'''Acute respiratory distress syndrome''' ('''ARDS'''), also known as '''respiratory distress syndrome''' ('''RDS''') or '''adult respiratory distress syndrome''' (in contrast with [[infant respiratory distress syndrome]], or [[infant respiratory distress syndrome|IRDS]]) is a serious and potentially life-threatening inflammatory lung condition that may occur in the setting of infection, toxic exposure, adverse drug reactions, trauma, or overall critical illness. 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]].
ARDS may be categorized as ''mild'', ''moderate'', or ''severe'' based on the magnitude of impaired oxygenation; however, even mild ARDS may progress to [[multiple organ failure]] if appropriate measures to improve oxygenation are not taken. The vast majority of patients diagnosed with ARDS are managed in an [[intensive care unit]], and most will require [[Mechanical ventilation indications for use|mechanical ventilation]] at some point during the course of their illness and recovery.
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>
Below is a table showing The Berlin definition of Acute Respiratory Distress Syndrome:<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>
{| class="wikitable"
!
! '''Acute Respiratory Distress Syndrome'''
|-
| '''Timing'''
| ❑ Within 1 week of a known clinical insult or new or worsening respiratory symptoms
|-
| '''Chest imaging''' <br>i.e., [[CXR]] or [[CT]]
| ❑ Bilateral opacities—not fully explained by effusions, lobar/lung collapse, or
nodules
|-
| '''Origin of edema'''
| ❑ Respiratory failure not fully explained by cardiac failure or fluid overload<br>❑ Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema<br> if no risk factor present
|-
| '''Oxygenation'''<br> (Corrected for altitude)
|
|-
| Mild
|❑ 200 mm Hg < PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 300 mmHg with PEEP or CPAP > 5 cm H<sub>2</sub>O
|-
| 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
|}
ARDS usually occurs within 24 to 48 hours of the initial injury or illness. The patient usually presents with [[shortness of breath]], [[tachypnea]], and symptoms related to the underlying cause, i.e. [[Shock (medical)|shock]].
An [[arterial blood gas]] analysis and [[chest X-ray]] allow formal diagnosis by inference using the aforementioned criteria. Although severe hypoxemia is generally included, the appropriate threshold defining abnormal PaO<sub>2</sub> has never been systematically studied.
Any cardiogenic cause of pulmonary edema should be excluded. This can be done by placing a [[pulmonary artery catheter]] for measuring the pulmonary artery wedge pressure. However, this is not necessary and is now rarely done as abundant evidence has emerged demonstrating that the use of pulmonary artery catheters does not lead to improved patient outcomes in critical illness including ARDS.
While CT scanning leads to more accurate images of the pulmonary parenchyma in ARDS, its has little utility in the clinical management of patients with ARDS, and remains largely a research tool. Plain Chest X-rays are sufficient to document bilateral alveolar infiltrates in the majority of cases
==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>
*'''Direct insult''': Pneumonia, aspiration pneumonitis, toxic inhalation, physical trauma to the lungs
*'''Indirect insult''': [[Sepsis]], [[TRALI|blood transfusion]], drug or toxin exposures, traumatic injury, [[pancreatitis]]
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==
==Epidemiology and Demographics==
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.
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]].
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:
==Risk Factors==
*[[Echocardiogram|'''Echocardiography''']] to assess heart function
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]].
*[[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'']])
==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.
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:
==Natural History, Complications, and Prognosis==
*Chest X-ray
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.
*[[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]]
==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.
Additional testing should be guided by clinical suspicion and the patient's medical history. These may include such tests as:
===History and Symptoms===
*Serum [[lipase]]
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]].
*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==
===Physical Examination===
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.
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]].
===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===
===Laboratory Findings===
*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>
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).
==Risk Factors==
===Imaging Findings===
Common risk factors in the development of ARDS are:
====Electrocardiogram====
*Advanced age
There are no [[EKG]] findings associated with ARDS.
*Chronic alcoholism
*Chronic liver disease
*Chronic kidney disease
*Cigarette smoke exposure
====X Ray====
X ray is the imaging modality of choice for ARDS. By definition, findings of ARDS on x ray include [[bilateral]] [[Pulmonary consolidation|airspace opacities]].
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>
====CT====
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.
== Natural History, Complications and Prognosis==
====Echocardiogram====
*ARDS typically occurs within the first week of the precipitating illness or trauma and usually progresses rapidly within the first 24 to 48 hours.
[[Echocardiogram|Echocardiography]] is not especially useful in the diagnosis of ARDS, except under circumstances where [[cardiogenic pulmonary edema]] has not yet been excluded.
*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 ==
===Other Diagnostic Studies===
===Diagnostic Criteria===
There are no additional diagnostic studies that are especially useful in the diagnosis and management of ARDS.
The diagnosis of ARDS is made when the following diagnostic criteria are met:
| ❑ 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 ===
====Mechanical Ventilation Therapy====
*[Disease name] is usually asymptomatic.
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).
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]
=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Physical examination may be remarkable for:
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]
=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].
*A [positive/negative] [test name] is diagnostic of [disease name].
===Surgery===
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
Surgical intervention is not recommended for the management of ARDS, except when a procedure might be recommended to treat the underlying cause.
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].
*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
== Treatment ==
===Prevention===
=== Medical Therapy ===
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.
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.
*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
*[Medical therapy 1] acts by [mechanism of action 1].
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].
=== Prevention ===
*There are no primary preventive measures available for [disease name].
*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
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]].
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.