Acute Respiratory Distress Syndrome

I. What every physician needs to know.

Acute Respiratory Distress Syndrome (ARDS) also known as, adult respiratory distress syndrome (previously non-cardiogenic pulmonary edema) is a syndrome of acute respiratory failure characterized by bilateral diffuse alveolar infiltrates on chest radiography and resulting hypoxemia.

ARDS begins with an injury that results in an inflammatory cascade with resulting vascular permeability and pulmonary edema. Loss of aerated lung tissue subsequently leads to hypoxemia and ventilation-perfusion abnormalities. All these factors contribute to decreased lung compliance. Uncontrolled ARDS can progress to an irreversible fibro-proliferative phase characterized by fibrosis of the lung parenchyma.

II. Diagnostic Confirmation: Are you sure your patient has acute respiratory distress syndrome?

ARDS is diagnosed when there is an acute onset of bilateral infiltrates on chest radiography, a normal pulmonary artery wedge pressure and absence of clinical evidence of left atrial hypertension, along with presence of impaired gas exchange with a PaO2/FiO2 ratio of = 300.

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This disease usually starts with symptoms beginning within one week of an injury or insult to the body and can only be declared as ARDS if cardiogenic pulmonary edema, fluid overload, and any other cause of the acute respiratory failure can be excluded.

ARDS can be divided into mild (PaO2/FiO2 is >200 mmHg, but =300 mmHg), moderate (PaO2/FiO2 is >100 mmHg, but =200 mmHg) and severe (PaO2/FiO2 is =100 mmHg) on ventilators setting that include PEEP = 5cm H2O.

A. History Part I: Pattern Recognition:

Symptoms of ARDS usually present within hours to days of a clinical insult. The majority of patients who develop ARDS are already being managed for a probable cause that could either be a life threatening infection or trauma. However, the differential is quite extensive with drug reaction, transfusion reaction, and fume inhalation injury representing just a few of the causes.

In general, common complaints include shortness of breath or difficulty breathing, rapid breathing, difficulty in catching breath leading to inability to complete sentences, palpitations due to tachycardia, cough, and chest pain. Additionally, as a result of decreased perfusion the patient may develop confusion, altered level of consciousness, profuse sweating, and fatigability.

The onset and duration of symptoms generally varies depending on the predisposing factors; for example, in cases of transfusion symptoms appear around 6-8 hours after the completion of the transfusion. Detailed history should be taken to identify septic conditions specifically with a presentation of fever, abdominal pain or any focus of infection. Exposure to blood products or any drug overdose has to be investigated. Patients should also be asked about the content, quantity and duration of exposure to toxic fumes, smoke and alcohol.

B. History Part 2: Prevalence:

In the United States, around 190,000 cases of ARDS are diagnosed per year.

ARDS has a number of predisposing factors including: cigarette smoking, tuberculosis, radiation exposure, chronic alcohol abuse, stroke patients with impaired gag reflex, near drowning patients, and obesity.

It has been shown to be more common in people who smoke or live near factories/industries or in highly polluted and congested cities, and in people living at high altitudes. African-Americans are known to have lower chances of getting the disease than Hispanics and Caucasians. Advancing age and female sex also seem to enhance the risk of ARDS, particularly after an inciting event.

Genetic association has also been identified which may contribute to ARDS.

There are a number of risk factors contributing to ARDS. Sepsis and pneumonia are by far the most common causes. Other important risk factors include drug abuse, aspiration, and severe trauma (especially bilateral lung contusions). Lung transplantation, blood and fluid transfusions have also been well described as causes of ARDS. Drugs that have been implicated as a cause include: aspirin, opioids, cocaine, phenothiazines, tricyclic antidepressants, amiodarone, nitrofurantoin, protamine, and other chemotherapeutic agents. Less common causes include pancreatitis, cardiopulmonary bypass surgery, disseminated intravascular coagulation, head injury, near drowning, toxic gas exposure, chemical exposure including chlorine and ammonia, and tick-born relapsing fever.

Some of the details discussed earlier are being reviewed again to formulate a pattern of history to be inquired during the evaluation of the patient with ARDS.

We should ask if patient suffered from a physical trauma including near drowning or any kind of toxic inhalation. It is important to inquire if the patient has a previous history of recurrent aspiration or stroke. We should also ask questions related to history of cancer or recent chemotherapeutic exposure. Question regarding any blood products exposure is necessary. Any hospital admission following infections or septic injury has to be excluded. Inquiring about any major surgeries including cardiothoracic or abdominal are imperative.

C. History Part 3: Competing diagnoses that can mimic acute respiratory distress syndrome.

Several pulmonary conditions can mimic ARDS and can be difficult to differentiate Illnesses that resemble ARDS include:

  • Cardiogenic pulmonary edema (evidence of cardiac distress such as myocardial infarction and impaired ejection fraction)

  • Idiopathic pulmonary fibrosis

  • Chronic interstitial lung diseases

  • Diffuse alveolar hemorrhage (confirmed by the detection of hemosiderin-laden macrophages on bronchoalveolar lavage)

  • Idiopathic acute eosinophilic pneumonia (unusually high number of eosinophils in the BAL)

  • Cryptogenic organizing pneumonia (CT scan and surgical lung biopsy needed for diagnosis)

  • Acute interstitial pneumonia (with no known underlying etiology)

  • Goodpasture’s syndrome (pulmonary hemorrhage with progressive glomerulonephritis)

  • Diffuse pneumonia

  • Malignancy (acute leukemia or lymphoma or lymphangitic spread of solid tumors)

  • Post-obstructive pulmonary edema (often happens after removal of an upper airway obstruction).

D. Physical Examination Findings.

Physical exam findings include dyspnea, cyanosis and bilateral rales on auscultation. Respiratory distress is usually appreciable. Other important physical exam findings include tachypnea, tachycardia and use of accessory muscles of respiration. Cough and chest tenderness have also been described. Signs of the underlying cause will also be present such as fever due to infection, or confusion from delirium or drug overdose.

Cardiogenic pulmonary edema is differentiated by S3 and elevated neck veins on physical examination. Chronic Interstitial lung disease usually presents with a prolonged illness, diffuse Velcro rales, and digital clubbing. Patients suffering from idiopathic acute eosinophilic pneumonia have an acute febrile illness with non-productive cough and dyspnea in most cases. Malignancies can present with symptoms of night sweats, significant weight loss, and malaise. If a patient has frank hemoptysis, hematuria, pale skin and shortness of breath, Goodpasture’s disease has to be considered.

E. What diagnostic tests should be performed?


1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A number of diagnostic, laboratory, and imaging tests may be done to diagnose ARDS. These include sputum culture (to identify underlying infection), Arterial blood gas, complete blood count (CBC – anemia can be revealed in settings of trauma or hemolysis), and blood culture B-type natriuretic peptide (less than 100pg/ml in a patient with bilateral infiltrates and dyspnea is highly indicative of ARDS). An echocardiogram can accompany this test to rule out cardiac disease with more confidence.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

  • Chest X-ray (bilateral pulmonary infiltrates which start as patchy and asymmetrical, diffuse whiteout appearances, and show areas of consolidation in the lung.

  • Chest computed tomography (CT) scan could help, whether done without contrast, or with contrast (to rule out pulmonary embolism as the cause of dyspnea).

  • BAL can also be useful in the diagnosis such as in cases of infection, alveolar- hemorrhage or interstitial pneumonia.

  • Lung biopsy is reserved for selected patients that have an undiagnosed underlying diagnosis even after performing the above procedures.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Pulmonary artery catheterization is also unnecessary in several cases.

III. Default Management.

Most current therapies for ARDS falls into two categories; supportive therapies (including mechanical ventilation), and those measures done to recruit alveoli.

Treating the underlying condition is critical.

ARDS patients can be severely hypoxemic and most of them eventually require intubation and mechanical ventilator support. Low tidal volume approach (4-6mL/kg) should be always used due to mortality benefit when compared to larger tidal volume ventilation (12mL/kg of ideal body weight).

It is important to recognize that high positive end expiratory pressure can be damaging, thus should be monitored and kept less than 30 cm of water.

Patient overall fluid balance should be carefully obtained. A daily goal of net fluid even or slightly negative should be attempted. Since infections are the most common cause of ARDS, a combination of antimicrobials is generally started and then tapered based on results of cultures and sensitivities.

Other care measures must be followed for all intubated patients which include sedation and intermittent sedation withdrawal, oral hygiene, eye care, aspiration precautions, frequent suctioning, head of the bed elevation, pain management, nutritional support, blood glucose control, gastrointestinal (GI) prophylaxis, blood transfusions, preventing nosocomial infections, sequential compression devices and chemical prophylaxis to prevent deep venous thrombosis.

Measures to recruit none affected, typically less effective, parts of the lungs such as the basis were studied, prone positioning found to significantly decreased mortality, and thus should be used when possible.

A. Immediate management.

Patients may present to the hospital in a very critical condition due to severe ARDS. The primary goal for these patients is to improve oxygenation. Stabilization of vital signs is an important first step. The most important step is to provide supplemental oxygenation preferably through noninvasive ventilation tactics. It can be administered through a Venti, or 100% non-rebreather mask to maintain PaO2 above 60 mmHg. If patient is not improving, immediate assistance must be provided for noninvasive ventilation or endotracheal tube mechanical ventilation.

ARDS patients tend to suffer from systemic failure. It is necessary to maintain adequate fluid resuscitation and mean arterial pressures for organ perfusion. Oxygen saturation monitoring and urine output charting has to be done cautiously. Antibiotics in ARDS patients are often started empirically to prevent deterioration of the condition. Once the patient’s vital signs are normalized, the focus should be towards identifying the cause of ARDS and treating accordingly.

B. Physical Examination Tips to Guide Management.

Periodic evaluations should be performed to document improvement or worsening of patient’s condition. On a physical exam, physician should observe breathing pattern, extremities for pallor, and patient’s heart rate and blood pressure and the ventilation details. Additional breath sounds (wheeze, rhonchi, and crepitations) can help guide the treatment. Fever can give clues to underlying infection. Care must be taken to prevent secondary infections from endotracheal intubation, urinary catheters and dependent skin areas. Sudden pallor, expected bleeding or bruising and hemodynamic instability must be monitored to help in identifying coagulation problems and preventing the patient from declining to disseminated intravascular coagulation (DIC).

Patients with ARDS are likely to undergo systemic complications including hematologic, renal, liver, and gastrointestinal. Hemodynamic stability, oxygenation, and acid–base monitoring is vital to guide management strategies.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Initially arterial blood gas analysis should be performed daily. This can be discontinued once the patient has been weaned off mechanical ventilation or if stable on mechanical ventilation. CBC and chemistry panel should be performed daily. Fluid electrolyte and serum creatinine levels should be checked daily to make sure systemic function is normal. Blood culture can be done after antibiotic therapy is initiated. Daily chest films are important for patients on mechanical support. All these tests can guide a physician about improvement or worsening of patient’s condition.

D. Long-term management.

No long-term monitoring is needed in patients who survive ARDS. In case of continued SOB, during rehabilitation phase, physical activity must be restricted for some time. Strict aspiration precautions should be taken. Pulmonary function tests can be periodically checked. Corticosteroids may be given for prolonged periods in certain cases. Beta agonists can be prescribed to improve shortness of breath. Long-term fluid management is very important. Thus, regular visits to the primary physician for check-ups are important.

E. Common Pitfalls and Side-Effects of Management.

Most commonly, pitfalls during treatment of ARDS are ventilator based issues. These include ventilator associated lung injury and barotrauma. Barotrauma refers to alveolar rupture due to excessively high pressure exposure that can lead to pneumothorax, subcutaneous emphysema, and loss of aerated tissue, ventilator associated infections and barotrauma. Mechanical ventilation has also been known to be associated with GI bleeding due to stress ulcers and increased intracranial pressure.

ARDS induced alveolar damage can lead to loss of oxygen transfusion surface, loss of surfactant production leading to collapse, and pulmonary hypertension over a period of time.

Side effects of fluid reduction management during ARDS include organ hypoperfusion, reduced renal clearance, and dehydration. Fluid levels should be monitored carefully.

Long term uses of corticosteroids and antibiotics have side effects of their own. Misuse of antibiotics can lead to the rise of resistant strains with increased morbidity. Clostridium difficile colitis is a well-known complication of antibiotic use. Prolonged hospital stay (associated with nosocomial infections), lack of movement during sedation/paralysis (can slow blood flow leading to an increased chance of deep vein thrombosis), and increased gastric pH (associated with stress ulcers) can all lead to several different complications.

IV. Management with Co-Morbidities.


A. Renal Insufficiency.

In patients with renal insufficiency and ARDS, a severely negative fluid balance leads to renal failure. A minor complication of mechanical ventilation is slight respiratory acidosis that becomes important in patients with renal failure or concomitant metabolic acidosis. Dialysis or hemofiltration may be considered in some patients who have acute renal failure to achieve the goal of negative fluid balance.

B. Liver Insufficiency.

Liver failure can be an initiating event in ARDS, or can ensue as part of multiorgan damage consecutively.

C. Systolic and Diastolic Heart Failure.

There will be no change in standard management, although ventilator settings should be closely adjusted as high PEEP could lead to detrimental outcomes in patients with severe CHF.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management

E. Diabetes or other Endocrine issues.

No change in standard management.

F. Malignancy.

Some fast spreading cancers and tumors such as leukemia and lymphomas may mimic the symptoms of ARDS, and have been shown to be an underlying cause of ARDS. The treatment in this scenario will be to provide the same respiratory symptomatic support while trying to cure the concomitant cancer.

A number of cancer drugs have also been implicated in causing respiratory distress, mainly: cytarabine, recombinant IL-2, gemcitabine, vinblastine, mitomycin, methotrexate, dacarbazine, and granulocyte colony stimulating factor. Stopping the implicated drug is also recommended in these cases.

G. Immunosuppression (HIV, chronic steroids, etc.).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

Patients with GI disease such as ulcers or acid reflux or nutritional deficiencies will need to be managed differently. Corticosteroids should not be used as they will aggravate the underlying ulcer. A nutrition consult should be obtained especially when patients with ARDS are intubated.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

A number of issues have to be watched for patients of ARDS on mechanical ventilation. It is imperative to give a detailed description regarding the primary etiology that led to ARDS in a particular patient. Blood gases and electrolytes are to be monitored routinely as they help prevent from sudden circulatory collapse and unexpected changes in the ventilation. Equipment failure and displacement of tube must be considered in case of respiratory failure. Obstruction by secretions, blood, kinking of the tube or a foreign body must also be considered as the possibilities. Positive pressure ventilation for more than 48 hours is a risk factor for GI bleeding so it should be discussed. Positive pressure ventilation (PPV) increases intracranial pressure and can also lead to spontaneous pneumothorax and Barotrauma. High PEEP may impair cardiac output leading to hypotension therefore the staff must be briefed before signing out.

B. Anticipated Length of Stay.

Patients with ARDS usually require a patient to spend around 3-4 weeks in the hospital with 2-3 weeks in ICU care. This may vary based on the severity of symptoms.

C. When is the Patient Ready for Discharge.

Patients with ADS can either be discharged to their home or to rehabilitation center.

A patient with ARDS will be ready for discharge when his or her oxygen saturation level has improved without ventilator support and appears stable to be sent home. The underlying cause (e.g., sepsis, trauma, infection, drug overdose, etc.) must also be cured to prevent a recurrence following discharge.

If a patient does not improve and ends up needing tracheostomy and peg tube placement, he or she should be transferred for rehabilitation in nursing home. Patients with stable ventilatory support should also be discharged to rehabilitation centers.

D. Arranging for Clinic Follow-up.


1. When should clinic follow up be arranged and with whom.

Patients should be advised to return for a follow-up visit to the hospital about 5-7 days after discharge. Follow-up visits and scheduling must be discussed with a responsible family member as well as the patient. Survivors should be advised to visit the pulmonologist at 3 to 6 months after discharge.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

CBC, arterial blood gas, serum electrolyte and creatinine levels should all be done before the patient is discharged to ensure improvement. Pulse oximetry should be done the day a patient is discharged.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Fluid and electrolyte levels, CBC, and pulmonary function tests should be done prior to the initial visit. Spirometry and pulse oximetry can also be performed.

E. Placement Considerations.

Recovery of the patient’s post ARDS decides his or her transfer from the hospital to home or to the Rehabilitation department. Some patients might have milder symptoms and recover enough to go home directly after hospital discharge. Others stay on a prolonged period on mechanical support, requiring physical rehabilitation after weaning off of the ventilator. Deconditioned patients also need rehabilitation centers prior to going home. These patients can be sent to a skilled nursing facility, nursing home, or long-term acute care hospitals.

Severely ill patients require LTAC facility as SNF would not suffice their need.

Patients who recover from ARDS are likely to develop a number of complications post discharge namely physical disabilities, anxiety, depression, and neurocognitive impairment, pervasive memories of critical care and behavior disturbances for the care giver.

F. Prognosis and Patient Counseling.

Most patients who develop ARDS do not die from respiratory failure, but rather from complications of a prolonged stay in the intensive care unit such as nosocomial infections or multiple organ dysfunction. Mortality estimates 26-58 %. The long-term morbidity and mortality depends on a number of causes. Pre-existing organ dysfunction from chronic liver disease, chronic alcohol abuse, sepsis or immunosuppression has been linked to increased mortality from ARDS. Surgical and trauma patients have better chances of survival. Elderly patients are known to have worse outcomes. But overall, mortality has decreased with improvements in general care and ventilatory techniques.

Patients with ARDS should be advised a few lifestyle changes. Physical activity should be restricted. Smoking, drugs and alcohol counseling should be given and their use must be discouraged. Exposure to toxic chemicals or fumes should be avoided. Healthy diet should be given as many people develop nutritional deficiencies after prolonged hospitalization and families should also be counseled to provide necessary support. Patient should be advised to strictly adhere to the treatment plan advised by the doctor.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

Discussed above.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

During hospitalization, prophylactic measures should be taken to avoid stress ulcers and pressure sores which can be achieved by using H2 blockers or Proton Pump Inhibitors and frequent change of position of the patient respectively. Nutritional consult is imperative to restabilize the nutritional imbalances. Deep venous thrombosis, an important adverse effect of lengthy stay in bed has to be prevented by heparin, lovenox, and/or sequential compression device.

Care must be taken to protect from ventilator associated injury and to avoid nosocomial infections by maintaining adequate oral hygiene and removal of urinary catheter as soon as it is not required.

On discharge the patient is advised to avoid exposure to toxic fumes and chemical agents strictly. Physiotherapy is an essential tool for prophylaxis. Influenza and pneumococcal vaccines should also be given before discharge.

VII. What's the evidence?

Harrison, T, Eugene, Braunwald, Stephen, Hauser, Dan, Longo, Larry, Jameson, Anthony, Fauci, Dennis, Kasper. “Acute Respiratory Distress Syndrome”. Harrison's Principles of Internal Medicine. 2001. pp. 1523-1526.

Anzueto, A, Frutos-Villar, F, Esteban, A. “Influence of body mass index on outcome of the mechanically ventilated patients”. Thorax. vol. 66. 2011. pp. 66

Ryb, GE, Cooper, C.

Heffernan, Dossett, Lightfoot. “Gender and ARDS in Critically Injured Adults: A Prospective Study”. J Trauma. vol. 71. 2011. pp. 878-885.

Gao, B. “Recent advances in genetic predisposition to clinical acute lung injury”. Am J Physiol Lung Cell Mol Physiol. vol. 296. 2009. pp. L713-L725.

McPhee, S, Papadakis, M, Michael, Rabow. “Acute Respiratory Distress Syndrome. Current Medical Diagnosis & Treatment”. 2011. pp. 314-316.

Kathuria, P. “Goodpasture Syndrome”.

Kallet, RH, Daniel, BM, Gropper, M. “Acute pulmonary edema following upper airway obstruction: case reports and brief”.

“Acute respiratory distress syndrome: Clinical features and diagnosis”.

“U.S Department of Health and Human Services. National Heart Lung and Blood Institute. How Is ARDS Diagnosed?”.

Harman, E. “Acute Respiratory Distress Syndrome Workup”. 2012.

Horlander, K. “Imaging in Acute Respiratory Distress Syndrome”. 2011.

Harman, E. “Acute Respiratory Distress Syndrome”. 2012.

Liu, K, Michael, M. “Advances in Critical Care for the Nephrologist: Acute Lung Injury/ARDS”. Clinical Journal of the American Society of Nephrology. 2008.

“K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease: USE OF DIURETICS IN CKD”.

Doyle, HR, Marino, IR, Miro, A, Scott, V, Martin, M, Fung, J, Kramer, D, Starzl, TE. “U.S National Library of Medicine. National Center for Biotechnology Information. Adult respiratory distress syndrome secondary to end-stage liver disease-successful outcome following liver transplantation”. 1993.

Nicholas, P, Briasoulis, E. “Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy”. 2001.

Li, JB, Deng, XM, Zhu, KM, Zhang, L. “National Center for Biotechnology Information. U.S National Library of Medicine. Retrospective analysis on acute respiratory distress syndrome in ICU 2007”.

MacCallum, NS, Evans, TW. “Epidemiology of acute lung injury”. Curr Opin Crit Care. vol. 11. 2005. pp. 43

What's new?

Brilliantly, a simple mechanical trick was able to significantly achieve what medications and invasive measures did not; prone positioning opposes gravity to recruit previously collapsed alveoli. Nevertheless, in the hospital setting it is not that simple to accomplish frequent prone positioning as it needs manpower, yet given mortality benefit this needs to be considered in every ARDS patient.

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