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The acute respiratory distress syndrome: Definitions, severity and clinical outcome An analysis of 101 clinical investigations
Abstract
To determine possible changes in outcome from acute respiratory distress syndrome (ARDS) and to compare severity of lung injury and methods of treatment from 1967 to 1994.
Computerized (Medline, Current Contents) and manual (Cumulated Index Medicus) literature search using the key word and/or title ARDS.
Only clinical studies published as full papers reporting data on both patient mortality (survival) and oxygenation index (PaO2/FIO2) were included. Single case reports, abstracts, reviews and editorials were excluded from evaluation.
Relevant data were extracted in duplicate, followed by quality checks on approximately 80% of data extracted.
101 papers reporting on 3264 patients were included: 48 studies (2207 patients) were performed in the USA, 43 studies (742 patients) in Europe and 10 studies (315 patients) elsewhere. Mortality reported in these studies was 53 +/- 22% (mean +/- SD), with no apparent trend towards a higher survival (1994: 22 studies, mortality 51 +/- 19%). The mean PaO2/FIO2 ratio remained unchanged throughout the observation period (118 +/- 47 mmHg). No correlation could be established between outcome and PaO2/FIO2 or lung injury score. Patients who underwent pressure-limited ventilation had a significantly lower mortality (35 +/- 20%) than patients on volume-cycled ventilation (54 +/- 22%) or patients for whom there was no precise information on ventilatory support (59 +/- 19%). Significantly lower PaO2/FIO2 ratios (61 +/- 17 mmHg) were observed in patients prior to extracorporeal lung assist, together with mortality rates in the range of those for conventionally treated patients (55 +/- 22%).
The mortality of ARDS patients remained constant throughout the period studied. Therefore, the standard for outcome in ARDS should be a mortality in the 50% range. Neither PaO2/FIO2 ratio nor lung injury score was a reliable predictor for outcome in ARDS. Patients might benefit from pressure-limited ventilatory support, as well as extracorporeal lung assist. Since crucial data were missing in most clinical studies, thus preventing direct comparison, we emphasize the importance of using standardized definitions and study entry criteria.
... Yet the evaluation of ARDS mortality performed through reviews continues to be a challenge because of the variability. For example, in a review including 101 studies with 3264 patients (1967-1994), a mortality of 53% was found, which remained stable over the period (50). Other researchers reported mortality of 44% from 89 studies (18,900 patients) without variation in time (4). ...
... Hence, this might explain the wide range of mortality found, between 17% and 89%. Other reviews also found ample heterogeneity: mortality between 20 and 68% and 0-84% (3,50). The study design might also cause additional variation: in observational studies, mortality was 20-78%, and in RCTs, 15-62% (4). ...
Objectives
Mortality due to acute respiratory distress syndrome (ARDS) is a major global health problem. Knowledge of epidemiological data on ARDS is crucial to design management, treatment strategies, and optimize resources. There is ample data regarding mortality of ARDS from high-income countries; in this review, we evaluated mortality due to ARDS in Latin America.
Data Sources
We searched in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Science Literature databases from 1967 to March 2023.
Study Selection
We searched prospective or retrospective observational studies and randomized controlled trials conducted in Latin American countries reporting ARDS mortality.
Data Extraction
Three pairs of independent reviewers checked all studies for eligibility based on their titles and abstracts. We performed meta-analysis of proportions using a random-effects model. We performed sensitivity analyses including studies with low risk of bias and with diagnosis using the Berlin definition. Subgroup analysis comparing different study designs, time of publication (up to 2000 and from 2001 to present), and studies in which the diagnosis of ARDS was made using Pa o 2 /F io 2 less than or equal to 200 and regional variations. Subsequently, we performed meta-regression analyses. Finally, we graded the certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation).
Data Synthesis
Of 3315 articles identified, 32 were included (3627 patients). Mortality was 52% in the pooled group (low certainty of evidence). In the sensitivity analysis (according to the Berlin definition), mortality was 46% (moderate certainty of evidence). In the subgroup analysis mortality was 53% (randomized controlled trials), 51% (observational studies), 66% (studies published up to 2000), 50% (studies after 2000), 44% (studies with Pa o 2 /F io 2 ≤ 200), 56% (studies from Argentina/Brazil), and 40% (others countries). No variables were associated with mortality in the meta-regression.
Conclusions
ARDS mortality in Latin America remains high, as in other regions. These results should constitute the basis for action planning to improve the prognosis of patients with ARDS (PROSPERO [CRD42022354035]).
... In cases of severe infections such as sepsis, steroids may improve the immune response [110]. Acute respiratory distress syndrome, which has a 40 -60% mortality rate, is the most lethal form of respiratory failure associated with systematic inflammatory responses [111], and several circulating and proinflammatory cytokines are involved in the onset and exacerbation of acute respiratory distress syndrome due to sepsis. The dysregulated inflammation due to the loss of autoregulatory function of the cytokines is the early pathophysiological cause of acute respiratory distress syndrome [112,113]. ...
Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.
... The mortality due to ARDS continues to remain high, although mortality clearly depends on the country, type of ICU, aetiology, defi nition of ARDS, etc. Mortality of ARDS in the western population from 1967 to 1994 was an average of 50%. 27 In 1998 a US centre recorded 65% mortality of ARDS patients, 28 another observational study by Bauer and colleagues 29 recorded mortality of 80%, Lu and colleagues from Shanghai reported 68% in-hospital mortality, 30 another Chinese group reported 55% mortality, 31 while from Belgium the mortality was 46%. 32 In India the mortality of ARDS patients still ranges from 48% to 60%. ...
Objective- Acute respiratory distress syndrome (ARDS) is a highly fatal syndrome especially in resource constrained settings. In this study we prospectively studied the aetiology of ARDS and short-term outcome.
Methods- Consecutive adults with suspected ARDS were screened. ARDS was diagnosed by the Berlin criteria. Aetiology was determined clinically, imaging, and microbiological investigations. Patients presenting with fever, prominent cough and expectoration had a throat swab tested for Influenza H1N1 virus. Outcome was discharge from hospital or death. Results- 42 patients, mean age 42.6 years were studied. All received mechanical ventilation. Thirteen (31%) had pulmonary-ARDS; H1N1 virus infection (n=5), pneumonia (n=7), and tuberculosis (n=1). Twenty-nine (69%) had extra-pulmonary ARDS; sepsis (n=16), scrub typhus (n =8). Thirty-three (78.5%) succumbed, of the 9 survivors scrub typhus was diagnosed in 7 patients. Conclusion- The etiology of ARDS in tropical medical setting is infection-related. ARDS due to scrub typhus appeared to be mild with good outcome.
Hyperbaric oxygenation (HBO2) is an important treatment given to various groups of patients exposed to pathologic situations (i.e., carbon monoxide exposure). Since many hyperbaric patients are critically ill and are being treated for life-threatening disorders, it is necessary to monitor various physiologic and biochemical parameters. This is a review of 193 publications covering a wide range of monitored parameters representing metabolic, hemodynamic, respiratory, electrical, and biochemical activities. The significance of monitoring the physiologic, medical, and specific oxygen toxicity effects during HBO2 exposure (MHBO2) is described and emphasized. Further development of new monitoring devices and technologies will enable the improvement of patient management during HBO2 treatment given under various medical conditions. This chapter also presents new ideas about possible future monitoring of brain functions under HBO2 conditions in experimental animals as well as under clinical conditions. Another conclusion was that the earliest possible HBO2 treatment after severe blunt trauma can significantly enhance victims’ survival. In another study it was concluded that applying optimal total dose, DHBOT may provide a maximum possible Efficacy of HBOT in treating patients with Acute Ischemic Stroke-AIS.
Despite its significant limitations, the ratio between the partial pressure of arterial oxygen and the fraction of inspired oxygen, the PaO2/FiO2 ratio, remains the standard tool to classify disease severity in ARDS. Treatment decisions and research enrollment have depended on this parameter for over fifty years. In addition, several variables have been studied over the past few decades, incorporating other physiologic considerations such as ventilation efficiency, lung mechanics, and right ventricular performance. This review describes the strengths and limitations of all relevant parameters, with the goal of helping us better understand disease severity and possible future treatment targets.
Objective:
To analyze the treatment of patients with severe stroke requiring respiratory support, and identify predictors of death.
Material and methods:
A multicenter observational clinical study «REspiratory Therapy for Acute Stroke» (RETAS) was conducted under the aegis of the «Federation of Anaesthesiologists and Reanimatologists» (FAR). The study involved 14 clinical centers and included 1289 stroke patients with respiratory support.
Results:
We found that initial hypoxemia in the 28-day period was associated with higher mortality than in absence of hypoxemia (in patients with 20 or more NIHSS scores) (76.22% versus 63.45%, p=0.004). Risk factors for lethal outcome: hyperventilation used to relieve intracranial hypertension compared with group of patients who were not treated with hyperventilation (in patients with 20 or more NIHSS scores) (79.55% versus 72.75%, p=0.0336); volume-controlled ventilation (VC) versus pressure-controlled ventilation (PC) (in patients with 20 or more NIHSS scores) (p<0.001); use of clinical methods for monitoring ICP in comparison with instrumental ones (87.64% versus 62.33%, p<0.001). It has been proved that the absence of nutritional insufficiency in patients with stroke is associated with a higher probability of a positive outcome (GOS 4 and 5) in comparison with patients with signs of nutritional insufficiency, for the group with NIHSS less than 14 points (p<0.001).
Conclusions:
A group of factors associated with a deterioration in the prognosis of outcomes in patients with stroke who are undergoing ventilation has been identified: hypoxemia at the start of respiratory support, lack of instrumental monitoring of ICP, the use of hyperventilation to correct ICP, ventilation with volume control (VC), as well as the presence of nutritional insufficiency.
: Acute respiratory distress syndrome is a heterogeneous disease which involves both the alveoli and pulmonary vessels. Acute cor pulmonale was initially considered as a marker of severity but its impact on outcome is still controversial.
: This was a prospective observational study conducted over a period of nine months in ICU of a tertiary care center in India. Out of 2028 patient admitted in ICU 64 patients with ARDS (Berlins definition) underwent transthoracic echocardiography within 3 days of admission after diagnosis.
: Acute cor pulmonale(ACP) was detected in 23 (36%) patients. Patients with ACP have greater the severity of disease and higher APACHE score as compared to those without ACP.Ph, PCO and P/F ratio appears to be the independent risk factor in patients for ACP in ARDS.Patients with ACP in ARDS had a higher incidence of shock and mortality(43.5%).
ACP is quite common in ARDS. Due to its effect on the outcome, it appears to be a major factor in deciding ventilatory strategy in patients with ARDS. Right ventricle protective approach of ventilation keeps lung and heart connected.
This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases.When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.
Objectives: To evaluate the outcome in patients with severe adult respiratory distress syndrome (ARDS) managed with limitation of peak inspiratory pressure to 30 to 40 cm H2O, low tidal volumes (4 to 7 mL/kg), spontaneous breathing using synchronized intermittent mandatory ventilation from the start of ventilation, and permissive hypercapnia without the use of bicarbonate to buffer acidosis. Also, to compare hospital mortality rate with that predicted by the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system and the "ventilator score." Setting: A ten-bed general intensive care unit in a university hospital. Design: Prospective, descriptive study. Patients: Fifty-three patients with severe ARDS having a lung injury score of >2.5. Interventions: Data recording. Results: The hospital mortality rate was significantly lower than that predicted by the APACHE II scores (26.4% vs. 53.3%, p = .004), even after correcting the latter for the effect of hypercapnic acidosis (26.4% vs. 51.1%, p = .008). The mortality rate increased with increasing number of organ failures, but was only 43% in patients with >=4 organ failures, 20.5% with <=3 organ failures, and 6.6% with only respiratory failure. The mean maximum Paco2, was 66.5 torr (range 38 to 158 torr [8.87 kPa, range 5.07 to 21.07]), and the mean arterial pH at the same time was 7.23 (range 6.79 to 7.45). There was no correlation between the maximum Paco2 or the corresponding pH and the total respiratory rate at the same time. No pneumothoraces developed during mechanical ventilation. Conclusions: These results lend further support to the hypothesis that limitation of peak inspiratory pressure and reduction of regional lung overdistention by the use of low tidal volumes with permissive hypercapnia may reduce ventilator-induced lung injury and improve outcome in severe ARDS. This hypothesis is supported by a large body of experimental evidence, which also suggests that ventilator-induced lung injury may result in the release of inflammatory mediators, and thus may have the potential to augment the development of multiple organ dysfunction. However, the hypothesis requires testing in a randomized trial as acute hypercapnia could potentially have some adverse as well as beneficial effects. (Crit Care Med 1994; 22:1568-1578)
Study Objective: To determine the epidemiology of multiple organ failure (MOF) in patients with the adult respiratory distress syndrome.
Patients: We followed up 50 patients with serial determinations of respiratory and nonrespiratory organ function for seven days after diagnosis.
Design: Data were stratified between patients who died and those who survived (defined as hospital discharge).
Measurements and Results: Values that did not differ at any time between the two groups of patients included oxygen availability, oxygen consumption, oxygen extraction, PaCO2, respiratory rate, heart rate, systolic blood pressure, cardiac output, stroke index, systemic vascular resistance, and temperature. Patients who died had greater defects in oxygenation (from day 1 through day 7). They also exhibited decreased arterial oxygen content (from day 1 to day 4), decreased mixed venous oxygen content (day 1), increased peak inspiratory pressure (present on day 2, persisted to day 5, reappeared on day 7), decreased diastolic blood pressure (seen on days 1 through 3, reappeared on day 7), and increased mean pulmonary artery pressure (seen on days 2 and 3). Nonsurvivors also exhibited greater degrees of thrombocytopenia (from day 1 to day 4). Decreases in pH (seen on day 1, reappeared from days 4 to 7), abnormalities in liver function (seen only on day 1), and increases in serum creatinine levels (appeared on day 7) were also observed.
Conclusions: Multiorgan dysfunction (MOD) was frequently observed in both groups of patients. Alterations in organ function and the pattern of abnormalities were often subtle and would not be characterized as significant organ dysfunction by most available organ scoring systems. Adult respiratory distress syndrome is a manifestation of systemic disease produced by widespread increases in endothelial permeability; lung dysfunction dominates the early clinical course. When respiratory function is supported, it becomes evident that alterations occur in other organs. Multiorgan failure is really a misnomer; the term emphasizes end-stage changes. Multiorgan dysfunction is common and often resolves without progressing to MOF. Alternatively, MOD can progress to MOF.
(Chest 1992; 101:320-26)
Objective.
—To analyze temporal trends in acute respiratory distress syndrome (ARDS) fatality rates since 1983 at one institution.Design.
—Cohort.Setting.
—Intensive care units of a large county hospital.Patients.
—Consecutive adult patients (≥18 years of age) meeting ARDS criteria were identified through daily surveillance of intensive care units (N=918 from 1983 through 1993). The major causes were sepsis syndrome in 37% and major trauma in 25%; 37% had other risks. Sixty-five percent were male. The median age was 45 years (range, 18 to 92 years); 70% were younger than 60 years.Main Outcome Measure.
—Hospital mortality.Results.
—Overall fatality rates showed no trend from 1983 to 1987, declined slightly in 1988 and 1989, and decreased to a low of 36% in 1993 (95% confidence interval, 25% to 46%). The crude rates were largely unchanged after adjustment for age, ARDS risk, and gender distribution. While patients both younger than 60 years and 60 years or older experienced declines in fatality rate, the larger decrease occurred in the younger cohort. In sepsis patients, ARDS fatality rates declined steadily, from 67% in 1990 to 40% in 1993 (95% confidence interval, 23% to 57%). The decline in sepsis-related ARDS fatality was confined largely to patients less than 60 years of age. Trauma patients and all other patients also experienced declines in fatality rates after 1987, although these trends were not as strong and consistent as in the sepsis population.Conclusions.
—In this large series, we observed a significant decrease in fatality rates occurring largely in patients younger than 60 years and in those with sepsis syndrome as their risk for ARDS. We are unable to determine the extent to which experimental therapies or other changes in treatment have contributed to the observed decline in the ARDS fatality rate. Institution-specific rates and temporal trends in ARDS fatality rates should be considered in clinical trials designed to prevent ARDS and the high mortality associated with this syndrome.(JAMA. 1995;273:306-309)