDS who had their ratio of dead space to tidal volume (ie. patients with a higher APACHE III score have an increased likelihood of death (odds ratio 1.The transpulmonary gradient is the difference between the mean pulmonary artery pressure and the pulmonary artery occlusion pressure.28-33]. (See "Predictive scoring systems in the intensive care unit". This is probably because they predict death from a nonrespiratory cause. a large body of emerging evidence suggests that many biomarkers and gene polymorphisms are associated with both susceptibility to ARDS
.73) . Mortality appears to increase as ARDS becomes more severe. increased dead space. 1. Dead space – Dead space ventilation early in the course of ARDS appears to correlate with mortality. Pulmonary vascular dysfunction appears to be an independent risk factor for 60-day mortality and fewer ventilator-free.
Oxygenation – The severity of hypoxemia determines whether the patient has mild ARDS (PaO2/FiO2>200 but ≤300 mmHg).00 to 1. moderate. and severe ARDS had mortality rates of 27. is associated with an increased risk of death or persistent hospitalization at 90 days (adjusted odds ratio.16-2. a high severity of illness score. while the pulmonary vascular resistance index is the transpulmonary gradient divided by the cardiac index.87) . 95% CI 1. a non-traumatic cause of the ARDS. ≥12 mmHg) or pulmonary vascular resistance index (ie. there is general agreement that improvement of oxygenation during the early ICU course correlates with survival . in patients with acute lung injury. Similarly.
anxiety. particularly with caregivers [47. The persistent nature of this abnormality was demonstrated by a prospective cohort study that followed 109 survivors of ARDS for five years . Whether this abnormal exercise endurance is due.) Packed red blood cell transfusion – Patients who receive packed red blood cell transfusions may have an increased likelihood of death (odds ratio 1. Such problems appear to be common. pervasive memories of critical care.46-52]. in part.68. Organization of the ICU – Patients cared for in an ICU that mandates transfer to an intensivist or co-management by an intensivist may have a decreased likelihood of death (odds ratio 0.7) . Examples include new physical disabilities. with one prospective cohort study estimating that the incidences of depressive symptoms and impaired physical function were 40 and 66 percent.48].10 per unit transfused. section on 'Glucocorticoids'.280. 95% CI 1.17) [16. as well as imaging abnormalities. and five years was 66. This was demonstrated by the ARDSNet low tidal volume trial. to decreased lung function is uncertain due to conflicting data.) Despite these abnormalities. respectively. Numerous studies have suggested that there is persistent impairment of lung function following the acute illness . and changes to relationships. severity of illness. and being in an ICU that does not mandate care by an intensivist. but the research may lead to new preventative and therapeutic strategies in the future. and ventilator strategy (adjusted odds ratio 0.
Fluid balance – A positive fluid balance may be associated with higher mortality [37. section on 'Outcomes'.
MORBIDITY AMONG SURVIVORS — Survivors of ARDS frequently have persistent.50. The practical utility of these observations is uncertain. 67. abnormal exercise endurance [41-47]. three. respectively. packed red blood cell transfusions. impaired neurocognitive function.39]. A constellation of other physical and psychological problems. while others have found little or no impairment [47. and 76 percent of predicted. In the prospective cohort study described above. 77 percent of those who were working at the time of their
. which found that a negative fluid balance at day 4 was associated with decreased mortality compared to a positive fluid balance.53-0. depression. 95% CI 0. 95% CI 1.89) .and outcome from ARDS .) Treatment with glucocorticoids – Patients who received glucocorticoids prior to the onset of ARDS may have an increased likelihood of death (odds ratio 4. The six minute walking distance at one. section on 'Fluid management'. (See "Supportive care and oxygenation in acute respiratory distress syndrome". (See "Novel therapies for the acute respiratory distress syndrome".38]. 95% CI 0. most survivors are able to return to work. can occur after the acute illness [43. many as long as five years after ICU discharge .53-56]. Treatment-related — Treatment-related predictors of mortality include a positive fluid balance.89) . glucocorticoid therapy prior to the onset of ARDS.04-1.65. after adjustment for factors such as age. (See "Management and prognosis of patients requiring prolonged mechanical ventilation".47-14. during the two years following acute lung injury .
while 17 percent did unpaid work within the home and six percent became full-time students .6 for more than 24 hours [57. mean pulmonary artery pressure. Beyond the Basics patient education pieces are longer. A better functional outcome at one year correlates with the absence of steroid treatment. absence of illness acquired during the ICU stay. at the 5th to 6th grade reading level. easy-to-read materials. more sophisticated. positive end-expiratory pressure (PEEP). ―The Basics‖ and ―Beyond the Basics. decreased compliance. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Baseline — Normal lung function requires that dry. and they answer the four or five key questions a patient might have about a given condition. The normal pulmonary capillary endothelium is selectively permeable: fluid crosses the membranes under the control of hydrostatic and oncotic forces. while serum proteins remain intravascular.‖ The Basics patient education pieces are written in plain language.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials. and more detailed.59]. There is no known correlation between ventilatory strategies and either long-term pulmonary function or health-related quality of life [43. and increased pulmonary arterial pressure. This is interrupted by lung injury. and rapid resolution of multiple organ failure and lung injury . causing excess fluid in both the interstitium and alveoli. We encourage you to print or e-mail these topics to your patients.)
Basics topics (see "Patient information: Adult respiratory distress syndrome (The Basics)")
PATHOPHYSIOLOGY — Healthy lungs regulate the movement of fluid to maintain a small amount of interstitial fluid and dry alveoli. Consequences include impaired gas exchange. initial intrapulmonary shunt fraction. and requirement of an FiO2 >0. Most of those who returned to work did so within two years after ICU discharge.acute illness returned to work. Abnormal lung function one year after recovery correlates with the following factors measured during the acute illness: lowest static thoracic compliance. although many required a gradual transition back to work.58]:
Persistent symptoms one year after recovery correlate with the duration of mechanical ventilation and the lowest static thoracic compliance during the acute illness . patent alveoli be closely situated to appropriately perfused capillaries (picture 1) .57. Here are the patient education articles that are relevant to this topic. (You can also locate patient education articles on a variety of subjects by searching on ―patient info‖ and the keyword(s) of interest.58]. Several studies have sought factors during the acute illness that predict long-term sequelae [44.48.
. These articles are best for patients who want a general overview and who prefer short.
IL-6. (See "Oxygenation and mechanisms of hypoxemia". Consequences — Lung injury has numerous consequences including impairment of gas exchange.rc (πmv . A simplified version of the equation is: Q = K x [(Pmv . overwhelming the lymphatics .) The balance of hydrostatic and oncotic forces normally allows small quantities of fluid into the interstitium. rc represents the reflection coefficient of the capillary barrier. A high minute volume is generally needed to maintain a normal arterial carbon dioxide tension (PaCO2). and πpmv the oncotic pressure in the perimicrovascular compartment. and increased pulmonary arterial pressure. K the permeability of the endothelial membrane.πpmv)] where Q represents the net transvascular flow of fluid. while increased physiologic dead space impairs carbon dioxide elimination [27.28]. but three mechanisms prevent alveolar edema (figure 1A-D) :
Retained intravascular protein maintains an oncotic gradient favoring reabsorption The interstitial lymphatics can return large quantities of fluid to the circulation Tight junctions between alveolar epithelial cells prevent leakage into the air spaces
Injury — ARDS is a consequence of an alveolar injury producing diffuse alveolar damage (picture 2 and picture 3) . It is a consequence of the stiffness of poorly or non-aerated lung. (See "Pathophysiology and etiology of edema in adults". These cytokines recruit neutrophils to the lungs. Damage to the capillary endothelium and alveolar epithelium allows protein to escape from the vascular space. reactive oxygen species and proteases) that damage the capillary endothelium and alveolar epithelium [13. Even small tidal volumes can exceed the lung's inspiratory capacity and cause a dramatic rise in airway pressures . resulting in alveolar collapse. The result is that the air spaces fill with bloody.) Decreased lung compliance – Decreased pulmonary compliance is one of the hallmarks of ARDS . πmv the oncotic pressure in the circulation.20-24]. where they become activated and release toxic mediators (eg. decreased lung compliance.
.Ppmv) . although hypercapnia is uncommon. In addition.The Starling equation describes the forces that direct fluid movement between the vessels and the interstitium . The oncotic gradient that favors resorption of fluid is lost and fluid pours into the interstitium. rather than the pressure-volume characteristics of residual functioning lung units . Ppmv the hydrostatic pressure in the perimicrovascular space. functional surfactant is lost. The injury causes release of pro-inflammatory cytokines such as tumor necrosis factor. and IL-8 [14-19]. The ability to upregulate alveolar fluid clearance may also be lost . proteinaceous edema fluid and debris from degenerating cells. Pmv the hydrostatic pressure within the lumen of the microvessels. interleukin (IL)-1.
Impaired gas exchange – Impaired gas exchange in ARDS is primarily due to ventilation-perfusion mismatching: physiologic shunting causes hypoxemia.
predisposing the lung to oxidative injury [50. epidemiology. squamous metaplasia.54].36]. the validity of the assumption that different inciting events cause a similar pattern of lung injury and similar clinical features has been questioned because numerous studies have found more severe reductions in lung compliance and less responsiveness to positive end-expiratory pressure (PEEP) when the ARDS was due to a pulmonary process than when it was due to an extrapulmonary precipitant. The clinical importance of PH in most patients with ARDS is uncertain. ETIOLOGIES AND PREDISPOSING FACTORS — ARDS has traditionally been conceptualized as a pattern of lung injury and clinical manifestations that can be caused by a variety of insults. Some patients progress to a fibrotic stage.48. but it is associated with an increased risk of death [35. interstitial infiltration by myofibroblasts. a proliferative stage develops.49]. chronic alcohol abuse may increase the risk of ARDS by enhancing inappropriate leukocyte adhesion to endothelial cells . proliferation of type II alveolar cells. characterized by resolution of pulmonary edema.
Pulmonary hypertension – Pulmonary hypertension (PH) occurs in up to 25 percent of patients with ARDS who undergo mechanical ventilation [31-33]. compared to 31 percent among patients who did not chronically abuse alcohol. and prognosis". and cyst formation. The incidence of ARDS among patients who chronically abuse alcohol was 70 percent. characterized by diffuse alveolar damage. More than 60 possible causes of ARDS have been identified and other potential causes continue to emerge as adverse pulmonary reactions to new therapies are observed (table 1). have also been identified. It should be the first etiology considered whenever ARDS develops in a patient who is predisposed to serious infection or in association with a new fever or hypotension. However. and early deposition of collagen. vascular compression by positive airway pressure. A possible explanation for these findings is that alcoholism may decrease the concentration of glutathione in the epithelial lining fluid.
. PH severe enough to cor pulmonale is rare. Causes include hypoxic vasoconstriction. This was illustrated by a prospective cohort study that determined the incidence of ARDS in 220 patients with septic shock .38]. After approximately seven to ten days. PATHOLOGIC STAGES — Patients with ARDS tend to progress through three relatively discrete pathologic stages (figure 2) . (See "Sepsis and the systemic inflammatory response syndrome: Definitions.) The risk of developing ARDS may be particularly high among septic patients with a history of alcoholism [50-52]. only a few common causes account for most cases of ARDS [8. However.53. diffuse fibrosis. airway collapse. parenchymal destruction. such as sepsis [40-43].45. Alternatively.44-47]. hypercarbia.
Increased airways resistance (Raw) is also a feature of ARDS. Sepsis — Sepsis is the most common cause of ARDS [44. but probably can't cause ARDS. The initial stage is the exudative stage. Factors that may predispose a patient to develop ARDS. and pulmonary vasoconstrictors . characterized by obliteration of normal lung architecture. although its clinical significance is uncertain [37.
Massive transfusion — Transfusion of more than 15 units of red blood cells is a risk factor for the development of ARDS . Massive traumatic tissue injury may directly precipitate or predispose a patient to ARDS [63. The unexpected development of ARDS may be the only indication that an intubated patient has developed a tracheoesophageal fistula. and healthcare-associated pneumonia in adults".46. Pneumonia — Community acquired pneumonia is probably the most common cause of ARDS that develops outside of the hospital . pathogenesis. Fat embolism after long bone fractures. and microbiology of community-acquired pneumonia in adults" and "Diagnostic approach to community-acquired pneumonia in adults". it does not appear to independently increase the risk of death . (See "Massive blood transfusion".66].) Sepsis may be the most common cause of ARDS that develops several days or more after severe trauma or burns. In this situation. Staphylococcus aureus. and other enteric gram negative bacteria are the most commonly implicated pathogens. and diagnosis of hospital-acquired. enteric gram negative organisms. Legionella pneumophila.) Severe trauma — ARDS is a complication of severe trauma. (See "Epidemiology. There are several situations during which ARDS seems to be particularly common following trauma :
Bilateral lung contusion following blunt trauma . (See "Fat embolism syndrome". Transfusion of smaller volumes of packed red blood cells may also increase the risk of developing ARDS. and a variety of respiratory viruses [61. (See "Epidemiology. This complication has decreased since immobilization for transport to the hospital became routine . This is a rare complication of intubation.56]. This suggests that gastric enzymes and small food particles also contribute to the lung injury. Pneumocystis jirovecii (formerly called Pneumocystis carinii).)
. Pseudomonas aeruginosa. however. ventilator-associated. pathogenesis. It was initially suggested that aspirated contents had to have a pH less than 2. ARDS typically appears 12 to 48 hours after the trauma.
Although ARDS can contribute to the length of critical illness following severe trauma. It is unknown whether the transfusion injures the lungs or the need for massive transfusion identifies patients who are at high risk for ARDS from other causes . microbiology. more recent animal studies have shown that aspiration of non-acidic gastric contents can also cause widespread damage to the lungs .62].) Nosocomial pneumonias can also progress to ARDS.Aspiration — Observational evidence indicates that ARDS will develop in approximately one-third of hospitalized patients who have a recognized episode of aspiration of gastric contents [44. Staphylococcus aureus. Common pathogens include Streptococcus pneumoniae . as well as increasing the risk of mortality among patients with established ARDS .5 to cause severe lung injury . Trauma-related ARDS has a significantly better prognosis than ARDS that is not related to trauma .
nitrofurantoin). Drugs that have been implicated include aspirin. although not all studies support this observation . in which seven percent of the cohort developed ARDS. (See "Primary lung graft dysfunction". resulting in a negative predictive value (ie. acute pancreatitis . lung transplant recipients are prone to primary graft failure. engraftment syndrome. but does not cause ARDS . Outside of the operating room.86]. occasionally precipitate ARDS after therapeutic doses.72]. the percent of patients with a LIPS <4 who will not develop ARDS) of 97 percent . protamine.75]. sepsis. phenothiazines. Radiologic contrast media can also provoke ARDS in susceptible individuals . (See "Transfusion-related acute lung injury (TRALI)". pneumonectomy . cardiopulmonary bypass [85. Insertion-deletion polymorphisms associated with the angiotensin converting enzyme (ACE) gene have also been suggested as a possible risk factor for ARDS . respiratory distress becomes apparent within six hours of completion of the transfusion. This devastating form of ARDS is attributed to imperfect preservation of the transplanted lung.92].) Hematopoietic stem cell transplant patients are at risk for ARDS due to a variety of infectious and noninfectious causes.Transfusion-related acute lung injury — Transfusion of even one unit of a plasmacontaining blood product sometimes causes ARDS [71. (See "Air embolism". Studies that link mutations in the surfactant protein B (SP-B) gene to an increased risk of ARDS support this notion [79. Other risk factors — Other possible risk factors for ARDS include cigarette smoking [83. The mechanism in incompletely understood and may be multifactorial.90]. including certain chemotherapeutic agents. Genetic determinants — It seems likely that there are genetic determinants that increase an individual's risk of developing ARDS. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation" and "Pulmonary complications after autologous hematopoietic cell transplantation". By definition. The lung injury appears to be partly related to the inflammation associated with chemoradiation conditioning regimens. and tricyclic antidepressants [74.) Lung and hematopoietic stem cell transplantation — During the first two or three days after surgery.) Drugs and alcohol — ARDS can occur following an overdose. trauma).91. the most common portal of entry for the air is a central venous catheter left open to the air . and diffuse alveolar hemorrhage . Noninfectious insults include idiopathic pneumonia syndrome. Fresh frozen plasma. A LIPS >4 predicted ARDS with a sensitivity and specificity of 69 and 78
. and packed red blood cell transfusions have all been implicated. This was demonstrated by a prospective cohort study of 5584 patients. obesity [89. opioids.80].) Venous air embolism can occasionally cause ARDS. as well as T cell alloreactivity. since only a small proportion of the patients who are exposed to typical insults actually develop ARDS . cocaine. (See "Drowning (submersion injuries)". platelet. and near drowning [56. Alcohol abuse increases the risk of ARDS due to other causes (eg.84]. Idiosyncratic reactions to other drugs (eg.) Lung injury prediction score — The lung injury prediction score (LIPS) identifies patients who are unlikely to develop ARDS.
multiple fractures (1. ―The Basics‖ and ―Beyond the Basics. using a retrospective derivation and prospective validation cohorts reported similar results . traumatic brain injury (2 points). causing excess fluid in both the interstitium and alveoli.35 or >4 L/min (2 points).) Patients with ARDS tend to progress through three relatively discrete pathologic stages: the exudative stage.
. chemotherapy (1 point). alcohol abuse (1 point). These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. hypoalbuminemia (1 point). aspiration (2 points). easy-to-read materials. The LIPS is the sum of the points assigned for each of the following predisposing conditions: shock (2 points). orthopedic spine surgery (1. The diagnostic criteria for ARDS are provided separately.) Healthy lungs regulate the movement of fluid to maintain a small amount of interstitial fluid and dry alveoli. oxyhemoglobin saturation <95 percent (1 point).)
Basics topics (see "Patient information: Adult respiratory distress syndrome (The Basics)")
SUMMARY AND RECOMMENDATIONS
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by the acute onset of bilateral alveolar infiltrates and hypoxemia. A smaller study.5 points). cardiac surgery (2.5 points). and fibrotic stage. 1 point). Consequences include impaired gas exchange. fraction of inspired oxygen >0. pneumonia (1. acute abdominal surgery (2 points). proliferative stage. Here are the patient education articles that are relevant to this topic.35. tachypnea >30 breaths/min (1. acidosis (pH <7. sepsis (1 point). and more detailed. 1. obesity (BMI >30. at the 5th to 6th grade reading level. (See 'Pathologic stages' above.) More than 60 possible causes of ARDS have been identified and other potential causes continue to emerge as adverse pulmonary reactions to new therapies are observed. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials.(See 'Pathophysiology' above. (See "Acute respiratory distress syndrome: Clinical features and diagnosis". aortic vascular surgery (3. near drowning (2 points).5 points). and increased pulmonary arterial pressure. smoke inhalation (2 points).5 points). more sophisticated. We encourage you to print or e-mail these topics to your patients.5 points). and diabetes mellitus (-1 point). section on 'Diagnostic criteria'. decreased compliance. In patients with ARDS. this regulation is interrupted by lung injury. (You can also locate patient education articles on a variety of subjects by searching on ―patient info‖ and the keyword(s) of interest. only a few common causes account for most cases of ARDS.5 points). However.‖ The Basics patient education pieces are written in plain language.5 points). and they answer the four or five key questions a patient might have about a given condition. Beyond the Basics patient education pieces are longer.5 points). respectively. lung contusion (1. These articles are best for patients who want a general overview and who prefer short.percent.
et al. Lancet 1967. 2:319. Artigas A. 2. Bigelow DB. Brigham KL. Bernard GR.Factors that may predispose a patient to develop ARDS have also been identified.
. Levine BE. Petty TL.) Use of UpToDate is subject to the Subscription and License Agreement. Ashbaugh DG. (See 'Etiologies and predisposing factors' above. The American-European Consensus Conference on ARDS. Acute respiratory distress in adults. REFERENCES 1.