Late Acute Respiratory Distress Syndrome Research Articles

Lower Late Development Rate of Acute Respiratory Distress Syndrome in Patients with Lower Mechanical Power or Driving Pressure.

For patients on ventilation without acute respiratory distress syndrome (ARDS), there are, as yet, limited data on ventilation strategies. We hypothesized that driving pressure (DP) and mechanical power (MP) may play key roles for the late development of ARDS in patients without initial ARDS. A post hoc analysis of a database from our previous cohort was performed. The mean DP/MP was computed from the data before ARDS development or until ventilator support was discontinued within 28 days. The association between DP/MP and late development of ARDS within 28 days was determined. One hundred and twelve patients were enrolled, among whom seven developed ARDS. Univariate Cox regression showed that congestive heart failure (CHF) history and higher levels of mean MP and DP were associated with ARDS development. Multivariate models revealed that the mean MP and mean DP were still factors independently associated with ARDS development at hazard ratios of 1.177 and 1.226 after adjusting for the CHF effect. Areas under the receiver operating characteristic curves for mean DP/MP in predicting ARDS development were 0.813 and 0.759, respectively. In conclusion, high mean DP and MP values may be key factors associated with late ARDS development. The mean DP had a better predicted value for the development of ARDS than the mean MP.

Intravenous vitamin C against acute respiratory distress syndrome: A narrative review

BackgroundThe use of intravenous vitamin C (IV-Vit-C) in the context of acute respiratory distress syndrome (ARDS) has been a topic of interest and research. ARDS is a severe and life-threatening form of respiratory failure that can be triggered by various factors, including infections, trauma, and inflammatory conditions. Some studies and clinical trials have explored the potential benefits of high-dose intravenous vitamin C in the treatment of ARDS, particularly in the context of severe respiratory illnesses such as those caused by viral infections. MethodsTwo literature reviews are performed by using the google scholar data base (scholar.google.com), one searching for “CITRIS-ALI”, and the other searching for “COVID-19 Vitamin C”, without any time restrictions, and selecting specific works, and citing or cited works, deemed appropriate. All the works included in the c19early.org data base are then indirectly considered through their statistical summary of improvements. ResultsMost of the studies support the use of IV-Vit-C against ARDS in general, including the COVID-19 induced ARDS. From the statistical analysis of 66 COVID-19 Vit-C studies, both IV and oral, there is a 18 % improvement in prophylaxis (RR 0.82 CI 0.69–0.97), a 37 % improvement in early treatment (RR 0.63, CI 0.41–0.98), and 21 % improvement in late treatment (RR 0.79, CI 0.70–0.88). Specific to this latter result are 39 studies of the 66. ConclusionsWhile IV-Vit-C was not a cure for COVID-19, it was a pragmatic but effectual means to reduce the COVID-19 mortality in cases of late infections and ARDS. IV and oral Vit-C may be considered one of the tools treating general ARDS.

Respiratory mechanics in late COVID-19 ARDS - arestrictive pattern is strongly associated with death. Acohort study.

COVID-19 is associated with severe respiratory distress and high mortality. We investigated the evolution of the respiratory mechanics in COVID-19 acute respiratory distress syndrome (ARDS) and the occurrence of a restrictive respiratory pattern. A retrospective, single-centre study including patients admitted to the ICU during the first wave of the pandemic (March-April 2020). A total of 141 consecutive patients were included. Many patients developed a restrictive pattern of respiratory mechanics during the course of the disease. Fifty-two patients died in the hospital (36.8%). In 29 cases (58% of the deceased) death was associated with a pattern of pulmonary mechanics, indicating a restrictive evolution of ARDS. Other diagnoses related to death were pulmonary embolism (n = 7, 14%), septic shock (n = 17, 33%), and other causes (n = 10, 20%), with some patients combining at least 2 of these diagnoses. In a multivariate analysis, age (OR = 1.06; 95% CI: 1.01-1.12; P = 0.029) and the administration of steroid pulses (OR = 2.7; 95% CI: 1.1-6.8; P = 0.03) were associated with the development of a restrictive pulmonary pattern and a higher level of plasmatic interleukin-6. COVID-19 ARDS is associated with high mortality associated with a specific pattern of respiratory mechanics and sustained activation of innate immunological response. Age and administration of high-dose steroid pulses are associated with this clinical picture.

Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury.

It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury. Prospective, longitudinal imaging study. Research imaging facility at The University of Pennsylvania (Philadelphia, PA) and Medical and Surgical ICUs at Massachusetts General Hospital (Boston, MA). Anesthetized swine and patients with acute respiratory distress syndrome (acute respiratory distress syndrome). Lung injury was induced by bronchial hydrochloric acid (3.5 mL/kg) in 10 ventilated Yorkshire pigs and worsened by supine nonprotective ventilation for 24 hours. Whole-lung CT was performed 2 hours after hydrochloric acid (Day 1) in both prone and supine positions and repeated at 24 hours (Day 2). Prone and supine images were registered (superimposed) in pairs to measure the effects of positioning on the aeration of each tissue unit. Two patients with early acute respiratory distress syndrome were compared with two patients with late acute respiratory distress syndrome, using electrical impedance tomography to measure the effects of body position on regional lung mechanics. Gas exchange and respiratory mechanics worsened over 24 hours, indicating lung injury progression. On Day 1, prone positioning reinflated 18.9% ± 5.2% of lung mass in the posterior lung regions. On Day 2, position-associated dorsal reinflation was reduced to 7.3% ± 1.5% (p < 0.05 vs Day 1). Prone positioning decreased aeration in the anterior lungs on both days. Although prone positioning improved posterior lung compliance in the early acute respiratory distress syndrome patients, it had no effect in late acute respiratory distress syndrome subjects. The effects of prone positioning on lung aeration may depend on the stage of lung injury and duration of prior ventilation; this may limit the clinical efficacy of this treatment if applied late.

Secretory Phospholipase A2-IIA Protein and mRNA Pools in Extracellular Vesicles of Bronchoalveolar Lavage Fluid from Patients with Early Acute Respiratory Distress Syndrome: A New Perception in the Dissemination of Inflammation?

Secretory phospholipase-IIA A2 (sPLA2-IIA) is expressed in a variety of cell types under inflammatory conditions. Its presence in the bronchoalveolar lavage (BAL) fluid of patients with acute respiratory distress syndrome (ARDS) is associated with the severity of the injury. Exosomal type extracellular vesicles, (EVs), are recognized to perform intercellular communication. They may alter the immune status of recipient target cells through cargo shuttling. In this work, we characterized the exosomal type EVs isolated from BAL fluid of patients with early and late ARDS as compared to control/non-ARDS patients, through morphological (confocal and electron microscopy) and biochemical (dynamic light scattering, qRT-PCR, immunoblotting) approaches. We provide evidence for the presence of an sPLA2-IIA-carrying EV pool that coprecipitates with exosomes in the BAL fluid of patients with ARDS. PLA2G2A mRNA was present in all the samples, although more prominently expressed in early ARDS. However, the protein was found only in EVs from early phase ARDS. Under both forms, sPLA2-IIA might be involved in inflammatory responses of recipient lung cells during ARDS. The perception of the association of sPLA2-IIA to the early diagnosis of ARDS or even with a mechanism of development and propagation of lung inflammation can help in the adoption of appropriate and innovative therapeutic strategies.

Early use of non-steroidal anti-inflammatory drugs in COVID-19 might reverse pathogenesis, prevent complications and improve clinical outcomes

The pathogenesis of Coronavirus disease 2019 is still obscure and the need for exploration of possible mechanisms to suggest drugs based on knowledge should never be delayed. In this manuscript, we present a novel theory to explain the pathogenesis of COVID-19; lymphocyte distraction theory upon which the author has used, in a preprinted protocol, non-steroidal anti-inflammatory drugs (NSAIDs); diclofenac potassium, ibuprofen and ketoprofen, successfully to treat COVID-19 patients. Furthermore, we agree with a recommendation that glucocorticoids should not be used routinely for COVID-19 patients and suggested to be beneficial only for patients with late acute respiratory distress syndrome. A clinical proof of ibuprofen safety in COVID-19 has been published by other researchers and we suggest that early administration of NSAIDs, including ibuprofen, in COVID-19 is not only safe but it might also prevent COVID-19 complications and this manuscript explains some of the suggested associated protective mechanisms.

How Could This Happen? : Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS).

In this rapid commentary, a mini-review is given of the present state-of-knowledge regarding the etiology and epidemiology of the new coronavirus 2019-nCoV and the risks for developing Acute respiratory distress syndrome (ARDS). The available knowledge on the viral genomics, molecular biology and pathogenicity of viruses of the Coronaviridae family and other Nidovirales, forms a helpful template for understanding the present pandemic outbreak. However, important questions remain unanswered about the underlying mechanism causing the very high case fatality ratios (CFR) and mechanisms regarding severe reactions like ARDS, fatal cardiac and renal failures, associated with a number of important comorbidity factors. Immunological reactions to lung alveoles in particular (involving lung macrophages and alveolar epithelial cell damage) in late phase ARDS in SARS-like CoV diseases, so far may not have received enough attention. Finally a shortlist of questions for high priority further research is suggested.

Monitoring of vascular endothelial growth factor and its soluble receptor levels in early trauma.

This clinical observation study aimed to investigate the relationship between the serum levels of vascular endothelial growth factor (VEGF) and its soluble receptors with the severity and the occurrence of late acute respiratory distress syndrome (ARDS) in early trauma. Sixty patients with multiple injuries were divided into three groups according to the Injury Severity Score (ISS) and the serum levels of VEGF, soluble VEGF receptor 1 (sVEGFR1), and sVEGFR2, were measured. Ten healthy people were recruited as controls. The incidence of late ARDS was also monitored, and its relationship to the above measures analyzed. VEGF was not associated with ISS (p > 0.05); sVEGFR1 was positively associated with ISS (r = 0.459, p < 0.0001); however, sVEGFR2 was negatively associated with ISS (r = 0.510, p < 0.0001). The serum VEGF levels between the ARDS group and the non-ARDS group showed no significant difference (p > 0.05). sVEGFR1 in the ARDS group was significantly higher than that in the non-ARDS group (p < 0.0001), and sVEGFR2 in the ARDS group was significantly lower than that in the non-ARDS group (p < 0.0001). In conclusion, the increasing of sVEGFR1 and the decreasing of sVEGFR2 in early trauma might be closely related to the occurrence of late ARDS. Prognostic study, level III.

The impact of the acute respiratory distress syndrome on outcome after oesophagectomy

BackgroundThe Acute Respiratory Distress Syndrome (ARDS) is a serious complication of major surgery and consumes substantial healthcare resources. Oesophagectomy is associated with high rates of ARDS. The aim of this study was to characterize patients and identify risk factors for developing ARDS after oesophagectomy. MethodsA secondary analysis of data from 331 patients gathered during the Beta Agonists Lung Injury Prevention Trial was undertaken. Characteristics and outcomes of patients with early (first 72 h postoperatively) and late (after 72 h) ARDS were determined. Linear and multivariate regression analysis was used to study the differences between early and late ARDS and identify risk factors. ResultsARDS was associated with more non-respiratory organ failure (early 44.1%, late 75.0%, no ARDS 27.6% P<0.001), longer ICU stay (mean early 12.1, late 20.2, no ARDS 7.3 days P<0.001) and longer hospital stay (mean early 18.1, late 24.5, no ARDS 14.2 days P<0.001) but no difference in mortality or quality of life. Older patients (OR 1.06 (1.00 to 1.13), P=0.045) and those with mid-oesophageal tumours (OR 7.48 (1.62–34.5), P=0.010) had a higher risk for ARDS. ConclusionsEarly and late ARDS after oesophagectomy increases intensive care and hospital length of stay. Given the high incidence of ARDS, cohorts of patients undergoing oesophagectomy may be useful as models for studies investigating ARDS prevention and treatment. Further investigations aimed at reducing perioperative ARDS are warranted.

Activated Protein C Nebulization in Severe Late Acute Respiratory Distress Syndrome

Activated Protein C Nebulization in Severe Late Acute Respiratory Distress Syndrome

History of mechanical ventilation may affect respiratory mechanics evolution in acute respiratory distress syndrome

Purpose The aim of this study was to investigate the effect of mechanical ventilation (MV) before acute respiratory distress syndrome (ARDS) on subsequent evolution of respiratory mechanics and blood gases in protectively ventilated patients with ARDS. Methods Nineteen patients with ARDS were stratified into 2 groups according to ARDS onset relative to the onset of MV: In group A (n = 11), MV was applied at the onset of ARDS; in group B (n = 8), MV had been initiated before ARDS. Respiratory mechanics and arterial blood gas were assessed in early (≤3 days) and late (8-11 days) ARDS, on zero positive end-expiratory pressure and positive end-expiratory pressure of 10 cm H 2O. Results In group A, Pa o 2/fractional inspired oxygen concentration increased (121 ± 43 vs 161 ± 60 mm Hg) and minimal resistance of respiratory system decreased (8.3 ± 1.8 vs 6.0 ± 2.1 cm H 2O L −1 s −1) from early to late ARDS. In group B, static elastance of respiratory system increased in the late stage (30.4 ± 7.8 vs 36.4 ± 9.9 cm H 2O/L). In both groups, positive end-expiratory pressure application resulted in Pa o 2/fractional inspired oxygen concentration improvement and minimal resistance of respiratory system decreases in both stages. Conclusion In protectively ventilated patients with ARDS, late alteration of respiratory mechanics occurs more commonly in patients who have been ventilated before ARDS onset, suggesting that the history of MV affects the subsequent progress of ARDS even when using protective ventilation.

A 6-year review of total parenteral nutrition use and association with late-onset acute respiratory distress syndrome among ventilated trauma victims

Aim To establish whether total parenteral nutrition (TPN) for ventilated trauma victims is associated with late-onset acute respiratory distress syndrome (ARDS) independent of ventilation and transfusion parameters. Method Intensive care unit data over 6 years from a level I centre regarding all trauma victims ≥16 years old who underwent mechanical ventilation within the first 48 h of admission were examined. Patients were prospectively followed for late ARDS. Variables were examined for significant changes over time and independent associations with late ARDS were determined. Results Of 2346 eligible patients among whom 404 (17.2%) were exposed to TPN, 192 (8.2%) met criteria for late ARDS. The incidence of late ARDS among those exposed to TPN was 28.7% (116/404) compared with 3.9% (76/1942) among those not so exposed. Adjustments for potential confounding associated risk factors were made. Conclusions TPN administration is independently associated with late ARDS, and its use among critically ill trauma victims should be carefully scrutinised.

Leukoreduction is Associated with a Decreased Incidence of Late Onset Acute Respiratory Distress Syndrome after Injury

Transfusions are known to be associated with Acute Respiratory Distress Syndrome (ARDS). Transfusion of leukoreduced products may be associated with a decreased incidence of late posttraumatic ARDS (late ARDS). Data from ventilated and transfused trauma patients were analyzed. Key variables in the first 48 hours of admission were studied for their associations with late ARDS and examined for changes over the 6 year study period. Late ARDS developed in 244 of the 1488 patients studied (16.4%). The incidence in patients given nonleukoreduced (NLR) product was 30.4 per cent (75/247) versus 13.6 per cent (169/1241) for patients not exposed [2.77 (2.02-3.73), P < 0.001]. Exposure to NLR products (50.9% in 2000 vs. 1.9% in 2005) and incidence of ARDS (26.3% in 2000 vs. 6.3% in 2005) significantly decreased. Treatment variables independently associated with late ARDS were NLR product exposure, Total Parenteral Nutrition exposure, Peak Inspiratory Pressure > or =30 mm Hg, fluid balance > or =2 liters at 48 hours, and transfusion of > or =10 units of any product. NLR product exposure has an association with an increased incidence of late onset posttraumatic ARDS which is independent of large volume transfusions. Leukoreduction should be routinely included in an overall treatment strategy to furthermore mitigate this complication in critically ill trauma patients.

An Update on the Diagnosis of Adrenal Insufficiency and the Use of Corticotherapy in Critical Illness

To examine recent literature regarding corticotherapy in critically ill patients suffering from sepsis, acute respiratory distress syndrome (ARDS), and severe community-acquired pneumonia (SCAP). Literature was identified through MEDLINE (1966-April 2007) using combinations of the key words hydrocortisone, adrenal insufficiency, acute respiratory distress syndrome, pneumonia, sepsis, and cortisol. Bibliographies of relevant articles were reviewed for additional citations. Presentations at recent critical care meetings were also incorporated. Articles were chosen based upon their relevance to the topics covered. Earlier studies using high-dose corticotherapy in the intensive care unit have shown treatment to be ineffective. Recent studies using extended courses of low-to-moderate doses of steroids have found favorable results; however, these results must be interpreted with caution due to limitations in the data. One trial of steroids in septic shock found a survival benefit in patients who failed to increase their baseline cortisol by greater than 9 microg/dL in response to adrenocorticotropic hormone, but these results were not reproduced in a subsequent Phase 3 trial. Recently, inaccuracies in measuring cortisol have been identified, making interpretation of cortisol concentrations difficult. A large-scale study failed to confirm a previously reported mortality benefit of corticotherapy in late ARDS, but preliminary data suggest a role for steroid treatment in early ARDS. Finally, a pilot study has found that hydrocortisone lowers morbidity and mortality in SCAP. Corticotherapy may be beneficial to some patients with sepsis. The decision to administer steroids in sepsis cannot be based on biochemical markers of adrenal function; rather, treatment should be considered in septic patients with vasopressor refractory hypotension. Although preliminary evidence suggests a role for steroids in early ARDS and SCAP, there are not enough data to suggest routine administration of steroids in these conditions. Additional studies are needed to assess corticotherapy in the critically ill.

Pulmonary Superinfection by Trichomonads in the Course of Acute Respiratory Distress Syndrome

The finding of trichomonads in bronchoalveolar lavage fluid (BALF) samples from an acute respiratory distress syndrome (ARDS) patient, never previously reported, incited us to search for these parasites retrospectively in the BALF of patients with ARDS or related pathologies. Eighty-four consecutive BALF samples have been reviewed. Results were compared with data from clinical files of patients included in this study. Detection and identification of trichomonads were based on cytologic characteristics. Subsequently, immunocytochemistry and in situ hybridization were performed in the last case of the series. Our results were as follows: (1) Trichomonads were detected in 25/84 BALFs (20/77 patients). Among the patients testing positive, 17 suffered from ARDS, about 30% of the ARDS patients included in the study. (2) Trichomonads were detected more frequently at a late ARDS stage. (3) No correlation was found between trichomonad detection and other data. (4) Within the group of trichomonad-infected ARDS patients, density of infection correlated with higher mortality. The late detection of these microorganisms in the course of ARDS suggested that trichomonad development is a secondary event. As BALFs obtained early in the course of ARDS were also included in the study, trichomonad incidence could be underestimated. The significance of trichomonad lung colonization in ARDS and its potential pathogenic role are unclear. Nevertheless, the question of an active role of trichomonads in the extension of alveolar lesions or in the limitation of recovery is clearly raised.

The Decreasing Incidence of Late Posttraumatic Acute Respiratory Distress Syndrome: the Potential Role of Lung Protective Ventilation and Conservative Transfusion Practice

A reduction in the incidence of posttraumatic Acute Respiratory Distress Syndrome (ARDS) has been demonstrated. It is hypothesized that ventilation strategies and restrictive transfusion policies are contributory. The purpose of this study is to examine the changes in ventilation and transfusion parameters over time and their associations with late posttraumatic ARDS. The surgical intensive care unit and blood bank databases from a Level I center during a 6-year period were analyzed. All mechanically ventilated trauma patients were screened for ARDS with onset after 48 hours of admission (late ARDS). Demographic, injury, resuscitation, ventilation parameters, and transfusion data were extracted. Variables were analyzed for significant changes during the duration of the study, and independent associations with ARDS were determined. There were 2,346 eligible patients and 192 (8.2%) of them met criteria for late ARDS. There was a significant decrease in the incidence of late ARDS by year (14.9% in 2000 to 3.8% in 2005). When comparing the first and second half of the study, there was a significant decrease in the percentage of patients transfused with packed red blood cells (49.0% versus 40.7%), patients with a peak inspiratory pressure > or = 30 mm Hg (64.9% versus 50.1%), and patients ventilated with a tidal volume/kg > or = 10 mL/kg (39.6% versus 21.8%). Early transfusions, peak inspiratory pressure > or = 30 mm Hg, and fluid balance > or = 2 L in the first 48 hours of admission were independently associated with ARDS. The increasing use of restrictive transfusion policies and ventilation strategies that potentially limit elevations in early peak inspiratory pressures are associated with a decreased incidence of late posttraumatic ARDS.

Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta‐analysis

Glucocorticoids have been shown to improve survival when used in patients with septic shock. The aim of this study was to analyse the role of glucocorticoids in decreasing mortality in acute respiratory distress syndrome (ARDS) both in the acute and the fibroproliferative phases. We searched the MEDLINE database for relevant studies published between 1980 and 2006, and included studies if the study design was a randomized controlled trial or observational study (comparing historical controls). The study population included patients with ARDS treated with glucocorticoids. We calculated the odds ratio and 95% confidence intervals (CI) for the outcome of mortality. Six trials met the inclusion criteria; three investigated the role of steroids in early stage disease (n = 300) and three investigated the role of steroids in late stage disease (n = 235). The odds of glucocorticoids decreasing mortality in patients with early ARDS were 0.57 (95% CI: 0.25-1.32) with a number needed to treat of 10 for benefit (818 harm to 5 benefit) whereas the odds of glucocorticoids decreasing mortality in patients with late ARDS was 0.58 (95% CI: 0.22-1.53) with a number needed to treat of 15 for harm (6 harm to 21 benefit). However, there was significant heterogeneity. Current evidence does not support a role for corticosteroids in the management of ARDS in either the early or late stages of the disease. More research is required to establish the role of steroids in specific subgroups of patients with severe sepsis and early ARDS who have relative adrenal insufficiency and patients with late ARDS 7-14 days after the onset of disease.

Changes in respiratory mechanics and gas exchange during the acute respiratory distress syndrome

The time course of impairment of respiratory mechanics and gas exchange in the acute respiratory distress syndrome (ARDS) remains poorly defined. We assessed the changes in respiratory mechanics and gas exchange during ARDS. We hypothesized that due to the changes in respiratory mechanics over time, ventilatory strategies based on rigid volume or pressure limits might fail to prevent overdistension throughout the disease process. Seventeen severe ARDS patients {PaO2/FiO2 10.1 (9.2-14.3) kPa; 76 (69-107) mmHg [median (25th-75th percentiles)] and bilateral infiltrates} were studied during the acute, intermediate, and late stages of ARDS (at 1-3, 4-6 and 7 days after diagnosis). Severity of lung injury, gas exchange, and hemodynamics were assessed. Pressure-volume (PV) curves of the respiratory system were obtained, and upper and lower inflection points (UIP, LIP) and recruitment were estimated. (1) UIP decreased from early to established (intermediate and late) ARDS [30 (28-30) cmH2O, 27 (25-30) cmH2O and 25 (23-28) cmH2O (P=0.014)]; (2) oxygenation improved in survivors and in patients with non-pulmonary etiology in late ARDS, whereas all patients developed hypercapnia from early to established ARDS; and (3) dead-space ventilation and pulmonary shunt were larger in patients with pulmonary etiology during late ARDS. We found a decrease in UIP from acute to established ARDS. If applied to our data, the inspiratory pressure limit advocated by the ARDSnet (30 cmH2O) would produce ventilation over the UIP, with a consequent increased risk of overdistension in 12%, 43% and 65% of our patients during the acute, intermediate and late phases of ARDS, respectively. Lung protective strategies based on fixed tidal volume or pressure limits may thus not fully avoid the risk of lung overdistension throughout ARDS.

Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome

Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Our objective was to determine the effects of pharmacologic treatments on clinical outcomes in adults with ALI or ARDS. We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January 2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to 2003); and bibliographies of review articles and included studies. Randomized controlled trials of pharmacologic treatments compared to no therapy or placebo for established ALI or ARDS in adults admitted to an intensive care unit, with measurement of early mortality (primary outcome), late mortality, duration of mechanical ventilation, ventilator-free days to day 28, or adverse events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and nutritional interventions, oxygen, and trials in other populations reporting outcomes in subgroups of patients with ALI or ARDS. Two reviewers independently screened titles and abstracts, rated studies for inclusion, extracted data and assessed methodologic quality of included studies. Disagreements were resolved by consensus in consultation with a third reviewer. For each pharmacologic therapy, we quantitatively pooled the results of studies using random effects models where permitted by the available data. We contacted study authors when clarification of the primary outcome was required. Thirty three trials randomizing 3272 patients met our inclusion criteria. Pooling of results showed no effect on early mortality of prostaglandin E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95% confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing 239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two interventions were beneficial in single small trials; corticosteroids given for late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to 0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to 0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show a beneficial effect on prespecified outcomes. Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention.

Pharmacologic Treatments for Acute Respiratory Distress Syndrome and Acute Lung Injury

Multiple pharmacologic treatments have been studied for patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Our objective was to systematically evaluate this literature to determine the effects of these interventions on important clinical outcomes. We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966-week 2, January 2004), EMBASE (1980-week 4, 2004), CINAHL (1982-week 2, January 2004), and HEALTHSTAR (1995-December 2003); proceedings from four conferences (1994-2003); and bibliographies of review articles and included studies. We included randomized controlled trials (RCTs) of pharmacologic treatments compared with no therapy or placebo for established ARDS and ALI in adults admitted to an intensive care unit, with measurement of early mortality, late mortality, duration of ventilation, ventilator-free days, non-pulmonary organ dysfunction, or adverse events. We excluded trials in other populations incorporating subgroup analyses of patients with ARDS and ALI and studies of nitric oxide, partial liquid ventilation, and fluid and nutritional interventions. Two reviewers independently screened studies and abstracted data from studies included in the analysis. Data were pooled using random effects models where appropriate. We retrieved 75 potentially relevant articles and abstracts, of which 33 trials randomizing 3272 patients met our selection criteria. Meta-analysis showed no effect on early mortality for alprostadil ([prostaglandin E(1)] seven studies; 693 patients; relative risk [RR] 0.95; 95% confidence interval [CI], 0.77, 1.17), acetylcysteine (five studies; 235 patients; RR 0.89; 95% CI, 0.65, 1.21), early high-dose corticosteroids (two studies; 180 patients; RR 1.12; 95% CI, 0.72, 1.74), or surfactant therapy (nine studies; 1418 patients; RR 0.93; 95% CI, 0.77, 1.12). Most trials of alprostadil, early high-dose corticosteroids, and surfactant therapy showed more adverse events in the active therapy arm. Single small RCTs demonstrated lower hospital mortality (24 patients, RR 0.20; 95% CI, 0.05, 0.81) with corticosteroids for late phase ARDS and lower 1-month mortality (30 patients, RR 0.67; 95% CI, 0.47, 0.95) with pentoxifylline for patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show beneficial effects on prespecified outcomes. Effective pharmacotherapy for ARDS is extremely limited. Corticosteroids for late phase ARDS and pentoxifylline for patients with metastatic cancer and ARDS reduced mortality in single small studies. However, further research is required to investigate their potential benefit in the treatment of ALI/ARDS.