Acute respiratory distress syndrome: Prognosis and outcomes in adults

Author:: Mark D Siegel, MD
Section Editor:: Polly E Parsons, MD
Deputy Editor:: Geraldine Finlay, MD

Literature review current through: Apr 2025. | This topic last updated: Aug 02, 2024.

INTRODUCTION —

Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure characterized by the acute onset of bilateral alveolar opacities and hypoxemia. ARDS management is largely supportive.

The prognosis of ARDS is reviewed here. The pathogenesis, etiology, clinical presentation, and management of ARDS are discussed separately.

●(See "Acute respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults".)

●(See "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults".)

●(See "Acute respiratory distress syndrome: Ventilator management strategies for adults".)

●(See "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults".)

●(See "Acute respiratory distress syndrome: Investigational or ineffective therapies in adults".)

MORTALITY —

ARDS is associated with high mortality, approximately 35 percent. Several predictors have been identified. However, accurate data are difficult to obtain since it is difficult to distinguish whether patients die from ARDS or with ARDS (ie, death is due to comorbidities such as cancer or associated organ dysfunction) [1,2].

Mortality rates — Mortality rates in patients with ARDS range from 26 to 60 percent [3-8]. Rates vary between institutions and countries, and confounding variables included in studies (eg, patient cohort characteristics, type of mortality reported, comorbidities, treatment strategies, and disease severity). These factors are discussed below. (See 'Predictors' below.)

Data suggest that survival has improved throughout the early 2010s [4,9-12] but has since plateaued. As examples:

●One observational study of 5159 patients who had enrolled in ARDSNet trials found a reduction in mortality from 35 to 28 percent between 1996 and 2013 [12]. The improved mortality may be attributed to patients with non-sepsis-related ARDS (eg, trauma) [9], better supportive care, and improved ventilatory strategies (eg, low tidal volume ventilation, prone positioning) [10,13]. (See "Acute respiratory distress syndrome: Ventilator management strategies for adults", section on 'Efficacy and harm' and "Acute respiratory distress syndrome: Prone ventilation in adults".)

●A retrospective analysis of nationwide mortality data from the National Center for Health Statistics showed that mortality rates plateaued between 2014 and 2018 [14].

Etiology of death — The etiology of death in ARDS varies. Among patients who die early (eg, first week of mechanical ventilation), the underlying cause of ARDS is the most common cause of death [9,15-17]. In contrast, among patients who die later in their clinical course, sepsis from nosocomial pneumonia is the most common cause of death [17]. One retrospective study reported that among 385 decedents with acute hypoxic respiratory failure, one-third of whom had ARDS, the main causes of death were sepsis (26 percent), pulmonary dysfunction (22 percent), and neurologic dysfunction (19 percent) [18]. At the time of death, multiorgan failure (MOF) was present in over two-thirds of patients and 70 percent were ventilated. Following withdrawal of life support, 85 percent of patients died.

Predictors — Many studies have identified factors that predict ARDS mortality. These include patient-, disease-, or treatment-related factors. No single factor has proven to be superior to the others. Common factors that may predict death from ARDS include increasing age, comorbidities, poor nutrition, severe ARDS, infection, and MOF (table 1).

Patient-related — Increasing age and comorbidities impact ARDS mortality.

Age — Older age is a risk factor for ARDS-related death [14,19-21]. In a cohort study of 1113 patients with ARDS, the mortality rate increased progressively with age, ranging from 24 percent among patients 15 to 19 years of age to 60 percent among patients ≥85 years [19].

Comorbidities — Underlying comorbidities are associated with ARDS-related hospital mortality, including the following [21-23]:

●Active cancer (especially hematologic cancers) (see "Prognosis of cancer patients in the intensive care unit")

●Immunosuppression

●Chronic liver failure

●Severe alcohol use

●Poor nutrition

Although it has been suggested that obesity may impact the mortality of critically ill patients with or without ARDS, evidence is conflicting, with some data suggesting lower mortality in association with obesity (the "obesity paradox") [24-32].

Disease-related — Disease-related predictors of mortality include poor gas exchange and severe ARDS, infection, MOF, and several others.

Poor gas exchange and disease severity — Poor gas exchange as evidenced by severe hypoxemia and hypercapnia (likely due to severe ARDS) indicates poor prognosis. Many of these parameters can be easily assessed at the bedside.

●Hypoxemia/ARDS severity – The severity of hypoxemia determines whether the patient has mild, moderate, or severe ARDS (table 2). The updated definition of ARDS and criteria for ARDS severity are provided separately. (See "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults", section on 'Clinical diagnosis'.)

Mortality increases as ARDS becomes more severe [6,33,34]. As examples:

•An observational study of 3670 patients with ARDS reported that patients with mild, moderate, and severe ARDS had mortality rates of 27, 32, and 45 percent, respectively [33].

•In a global study of 3022 patients, the unadjusted hospital mortality was reported to be 35 percent for mild ARDS, 40 percent for moderate ARDS, and 46 percent for severe ARDS [6].

•Among those with mild ARDs, one-half worsen and the other one-half remain in the mild category or improve [34]. In-hospital mortality was 10 percent among those with mild illness who improved within the first week, 30 percent in those with persistent mild ARDS, and 37 percent in those with worsening ARDS.

Additional studies have found that oxygenation deterioration correlates with mortality [34] while oxygenation improvement during the early intensive care unit (ICU) course correlates with survival [35].

Extensive involvement on the chest radiograph, is associated with increased mortality [1]. Similarly, early deterioration in the appearance of the chest radiograph over the first few days after ARDS onset is associated with increased 90-day mortality [36].

Severity of illness scores correlate with mortality. As an example, patients with a higher Acute Physiologic and Chronic Health Evaluation (APACHE) III score have an increased likelihood of death (odds ratio [OR] 1.78 per 25-point increase, 95% CI 1.16-2.73) [20]. Similarly, in another prospective cohort study, severity of illness indices including lower pH, lower PaO₂/FiO₂ ratio, and higher Sequential (sepsis-related) Organ Failure Assessment (SOFA) score were associated with poorer outcomes [21] These scores are most commonly used in research studies rather than for calculating individual mortality at the bedside. (See "Predictive scoring systems in the intensive care unit", section on 'Acute Physiologic and Chronic Health Evaluation (APACHE)' and "Predictive scoring systems in the intensive care unit", section on 'Sequential (sepsis-related) Organ Failure Assessment (SOFA)'.)

●Hypercapnia – Severe hypercapnia (partial arterial pressure of carbon dioxide [PaCO₂] ≥50 mmHg) may also indicate increased mortality, higher complication rates, and more organ failures [37].

Dead space ventilation in early ARDS correlates with mortality. This was illustrated by a series of 179 patients with early ARDS that reported an increase in the odds of death by 45 percent for every 0.05 increase in dead space fraction (ie, ratio of dead space to tidal volume [Vd/Vt] measured by exhaled CO₂) [38].

Another bedside variable, the ventilatory ratio (VR), defined as (minute ventilation [mL/minute] x PaCO₂)/(predicted body weight x 100 x 37.5), correlates with increased mortality, even after adjusting for other factors, such as arterial oxygen pressure (PaO₂)/fraction of inspired oxygen (FiO₂) ratio and severity of illness [39]. However, this ratio is not commonly used in practice.

Infection and multiorgan failure — Infection and/or multiorgan dysfunction are better predictors of mortality than respiratory parameters (eg, respiratory rate, oxygenation) [2,9,40-45]. This is probably because they predict death from a nonrespiratory cause in ARDS, which is more common than death due to respiratory failure.

Others — Other factors associated with poor outcomes from ARDS include the following:

●Non-trauma-related ARDS – Patients with trauma-related ARDS appear to have improved survival than patients with non-trauma-related ARDS [46].

●Diffuse alveolar damage (DAD) – The presence of DAD on lung biopsy is also associated with a worse prognosis compared with those with non-DAD-associated ARDS [47]. However, most cases of ARDS do not undergo biopsy.

●Vascular dysfunction – Indices of vascular dysfunction are not routinely used but do correlate with death in patients with ARDS.

•Pulmonary vascular dysfunction – Pulmonary vascular dysfunction may be an independent risk factor for 60-day mortality and fewer ventilator-free, ICU-free, and hypotension- or vasopressor-free days [48]. Pulmonary vascular dysfunction is indicated by an elevated transpulmonary gradient (ie, ≥12 mmHg; difference between the mean pulmonary artery pressure and the pulmonary artery occlusion pressure) or pulmonary vascular resistance index (ie, >285 dyne-sec/cm; transpulmonary gradient divided by the cardiac index). These calculations require a pulmonary artery catheter (PAC) for accurate measurement. While PACs were placed frequently in the past, their routine use has fallen out of favor. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults" and "Pulmonary artery catheterization: Interpretation of hemodynamic values and waveforms in adults".)

•High extravascular lung water and pulmonary vascular permeability – Higher extravascular lung water and pulmonary vascular permeability indices correlate independently with 28-day mortality [49]. The Radiographic Assessment of Lung Edema (RALE) score, which assesses the extent of pulmonary edema by evaluating the densities of alveolar opacities on the chest radiograph, correlates with overall survival and 28- and 90-day mortality rates [50]. Further study is warranted before RALE can be routinely used.

●Laboratory and genetic – Routine laboratory parameters are not helpful for predicting the outcome of ARDS. However, a large body of emerging evidence suggests that many biomarkers and gene polymorphisms are associated with both susceptibility to ARDS and outcome from ARDS [51]. The practical utility of these observations is uncertain.

Other analyses have suggested the existence of two biologically and clinically distinct subphenotypes of ARDS, hypo- and hyperinflammatory (Type 1 and Type 2, respectively); increased mortality is associated with the hyperinflammatory subtype [1,52-54].

Treatment-related — Treatment-related predictors of mortality include a positive fluid balance, glucocorticoid therapy prior to the onset of ARDS, packed red blood cell transfusions, being in an ICU that does not mandate care by an intensivist, late intubation, and ventilatory parameters.

●Fluid balance – In patients with ARDS, positive fluid balance may be associated with higher mortality [55,56]. This was demonstrated in a subgroup analysis of the ARDSNet low tidal volume trial, which found that a negative fluid balance at day 4 was associated with decreased mortality compared with a positive fluid balance, after adjustment for factors such as age, severity of illness, and ventilator strategy (adjusted OR 0.5, 95% CI 0.28-0.89) [56]. This study is discussed in greater detail separately. (See "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults", section on 'Conservative fluid management'.)

●Prior treatment with glucocorticoids – Patients who received glucocorticoids prior to the onset of ARDS may increase the likelihood of death (OR 4.65, 95% CI 1.47-14.7) [20].

●Packed red blood cell transfusion – Patients who receive packed red blood cell transfusions may have an increased likelihood of death (OR 1.1 per unit transfused, 95% CI 1.04-1.17) [20,57]. (See "Use of blood products in the critically ill".)

●ICU resources – Patients in an ICU that mandates transfer to an intensivist or comanagement by an intensivist may have a decreased likelihood of death (OR 0.68, 95% CI 0.53-0.89) [58]. Patients cared for in hospitals with fewer ICU beds may have increased mortality [21]. After adjusting for confounders, one study found lower mortality in ICUs that cared for higher numbers of patients with ARDS [59].

●Late intubation – Patients who are intubated late in the course of the disease may have a higher risk of death from ARDS when compared with patients who are intubated early and those who are never intubated (56 versus 26 versus 26 percent) [60]. Although unproven, it suggests that initial strategies, such as noninvasive ventilation and high-flow oxygen, may indirectly affect mortality by impacting the timing of intubation. (See "Evaluation and management of the nonventilated, hospitalized adult patient with acute hypoxemia", section on 'Patients with escalating oxygen needs'.)

●Ventilator parameters – Several studies have reported select ventilator parameters that impact outcomes in ARDS [21,61]. For example, in one study of 2377 ARDS patients, higher positive end-expiratory pressure and lower peak, plateau, and driving pressures were associated with improved ARDS survival [21]. (See "Acute respiratory distress syndrome: Ventilator management strategies for adults".)

Predictors of improved survival include lung protective ventilation strategies and prone positioning, which are discussed separately. (See "Acute respiratory distress syndrome: Ventilator management strategies for adults", section on 'Efficacy and harm' and "Acute respiratory distress syndrome: Prone ventilation in adults".)

MORBIDITY AMONG SURVIVORS —

Morbidity is common among survivors of ARDS [62]. Symptoms are similar to those observed in survivors of any critical illness (post-intensive care syndrome; PICS) and often have one or more of the following components: cognitive, psychological, and physical dysfunction. This dysfunction commonly leads to a poor quality of life and delayed or inability to return to work. While symptoms may resolve slowly, many are persistent for one year or longer and some may be permanent.

Data that describe morbidities after ARDS are discussed in this section. Data that describe long-term outcomes from critical illness other than ARDS (ie, PICS) and long-term symptoms in critically ill patients with COVID-19 are discussed separately. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation" and "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")".)

Evaluation and treatment — A high index of suspicion is critical for the identification ARDS sequalae. We approach these patients in a similar fashion to those following non-ARDS-related critical illness. This evaluation and management of symptoms are discussed in detail separately. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Diagnostic evaluation' and "Post-intensive care syndrome (PICS): Treatment and prognosis".)

Cognitive, psychological, physical dysfunction — Symptoms following ARDS commonly fall into three common domains: cognitive, physical, and psychological. Symptoms generally improve over time but may last for up to a year or longer.

●Cognitive dysfunction – Rates of cognitive dysfunction following ARDS vary among studies, ranging from 30 to 55 percent [62-65]. Factors which may be associated with long-term cognitive impairment include pre-existing impairment, severity of hypoxemia, neurologic injury, delirium, mechanical ventilation, duration of sedative use, and systemic inflammation [66].

Incidence, risk factors, and symptoms of cognitive dysfunction following critical illness are described in detail separately. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Cognitive impairment'.)

●Psychological dysfunction – Psychological illnesses are common among survivors of ARDS ranging from 36 to 66 percent. Depression, anxiety, and post-traumatic stress disorder are the most common disorders reported [62,64,67-69].

Risk factors for psychological symptoms included younger age, female sex, unemployment, alcohol misuse, greater opioid use in the intensive care unit (ICU), and pre-existing mental health whereas there was no association between symptoms and severity of illness or ICU length of stay [68].

Incidence, risk factors, and symptoms of psychological dysfunction following critical illness are described in detail separately. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Psychiatric impairment'.)

●Physical dysfunction – Approximately 38 to 66 percent of ARDS survivors have persistent, abnormal exercise endurance and functional disabilities [62,67,70-78]. As examples:

•A meta-analysis of 48 studies, totaling over 11,000 survivors of ARDS, reported a lower than predicted six-minute walk distance (57 percent predicted at three months, 63 percent predicted at six months, and 66 percent predicted at 12 months) [62].

•A prospective cohort study reported persistent dysfunction in some patients at five years [72]. Risk factors for physical dysfunction were longer ICU stay and prior depressive symptoms.

Data suggest that many ARDS survivors experience additional physical decline after their critical illness. For example, in one prospective cohort study of 193 ARDS survivors, 69 percent experienced decline in more than one physical measure, such as muscle strength, exercise capacity, and physical functioning [79]. Significant risk factors for subsequent physical decline included increased age and pre-ARDS comorbidity.

A longitudinal prospective cohort study of 156 ARDS survivors showed an association between muscle weakness at hospital discharge and increased five-year mortality [76]. Fifty percent experienced either persistent or resolving weakness trajectories during the follow up period, and these were associated with more than a threefold greater hazard of death compared with patients without weakness.

A better functional outcome at one year appears to correlate with rapid resolution of multiorgan failure and lung injury [78].

Incidence, risk factors, and symptoms of physical dysfunction following critical illness and ICU-acquired weakness are described in detail separately. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Physical impairment' and "Neuromuscular weakness related to critical illness".)

Lung dysfunction — Up to one-half of patients who survive ARDS have compromised lung function as evidenced by abnormal pulmonary function tests (PFTs) [70,72,78]. Lung dysfunction following ARDS may last for as long as five years [70,72,78]. However, it is uncertain whether decreased lung function always results in physical impairment.

A reduction in diffusion capacity is the most common parameter affected, but reduced spirometry and lung volumes can also be seen. For example, in one retrospective study of ARDS survivors, approximately 80 percent of patients had a reduction in diffusion capacity and a smaller percentage had airflow obstruction (20 percent) or restriction (20 percent) on spirometry and lung volumes [70].

In most patients, lung volumes and spirometry improve to 80 percent or more of predicted values by six months, but diffusion capacity may take longer (eg, five years) [70,72,78]. A small percentage of patients are left with residual deficits and supplemental oxygen is rarely required [70,73-75,80]. (See "Overview of pulmonary function testing in adults".)

Risk factors for abnormal PFTs include severe ARDS, low lung compliance, hypotension, high positive end-expiratory pressure requirement, and fraction of inspired oxygen >0.6 for more than 24 hours [74,75,80-82].

Incidence, risk factors, and symptoms of abnormal lung function following critical illness are described in detail separately. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Physical impairment' and "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Other'.)

Other sequalae — Additional sequelae of ARDS include complications of endotracheal intubation, imaging abnormalities, increased risk of death, poor quality of life, and family stress (also known as PICS-family) [5,83-85].

●Complications of intubation – Patients with ARDS may experience complications associated with prolonged intubation including laryngotracheal stenosis, tracheomalacia, and speech or swallowing impairment, the details of which are discussed separately. (See "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients".)

●Imaging abnormalities – Although most patients experience excellent radiologic recovery at 180 days postdiagnosis, abnormalities persist in a significant minority and correlate with worse pulmonary function and quality of life [83,85].

●Increased mortality – One prospective cohort study of 646 ARDS survivors reported mortality at one year that was substantially higher than in-hospital mortality (41 versus 24 percent) [5]. Important predictors of death were the presence of comorbidities and discharge to another facility (eg, hospital, long-term acute care facility, nursing home, hospice). (See "Management and prognosis of patients requiring prolonged mechanical ventilation in long-term acute care hospitals (LTACH)", section on 'Prognosis'.)

●PICS-family – All of these morbidities place substantial stress on family members/caregivers many of whom are in decision-making and caretaker roles for their loved ones [84]. (See "Management and prognosis of patients requiring prolonged mechanical ventilation in long-term acute care hospitals (LTACH)" and "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Post-intensive care syndrome-family'.)

Returning to work — Despite the abnormalities in cognitive, psychological, and physical dysfunction, many patients return to work but are delayed in their return, which may take a year or longer.

In a prospective five-year study of ARDS survivors, 77 percent of those who were working at the time of their acute illness returned to work while 17 percent did unpaid work within the home and 6 percent became full-time students [72]. Most of those who returned to work did so within two years of ICU discharge, although many required a gradual transition back to work. In another study, nearly one-half of previously employed ARDS survivors were jobless 12 months after ARDS [86]. In another study, among long-term ARDS survivors who were previously employed, 51 percent had not returned to work at one year and 31 percent had not returned by five years [87].

Risk factors for delayed return to work include long hospital stay, comorbidity burden preceding ARDS, longer duration of mechanical ventilation (up to five days), and discharge to a healthcare facility [86,87]. (See "Management and prognosis of patients requiring prolonged mechanical ventilation in long-term acute care hospitals (LTACH)".)

INFORMATION FOR PATIENTS —

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Acute respiratory distress syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Mortality – Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure. (See 'Mortality' above.)

•ARDS has a high 28-day mortality of approximately 35 percent (range 26 to 60 percent). Survival improved through the early 2010s, after which rates appears to have plateaued. (See 'Mortality rates' above.)

•The underlying cause of the ARDS is the usual cause of death among patients who die early. In contrast, sepsis due to nosocomial pulmonary infection and multiorgan failure (MOF) contribute substantially to mortality among patients who die later in their clinical course. Patients seldom die directly from respiratory failure. (See 'Etiology of death' above.)

•Numerous factors may predict mortality, but no single factor is superior to the others. Common factors that may predict death from ARDS include increasing age, comorbidities, severe ARDS, infection, and MOF (table 1). (See 'Predictors' above.)

●Morbidity – Morbidity is common among ARDS survivors. Symptoms are similar to those observed in survivors of any critical illness (post-intensive care syndrome [PICS]).

•Survivors of ARDS can develop cognitive (30 to 55 percent), psychological (36 to 66 percent; eg, depression, anxiety, and post-traumatic stress disorder), and physical impairments (38 to 66 percent; eg, lower six-minute walk distance) that may last for months to years following their acute illness. (See 'Cognitive, psychological, physical dysfunction' above.)

•Up to one-half of patients who survive ARDS have abnormal pulmonary function tests, most often a low diffusion capacity. However, it is uncertain whether decreased lung function results in physical impairment. (See 'Lung dysfunction' above and 'Morbidity among survivors' above.)

•Additional sequelae of ARDS include complications of endotracheal intubation, imaging abnormalities, increased risk of death, poor quality of life, and family stress (also known as PICS-family). (See 'Other sequalae' above.)

•Survivors may also experience an impaired ability to return to work for at least two to five years following the acute illness. (See 'Returning to work' above.)

•We evaluate and manage these patients in a similar fashion to those following non-ARDS-related critical illness. This evaluation and management are discussed in detail separately. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Diagnostic evaluation' and "Post-intensive care syndrome (PICS): Treatment and prognosis".)

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Topic 1601 Version 45.0

خرید پکیج

Acute respiratory distress syndrome: Prognosis and outcomes in adults

References