Acute respiratory distress syndrome#Terminology

The signs and symptoms of ARDS often begin within two hours of an inciting event, but have been known to take as long as 1–3 days; diagnostic criteria require a known insult to have happened within 7 days of the syndrome. Signs and symptoms may include shortness of breath, fast breathing, and a low oxygen level in the blood due to abnormal ventilation.{{Cite journal|title = Acute lung injury and the acute respiratory distress syndrome in the injured patient|journal = Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine|date=August 2012|doi = 10.1186/1757-7241-20-54|pmid = 22883052|pmc = 3518173|last = Bakowitz|first = Magdalena|volume=20|pages=54 | doi-access=free }}Marino (2006), pp 435 Other common symptoms include muscle fatigue and general weakness, low blood pressure, a dry, hacking cough, and fever.{{Cite journal|last1=Bakowitz|first1=Magdalena|last2=Bruns|first2=Brandon|last3=McCunn|first3=Maureen|date=2012-08-10|title=Acute lung injury and the acute respiratory distress syndrome in the injured patient|journal=Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine|volume=20|pages=54|doi=10.1186/1757-7241-20-54|issn=1757-7241|pmc=3518173|pmid=22883052 |doi-access=free }}

Complications may include the following:

• Lungs: barotrauma (volutrauma), pulmonary embolism (PE), pulmonary fibrosis, ventilator-associated pneumonia (VAP)
• Gastrointestinal: bleeding (ulcer), dysmotility, pneumoperitoneum, bacterial translocation
• Neurological: hypoxic brain damage
• Cardiac: abnormal heart rhythms, myocardial dysfunction
• Kidney: acute kidney failure, positive fluid balance
• Mechanical: vascular injury, pneumothorax (by placing pulmonary artery catheter), tracheal injury/stenosis (result of intubation and/or irritation by endotracheal tube)
• Nutritional: malnutrition (catabolic state), electrolyte abnormalities

Other complications that are typically associated with ARDS include:

• Atelectasis: small air pockets within the lung collapse
• Complications that arise from treatment in a hospital: blood clots formed by lying down for long periods of time, weakness in muscles that are used for breathing, stress ulcers, and issues with mental health and depression.
• Failure of multiple organs
• Pulmonary hypertension or increase in blood pressure in the main artery from the heart to the lungs. This complication typically occurs due to the restriction of the blood vessel due to inflammation of the mechanical ventilation

There are direct and indirect causes of ARDS depending whether the lungs are initially affected. Direct causes include pneumonia (including bacterial and viral), aspiration, inhalational lung injury, lung contusion, chest trauma, and near-drowning. Indirect causes include sepsis, shock, pancreatitis, trauma (e.g. fat embolism), cardiopulmonary bypass, TRALI, burns, increased intracranial pressure.{{Cite journal |last1=Fan |first1=Tracey H. |last2=Huang |first2=Merry |last3=Gedansky |first3=Aron |last4=Price |first4=Carrie |last5=Robba |first5=Chiara |last6=Hernandez |first6=Adrian V. |last7=Cho |first7=Sung-Min |date=December 2021 |title=Prevalence and Outcome of Acute Respiratory Distress Syndrome in Traumatic Brain Injury: A Systematic Review and Meta-Analysis |journal=Lung |language=en |volume=199 |issue=6 |pages=603–610 |doi=10.1007/s00408-021-00491-1 |pmid=34779897 |issn=0341-2040|pmc=8590970 }} Fewer cases of ARDS are linked to large volumes of fluid used during post-trauma resuscitation.{{cite journal|last=Cherkas |first=David |title=Traumatic Hemorrhagic Shock: Advances In Fluid Management |journal=Emergency Medicine Practice |date=Nov 2011 |volume=13 |issue=11 |pages=1–19; quiz 19–20 |pmid=22164397 }}

{{Main|Pathophysiology of acute respiratory distress syndrome}}

File:Hyaline membranes - intermed mag.jpg of diffuse alveolar damage, the histologic correlate of ARDS. H&E stain.]]

ARDS is a form of fluid accumulation in the lungs not explained by heart failure (noncardiogenic pulmonary edema). It is typically provoked by an acute injury to the lungs that results in flooding of the lungs' microscopic air sacs responsible for the exchange of gases such as oxygen and carbon dioxide with capillaries in the lungs.{{cite journal|last1=Boyle|first1=AJ|last2=Mac Sweeney|first2=R|last3=McAuley|first3=DF|title=Pharmacological treatments in ARDS; a state-of-the-art update|journal=BMC Med|volume=11|pages=166|date=August 2013|pmid=23957905|pmc=3765621|doi=10.1186/1741-7015-11-166 |doi-access=free }} Additional common findings in ARDS include partial collapse of the alveoli (atelectasis) and low levels of oxygen in the blood (hypoxemia). The clinical syndrome is associated with pathological findings including pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of chemical signals and other inflammatory mediators secreted by local epithelial and endothelial cells.{{citation needed|date=November 2020}}

Neutrophils and some T-lymphocytes quickly migrate into the inflamed lung tissue and contribute in the amplification of the phenomenon. The typical histological presentation involves diffuse alveolar damage and hyaline membrane formation in alveolar walls. Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress.{{citation needed|date=November 2020}}

One research group has reported that broncho-alveolar lavage fluid in later-stage ARDS often contains trichomonads,{{Cite journal |vauthors=Duboucher C, Barbier C, Beltramini A, Rona M, Ricome JL, Morel G, Capron M, Pierce RJ, Dei-Cas E, Viscogliosi E |date=September 2007 |title=Pulmonary Superinfection by Trichomonads in the Course of Acute Respiratory Distress Syndrome |url=https://link.springer.com/10.1007/s00408-007-9022-1 |journal=Lung |language=en |volume=185 |issue=5 |pages=295–301 |doi=10.1007/s00408-007-9022-1 |pmid=17701244 |s2cid=12175132 |issn=0341-2040|url-access=subscription }} in an amoeboid form (i.e. lacking their characteristic flagellum) which makes them difficult to identify under the microscope.{{Cite journal |vauthors=Duboucher C |date=March 2021 |title=SARS-CoV-2 and superimposed infection by trichomonads |journal=Journal of Infection |language=en |volume=82 |issue=3 |pages=e22–e23 |doi=10.1016/j.jinf.2020.11.038 |pmc=7834870 |pmid=33271170}}

File:Transfusion-related acute lung injury chest X-ray.gif (left) which led to ARDS. Right is the same patient with resolved injury 72 hours after ventilator support. Note the clearance of bilateral diffuse infiltrates.]]

Diagnostic criteria for ARDS have changed over time as understanding of the pathophysiology has evolved. The international consensus criteria for ARDS were most recently updated in 2012 and are known as the "Berlin definition".{{cite journal |vauthors=Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS |s2cid=36276275 |date=Jun 2012 | title = Acute respiratory distress syndrome: the Berlin Definition. ARDS Definition Task Force | journal = JAMA | volume = 307 | issue = 23| pages = 2526–33 | doi = 10.1001/jama.2012.5669 | pmid = 22797452 }}{{cite journal |vauthors=Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A |s2cid=13556499 |date=Oct 2012 | title = The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material | journal = Intensive Care Med. | volume = 38 | issue = 10| pages = 1573–82 | doi=10.1007/s00134-012-2682-1|display-authors=etal | pmid=22926653| doi-access=free }} Erratum in: Intensive Care Med. 2012 Oct;38(10):1731-2. {{PMID|22926653}} In addition to generally broadening the diagnostic thresholds, other notable changes from the prior 1994 consensus criteria include discouraging the term "acute lung injury", and defining grades of ARDS severity according to degree of decrease in the oxygen content of the blood.{{Citation |last1=Diamond |first1=Matthew |title=Acute Respiratory Distress Syndrome |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK436002/ |access-date=2024-11-29 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28613773 |last2=Peniston |first2=Hector L. |last3=Sanghavi |first3=Devang K. |last4=Mahapatra |first4=Sidharth}}

According to the 2012 Berlin definition, adult ARDS is characterized by the following: {{Cite web |title=Acute Respiratory Distress Syndrome (ARDS) |url=https://www.dynamed.com/condition/acute-respiratory-distress-syndrome-ards#GUID-0C523E79-54EB-484D-9500-3CB258D9079D |access-date=2024-11-29 |website=Dynamed}}

• lung injury of acute onset, within 1 week of an apparent clinical insult and with the progression of respiratory symptoms
• bilateral opacities on chest imaging (chest radiograph or CT) not explained by other lung pathology (e.g. effusion, lobar/lung collapse, or nodules)
• respiratory failure not explained by heart failure or volume overload
• decreased Fraction of inspired oxygen#PaO2/FiO2 ratio ratio (a decreased Pa{{chem|O|2}}/Fi{{chem|O|2}} ratio indicates reduced arterial oxygenation from the available inhaled gas):
• mild ARDS: 201 – 300 mmHg (≤ 39.9 kPa)
• moderate ARDS: 101 – 200 mmHg (≤ 26.6 kPa)
• severe ARDS: ≤ 100 mmHg (≤ 13.3 kPa)
• The Berlin definition requires a minimum positive end expiratory pressure (PEEP) of 5 cm{{chem|H|2|O}} for consideration of the Pa{{chem|O|2}}/Fi{{chem|O|2}} ratio. This degree of PEEP may be delivered noninvasively with CPAP to diagnose mild ARDS.

The 2012 "Berlin criteria" are a modification of the prior 1994 consensus conference definitions (see history).

Radiologic imaging has long been a criterion for diagnosis of ARDS. Original definitions of ARDS specified that correlative chest X-ray findings were required for diagnosis, the diagnostic criteria have been expanded over time to accept CT and ultrasound findings as equally contributory. Generally, radiographic findings of fluid accumulation (pulmonary edema) affecting both lungs and unrelated to increased cardiopulmonary vascular pressure (such as in heart failure) may be suggestive of ARDS.{{cite web |url= https://www.lecturio.com/concepts/acute-respiratory-distress-syndrome/ | title= Acute Respiratory Distress Syndrome

| website= The Lecturio Medical Concept Library |access-date= 27 June 2021}}

Ultrasound findings suggestive of ARDS include the following:

• Anterior subpleural consolidations
• Absence or reduction of lung sliding
• "Spared areas" of normal parenchyma
• Pleural line abnormalities (irregular thickened fragmented pleural line)
• Nonhomogeneous distribution of B-lines (a characteristic ultrasound finding suggestive of fluid accumulation in the lungs){{Cite journal|last1=Volpicelli|first1=Giovanni|last2=Elbarbary|first2=Mahmoud|last3=Blaivas|first3=Michael|last4=Lichtenstein|first4=Daniel A.|last5=Mathis|first5=Gebhard|last6=Kirkpatrick|first6=Andrew W.|last7=Melniker|first7=Lawrence|last8=Gargani|first8=Luna|last9=Noble|first9=Vicki E.|date=2012-04-01|title=International evidence-based recommendations for point-of-care lung ultrasound|journal=Intensive Care Medicine|volume=38|issue=4|pages=577–591|doi=10.1007/s00134-012-2513-4|issn=1432-1238|pmid=22392031|doi-access=free}}

Acute respiratory distress syndrome is usually treated with mechanical ventilation in the intensive care unit (ICU). Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the airway (endotracheal intubation), or by tracheostomy when prolonged ventilation (≥2 weeks) is necessary. The role of non-invasive ventilation is limited to the very early period of the disease or to prevent worsening respiratory distress in individuals with atypical pneumonias, lung bruising, or major surgery patients, who are at risk of developing ARDS. Treatment of the underlying cause is crucial. Appropriate antibiotic therapy is started as soon as culture results are available, or if infection is suspected (whichever is earlier). Empirical therapy may be appropriate if local microbiological surveillance is efficient. Where possible the origin of the infection is removed. When sepsis is diagnosed, appropriate local protocols are followed.{{citation needed|date=November 2020}}

{{Further|Dual-control modes of ventilation|l1=Pressure regulated volume control}}

The overall goal of mechanical ventilation is to maintain acceptable gas exchange to meet the body's metabolic demands and to minimize adverse effects in its application. The parameters PEEP (positive end-expiratory pressure, to keep alveoli open), mean airway pressure (to promote recruitment (opening) of easily collapsible alveoli and predictor of hemodynamic effects), and plateau pressure (best predictor of alveolar overdistention) are used.{{cite journal |author=Malhotra A |title=Low-tidal-volume ventilation in the acute respiratory distress syndrome |journal=N Engl J Med |volume=357 |issue=11 |pages=1113–20 |year=2007 |pmid=17855672 |doi=10.1056/NEJMct074213 |pmc=2287190}}

Previously, mechanical ventilation aimed to achieve tidal volumes (V_t) of 12–15 ml/kg (where the weight is ideal body weight rather than actual weight). Recent studies have shown that high tidal volumes can overstretch alveoli resulting in volutrauma (secondary lung injury). The ARDS Clinical Network, or ARDSNet, completed a clinical trial that showed improved mortality when people with ARDS were ventilated with a tidal volume of 6 ml/kg compared to the traditional 12 ml/kg. Low tidal volumes (V_t) may cause a permitted rise in blood carbon dioxide levels and collapse of alveoli because of their inherent tendency to increase shunting within the lung. Physiologic dead space cannot change as it is ventilation without perfusion. A shunt is a perfusion without ventilation within a lung region.{{citation needed|date=November 2020}}

Low tidal volume ventilation was the primary independent variable associated with reduced mortality in the NIH-sponsored ARDSNet trial of tidal volume in ARDS. Plateau pressure less than 30 cm {{chem|H|2|O}} was a secondary goal, and subsequent analyses of the data from the ARDSNet trial and other experimental data demonstrate that there appears to be no safe upper limit to plateau pressure; regardless of plateau pressure, individuals with ARDS fare better with low tidal volumes.{{cite journal|last1=Hager|first1=DN|last2=Krishnan|first2=JA|last3=Hayden|first3=DL|last4=Brower|first4=RG|last5=ARDS Clinical Trials Network|title=Tidal volume reduction in patients with acute lung injury when plateau pressures are not high|journal=American Journal of Respiratory and Critical Care Medicine|date=November 2005|volume=172|issue=10|pages=1241–5|pmid=16081547|doi=10.1164/rccm.200501-048cp|pmc=2718413}}

No particular ventilator mode is known to improve mortality in acute respiratory distress syndrome (ARDS).{{cite journal |last1= Bein |first1= T |last2= Grasso |first2= S |last3= Moerer |first3= O |last4= Quintel |first4= M |last5= Guerin |first5= C |last6= Deja |first6= M |last7= Brondani |first7= A |last8= Mehta |first8= S |date= 2016 |title= The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia |journal= Intensive Care Medicine

|volume= 42 |issue= 5 |pages= 699–711 |doi= 10.1007/s00134-016-4325-4 | pmid= 27040102 |pmc= 4828494 }}

Some practitioners favor airway pressure release ventilation when treating ARDS. Well documented advantages to APRV ventilation{{cite journal |last1=Frawley |first1=P. Milo |last2=Habashi |first2=Nader M. |title=Airway Pressure Release Ventilation: Theory and Practice |journal=AACN Clinical Issues |date=May 2001 |volume=12 |issue=2 |pages=234–246 |doi=10.1097/00044067-200105000-00007 |pmid=11759551 }} include decreased airway pressures, decreased minute ventilation, decreased dead-space ventilation, promotion of spontaneous breathing, almost 24-hour-a-day alveolar recruitment, decreased use of sedation, near elimination of neuromuscular blockade, optimized arterial blood gas results, mechanical restoration of FRC (functional residual capacity), a positive effect on cardiac output{{cite journal|title=Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome|journal=Critical Care|first1=Lewis J.|last1=Kaplan|first2=Heatherlee|last2=Bailey|first3=Vincent|last3=Formosa|date=2 July 2001|volume=5|issue=4|pages=221–6|doi=10.1186/cc1027|pmid=11511336|pmc=37408 |doi-access=free }} (due to the negative inflection from the elevated baseline with each spontaneous breath), increased organ and tissue perfusion and potential for increased urine output secondary to increased kidney perfusion.{{citation needed|date=November 2020}}

A patient with ARDS, on average, spends between 8 and 11 days on a mechanical ventilator; APRV may reduce this time significantly and thus may conserve valuable resources.{{Cite journal|last1=Carsetti|first1=Andrea|last2=Damiani|first2=Elisa|last3=Domizi|first3=Roberta|last4=Scorcella|first4=Claudia|last5=Pantanetti|first5=Simona|last6=Falcetta|first6=Stefano|last7=Donati|first7=Abele|last8=Adrario|first8=Erica|date=2019-04-04|title=Airway pressure release ventilation during acute hypoxemic respiratory failure: a systematic review and meta-analysis of randomized controlled trials|journal=Annals of Intensive Care|volume=9|issue=1|page=44|doi=10.1186/s13613-019-0518-7|issn=2110-5820|pmc=6449410|pmid=30949778 |doi-access=free }}

Positive end-expiratory pressure (PEEP) is used in mechanically ventilated people with ARDS to improve oxygenation. In ARDS, three populations of alveoli can be distinguished. There are normal alveoli that are always inflated and engaging in gas exchange, flooded alveoli which can never, under any ventilatory regime, be used for gas exchange, and atelectatic or partially flooded alveoli that can be "recruited" to participate in gas exchange under certain ventilatory regimens. The recruitable alveoli represent a continuous population, some of which can be recruited with minimal PEEP, and others can only be recruited with high levels of PEEP. An additional complication is that some alveoli can only be opened with higher airway pressures than are needed to keep them open, hence the justification for maneuvers where PEEP is increased to very high levels for seconds to minutes before dropping the PEEP to a lower level. PEEP can be harmful; high PEEP necessarily increases mean airway pressure and alveolar pressure, which can damage normal alveoli by overdistension resulting in DAD. A compromise between the beneficial and adverse effects of PEEP is inevitable.{{citation needed|date=November 2020}}

The 'best PEEP' used to be defined as 'some' cm{{chem|H|2|O}} above the lower inflection point (LIP) in the sigmoidal pressure-volume relationship curve of the lung. Recent research has shown that the LIP-point pressure is no better than any pressure above it, as recruitment of collapsed alveoli{{mdash}}and, more importantly, the overdistension of aerated units{{mdash}}occur throughout the whole inflation. Despite the awkwardness of most procedures used to trace the pressure-volume curve, it is still used by some{{who|date=October 2013}} to define the minimum PEEP to be applied to their patients. Some new ventilators can automatically plot a pressure-volume curve.{{citation needed|date=August 2022}}

PEEP may also be set empirically. Some authors{{who|date=October 2013}} suggest performing a 'recruiting maneuver'{{mdash}}a short time at a very high continuous positive airway pressure, such as 50 cm{{chem|H|2|O}} (4.9 kPa){{mdash}}to recruit or open collapsed units with a high distending pressure before restoring previous ventilation. The final PEEP level should be the one just before the drop in Pa{{chem|O|2}} or peripheral blood oxygen saturation during a step-down trial. A large randomized controlled trial of patients with ARDS found that lung recruitment maneuvers and PEEP titration was associated with high rates of barotrauma and pneumothorax and increased mortality.{{Cite journal|last1=Cavalcanti|first1=Alexandre Biasi|last2=Suzumura|first2=Érica Aranha|last3=Laranjeira|first3=Ligia Nasi|last4=Paisani|first4=Denise de Moraes|last5=Damiani|first5=Lucas Petri|last6=Guimarães|first6=Helio Penna|last7=Romano|first7=Edson Renato|last8=Regenga|first8=Marisa de Moraes|last9=Taniguchi|first9=Luzia Noriko Takahashi|last10=Teixeira|first10=Cassiano|last11=Oliveira|first11=Roselaine Pinheiro de|date=2017-10-10|title=Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial|url= |journal=JAMA|language=en|volume=318|issue=14|pages=1335–1345|doi=10.1001/jama.2017.14171|pmid=28973363|issn=0098-7484|pmc=5710484}}

Intrinsic PEEP (iPEEP) or auto-PEEP{{mdash}}first described by John Marini of St. Paul Regions Hospital{{mdash}}is a potentially unrecognized contributor to PEEP in intubated individuals. When ventilating at high frequencies, its contribution can be substantial, particularly in people with obstructive lung disease such as asthma or chronic obstructive pulmonary disease (COPD). iPEEP has been measured in very few formal studies on ventilation in ARDS, and its contribution is largely unknown. Its measurement is recommended in the treatment of people who have ARDS, especially when using high-frequency (oscillatory/jet) ventilation.{{citation needed|date=November 2020}}

{{Main|Proning}}

The position of lung infiltrates in acute respiratory distress syndrome is non-uniform. Repositioning into the prone position (face down) might improve oxygenation by relieving atelectasis and improving perfusion. If this is done early in the treatment of severe ARDS, it confers a mortality benefit of 26% compared to supine ventilation.{{cite journal |vauthors=Sud S, Friedrich JO, Adhikari NK | title=Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis |date=8 Jul 2014 | journal=CMAJ | volume=186 | issue=10 | pages=E381–90 | doi=10.1503/cmaj.140081 | pmid=24863923 | pmc=4081236|display-authors=etal}}{{Cite journal |last1=Bhandari |first1=Abhishta P. |last2=Nnate |first2=Daniel A. |last3=Vasanthan |first3=Lenny |last4=Konstantinidis |first4=Menelaos |last5=Thompson |first5=Jacqueline |date=2022-06-06 |title=Positioning for acute respiratory distress in hospitalised infants and children |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=6 |pages=CD003645 |doi=10.1002/14651858.CD003645.pub4 |issn=1469-493X |pmc=9169533 |pmid=35661343}} However, attention should be paid to avoid the SIDS in the management of the respiratory distressed infants by continuous careful monitoring of their cardiovascular system.

Several studies have shown that pulmonary function and outcome are better in people with ARDS who lost weight or whose pulmonary wedge pressure was lowered by diuresis or fluid restriction.

As of 2019, it is uncertain whether or not treatment with corticosteroids improves overall survival. Corticosteroids may increase the number of ventilator-free days during the first 28 days of hospitalization. One study found that dexamethasone may help.{{Cite journal |pmid = 32043986|year = 2020|last1 = Villar|first1 = J.|last2 = Ferrando|first2 = C.|last3 = Martínez|first3 = D.|last4 = Ambrós|first4 = A.|last5 = Muñoz|first5 = T.|last6 = Soler|first6 = J. A.|last7 = Aguilar|first7 = G.|last8 = Alba|first8 = F.|last9 = González-Higueras|first9 = E.|last10 = Conesa|first10 = L. A.|last11 = Martín-Rodríguez|first11 = C.|last12 = Díaz-Domínguez|first12 = F. J.|last13 = Serna-Grande|first13 = P.|last14 = Rivas|first14 = R.|last15 = Ferreres|first15 = J.|last16 = Belda|first16 = J.|last17 = Capilla|first17 = L.|last18 = Tallet|first18 = A.|last19 = Añón|first19 = J. M.|last20 = Fernández|first20 = R. L.|last21 = González-Martín|first21 = J. M.|author22 = dexamethasone in ARDS network|s2cid = 211077493|title = Dexamethasone treatment for the acute respiratory distress syndrome: A multicentre, randomised controlled trial|journal = The Lancet. Respiratory Medicine|volume = 8|issue = 3|pages = 267–276|doi = 10.1016/S2213-2600(19)30417-5}} The combination of hydrocortisone, ascorbic acid, and thiamine also requires further study as of 2018.{{cite journal |last1=Moskowitz |first1=A |last2=Andersen |first2=LW |last3=Huang |first3=DT |last4=Berg |first4=KM |last5=Grossestreuer |first5=AV |last6=Marik |first6=PE |last7=Sherwin |first7=RL |last8=Hou |first8=PC |last9=Becker |first9=LB |last10=Cocchi |first10=MN |last11=Doshi |first11=P |last12=Gong |first12=J |last13=Sen |first13=A |last14=Donnino |first14=MW |title=Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. |journal=Critical Care |date=29 October 2018 |volume=22 |issue=1 |pages=283 |doi=10.1186/s13054-018-2217-4 |pmid=30373647|pmc=6206928 |doi-access=free }}

Inhaled nitric oxide (NO) selectively widens the lung's arteries which allows for more blood flow to open alveoli for gas exchange. Despite evidence of increased oxygenation status, there is no evidence that inhaled nitric oxide decreases morbidity and mortality in people with ARDS.{{cite journal|last1=Adhikari|first1=NK|last2=Burns|first2=KE|last3=Friedrich|first3=JO|last4=Granton|first4=JT|last5=Cook|first5=DJ|last6=Meade|first6=MO|title=Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis|journal=BMJ |edition=Clinical research|date=14 April 2007|volume=334|issue=7597|pages=779|pmid=17383982|pmc=1852043|doi=10.1136/bmj.39139.716794.55}} Furthermore, nitric oxide may cause kidney damage and is not recommended as therapy for ARDS regardless of severity.{{cite journal|last1=Adhikari|first1=NK|last2=Dellinger|first2=RP|last3=Lundin|first3=S|last4=Payen|first4=D|last5=Vallet|first5=B|last6=Gerlach|first6=H |last7=Park|first7=KJ|last8=Mehta|first8=S|last9=Slutsky|first9=AS|last10=Friedrich|first10=JO|s2cid=12204105|title=Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis|journal=Critical Care Medicine|date=February 2014|volume=42|issue=2|pages=404–12|pmid=24132038|doi=10.1097/CCM.0b013e3182a27909|type=Systematic Review & Meta-Analysis}}

Alvelestat (AZD 9668) had been quoted according to one review article.Herrero R., Rojas Y., Esteban A. (2014) Novel Pharmacologic Approaches for the Treatment of ARDS. In: Vincent JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2014. Annual Update in Intensive Care and Emergency Medicine, vol 2014. Springer, Cham. https://doi.org/10.1007/978-3-319-03746-2_18

Extracorporeal membrane oxygenation (ECMO) is mechanically applied prolonged cardiopulmonary support. There are two types of ECMO: Venovenous which provides respiratory support and venoarterial which provides respiratory and hemodynamic support. People with ARDS who do not require cardiac support typically undergo venovenous ECMO. Multiple studies have shown the effectiveness of ECMO in acute respiratory failure.{{cite journal|last1=Makdisi|first1=G|last2=Wang|first2=IW|title=Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology|journal=Journal of Thoracic Disease|date=July 2015|volume=7|issue=7|pages=E166–76|pmid=26380745|doi=10.3978/j.issn.2072-1439.2015.07.17|pmc=4522501}}{{cite journal|last1=Hemmila|first1=MR|last2=Rowe|first2=SA|last3=Boules|first3=TN|last4=Miskulin|first4=J|last5=McGillicuddy|first5=JW|last6=Schuerer|first6=DJ|last7=Haft|first7=JW|last8=Swaniker|first8=F|last9=Arbabi|first9=S|last10=Hirschl|first10=RB|last11=Bartlett|first11=RH|title=Extracorporeal life support for severe acute respiratory distress syndrome in adults|journal=Annals of Surgery|date=October 2004|volume=240|issue=4|pages=595–605; discussion 605–7|pmid=15383787|pmc=1356461|doi=10.1097/01.sla.0000141159.90676.2d}}{{cite journal|last1=Brogan|first1=TV|last2=Thiagarajan|first2=RR|last3=Rycus|first3=PT|last4=Bartlett|first4=RH|last5=Bratton|first5=SL|s2cid=526020|title=Extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database|journal=Intensive Care Medicine|date=December 2009|volume=35|issue=12|pages=2105–14|pmid=19768656|doi=10.1007/s00134-009-1661-7|doi-access=free}} Specifically, the CESAR (Conventional ventilatory support versus Extracorporeal membrane oxygenation for Severe Acute Respiratory failure) trial{{cite journal|last1=Peek|first1=GJ|last2=Mugford|first2=M|last3=Tiruvoipati|first3=R|last4=Wilson|first4=A|last5=Allen|first5=E|last6=Thalanany|first6=MM|last7=Hibbert|first7=CL|last8=Truesdale|first8=A|last9=Clemens|first9=F|last10=Cooper|first10=N|last11=Firmin|first11=RK|last12=Elbourne|first12=D|last13=CESAR trial|first13=collaboration|s2cid=15191122|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|date=17 October 2009|volume=374|issue=9698|pages=1351–63|pmid=19762075|doi=10.1016/S0140-6736(09)61069-2}} demonstrated that a group referred to an ECMO center demonstrated significantly increased survival compared to conventional management (63% to 47%).{{cite book|editor1-first=Fabio|editor1-last=Sangalli|editor2-first=Nicolò|editor2-last=Patroniti|editor3-first=Antonio|editor3-last=Pesenti|title=ECMO-Extracorporeal Life Support in Adults|date=2014|publisher=Springer |isbn=978-88-470-5427-1}}

As of 2019, there is no evidence showing that treatments with exogenous surfactants, statins, beta-blockers or n-acetylcysteine decreases early mortality, late all-cause mortality, duration of mechanical ventilation, or number of ventilator-free days.

The overall prognosis of ARDS is poor, with mortality rates of approximately 40%.{{Cite journal|last1=Lewis|first1=Sharon R.|last2=Pritchard|first2=Michael W.|last3=Thomas|first3=Carmel M.|last4=Smith|first4=Andrew F.|date=July 23, 2019|title=Pharmacological agents for adults with acute respiratory distress syndrome|journal=The Cochrane Database of Systematic Reviews|volume=7|issue=7 |pages=CD004477|doi=10.1002/14651858.CD004477.pub3|issn=1469-493X|pmc=6646953|pmid=31334568}} Exercise limitation, physical and psychological sequelae, decreased physical quality of life, and increased costs and use of health care services are important sequelae of ARDS.{{citation needed|date=November 2020}}

The annual rate of ARDS is generally 13–23 people per 100,000 in the general population.{{cite journal |vauthors=Lewandowski K, Lewandowski M | year = 2006 | title = Epidemiology of ARDS | journal = Minerva Anestesiol | volume = 72 | issue = 6| pages = 473–7 | pmid = 16682918 }} It is more common in people who are mechanically ventilated with acute lung injury (ALI) occurring in 16% of ventilated people. Rates increased in 2020 due to COVID-19, with some cases also appearing similar to HAPE.{{cite journal |last1=Guo |first1=YR |last2=Cao |first2=QD |last3=Hong |first3=ZS |last4=Tan |first4=YY |last5=Chen |first5=SD |last6=Jin |first6=HJ |last7=Tan |first7=KS |last8=Wang |first8=DY |last9=Yan |first9=Y |title=The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. |journal=Military Medical Research |date=13 March 2020 |volume=7 |issue=1 |pages=11 |doi=10.1186/s40779-020-00240-0 |pmid=32169119|pmc=7068984 |doi-access=free }}{{cite journal |last1=Solaimanzadeh |first1=I |title=Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19). |journal=Cureus |date=20 March 2020 |volume=12 |issue=3 |pages=e7343 |doi=10.7759/cureus.7343 |doi-access=free |pmid=32226695|pmc=7096066 }}

Worldwide, severe sepsis is the most common trigger causing ARDS.{{cite book|last1=Goldman|first1=Lee|title=Goldman's Cecil Medicine|publisher=Elsevier Saunders|location=Philadelphia|isbn=978-1437727883|year=2011|pages=635|edition=24th}} Other triggers include mechanical ventilation, sepsis, pneumonia, Gilchrist's disease, drowning, circulatory shock, aspiration, trauma{{mdash}}especially pulmonary contusion{{mdash}}major surgery, massive blood transfusions,{{cite journal |last1=Vlaar |first1=Alexander P. J. |last2=Binnekade |first2=Jan M. |last3=Prins |first3=David |last4=van Stein |first4=Danielle |last5=Hofstra |first5=Jorrit J. |last6=Schultz |first6=Marcus J. |last7=Juffermans |first7=Nicole P. |s2cid=12118692 |title=Risk factors and outcome of transfusion-related acute lung injury in the critically ill: A nested case–control study* |journal=Critical Care Medicine |date=March 2010 |volume=38 |issue=3 |pages=771–778 |doi=10.1097/CCM.0b013e3181cc4d4b |pmid=20035217 }} smoke inhalation, drug reaction or overdose, fat emboli and reperfusion pulmonary edema after lung transplantation or pulmonary embolectomy. However, the majority of patients with all these conditions mentioned do not develop ARDS. It is unclear why some people with the mentioned factors above do not develop ARDS and others do.{{citation needed|date=August 2022}}

Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients and may be either causes or complications of ARDS. Alcohol excess appears to increase the risk of ARDS.{{cite journal |vauthors=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 |doi=10.1001/jama.1996.03530250054027|pmid = 8531287 }} Diabetes was originally thought to decrease the risk of ARDS, but this has shown to be due to an increase in the risk of pulmonary edema.{{cite journal |title = Diabetic patients have a decreased incidence of acute respiratory distress syndrome|vauthors=Moss M, Guidot DM, Steinberg KP |s2cid=29504738 |journal = Crit Care Med |year = 2000 |volume = 28 |issue = 7 |pages = 2187–92 |pmid = 10921539|display-authors=etal |doi=10.1097/00003246-200007000-00001}}{{cite journal| journal = Crit Care Med |year = 2012 |volume = 40 |issue = 6 |pages = 1835–1843 |title = In the critically ill patient, diabetes predicts mortality independent of statin therapy but is not associated with acute lung injury: A cohort study |vauthors=Koh GC, Vlaar AP, Hofstra JJ |pmid = 22488007 |doi=10.1097/CCM.0b013e31824e1696 |pmc=3379571|display-authors=etal}} Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation.{{citation needed|date=January 2015}}

Acute respiratory distress syndrome was first described in 1967 by Ashbaugh et al.{{cite book |vauthors=Irwin RS, Rippe JM | title = Irwin and Rippe's Intensive Care Medicine | edition = 5th | publisher = Lippincott Williams & Wilkins | year = 2003 | isbn = 978-0-7817-3548-3 }}{{cite journal |vauthors=Ashbaugh D, Bigelow D, Petty T, Levine B | title = Acute respiratory distress in adults | journal = Lancet | volume = 2 |issue = 7511 | pages = 319–23 | year = 1967 | pmid = 4143721 | doi = 10.1016/S0140-6736(67)90168-7| pmc = 1923469 }} Initially there was no clearly established definition, which resulted in controversy regarding the incidence and death of ARDS.

In 1988, an expanded definition was proposed, which quantified physiologic respiratory impairment.

In 1994, a new definition was recommended by the American-European Consensus Conference Committee {{cite journal |vauthors=Bernard G, Artigas A, Brigham K, Carlet J, Falke K, Hudson L, Lamy M, Legall J, Morris A, Spragg R | title = The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination | journal = Am J Respir Crit Care Med | volume = 149 | issue = 3 Pt 1 |pages = 818–24 | year = 1994 | pmid = 7509706 | doi=10.1164/ajrccm.149.3.7509706}} which recognized the variability in severity of pulmonary injury.{{cite journal |vauthors=Ware L, Matthay M | title = The acute respiratory distress syndrome | journal = N Engl J Med | volume = 342 | issue = 18 | pages = 1334–49 | year = 2000 | pmid = 10793167 | doi = 10.1056/NEJM200005043421806}}

The definition required the following criteria to be met:

• acute onset, persistent dyspnea
• bilateral infiltrates on chest radiograph consistent with pulmonary edema
• hypoxemia, defined as Pa{{chem|O|2}}:Fi{{chem|O|2}} < 200 mmHg (26.7 kPa)
• absence of left atrial (LA) hypertension
• pulmonary artery wedge pressure < 18 mmHg (obtained by pulmonary artery catheterization)
• if no measured LA pressure available, there must be no other clinical evidence to suggest elevated left heart pressure.

If Pa{{chem|O|2}}:Fi{{chem|O|2}} < 300 mmHg (40 kPa), then the definitions recommended a classification as "acute lung injury" (ALI). Note that according to these criteria, arterial blood gas analysis and chest X-ray were required for formal diagnosis. Limitations of these definitions include lack of precise definition of acuity, nonspecific imaging criteria, lack of precise definition of hypoxemia with regards to PEEP (affects arterial oxygen partial pressure), arbitrary Pa{{chem|O|2}} thresholds without systematic data.{{cite journal |last1=Abraham |first1=Edward |last2=Matthay |first2=Michael A. |last3=Dinarello |first3=Charles A. |last4=Vincent |first4=Jean-Louis |last5=Cohen |first5=Jonathan |last6=Opal |first6=Steven M. |last7=Glauser |first7=Michel |last8=Parsons |first8=Polly |last9=Fisher |first9=Charles J. |last10=Repine |first10=John E. |s2cid=19636525 |title=Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: Time for a reevaluation |journal=Critical Care Medicine |date=January 2000 |volume=28 |issue=1 |pages=232–235 |doi=10.1097/00003246-200001000-00039 |pmid=10667529 }}

In 2012, the Berlin Definition of ARDS was devised by the European Society of Intensive Care Medicine, and was endorsed by the American Thoracic Society and the Society of Critical Care Medicine. These recommendations were an effort to both update classification criteria in order to improve clinical usefulness and to clarify terminology. Notably, the Berlin guidelines discourage the use of the term "acute lung injury" or ALI, as the term was commonly being misused to characterize a less severe degree of lung injury. Instead, the committee proposes a classification of ARDS severity as mild, moderate, or severe according to arterial oxygen saturation. The Berlin definitions represent the current international consensus guidelines for both clinical and research classification of ARDS.{{citation needed|date=August 2022}}

ARDS is the severe form of acute lung injury (ALI), and of transfusion-related acute lung injury (TRALI), though there are other causes. The Berlin definition included ALI as a mild form of ARDS.{{cite web |title=Meet the New ARDS: Expert panel announces new definition, severity classes |url=https://pulmccm.org/ards-review/consensus-panel-announces-new-definition-severity-classes-for-ards-jama/ |website=PulmCCM |date=30 December 2012}} However, the criteria for the diagnosis of ARDS in the Berlin definition excludes many children, and a new definition for children was termed pediatric acute respiratory distress syndrome (PARDS); this is known as the PALICC definition (2015).{{cite journal |last1=Khemani|display-authors=et al |first1=RG |title=Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. |journal=The Lancet. Respiratory Medicine |volume=7 |issue=2 |pages=115–128 |doi=10.1016/S2213-2600(18)30344-8 |pmid=30361119|year=2019 |pmc=7045907 }}{{cite journal |last1=Pediatric Acute Lung Injury Consensus Conference |first1=Group. |title=Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. |journal=Pediatric Critical Care Medicine |date=June 2015 |volume=16 |issue=5 |pages=428–39 |doi=10.1097/PCC.0000000000000350 |pmid=25647235|pmc=5253180 }}

There is ongoing research on the treatment of ARDS by interferon (IFN) beta-1a to aid in preventing leakage of vascular beds. Traumakine (FP-1201-lyo) is a recombinant human IFN beta-1a drug, developed by the Finnish company Faron Pharmaceuticals, which is undergoing international phase-III clinical trials after an open-label, early-phase trial showed an 81% reduction-in-odds of 28-day mortality in ICU patients with ARDS.{{Cite journal|last1=Bellingan|first1=Geoff|last2=Maksimow|first2=Mikael|last3=Howell|first3=David C.|last4=Stotz|first4=Martin|last5=Beale|first5=Richard|last6=Beatty|first6=Monika|last7=Walsh|first7=Timothy|last8=Binning|first8=Alexander|last9=Davidson|first9=Alan|date=February 2014|title=The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study|journal=The Lancet. Respiratory Medicine|volume=2|issue=2|pages=98–107|doi=10.1016/S2213-2600(13)70259-5|issn=2213-2600|pmid=24503265}} The drug is known to function by enhancing lung CD73 expression and increasing production of anti-inflammatory adenosine, such that vascular leaking and escalation of inflammation are reduced.{{Cite journal|last1=Kiss|first1=Jan|last2=Yegutkin|first2=Gennady G.|last3=Koskinen|first3=Kaisa|last4=Savunen|first4=Timo|last5=Jalkanen|first5=Sirpa|last6=Salmi|first6=Marko|date=November 2007|title=IFN-β protects from vascular leakage via up-regulation of CD73|journal=European Journal of Immunology|volume=37|issue=12|pages=3334–3338|doi=10.1002/eji.200737793|pmid=18034430|s2cid=8089872|issn=1521-4141|doi-access=free}}

Aspirin has been studied in those who are at high risk and was not found to be useful.

An intravenous ascorbic acid treatment was tested in the 2019 RCT, in people with ARDS due to sepsis and there was no change in primary endpoints.{{cite web |title=PulmCrit- CITRIS-ALI: Can a secondary endpoint stage a coup d'état? |url=https://emcrit.org/pulmcrit/pulmcrit-citris-ali-can-a-secondary-endpoint-stage-a-coup-detat/ |website=PulmCrit |date=1 October 2019}}

• Respiratory monitoring

{{Reflist}}

• {{cite book |last=Marino |first=Paul |year=2006 |title=The ICU Book |location=Baltimore |publisher=Williams & Wilkins |isbn=978-0781748025 }}
• {{cite journal |vauthors=Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR |s2cid=38941988 |date=1 August 2005 |title=A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury |journal=Crit. Care Med. |volume=33 |issue=8 |pages=1681–7 |pmid=16096441 |doi= 10.1097/01.CCM.0000171539.47006.02}}
• {{cite journal |vauthors=Jackson WL, Shorr AF |date=1 June 2005 |title=Blood transfusion and the development of acute respiratory distress syndrome: more evidence that blood transfusion in the intensive care unit may not be benign |journal=Crit. Care Med. |volume=33 |issue=6 |pages=1420–1 |pmid=15942365 |doi= 10.1097/01.CCM.0000167073.99222.50}}
• {{cite journal |vauthors=Mortelliti MP, Manning HL |date=May 2002 |title=Acute respiratory distress syndrome |journal=Am Fam Physician |volume=65 |issue=9 |pages=1823–30 |pmid=12018805 |url=http://www.aafp.org/afp/20020501/1823.html |access-date=2005-08-28 |archive-date=2008-09-06 |archive-url=https://web.archive.org/web/20080906182419/http://www.aafp.org/afp/20020501/1823.html |url-status=dead }}
• {{cite journal |last1=Metnitz |first1=P. G. H. |last2=Bartens |first2=C. |last3=Fischer |first3=M. |last4=Fridrich |first4=P. |last5=Steltzer |first5=H. |last6=Druml |first6=W. |s2cid=11377820 |title=Antioxidant status in patients with acute respiratory distress syndrome |journal=Intensive Care Medicine |date=17 February 1999 |volume=25 |issue=2 |pages=180–185 |doi=10.1007/s001340050813 |pmid=10193545 }}

{{Medical resources

| ICD10 = {{ICD10|J|80||j|80}}

| ICD9 = {{ICD9|518.5}}, {{ICD9|518.82}}

| ICDO =

| OMIM =

| MedlinePlus = 000103

| eMedicineSubj = article

| eMedicineTopic = 165139

| DiseasesDB = 892

| MeshID = D012128

| SNOMED CT = 67782005

}}

{{Wikibooks|Intensive Care Medicine|clinical/ards|ARDS}}

• [http://www.ardsnet.org/ ARDSNet]—the NIH / NHLBI ARDS Network
• [https://web.archive.org/web/20151214175951/http://ards.org/ ARDS Support Center]—information for patients with ARDS

{{Respiratory pathology}}

{{Intensive care medicine}}

{{Authority control}}

{{DEFAULTSORT:Acute Respiratory Distress Syndrome}}

Category:Causes of death

Category:Intensive care medicine

Category:Respiratory diseases principally affecting the interstitium

Category:Respiratory physiology

Category:Syndromes affecting the respiratory system