'''Acute respiratory distress syndrome''' ('''ARDS'''), originally known as '''adult respiratory distress syndrome''' (to contrast with [[infant respiratory distress syndrome|neonatal respiratory distress syndrome]]) is a serious and potentially life-threatening inflammatory lung condition that develops rapidly (usually within 24 to 48 hours) in the setting of sepsis, toxic exposures, adverse drug reactions, trauma, or other critical illnesses. ARDS is characterized by inflammation of the lung parenchyma resulting in increased permeability of the [[Alveolar-capillary barrier|alveolar-capillary membrane]], non-cardiogenic [[pulmonary edema]], impaired gas exchange, and decreased lung [[Compliance (physiology)|compliance]].
'''Acute respiratory distress syndrome''' ('''ARDS'''), originally known as '''adult respiratory distress syndrome''' (to contrast with [[infant respiratory distress syndrome|''neonatal respiratory distress syndrome'']]) is a serious and potentially life-threatening [[inflammation|inflammatory]] lung condition that develops rapidly (usually within 24 to 48 hours) in the setting of [[sepsis]], [[toxin|toxic exposures]], [[adverse drug reaction|adverse drug reactions]], [[trauma]], or other critical illnesses. ARDS is characterized by [[inflammation]] of the lung [[parenchyma]] resulting in increased [[permeability]] of the [[Alveolar-capillary barrier|alveolar-capillary membrane]], non-cardiogenic [[pulmonary edema]], impaired [[gas exchange]], and decreased lung [[Compliance (physiology)|compliance]].
The vast majority of patients with ARDS are managed in an [[intensive care unit]], and nearly all will require [[Mechanical ventilation indications for use|mechanical ventilation]] at some point during the course of their illness and recovery. ARDS may be categorized as ''mild'', ''moderate'', or ''severe'' based on the degree to which oxygenation is impaired; however, all levels of severity carry a high mortality rate if appropriate measures to improve oxygenation and minimize the risk of further lung injury are not taken.<ref name="pmid22797452">{{cite journal| author=ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E et al.| title=Acute respiratory distress syndrome: the Berlin Definition. | journal=JAMA | year= 2012 | volume= 307 | issue= 23 | pages= 2526-33 | pmid=22797452 | doi=10.1001/jama.2012.5669 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797452 }} </ref>
The vast majority of patients with ARDS are managed in an [[intensive care unit|intensive care unit (ICU)]], where many will require [[Mechanical ventilation indications for use|mechanical ventilation]] at some point during the course of their illness and recovery. ARDS may be categorized as ''mild'', ''moderate'', or ''severe'' based on the degree to which [[oxygenation]] is impaired; however, all levels of severity carry a high [[mortality rate]] if appropriate measures to improve oxygenation and minimize the risk of further lung injury are not taken.<ref name="pmid22797452">{{cite journal| author=ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E et al.| title=Acute respiratory distress syndrome: the Berlin Definition. | journal=JAMA | year= 2012 | volume= 307 | issue= 23 | pages= 2526-33 | pmid=22797452 | doi=10.1001/jama.2012.5669 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797452 }} </ref>
==Historical Perspective==
==Historical Perspective==
Although the first pathologic descriptions of what was likely ARDS date back to the 19th century, our understanding of the distinct pathophysiologic features of ARDS evolved alongside the development of medical technologies that facilitated a more in-depth study of the syndrome. The advent of [[projectional radiography|radiography]] permitted visualization of the bilateral pulmonary infiltrates (originally termed ''double [[pneumonia]]''), while the development of [[ABG|arterial blood gas measurement]] and [[mechanical ventilation|positive-pressure mechanical ventilation]] allowed for identification of the impaired oxygenation and reduced lung compliance that are now recognized as central features of ARDS.<ref name="pmid16020801">{{cite journal| author=Bernard GR| title=Acute respiratory distress syndrome: a historical perspective. | journal=Am J Respir Crit Care Med | year= 2005 | volume= 172 | issue= 7 | pages= 798-806 | pmid=16020801 | doi=10.1164/rccm.200504-663OE | pmc=2718401 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16020801 }} </ref>
Although the pathologic features of ARDS were first documented in the 19th century, the modern definition of ARDS did not arise until the 1960s. In 2012, the Berlin Definition of ARDS became the standard diagnostic criteria and definition of the syndrome.
Ashbaugh and colleagues published he first description of what is now widely recognized as ARDS in a case series of 12 patients with rapidly progressive respiratory failure with bilateral pulmonary infiltrates and profound hypoxemia following trauma or infection in ''The Lancet'' in 1967.<ref name="pmid4143721">{{cite journal| author=Ashbaugh DG, Bigelow DB, Petty TL, Levine BE| title=Acute respiratory distress in adults. | journal=Lancet | year= 1967 | volume= 2 | issue= 7511 | pages= 319-23 | pmid=4143721 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4143721 }} </ref> The clinical syndrome was called the "adult respiratory distress syndrome" (ARDS) to distinguish it from the respiratory distress syndrome of infancy due to [[hyaline membrane disease]], although the ''A'' in ARDS was later changed from ''acute'' to ''adult'' once it was recognized that the syndrome could also present in infants as a distinct entity from hyaline membrane disease.
==Classification==
==Classification==
The current ARDS diagnostic criteria (commonly referred to as the ''Berlin Criteria'' or ''Berlin Definition'') were established by the ARDS Definition Task Force in 2012. [[#Diagnostic Criteria|The Berlin Criteria]] classify ARDS as ''mild'', ''moderate'', and ''severe'' based on the degree of oxygenation impairment and serve as a means of risk-stratifying patients.<ref name="pmid22797452">{{cite journal| author=ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E et al.| title=Acute respiratory distress syndrome: the Berlin Definition. | journal=JAMA | year= 2012 | volume= 307 | issue= 23 | pages= 2526-33 | pmid=22797452 | doi=10.1001/jama.2012.5669 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797452 }} </ref>
ARDS may be classified according to [[Acute respiratory distress syndrome diagnostic criteria|2012 Berlin Definition]] into three subtypes: ''mild'', ''moderate'', and ''severe''. These levels of severity are based on the degree to which [[oxygenation]] relative to the amount of [[supplemental oxygen]] is being delivered to the patient via [[positive pressure ventilation]].<ref name="pmid22797452">{{cite journal| author=ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E et al.| title=Acute respiratory distress syndrome: the Berlin Definition. | journal=JAMA | year= 2012 | volume= 307 | issue= 23 | pages= 2526-33 | pmid=22797452 | doi=10.1001/jama.2012.5669 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797452 }} </ref>
==Pathophysiology==
==Pathophysiology==
ARDS typically develops within 24 to 48 hours of the provoking illness or injury and is classically divided into three phases:<br>
ARDS is a syndrome of [[inflammation]] and increased [[permeability]] with the lung parenchyma that leads to loss of [[pneumocyte|type I pneumocytes]], impaired [[gas exchange]], inappropriate [[cell proliferation]] within [[alveolus|alveoli]], and, in survivors, [[fibrosis]].
*'''Exudative phase (''within 24-48 hours'')''': Systemic inflammation results in increased alveolar capillary permeability and leads to the formation of hyaline membranes along alveolar walls, accumulation of proteinaceous exudate within the alveolar air spaces (''non-cardiogenic pulmonary edema''), and extravasation of inflammatory cells (predominantly [[neutrophils|neutrophils]] and [[macrophages|macrophages]]) into the lung parenchyma, leading to extensive alveolar damage and sometimes hemorrhage into alveoli
*'''Proliferative phase (''within 5-7 days'')''': Fibroblast proliferation, collagen deposition, and early fibrotic changes are observed within the pulmonary interstitium as alveolar exudate and hyaline membranes begin to be absorbed
*'''Fibrotic phase (''within several weeks'')''': Most patients with ARDS will develop some degree of pulmonary fibrosis, of which at least one-quarter will go on to develop a restrictive ventilatory defect on pulmonary function tests<ref name="pmid23520315">{{cite journal| author=Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP| title=The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. | journal=Eur Respir J | year= 2014 | volume= 43 | issue= 1 | pages= 276-85 | pmid=23520315 | doi=10.1183/09031936.00196412 | pmc=4015132 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23520315 }} </ref>; the development and extent of pulmonary fibrosis in ARDS correlates with an increased mortality risk<ref name="pmid7813276">{{cite journal| author=Martin C, Papazian L, Payan MJ, Saux P, Gouin F| title=Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients. | journal=Chest | year= 1995 | volume= 107 | issue= 1 | pages= 196-200 | pmid=7813276 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7813276 }} </ref>
===Genetic Susceptibility===
The role of genetics in the development of ARDS is an ongoing area of research. While studies have demonstrated associations between certain genetic factors (including [[single-nucleotide polymorphisms|single-nucleotide polymorphisms]] and allelic variants of [[angiotensin-converting enzyme|angiotensin-converting enzyme]]<ref name="pmid16484896">{{cite journal| author=Jerng JS, Yu CJ, Wang HC, Chen KY, Cheng SL, Yang PC| title=Polymorphism of the angiotensin-converting enzyme gene affects the outcome of acute respiratory distress syndrome. | journal=Crit Care Med | year= 2006 | volume= 34 | issue= 4 | pages= 1001-6 | pmid=16484896 | doi=10.1097/01.CCM.0000206107.92476.39 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16484896 }} </ref><sup>,</sup><ref name="pmid23364437">{{cite journal| author=Cardinal-Fernández P, Ferruelo A, El-Assar M, Santiago C, Gómez-Gallego F, Martín-Pellicer A et al.| title=Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis. | journal=Shock | year= 2013 | volume= 39 | issue= 3 | pages= 255-60 | pmid=23364437 | doi=10.1097/SHK.0b013e3182866ff9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23364437 }} </ref>) and increased susceptibility to developing ARDS, the nature and implications of these relationships remain uncertain.<ref name="pmid23048207">{{cite journal| author=Tejera P, Meyer NJ, Chen F, Feng R, Zhao Y, O'Mahony DS et al.| title=Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin. | journal=J Med Genet | year= 2012 | volume= 49 | issue= 11 | pages= 671-80 | pmid=23048207 | doi=10.1136/jmedgenet-2012-100972 | pmc=3654537 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23048207 }} </ref>
===Pathology===
*On gross pathology, the lungs are firm, boggy, and dusky, and they typically weigh more than healthy lungs due to edema
*On microscopic histopathological analysis, the lung parenchyma demonstrates [http://www.wikidoc.org/index.php/File:Hyaline_membranes_-_very_high_mag.jpg hyaline membranes] lining the alveolar air spaces, edema fluid within alveoli and the interstitium, shedding of type I pneumocytes and proliferation of type II pneumocytes, infiltration of polymorphonuclear and other inflammatory cells into the interstitial and alveolar compartments, thrombosis and obliteration of pulmonary capillaries, and occasionally hemorrhage into alveoli
:*Features specific to the underlying disease process (e.g., [[pneumonia|bacterial pneumonia]] or [[aspiration pneumonitis|aspiration pneumonitis]]) are often seen as well
:*As ARDS progresses, alveolar infiltrates are reabsorbed and the inflammatory milieu is replaced by increased collagen deposition and proliferating fibroblasts, culminating in interstitial fibrosis
[[File:Hyaline membranes - very high mag.jpg|thumb|Hyaline membranes - very high magnification]]
==Causes==
==Causes==
ARDS may occur as the result of either a ''direct'' or ''indirect'' insult to the lungs:
ARDS may be caused by either direct or indirect insults to the lung. Common causes of ARDS include [[sepsis]], [[aspiration pneumonia|aspiration pneumonitis]], and [[transfusion-related acute lung injury|transfusion-related acute lung injury (TRALI)]].<ref name="pmid7091520">{{cite journal| author=Pepe PE, Potkin RT, Reus DH, Hudson LD, Carrico CJ| title=Clinical predictors of the adult respiratory distress syndrome. | journal=Am J Surg | year= 1982 | volume= 144 | issue= 1 | pages= 124-30 | pmid=7091520 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7091520 }} </ref>
Sepsis is the most common cause of ARDS, followed by aspiration pneumonitis and [[transfusion-related acute lung injury]]<ref name="pmid7091520">{{cite journal| author=Pepe PE, Potkin RT, Reus DH, Hudson LD, Carrico CJ| title=Clinical predictors of the adult respiratory distress syndrome. | journal=Am J Surg | year= 1982 | volume= 144 | issue= 1 | pages= 124-30 | pmid=7091520 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7091520 }} </ref>
==Differentiating ARDS from Other Diseases==
Certain medical comorbidities (e.g., [[chronic liver disease|chronic liver]] or [[chronic kidney disease|kidney disease]], [[alcoholism]], [[Human Immunodeficiency Virus (HIV)|infection with the human immunodeficiency virus]], [[organ transplantation|prior organ transplantation]]) predispose to the development of ARDS, and the risk for developing ARDS increases along with the number of acute insults (e.g., pneumonia and pancreatitis versus pancreatitis alone).
ARDS must be differentiated from other diseases that cause [[hypoxemia]] and pulmonary infiltrates, such as [[pneumonia]], [[pulmonary contusion]], [[pulmonary edema]], and [[pulmonary hemorrhage]]. Prior to the development of the [[Acute respiratory distress syndrome diagnostic criteria|Berlin Definition]] in 2012, a greater emphasis was placed on excluding other potential illnesses prior to making a diagnosis of ARDS. While it is important to recognize and treat and underlying cause of the patient's impaired [[ventilation]] and [[hypoxemia]], this search for potential etiologies should not delay any focused efforts to improve [[oxygenation]] and [[ventilation]].
==Differentiating ARDS from other Diseases==
Prior to the development of the Berlin Definition in 2012, a greater emphasis was placed on excluding other potential illnesses prior to making a diagnosis of ARDS. While it is important to recognize and treat and underlying cause of the patient's impaired ventilation and hypoxemia, this search for potential etiologies should not delay any efforts to improve oxygenation and ventilation.
On chest X-ray, the bilateral, non-cardiogenic pulmonary infiltrates of ARDS may appear similar to those of cardiogenic (''hydrostatic'') [[pulmonary edema]]. Therefore, it is necessary to formally assess cardiac function and volume status if ARDS is suspected but no clear precipitating insult (e.g., sepsis, trauma, toxic inhalation) can be identified. The preferred methods for making this assessment in the ICU are:
*[[Echocardiogram|'''Echocardiography''']] to assess heart function
*[[Central venous catheter|'''Central venous catheterization''']] to measure [[central venous pressure]]
*[[Swan-Ganz catheter|'''Pulmonary artery (Swan-Ganz) catheterization''']] to measure right-sided heart pressures and [[pulmonary capillary wedge pressure]] (a surrogate of [[left atrial pressure|''left atrial pressure'']])
Because ARDS is a clinical syndrome that, by definition, occurs in the setting of another illness or insult, identification and treatment of the underlying cause of ARDS is essential. Some standard components of this workup include:
*Chest X-ray
*[[Arterial blood gas|Arterial blood gases]]
*Complete blood count with differential
*Comprehensive metabolic panel (serum electrolytes, blood urea nitrogen and creatinine, and tests of liver function)
*Coagulation markers ([[partial thromboplastin time]] and [[prothrombin time]] with [[international normalized ratio]])
*Blood, sputum, and urine cultures
*Serum [[lactate]]
Additional testing should be guided by clinical suspicion and the patient's medical history. These may include such tests as:
*Tests for atypical pathogens that may cause pneumonia, for example:
:*[[Legionella pneumophila|''Legionella pneumophila'']] culture and urine antigen testing
:*[[Mycoplasma pneumoniae|''Mycoplasma pneumoniae'']] culture and antibody titers
:*[[Pneumocystis jirovecii|''Pneumocystis jirovecii'']] sputum silver stain and culture
:*[[Mycobacterium tuberculosis|''Mycobacterium tuberculosis'']] sputum smear and culture
==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence of ARDS in the United States is estimated at around 75 cases per 100,000 person-years, which amounts to roughly 150,000 new cases per year.<ref name="pmid3410685">{{cite journal| author=Lucas AC| title=The future of radiological instrumentation. | journal=Health Phys | year= 1988 | volume= 55 | issue= 2 | pages= 191-5 | pmid=3410685 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3410685 }} </ref> There is substantial variance in the rates of ARDS between different countries and geographic regions due to factors such as mean life expectancy, prevalence of different risk factors and comorbidities, and access to health care.
The incidence of ARDS in the United States is estimated at approximately 75 cases per 100,000 individuals, which amounts to roughly 150,000 new cases annually.<ref name="pmid3410685">{{cite journal| author=Lucas AC| title=The future of radiological instrumentation. | journal=Health Phys | year= 1988 | volume= 55 | issue= 2 | pages= 191-5 | pmid=3410685 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3410685 }} </ref> There is substantial variance in the rates of ARDS between different countries and geographic regions due to factors such as mean [[life expectancy]], prevalence of different [[risk factors]] and [[comorbidities]], and access to [[healthcare]].
===Age===
*Advanced age is a non-modifiable risk factor for the development of ARDS
===Gender===
*Some studies have suggested that women are slightly more likely than men to develop ARDS, however, the mortality rate may be slightly higher among men than women<ref name="pmid12163776">{{cite journal| author=Moss M, Mannino DM| title=Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979- 1996). | journal=Crit Care Med | year= 2002 | volume= 30 | issue= 8 | pages= 1679-85 | pmid=12163776 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12163776 }} </ref><sup>,</sup><ref name="pmid21986736">{{cite journal| author=Heffernan DS, Dossett LA, Lightfoot MA, Fremont RD, Ware LB, Sawyer RG et al.| title=Gender and acute respiratory distress syndrome in critically injured adults: a prospective study. | journal=J Trauma | year= 2011 | volume= 71 | issue= 4 | pages= 878-83; discussion 883-5 | pmid=21986736 | doi=10.1097/TA.0b013e31822c0d31 | pmc=3201740 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21986736 }} </ref>
===Race===
*There does not appear to be a racial predilection for ARDS, however, in the United States the mortality rate among African Americans with ARDS is higher than for whites<ref name="pmid12163776">{{cite journal| author=Moss M, Mannino DM| title=Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979- 1996). | journal=Crit Care Med | year= 2002 | volume= 30 | issue= 8 | pages= 1679-85 | pmid=12163776 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12163776 }} </ref>
==Risk Factors==
==Risk Factors==
Common risk factors in the development of ARDS are:
The most potent risk factor in the development of ARDS is [[chronic alcoholism]].<ref name="pmid8531287">{{cite journal| author=Moss M, Bucher B, Moore FA, Moore EE, Parsons PE| title=The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. | journal=JAMA | year= 1996 | volume= 275 | issue= 1 | pages= 50-4 | pmid=8531287 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8531287 }} </ref><ref name="pmid12682442">{{cite journal| author=Moss M, Burnham EL| title=Chronic alcohol abuse, acute respiratory distress syndrome, and multiple organ dysfunction. | journal=Crit Care Med | year= 2003 | volume= 31 | issue= 4 Suppl | pages= S207-12 | pmid=12682442 | doi=10.1097/01.CCM.0000057845.77458.25 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12682442 }} </ref> Other risk factors include [[elderly|advanced age]], [[smoking|cigarette smoke exposure]], and [[chronic liver disease]].
*Advanced age
*Chronic [[alcoholism]]
*[[Chronic liver disease]]
*[[Chronic kidney disease]]
*Cigarette smoke exposure
*[[Hypoalbuminemia|Hypoproteinemia]]<ref name="pmid11008971">{{cite journal| author=Mangialardi RJ, Martin GS, Bernard GR, Wheeler AP, Christman BW, Dupont WD et al.| title=Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis. Ibuprofen in Sepsis Study Group. | journal=Crit Care Med | year= 2000 | volume= 28 | issue= 9 | pages= 3137-45 | pmid=11008971 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11008971 }} </ref>
The association between chronic alcoholism and a higher risk of developing ARDS has been demonstrated in several research studies.<ref name="pmid8531287">{{cite journal| author=Moss M, Bucher B, Moore FA, Moore EE, Parsons PE| title=The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. | journal=JAMA | year= 1996 | volume= 275 | issue= 1 | pages= 50-4 | pmid=8531287 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8531287 }} </ref><sup>,</sup><ref name="pmid12682442">{{cite journal| author=Moss M, Burnham EL| title=Chronic alcohol abuse, acute respiratory distress syndrome, and multiple organ dysfunction. | journal=Crit Care Med | year= 2003 | volume= 31 | issue= 4 Suppl | pages= S207-12 | pmid=12682442 | doi=10.1097/01.CCM.0000057845.77458.25 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12682442 }} </ref> In one such study, patients with a history of alcohol abuse were roughly twice as likely to develop ARDS and experienced a mortality rate that was 36% higher than age-, sex-, and disease-matched patients without a history of alcohol abuse.<ref name="pmid8531287">{{cite journal| author=Moss M, Bucher B, Moore FA, Moore EE, Parsons PE| title=The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. | journal=JAMA | year= 1996 | volume= 275 | issue= 1 | pages= 50-4 | pmid=8531287 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8531287 }} </ref>
==Screening==
There are no screening tools for ARDS. The best way to make an early diagnosis of ARDS is to apply the [[Acute respiratory distress syndrome diagnostic criteria|diagnostic criteria]] to any patient with bilateral pulmonary infiltrates on [[chest x ray]], and new/worsening [[hypoxemia]] with an increasing [[Oxygen therapy|supplemental oxygen]] requirement in whom a [[Acute respiratory distress syndrome causes|potential cause]] or [[Acute respiratory distress syndrome risk factors|risk factor]] for ARDS exists.
== Natural History, Complications and Prognosis==
==Natural History, Complications, and Prognosis==
*ARDS typically occurs within the first week of the precipitating illness or trauma and usually progresses rapidly within the first 24 to 48 hours.
If left untreated, 70% of patients with ARDS may progress to [[mortality]].<ref name="pmid11056707">{{cite journal| author=Reynolds HN, McCunn M, Borg U, Habashi N, Cottingham C, Bar-Lavi Y| title=Acute respiratory distress syndrome: estimated incidence and mortality rate in a 5 million-person population base. | journal=Crit Care | year= 1998 | volume= 2 | issue= 1 | pages= 29-34 | pmid=11056707 | doi=10.1186/cc121 | pmc=28999 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11056707 }} </ref> Common complications to ARDS include [[weakness]], impaired [[spirometry|lung function]], and [[brain death]]. Prognosis for patients with ARDS is generally poor and varies based on the severity of illness, the precipitating insult, and medical comorbidities.
*The early clinical features of ARDS include:
:*Hypoxemia (a declining peripheral blood oxygen saturation [SpO<sub>2</sub>] on [[pulse oximetry]] or a declining partial pressure of oxygen [PaO<sub>2</sub>] on [[arterial blood gas]] analysis) requiring high concentrations of supplemental oxygen (i.e., a higher [[fraction of inspired oxygen]] [FIO<sub>2</sub>]) or positive pressure ventilation (i.e., a higher [[continuous positive airway pressure]] [CPAP] or a higher [[positive end-expiratory pressure]] [PEEP]) in order to maintain acceptable blood oxygenation
:*Tachypnea and labored breathing
:*Tachycardia
:*Signs or symptoms that suggest worsening of the underlying illness
*Left untreated, the mortality rate from ARDS is estimated to be upwards of 70%.<ref name="pmid11056707">{{cite journal| author=Reynolds HN, McCunn M, Borg U, Habashi N, Cottingham C, Bar-Lavi Y| title=Acute respiratory distress syndrome: estimated incidence and mortality rate in a 5 million-person population base. | journal=Crit Care | year= 1998 | volume= 2 | issue= 1 | pages= 29-34 | pmid=11056707 | doi=10.1186/cc121 | pmc=28999 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11056707 }} </ref> Long-term sequelae are more likely to develop among those who do not receive adequate treatment and include:
:*Significant weakness due to muscle atrophy, sometimes leading to lifelong physical disability
:*Impaired lung function
:*Chronic ventilator dependency
:*Pulmonary fibrosis
:*Psychiatric illness (e.g., [[post-traumatic stress disorder]] [PTSD], [[anxiety]], and [[depression]])
:*Cognitive impairment
*The most common complications of ARDS are those associated with a prolonged ICU stay:
:*Secondary or nosocomial infections (e.g., [[hospital-acquired pneumonia|ventilator-associated pneumonia]] [VAP] or [[Intravascular device related infections|central line-associated blood stream infection]] [CLABSI])
*Prognosis for patients with ARDS varies based on the severity of illness, the precipitating insult, and medical comorbidities:
:*The mortality rate among patients with ARDS due to trauma appears to be lower than among patients with ARDS due to sepsis<ref name="pmid20507948">{{cite journal| author=Sheu CC, Gong MN, Zhai R, Chen F, Bajwa EK, Clardy PF et al.| title=Clinical characteristics and outcomes of sepsis-related vs non-sepsis-related ARDS. | journal=Chest | year= 2010 | volume= 138 | issue= 3 | pages= 559-67 | pmid=20507948 | doi=10.1378/chest.09-2933 | pmc=2940067 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20507948 }} </ref>
:*The ARDS Definition Task Force calculated 90-day morality rates for mild, moderate, and severe ARDS as 27%, 32%, and 45%, respectively<ref name="pmid22797452">{{cite journal| author=ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E et al.| title=Acute respiratory distress syndrome: the Berlin Definition. | journal=JAMA | year= 2012 | volume= 307 | issue= 23 | pages= 2526-33 | pmid=22797452 | doi=10.1001/jama.2012.5669 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797452 }} </ref>
:*One study of patients diagnosed with ARDS in Maryland, United States, from 1992 through 1995 calculated an in-hospital mortality rate of 36% to 52%<ref name="pmid11056707">{{cite journal| author=Reynolds HN, McCunn M, Borg U, Habashi N, Cottingham C, Bar-Lavi Y| title=Acute respiratory distress syndrome: estimated incidence and mortality rate in a 5 million-person population base. | journal=Crit Care | year= 1998 | volume= 2 | issue= 1 | pages= 29-34 | pmid=11056707 | doi=10.1186/cc121 | pmc=28999 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11056707 }} </ref>
:*The 1-year mortality rate for patients with ARDS who survive to hospital discharge varies widely between different studies and is estimated to be anywhere from 11% to over 40%<ref name="pmid12594312">{{cite journal| author=Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F et al.| title=One-year outcomes in survivors of the acute respiratory distress syndrome. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 8 | pages= 683-93 | pmid=12594312 | doi=10.1056/NEJMoa022450 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12594312 }} </ref><sup>,</sup><ref name="pmid20384998">{{cite journal| author=Linko R, Suojaranta-Ylinen R, Karlsson S, Ruokonen E, Varpula T, Pettilä V et al.| title=One-year mortality, quality of life and predicted life-time cost-utility in critically ill patients with acute respiratory failure. | journal=Crit Care | year= 2010 | volume= 14 | issue= 2 | pages= R60 | pmid=20384998 | doi=10.1186/cc8957 | pmc=2887181 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20384998 }} </ref><sup>,</sup><ref name="pmid24435201">{{cite journal| author=Wang CY, Calfee CS, Paul DW, Janz DR, May AK, Zhuo H et al.| title=One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome. | journal=Intensive Care Med | year= 2014 | volume= 40 | issue= 3 | pages= 388-96 | pmid=24435201 | doi=10.1007/s00134-013-3186-3 | pmc=3943651 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24435201 }} </ref>
== Diagnosis ==
==Diagnosis==
===Diagnostic Criteria===
===Diagnostic Criteria===
The diagnosis of ARDS is made when the following diagnostic criteria are met:<ref name="pmid22797452">{{cite journal| author=ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E et al.| title=Acute respiratory distress syndrome: the Berlin Definition. | journal=JAMA | year= 2012 | volume= 307 | issue= 23 | pages= 2526-33 | pmid=22797452 | doi=10.1001/jama.2012.5669 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797452 }} </ref>
Established by the ARDS Definition Task Force in 2012, the Berlin Definition is the most current set of diagnostic criteria for ARDS.
{| class="wikitable"
|-
! colspan="2" style="text-align: center;" | '''Acute Respiratory Distress Syndrome – The Berlin Definition (2012)'''
|-
| '''Timing'''
| ❑ Within 1 week of a known clinical insult or new or worsening respiratory symptoms
|-
| '''Chest imaging''' <sup>'''a'''</sup>
| ❑ Bilateral opacities – not fully explained by effusions, lobar/lung collapse, or nodule
|-
| '''Origin of edema'''
| ❑ Respiratory failure not fully explained by cardiac failure or fluid overload <sup>'''b'''</sup>
| ❑ 200 mm Hg < PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 300 mmHg with PEEP or CPAP > 5 cm H<sub>2</sub>O <sup>'''d'''</sup>
|-
|
:''Moderate''
| ❑ 100 mm Hg < PaO<sub>2</sub>/FIO<sub>2</sub> ≤ 200 mm Hg with PEEP ≥ 5 cm H<sub>2</sub>O
|-
|
:''Severe''
| ❑ PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 100 mm Hg with PEEP ≥ 5 cm H<sub>2</sub>O
|-
! colspan="2" style="text-align: left;" |
:<span style="font-size:85%; line-height: 0.0em;"><sup>'''a'''</sup> ''[[X-ray]] or [[CT scan]] of the chest''</span><br>
:<span style="font-size:85%; line-height: 0.0em;"><sup>'''b'''</sup> ''Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present''</span><br>
:<span style="font-size:85%; line-height: 0.0em;"><sup>'''c'''</sup> ''If altitude is higher than 1000 m, the correction factor should be calculated as follows: PaO<sub>2</sub>/FIO<sub>2</sub> x (barometric pressure/760)''</span>
:<span style="font-size:85%; line-height: 0.0em;"><sup>'''d'''</sup> ''Positive pressure may be delivered noninvasively in the mild ARDS group''</span><br>
|}
=== Symptoms ===
Symptoms of ARDS are fairly nonspecific and typically include:
*[[Tachypnea]]
*[[Shortness of breath]]
*[[Tachycardia]]
*Symptoms associated with the underlying illness/trauma
=== Physical Examination ===
===History and Symptoms===
There are no physical exam findings specific to/pathognomonic of ARDS. The most notable physical exam findings tend to be those of the underlying illness/trauma.
The history of a patient with ARDS varies according to the underlying cause. The symptoms of ARDS are fairly nonspecific and typically include [[Tachypnea|rapid breathing]], [[shortness of breath]], and [[Tachycardia|rapid heartbeat]].
=== Laboratory Findings ===
The most important laboratory finding in ARDS is an arterial partial pressure of oxygen (PaO<sub>2</sub> that is inappropriately low relative to the fraction of inspired oxygen (FIO<sub>2</sub>) that is being administered to the patient. This is referred to as the PaO<sub>2</sub> to FIO<sub>2</sub> ratio (sometimes abbreviated as ''P/F ratio'') and is calculated by dividing the PaO<sub>2</sub> (in mm Hg) by the FIO<sub>2</sub> (as a decimal):
*A patient with a '''PaO<sub>2</sub> of 80 mm Hg''' who is mechanically ventilated with an '''FIO<sub>2</sub> of 35%''' and a '''PEEP of 5 cm H<sub>2</sub>O''' has a '''PaO<sub>2</sub>/FIO<sub>2</sub> ratio of 80/0.35 = 229''' (''mild ARDS'')
*A patient with a '''PaO<sub>2</sub> of 80 mm Hg''' who is mechanically ventilated with an '''FIO<sub>2</sub> of 50%''' and a '''PEEP of 5 cm H<sub>2</sub>O''' has a '''PaO<sub>2</sub>/FIO<sub>2</sub> ratio of 80/0.40 = 160''' (''moderate ARDS'')
*A patient with a '''PaO<sub>2</sub> of 80 mm Hg''' who is mechanically ventilated with an '''FIO<sub>2</sub> of 80%''' and a '''PEEP of 5 cm H<sub>2</sub>O''' has a '''PaO<sub>2</sub>/FIO<sub>2</sub> ratio of 80/0.80 = 100''' (''severe ARDS'')
===Physical Examination===
There are no physical exam findings specific to or [[pathognomonic]] of ARDS. The most notable physical exam findings tend to be those of the underlying illness or injury, as well as those of [[respiratory distress]], [[critical illness]], [[shock]], and [[end organ damage]].
Other notable laboratory findings are those that support an underlying diagnosis that led to the development of ARDS (e.g., positive blood cultures and an elevated white blood cell count in a septic patient or an elevated lipase in a patient with acute pancreatitis).
===Laboratory Findings===
Laboratory findings consistent with the diagnosis of ARDS include an [[PaO2|arterial partial pressure of oxygen (PaO<sub>2</sub>)]] that is inappropriately low relative to the [[FiO2|fraction of inspired oxygen (FIO<sub>2</sub>)]] that is being breathed by the patient. This is referred to as the PaO<sub>2</sub>/FIO<sub>2</sub> ratio (sometimes abbreviated as ''P/F ratio'') and is calculated by dividing the PaO<sub>2</sub> (in mmHg) by the FIO<sub>2</sub> (as a decimal rather than a percentage).
===Imaging Findings===
===Imaging Findings===
'''Chest X-ray''' is the preferred imaging modality in the assessment of ARDS. Classic findings of ARDS on chest X-ray include:[[File:ARDS-xray.jpg|thumb|ARDS on chest X-ray of a 65-year-old man who was admitted to the ICU with necrotizing fasciitis, sepsis, acute renal failure, and progressive respiratory failure requiring mechanical ventilation<ref name="ARDS on chest X-ray">Case courtesy of Associate Professor Frank Gaillard, M.D. "http://radiopaedia.org/cases/35985"</ref>]]
====Electrocardiogram====
*Diffuse, hazy airspace opacities that are bilateral but often asymmetric
There are no [[EKG]] findings associated with ARDS.
*Obscuration of the [[pulmonary vasculature|pulmonary vessels]]
'''Computed tomography (CT)''' may also be used in the evaluation of patients with ARDS. Although there are no CT findings that are diagnostic of ARDS, some common features include:[[File:ARDS-CT.jpg|thumb|ARDS on chest CT scan of a 50-year-old woman with sepsis and rapidly progressive multi-organ failure<ref name="ARDS on chest CT scan">Case courtesy of Dr. Sajoscha Sorrentino, M.D. "http://radiopaedia.org/cases/16290"</ref>]]
*Pulmonary opacification that appears more dense in the dependent lung zones
*[[Ground-glass opacities]] that may either be patchy or diffuse
*Islands of normal-appearing lung parenchyma
=== Other Diagnostic Studies ===
There are no other diagnostic studies specific to ARDS beyond chest radiography to identify bilateral airspace opacities and arterial blood gas analysis to calculate the PaO<sub>2</sub>/FIO<sub>2</sub> ratio.
== Treatment ==
====X Ray====
=== Medical Therapy ===
X ray is the imaging modality of choice for ARDS. By definition, findings of ARDS on x ray include [[bilateral]] [[Pulmonary consolidation|airspace opacities]].
Medical therapies for ARDS that have been demonstrated to improve outcomes are:
*'''Lower [[tidal volume]] ventilation''' (≤ 6 ml/kg predicted body weight) is associated with reduced mortality and a greater number of ventilator-free days<ref name="pmid10793162">{{cite journal| author=| title=Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. | journal=N Engl J Med | year= 2000 | volume= 342 | issue= 18 | pages= 1301-8 | pmid=10793162 | doi=10.1056/NEJM200005043421801 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10793162 }} </ref>
:*Lower tidal volume ventilation should be continued even if the arterial partial pressure of carbon dioxide (PaCO<sub>2</sub>) rises (this is called ''permissive hypercapnia'')
:*Permissive hypercapnia usually results in a drop in blood pH, however, treatment of [[acidemia]] (e.g., intravenous administration of [[sodium bicarbonate]] or [[tromethamine]]) is not indicated if the pH remains at or above 7.15 to 7.20
*'''Higher [[positive end-expiratory pressure|positive end-expiratory pressure (PEEP)]]''' combined with lower tidal volume ventilation is associated with decreased mortality in patients with '''moderate or severe ARDS (PaO<sub>2</sub>/FIO<sub>2</sub> ≤ 200)'''<ref name="pmid20197533">{{cite journal| author=Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD et al.| title=Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. | journal=JAMA | year= 2010 | volume= 303 | issue= 9 | pages= 865-73 | pmid=20197533 | doi=10.1001/jama.2010.218 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20197533 }} </ref>
*'''[[Mechanical ventilation initial ventilator settings#Proning|Prone positioning''']] for at least 16 consecutive hours each day is associated with improved 28-day and 90-day survival in patients with '''ARDS and a PaO<sub>2</sub>/FIO<sub>2</sub> ratio < 150 on an FIO<sub>2</sub> ≥ 60% and PEEP ≥ 5 mm Hg'''
*'''[[Cisatracurium]]''', when started within the first 48 hours of ARDS diagnosis and continued for 48 hours, have been associated with improved 90-day survival, a greater number of ventilator-free days, and a decreased incidence of [[barotrauma]]<ref name="pmid20843245">{{cite journal| author=Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A et al.| title=Neuromuscular blockers in early acute respiratory distress syndrome. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 12 | pages= 1107-16 | pmid=20843245 | doi=10.1056/NEJMoa1005372 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20843245 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21242357 Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-3] </ref>
In 1994 the National Institutes of Health (NIH) and National Heart, Lung, and Blood Institute (NHLBI) founded the ARDS Network (often abbreviated as ''ARDSnet'') – a consortium of over 40 hospitals that conduct clinical research trials aimed at improving care for patients with ARDS. In order to simplify the mechanical ventilation of patients with ARDS, the NIH-NHLBI ARDS Network has compiled a [http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf '''Mechanical Ventilation Protocol Summary'''] that outlines the mechanical ventilation strategies associated with better outcomes in an easy-to-use format for ICU health care providers.<ref>NIH-NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary. "http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf"</ref>
There are no findings on [[computed tomography|computed tomography (CT)]] that are diagnostic of ARDS. CT scan may be used to better define the extent of lung injury or identify potential underlying causes of ARDS.
=== Alternative Mechanical Ventilation Strategies ===
====Echocardiogram====
Several specialized modes of mechanical ventilation have been tested in ARDS, however, none carries a morbidity or mortality benefit and should only be considered if oxygenation does not improve with a judicious trial of the first-line mechanical ventilation strategies as outlined by the ARDS Network.<ref>NIH-NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary. "http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf"</ref>
[[Echocardiogram|Echocardiography]] is not especially useful in the diagnosis of ARDS, except under circumstances where [[cardiogenic pulmonary edema]] has not yet been excluded.
*[[Mechanical ventilation modes of ventilation#High Frequency Ventilation (HFV)|'''High-frequency oscillatory ventilation (HFOV)''']] may improve oxygenation in patients with '''moderate to severe ARDS and severe refractory hypoxemia''', however, initiation of HFOV early in the course of ARDS (i.e., prior to low tidal volume/high PEEP mechanical ventilation) has been associated with ''increased mortality'' compared to low tidal volume/high PEEP ventilation<ref name="pmid12231488">{{cite journal| author=Derdak S, Mehta S, Stewart TE, Smith T, Rogers M, Buchman TG et al.| title=High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. | journal=Am J Respir Crit Care Med | year= 2002 | volume= 166 | issue= 6 | pages= 801-8 | pmid=12231488 | doi=10.1164/rccm.2108052 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12231488 }} </ref><sup>,</sup><ref name="pmid23339639">{{cite journal| author=Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P et al.| title=High-frequency oscillation in early acute respiratory distress syndrome. | journal=N Engl J Med | year= 2013 | volume= 368 | issue= 9 | pages= 795-805 | pmid=23339639 | doi=10.1056/NEJMoa1215554 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23339639 }} </ref>
*'''[[Acute respiratory distress syndrome mechanical ventilation therapy#APRV (Airway Pressure Release Ventilation) and ARDS / ALI |Airway pressure release ventilation (APRV)]]''' appears to be safe in ARDS, and may be associated with reduced paralytic and sedative use as well as an increase in the number of ventilator-free days<ref name="pmid19727373">{{cite journal| author=Daoud EG| title=Airway pressure release ventilation. | journal=Ann Thorac Med | year= 2007 | volume= 2 | issue= 4 | pages= 176-9 | pmid=19727373 | doi=10.4103/1817-1737.36556 | pmc=2732103 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19727373 }} </ref><sup>,</sup><ref name="pmid21762559">{{cite journal| author=Daoud EG, Farag HL, Chatburn RL| title=Airway pressure release ventilation: what do we know? | journal=Respir Care | year= 2012 | volume= 57 | issue= 2 | pages= 282-92 | pmid=21762559 | doi=10.4187/respcare.01238 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21762559 }} </ref>
There is growing evidence to support the use of [[extracorporeal membrane oxygenation]] (ECMO) for severe ARDS that fails to improve despite judicious application of the ARDS Network low tidal volume/high PEEP ventilation strategy.<ref name="pmid3090285">{{cite journal| author=Gattinoni L, Pesenti A, Mascheroni D, Marcolin R, Fumagalli R, Rossi F et al.| title=Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure. | journal=JAMA | year= 1986 | volume= 256 | issue= 7 | pages= 881-6 | pmid=3090285 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3090285 }} </ref>
There are no additional diagnostic studies that are especially useful in the diagnosis and management of ARDS.
<sup>,</sup><ref name="pmid19762075">{{cite journal| author=Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM et al.| title=Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. | journal=Lancet | year= 2009 | volume= 374 | issue= 9698 | pages= 1351-63 | pmid=19762075 | doi=10.1016/S0140-6736(09)61069-2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19762075 }} </ref> ECMO facilitates gas exchange in circumstances where adequate oxygenation and ventilation cannot be achieved through the lungs themselves. There are two main forms of ECMO, both of which have been used successfully in the treatment of severe ARDS:
*'''Veno-venous (VV)-ECMO''': Venous blood is removed through an outflow cannula placed in a large vein (usually the right femoral vein or inferior vena cava) and passed through an oxygenator where gas exchange occurs (CO<sub>2</sub> is removed and O<sub>2</sub> is introduced) before being returned to the body through an inflow cannula placed in another large vein (usually the right internal jugular vein or superior vena cava)
:*Supports gas exchange but does not provide any hemodynamic support
*'''Veno-arterial(VA)-ECMO''': Venous blood is removed through an outflow cannula placed in a large vein (usually the right femoral vein or inferior vena cava) and passed through an oxygenator where gas exchange occurs (CO<sub>2</sub> is removed and O<sub>2</sub> is introduced) before being returned to the body through an inflow cannula placed in a large artery (usually the right femoral artery or right carotid artery)
ECMO works by removing venous blood (e.g., the right femoral vein, right internal jugular vein, or the right atrium)
:*Supports gas exchange and provides hemodynamic support by bypassing the heart completely
The use of ECMO in the treatment of ARDS is an ongoing area of research, and referral to a medical center with ample experience in the use of ECMO for ARDS should be considered for patients with ARDS who are failing traditional management strategies and may be candidates for ECMO.
==Treatment==
===Medical Therapy===
The majority of medical therapies for ARDS are aimed at treating its underlying cause (e.g., [[antimicrobials]] for [[infection]]).
=== Inhaled Pulmonary Vasodilators ===
====Mechanical Ventilation Therapy====
'''Inhaled pulmonary vasodilators''' have been used to improve hypoxemia by reversing [[ventilation/perfusion mismatching|ventilation/perfusion (V/Q) mismatching]], however, studies of [[inhaled nitric oxide|inhaled nitric oxide (iNO)]] and [[epoprostenol|inhaled prostacyclin]] have not demonstrated a survival benefit.<ref name="pmid15069048">{{cite journal| author=Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K et al.| title=Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. | journal=JAMA | year= 2004 | volume= 291 | issue= 13 | pages= 1603-9 | pmid=15069048 | doi=10.1001/jama.291.13.1603 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15069048 }} </ref><sup>,</sup><ref name="pmid24132038">{{cite journal| author=Adhikari NK, Dellinger RP, Lundin S, Payen D, Vallet B, Gerlach H et al.| title=Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis. | journal=Crit Care Med | year= 2014 | volume= 42 | issue= 2 | pages= 404-12 | pmid=24132038 | doi=10.1097/CCM.0b013e3182a27909 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24132038 }} </ref><sup>,</sup><ref name="pmid8630585">{{cite journal| author=Walmrath D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W| title=Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. | journal=Am J Respir Crit Care Med | year= 1996 | volume= 153 | issue= 3 | pages= 991-6 | pmid=8630585 | doi=10.1164/ajrccm.153.3.8630585 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8630585 }} </ref><sup>,</sup><ref name="pmid8970353">{{cite journal| author=Zwissler B, Kemming G, Habler O, Kleen M, Merkel M, Haller M et al.| title=Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. | journal=Am J Respir Crit Care Med | year= 1996 | volume= 154 | issue= 6 Pt 1 | pages= 1671-7 | pmid=8970353 | doi=10.1164/ajrccm.154.6.8970353 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8970353 }} </ref> It is important to monitor the platelet count when initiating treatment with inhaled prostacyclin due to the low risk of thrombocytopenia.
Most patients with ARDS will require [[endotracheal intubation]] and [[mechanical ventilation]] at some point during the course of their illness and recovery. A mechanical ventilation strategy using lower [[Lung volumes|tidal volumes]] of 6 mL/kg predicted body weight and higher levels of [[PEEP|positive end-expiratory pressure (PEEP)]] has been shown to be most effective at improving oxygenation and minimizing [[barotrauma|volutrauma]] (injury to stiff lungs resulting from overdistention).
=== Surgery ===
===Surgery===
Surgical treatment plays no role in the management of ARDS, except where an operation might be recommended to treat the underlying cause.
Surgical intervention is not recommended for the management of ARDS, except when a procedure might be recommended to treat the underlying cause.
=== Prevention ===
===Prevention===
There are no primary preventive measures available for ARDS. The best prevention strategy for ARDS is early recognition and treatment of medical conditions that have the potential to cause ARDS.
There are no primary preventive measures available for ARDS. The only prevention strategy for ARDS is early recognition and treatment of medical conditions that have the potential to cause ARDS.
== Follow-Up Care==
Secondary prevention strategies for ARDS include aggressive treatment of the underlying cause and the early application of [[Acute respiratory distress syndrome mechanical ventilation therapy#Non-Invasive Positive Pressure Ventilation|noninvasive methods of oxygenation]] to slow or prevent the worsening of ARDS and potentially reduce the need for [[tracheal intubation|intubation]] and [[mechanical ventilation]].
Although there is no single follow-up strategy for patients who are successfully treated for ARDS, many ARDS survivors suffer from one or more long-term sequelae of their illness, including severe weakness or [[critical illness myopathy]], impaired exercise tolerance, deterioration in lung function, pulmonary fibrosis, psychiatric illness (e.g., PTSD, depression, anxiety), and cognitive impairment.<ref name="pmid12594312">{{cite journal| author=Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F et al.| title=One-year outcomes in survivors of the acute respiratory distress syndrome. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 8 | pages= 683-93 | pmid=12594312 | doi=10.1056/NEJMoa022450 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12594312 }} </ref> Follow-up for ARDS survivors should focus on addressing these potential issues on an individualized basis, and should include, at a minimum, follow-up [[Spirometry|pulmonary function tests]] and six-minute walk distance tests after discharge from the hospital and at intervals of 3, 6, or 12 months to watch for improvement.
The vast majority of patients with ARDS are managed in an intensive care unit (ICU), where many will require mechanical ventilation at some point during the course of their illness and recovery. ARDS may be categorized as mild, moderate, or severe based on the degree to which oxygenation is impaired; however, all levels of severity carry a high mortality rate if appropriate measures to improve oxygenation and minimize the risk of further lung injury are not taken.[1]
Historical Perspective
Although the pathologic features of ARDS were first documented in the 19th century, the modern definition of ARDS did not arise until the 1960s. In 2012, the Berlin Definition of ARDS became the standard diagnostic criteria and definition of the syndrome.
ARDS must be differentiated from other diseases that cause hypoxemia and pulmonary infiltrates, such as pneumonia, pulmonary contusion, pulmonary edema, and pulmonary hemorrhage. Prior to the development of the Berlin Definition in 2012, a greater emphasis was placed on excluding other potential illnesses prior to making a diagnosis of ARDS. While it is important to recognize and treat and underlying cause of the patient's impaired ventilation and hypoxemia, this search for potential etiologies should not delay any focused efforts to improve oxygenation and ventilation.
Epidemiology and Demographics
The incidence of ARDS in the United States is estimated at approximately 75 cases per 100,000 individuals, which amounts to roughly 150,000 new cases annually.[3] There is substantial variance in the rates of ARDS between different countries and geographic regions due to factors such as mean life expectancy, prevalence of different risk factors and comorbidities, and access to healthcare.
If left untreated, 70% of patients with ARDS may progress to mortality.[6] Common complications to ARDS include weakness, impaired lung function, and brain death. Prognosis for patients with ARDS is generally poor and varies based on the severity of illness, the precipitating insult, and medical comorbidities.
Diagnosis
Diagnostic Criteria
Established by the ARDS Definition Task Force in 2012, the Berlin Definition is the most current set of diagnostic criteria for ARDS.
History and Symptoms
The history of a patient with ARDS varies according to the underlying cause. The symptoms of ARDS are fairly nonspecific and typically include rapid breathing, shortness of breath, and rapid heartbeat.
Laboratory findings consistent with the diagnosis of ARDS include an arterial partial pressure of oxygen (PaO2) that is inappropriately low relative to the fraction of inspired oxygen (FIO2) that is being breathed by the patient. This is referred to as the PaO2/FIO2 ratio (sometimes abbreviated as P/F ratio) and is calculated by dividing the PaO2 (in mmHg) by the FIO2 (as a decimal rather than a percentage).
X ray is the imaging modality of choice for ARDS. By definition, findings of ARDS on x ray include bilateralairspace opacities.
CT
There are no findings on computed tomography (CT) that are diagnostic of ARDS. CT scan may be used to better define the extent of lung injury or identify potential underlying causes of ARDS.
There are no additional diagnostic studies that are especially useful in the diagnosis and management of ARDS.
Treatment
Medical Therapy
The majority of medical therapies for ARDS are aimed at treating its underlying cause (e.g., antimicrobials for infection).
Mechanical Ventilation Therapy
Most patients with ARDS will require endotracheal intubation and mechanical ventilation at some point during the course of their illness and recovery. A mechanical ventilation strategy using lower tidal volumes of 6 mL/kg predicted body weight and higher levels of positive end-expiratory pressure (PEEP) has been shown to be most effective at improving oxygenation and minimizing volutrauma (injury to stiff lungs resulting from overdistention).
Surgery
Surgical intervention is not recommended for the management of ARDS, except when a procedure might be recommended to treat the underlying cause.
Prevention
There are no primary preventive measures available for ARDS. The only prevention strategy for ARDS is early recognition and treatment of medical conditions that have the potential to cause ARDS.
Secondary prevention strategies for ARDS include aggressive treatment of the underlying cause and the early application of noninvasive methods of oxygenation to slow or prevent the worsening of ARDS and potentially reduce the need for intubation and mechanical ventilation.