Acute respiratory distress syndrome (ARDS) is a life-threatening condition of critically ill patients, characterized by poor oxygenation and non-compliant or "stiff" lungs. The disorder is associated with capillary endothelial injury and diffuse alveolar damage.
ARDS is defined as an acute disorder characterized by bilateral lung infiltrates and severe progressive hypoxemia in the absence of any evidence of cardiogenic pulmonary edema. ARDS is defined by the patient's arterial blood (Pa02) to the fraction of the oxygen in the inspired air (Fi02). These patients usually have a Pa02/Fi02 ratio of less than 200.
Once ARDS develops, patients usually have varying degrees of pulmonary artery vasoconstriction and subsequently, may develop pulmonary hypertension. ARDS carries a high mortality, and few effective therapeutic modalities exist to ameliorate this deadly condition.
ARDS has many risk factors. Besides pulmonary infection or aspiration, extra-pulmonary sources include sepsis, trauma, massive transfusion, drowning, drug overdose, fat embolism, and pancreatitis. These extra-thoracic illnesses and/or injuries trigger an inflammatory reaction resulting in remote pulmonary damage.
Risk factors for ARDS include:
Estimates of the incidence of ARDS in the United States range from 64.2 to 78.9 cases/100,000 person-years. Twenty-five percent of ARDS cases are initially classified as mild and 75% as moderate or severe. However, a third of the mild cases go on to progress to moderate or severe disease. A literature review revealed a mortality decrease of 1.1% per year for the period 1994 through 2006. However, the overall pooled mortality rate for all the studies evaluated was still a very significant 43%.
ARDS represents a stereotypic response to various etiologies. It progresses through different phases, starting with alveolar capillary damage, to lung resolution, culminating in a fibroproliferative phase. The pulmonary epithelial and endothelial cellular damage is characterized by inflammation, apoptosis, necrosis, and increased alveolar-capillary permeability, which leads to the development of alveolar edema. Alveolar edema, in turn, worsens oxygenation, leading to hypoxemia. A hallmark of the damage seen in ARDS is that it is not uniform. Segments of the lung may be more severely affected resulting in more decreased regional lung compliance. This intra-pulmonary differential in pathology results in differential response to oxygenation strategies. While increased positive end-expiratory pressure (PEEP) may improve oxygen diffusion of affected alveoli, it may result in deleterious volutrauma, barotrauma, or atelectrauma of adjacent unaffected alveoli. 
The key histologic changes in ARDS reveal the presence of diffuse alveolar damage. Other findings may include alveolar hemorrhage, pulmonary capillary congestion, interstitial edema, and hyaline membrane formation. None of these changes are specific for the disease. 
The syndrome is characterized by the development of dyspnea and hypoxemia which progressively gets worse within hours to days, requiring mechanical ventilation and intensive care unit (ICU)-level care. The history is directed at identifying the underlying disease which has precipitated the ARDS. Bear in mind that this disease may be extra-thoracic. Patients start to initially complain of mild dyspnea but within 12-24 hours, the respiratory distress can become severe requiring mechanical ventilation.
The physical examination will include findings associated with the respiratory system such as tachypnea and increased work of breathing. Despite 100% oxygen, patients have low oxygen saturation. There is associated peripheral vasoconstriction, hypotension, and cold extremities. Cyanosis in the extremities is not uncommon.
Chest auscultation usually reveals bilateral rales.
The physical exam should also be directed to identify associated organ failures such as shock or coma.
The diagnosis of ARDS is made based on the following criteria: acute onset, bilateral CXR infiltrates non-cardiogenic and a PaO2/FiO2 ratio of less than 300. It is further sub-classified into mild (PaO2/FiO2 200 to 300), moderate (PaO2/FiO2 100 to 200), and severe (PaO2/FiO2 less than 100) forms. Mortality and ventilatory free days increase with severity as expected.
CT scan may be required in cases of pneumothorax, pleural effusions, medicational adenopathy, and barotrauma.
Assessment of ventricular function may be required to differentiate from or quantify the contribution of congestive heart failure to the overall clinical picture. This assessment can be achieved via invasive methods such as pulmonary artery catheter measurements or non-invasive methods such as thoracic bioimpedance or pulse contour analysis.
Invasive monitoring using a central line may be required in most patients. The use of pulmonary artery catheters is controversial and should be avoided.
Bronchoscopy may be required to assess pulmonary infections and obtain material for culture.
Other laboratory and/or radiographic tests will be guided by the underlying disease process which has triggered the inflammatory process that has led to the ARDS. Also, laboratory tests will be needed as patients with ARDS are highly likely to develop or be to suffer from associated multiorgan failure including but not limited to renal, hepatic, and hematopoietic failures. 
No drug has proven to be effective in preventing or managing ARDS. The major treatment is supportive along with adequate nutrition. Evidence suggests that ventilatory strategies if left unchecked, can exacerbate alveolar damage and perpetuate lung injury in the context of ARDS. Care is placed in preventing volutrauma (exposure to large tidal volumes), barotrauma (exposure to high plateau pressures), and atelectrauma (exposure to atelectasis). 
A lung protective ventilatory strategy is advocated to reduce lung injury. The NIH-NHLBI ARDS Clinical Network Mechanical Ventilation Protocol (ARDSnet) sets the following goals: TV 4 to 8 ml per kg IBW, RR up to 35 bpm, SpO2 88% to 95%, plateau pressure less than 30 cm H2O, pH goal 7.30 to 7.45, inspiratory-to-expiratory time ratio less than 1.,
To maintain oxygenation, ARDSnet recognizes the benefit of PEEP. The protocol allows for a low or a high PEEP strategy relative to FiO2. Either strategy tolerates a PEEP of up to 24 cm H2O in patients requiring 100% FiO2. The inspiratory-to-expiratory time ratio goal may need to be sacrificed and an inverse inspiratory-to-expiratory time ratio strategy instituted to improve oxygenation.
Novel invasive ventilation strategies have been developed to improve oxygenation. These include airway pressure release ventilation and high-frequency oscillation ventilation. These open-lung ventilation strategies can be supplemented with recruitment maneuvers.
Patients with mild and some with moderate ARDS may benefit from non-invasive ventilation to avoid endotracheal intubation and invasive mechanical ventilation. These modalities include continuous positive airway pressure (CPAP), bilevel airway pressure (BiPAP), proportional-assist ventilation, and high flow nasal cannula.
Plateau pressure less than 30 cm H2O can be achieved using several strategies. The first one is to maintain as low VT and PEEP as possible. Also, increasing the rise and/or inspiration times can also help maintain the Pplat goal. Finally, the flow rate can be decreased as an adjunct to decreasing the Pplat. High Pplat is also a product of decreased lung compliance, a salient feature of ARDS pathophysiology.
Improving lung compliance will improve Pplat and oxygenation goals attainment. Neuromuscular blockers have been used in this endeavor. Neuromuscular blockers instituted during the first 48 hrs of ARDS was found to improve 90-day survival and increase time off the ventilator. Other causes of decreased lung compliance should be sought and addressed. These include but are not limited to, pneumothorax, hemothorax, thoracic compartment syndrome, and intraabdominal hypertension.
Prone position has shown benefit in about 50-70% of patients. The improvement in oxygenation is rapid and allows reduction in Fi02 and PEEP. The prone position is safe but there is a risk of dislodgement of lines and tubes. It is believed that in the prone position there is recruitment of dependent lung zones, improved diaphragmatic excursion and increased functional residual capacity. To derive the benefits, the patient needs to be maintained in the prone position for at least 8 hours a day.
Non-ventilatory strategies have included prone positioning  and conservative fluid management once resuscitation has been achieved. Recently, extracorporeal membrane oxygenation has also been advocated as salvage therapy in refractory hypoxemic ARDS.
Nutritional support via enteral feeding is recommended. A high fat low carbohydrate diet containing gamma linolenic acid and eicosapentaeenoic acid have been shown in some studies to improve oxygenation.
To prevent pressure sores and improve muscle function, frequent patient positioning is recommended. Physical therapy should be involved in exercising the patient.
The prognosis for ARDS was abysmal until very recently. There were reports of 30% to 40% mortality up until the 90s, but over the past 2 decades, improvements in technology, a better understanding of mechanical ventilation and better antibiotics, the mortality rates have dropped significantly. The major cause of death in ARDS patients was from sepsis or multiorgan failure. While mortality rates are now around 9% to 20%, the disorder has significant morbidity. Patients remain in the hospital for months and have significant weight loss, poor muscle function, and functional impairment. The hypoxia also leads to a variety of cognitive changes which persist for many months after discharge. For many survivors, returning to a normal life is not possible as they continue to have poor weight gain and no exercise endurance. The quality of life of survivors is poor.
Tracheostomy and PEG
Many patients with ARDS end up requiring a tracheostomy and a percutaneous feeding tube in the recovery phase. The tracheostomy facilitates weaning from the ventilator, make it easy to clear up the secretions and is more comfortable for the patient, compared to the oral endotracheal tube. The tracheostomy is usually done at 2 to 3 weeks, followed by a percutaneous feeding tube.
The majority of ARDS have difficulty eating, and muscle wasting is very common. These patients are either given enteral or parenteral feeding, depending on the condition of the gastrointestinal tract. Some experts recommend a low carbohydrate high fat diet as it has anti-inflammatory and vasodilating benefits. Almost every type of nutritional supplement has been studied in ARDS patients, but so far, none has proven to be the magic bullet.
Since patients with ARDS are bedridden frequent changes in position are highly recommended to prevent bedsores and deep vein thrombosis. In patients who are alert, one can minimize the sedation and sit them in a chair.
Management of ARDS patients requires a multidisciplinary team of healthcare workers that include:
Even though many risk factors for ARDS are known, there is no way of preventing ARDS. However, careful management of fluid in high-risk patients can be helpful. Steps should be taken to prevent aspiration by keeping the head of bed elevated before feeding.
ARDS is a serious disorder of the lung which has the potential to cause death. Patients with ARDS require mechanical ventilation because of hypoxia. The management is usually in the ICU with a team of healthcare workers. ARDS has repercussions beyond the lung. The prolonged mechanical ventilation often leads to bed sores, deep vein thrombosis, multiorgan failure, weight loss, and poor overall functioning. It is important to have an integrated, streamlined approach to management of ARDS because it usually affects many other organs in the body. These patients need nutritional support, chest therapy, treatment for sepsis, and even dialysis. Many of these patients remain in the hospital for months and even those who survive face severe challenges as a result of a loss of muscle mass and cognitive changes (due to hypoxia). There is ample evidence showing that an interprofessional team approach leads to better outcomes as it facilitates communication and ensures timely intervention. The team should consist of the following:
Despite advances in critical care, ARDS still has high morbidity and mortality. Even those who survive have a very poor quality of life. While many risk factors are known for ARDS, there is no way to prevent the condition. Besides the restriction of fluids in high-risk patients, close monitoring by the nurses for hypoxia is vital. The earlier the hypoxia is identified, the better the outcome.
Unfortunately, even those who survive have a long recovery period and most never regain full functional status and remain disabled for life. Many continue to have dyspnea even with mild exertion and thus are dependent on care from others. (Level V)
|||Hypoxemia in the ICU: prevalence, treatment, and outcome. Annals of intensive care. 2018 Aug 13 [PubMed PMID: 30105416]|
|||Calfee CS,Delucchi KL,Sinha P,Matthay MA,Hackett J,Shankar-Hari M,McDowell C,Laffey JG,O'Kane CM,McAuley DF, Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. The Lancet. Respiratory medicine. 2018 Aug 2 [PubMed PMID: 30078618]|
|||Yang P,Formanek P,Scaglione S,Afshar M, Risk Factors and Outcomes of Acute Respiratory Distress Syndrome in Critically Ill Patients with Cirrhosis. Hepatology research : the official journal of the Japan Society of Hepatology. 2018 Aug 7 [PubMed PMID: 30084205]|
|||Walkey AJ,Summer R,Ho V,Alkana P, Acute respiratory distress syndrome: epidemiology and management approaches. Clinical epidemiology. 2012; [PubMed PMID: 22866017]|
|||Zambon M,Vincent JL, Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 2008 May [PubMed PMID: 18263687]|
|||Sharma NS,Lal CV,Li JD,Lou XY,Viera L,Abdallah T,King R,Sethi J,Kanagarajah P,Restrepo-Jaramillo R,Sales-Conniff A,Wei S,Jackson PL,Blalock JE,Gaggar A,Xu X, The Neutrophil Chemoattractant Peptide Proline-Glycine-Proline Is Associated With Acute Respiratory Distress Syndrome (ARDS). American journal of physiology. Lung cellular and molecular physiology. 2018 Aug 9 [PubMed PMID: 30091378]|
|||Chamarthy MR,Kandathil A,Kalva SP, Pulmonary vascular pathophysiology. Cardiovascular diagnosis and therapy. 2018 Jun [PubMed PMID: 30057870]|
|||Huang D,Ma H,Xiao Z,Blaivas M,Chen Y,Wen J,Guo W,Liang J,Liao X,Wang Z,Li H,Li J,Chao Y,Wang XT,Wu Y,Qin T,Su K,Wang S,Tan N, Diagnostic value of cardiopulmonary ultrasound in elderly patients with acute respiratory distress syndrome. BMC pulmonary medicine. 2018 Aug 13 [PubMed PMID: 30103730]|
|||Chen WL,Lin WT,Kung SC,Lai CC,Chao CM, The Value of Oxygenation Saturation Index in Predicting the Outcomes of Patients with Acute Respiratory Distress Syndrome. Journal of clinical medicine. 2018 Aug 8 [PubMed PMID: 30096809]|
|||Rawal G,Yadav S,Kumar R, Acute Respiratory Distress Syndrome: An Update and Review. Journal of translational internal medicine. 2018 Jun [PubMed PMID: 29984201]|
|||Cherian SV,Kumar A,Akasapu K,Ashton RW,Aparnath M,Malhotra A, Salvage therapies for refractory hypoxemia in ARDS. Respiratory medicine. 2018 Aug [PubMed PMID: 30053961]|
|||Papazian L,Forel JM,Gacouin A,Penot-Ragon C,Perrin G,Loundou A,Jaber S,Arnal JM,Perez D,Seghboyan JM,Constantin JM,Courant P,Lefrant JY,Guérin C,Prat G,Morange S,Roch A, Neuromuscular blockers in early acute respiratory distress syndrome. The New England journal of medicine. 2010 Sep 16 [PubMed PMID: 20843245]|
|||Guérin C,Reignier J,Richard JC,Beuret P,Gacouin A,Boulain T,Mercier E,Badet M,Mercat A,Baudin O,Clavel M,Chatellier D,Jaber S,Rosselli S,Mancebo J,Sirodot M,Hilbert G,Bengler C,Richecoeur J,Gainnier M,Bayle F,Bourdin G,Leray V,Girard R,Baboi L,Ayzac L, Prone positioning in severe acute respiratory distress syndrome. The New England journal of medicine. 2013 Jun 6 [PubMed PMID: 23688302]|
|||Wiedemann HP,Wheeler AP,Bernard GR,Thompson BT,Hayden D,deBoisblanc B,Connors AF Jr,Hite RD,Harabin AL, Comparison of two fluid-management strategies in acute lung injury. The New England journal of medicine. 2006 Jun 15 [PubMed PMID: 16714767]|
|||Brodie D,Bacchetta M, Extracorporeal membrane oxygenation for ARDS in adults. The New England journal of medicine. 2011 Nov 17 [PubMed PMID: 22087681]|
|||Combes A,Hajage D,Capellier G,Demoule A,Lavoué S,Guervilly C,Da Silva D,Zafrani L,Tirot P,Veber B,Maury E,Levy B,Cohen Y,Richard C,Kalfon P,Bouadma L,Mehdaoui H,Beduneau G,Lebreton G,Brochard L,Ferguson ND,Fan E,Slutsky AS,Brodie D,Mercat A, Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. The New England journal of medicine. 2018 May 24 [PubMed PMID: 29791822]|
|||Gadre SK,Duggal A,Mireles-Cabodevila E,Krishnan S,Wang XF,Zell K,Guzman J, Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD). Medicine. 2018 Apr [PubMed PMID: 29703009]|
|||Chiumello D,Coppola S,Froio S,Gotti M, What's Next After ARDS: Long-Term Outcomes. Respiratory care. 2016 May [PubMed PMID: 27121623]|
|||Villar J,Schultz MJ,Kacmarek RM, The LUNG SAFE: a biased presentation of the prevalence of ARDS! Critical care (London, England). 2016 Apr 25 [PubMed PMID: 27109238]|
|||Bos LD,Cremer OL,Ong DS,Caser EB,Barbas CS,Villar J,Kacmarek RM,Schultz MJ, External validation confirms the legitimacy of a new clinical classification of ARDS for predicting outcome. Intensive care medicine. 2015 Nov [PubMed PMID: 26202043]|
|||Bein T,Weber-Carstens S,Apfelbacher C, Long-term outcome after the acute respiratory distress syndrome: different from general critical illness? Current opinion in critical care. 2018 Feb; [PubMed PMID: 29189296]|