Outcome In Adult Respiratory Distress Syndrome Research Articles

Adult respiratory distress syndrome: do selective anticoagulants help?

The adult respiratory distress syndrome (ARDS) is a form of acute lung injury that is characterized by florid extravascular fibrin deposition. Thrombosis in the pulmonary vasculature and disseminated intravascular coagulation have also been observed in association with ARDS. Fibrin deposition does not occur in the normal lung but is virtually universal in acute lung injury induced by disparate insults. A large body of basic and preclinical evidence further implicates abnormalities of pathways of fibrin turnover in the pathogenesis of acute inflammation and fibrotic repair. Coagulation is locally upregulated in the injured lung, while fibrinolytic activity is depressed. These abnormalities occur concurrently and favor alveolar fibrin deposition. The systemic derangements of fibrin turnover in sepsis are similar to those that occur in the injured lung. Recent clinical trials demonstrate that interventions using selective anticoagulation can provide a mortality advantage and that selective anticoagulants differ in their ability to provide clinical benefit. Preclinical trials in primates with sepsis-induced ARDS now indicate that anticoagulant interventions that block the extrinsic coagulation pathway can protect against the development of pulmonary fibrin deposition as well as lung dysfunction and acute inflammation. These observations provide proof of principle that key steps in the coagulation cascade are appropriate therapeutic targets to prevent the development of acute lung injury in ARDS. Ongoing studies and prior publications also support the hypothesis that reversal of the fibrinolytic defect in ARDS could protect against the development of acute lung injury. In all, these studies suggest that fibrin deposition in the injured lung as well as abnormalities of coagulation and fibrinolysis are integral to the pathogenesis of ARDS. The ability of selective anticoagulants to effectively and safely alter clinical outcome in ARDS remains to be determined.

Adapting prognostic respiratory variables of ARDS in children to small-scale community needs

Purpose: The clinical literature on the incidence and subsequent mortality of adult respiratory distress syndrome (ARDS) has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of ARDS in smaller community-based intensive care units. We aimed to delineate early clinical respiratory predictors of death in children with ARDS on the modest scale of a community hospital. Materials and Methods: A retrospective chart review of children with ARDS needing conventional mechanical ventilation admitted to our pediatric intensive care unit from 1984 to 1997. The diagnosis of ARDS was based on acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin and severe hypoxemia defined by partial pressure of oxygen <200 mm Hg during positive end-expiratory pressure (PEEP) of 6 cm H 2O or greater for a minimum of 24 hours. Demographic, clinical, and physiological data including Pao 2/F io 2, A-a do 2, and ventilation index were retrieved. Results: Fifty-six children with ARDS aged 8 ± 5.5 years (range, 50 days to 21 years) were identified. The mortality rate was 50%. Early predictors of death included the peak inspiratory pressure (PIP), ventilation index, and PEEP on the third day after diagnosis: Nonsurvivors had significantly higher PIP (35.3 ± 10.5 cm H 2O vs 44.4 ± 10.7 cm H 2O, P < .001), PEEP (8 ± 2.8 cm H 2O VS 10.7.0 ± 3.5 cm H 2O, P < .01), and ventilation index (49.14 ± 20.4 mm Hg · cm H 2O/minute vs 61.6 ± 51.1 mm Hg · cm H 2O/minute) than survivors. In contrast, P ao 2/F io 2 and A-a D0 2 were capable of predicting outcome by day 5 and thereafter. Conclusions: A small-scale mortality outcome for ARDS is comparable to large tertiary referral institutions. The PIP, PEEP, and ventilation index are valuable for predicting outcome in ARDS by the third day of conventional therapy. The development of a local risk profile may assist in decision-making of early application of supportive therapies in this population.

Persistent Elevation of Inflammatory Cytokines Predicts a Poor Outcome in ARDS: Plasma IL-1β and IL-6 Levels Are Consistent and Efficient Predictors of Outcome Over Time

Inflammatory cytokines have been related to the development of adult respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction syndrome (MODS). We tested the hypothesis that unfavorable outcome in patients with ARDS is related to the presence of a persistent inflammatory response. For this purpose, we evaluated the behavior of inflammatory cytokines during progression of ARDS and the relationship of plasma inflammatory cytokines with clinical variables and outcome.We prospectively studied 27 consecutive patients with severe medical ARDS. Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukins (ILs) 1 beta, 2, 4, 6, and 8 were measured (enzyme-linked immunosorbent assay [ELISA] method) on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients were receiving mechanical ventilation. Subgroups of patients were identified based on outcome, cause of ARDS, presence or absence of sepsis, shock, and MODS at the time ARDS developed. Subgroups were compared for levels of plasma inflammatory cytokines on day 1 of ARDS and over time.Of the 27 patients, 13 survived ICU admission and 14 died (a mortality rate of 52%). Overall mortality was higher in patients with sepsis (86 vs 38%, p < 0.02). The mean initial plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 were significantly higher in nonsurvivors (p < 0.0001) and in those patients with sepsis (p < 0.0001). Plasma levels of IL-1 beta (p < 0.01) and IL-6 (p = 0.03) were more strongly associated with patient outcome than cause of ARDS (p = 0.8), lung injury score (LIS), APACHE II score, sepsis (p = 0.16), shock, or MODS score. Plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 remained significantly elevated over time (p < 0.0001) in those who died. Although it was the best early predictor of death (p < 0.001), plasma IL-2 > 200 pg/mL lost its usefulness after the first 48 h. A plasma IL-1 beta or IL-6 level > 400 pg/mL on any day in the first week of ARDS was associated with a low likelihood of survival.Our findings indicate that unfavorable outcome in acute lung injury is related to the degree of inflammatory response at the onset and during the course of ARDS. Patients with higher plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 on day 1 of ARDS had persistent elevation of these inflammatory cytokines over time and died. Survivors had lesser elevations of plasma inflammatory cytokines on day 1 of ARDS and a rapid reduction over time. Plasma IL-1 beta and IL-6 levels were consistent and efficient predictors of outcome.

Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: A prospective study

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." A ten-bed general intensive care unit in a university hospital. Prospective, descriptive study. Fifty-three patients with severe ARDS having a lung injury score of > or = 2.5. Data recording. 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 > or = 4 organ failures, 20.5% with < or = 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. 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.

Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: A prospective study

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)

Ga-67 lung uptake in patients with adult respiratory distress syndrome. Association with lung infection and patients' prognosis.

Nine patients with adult respiratory distress syndrome (ARDS) were studied with Ga-67 imaging in search for a site of infection. Different degrees and two patterns of Ga-67 lung uptake scoring in comparison with liver uptake were demonstrated. All patients had diffuse lung uptake, whereas five of them also showed additional focal lung activity. In only one patient was an abdominal focal uptake detected. Chest radiographs of all patients revealed diffuse and focal lung infiltrates that correlated with the Ga-67 uptake patterns. Therefore, Ga-67 imaging was unhelpful in differentiating patients with ARDS with lung infection from patients without lung infection. The intensity of Ga-67 uptake, as expressed by Ga-67 scoring, correlated with the course and outcome of ARDS. Patients exhibiting a high Ga-67 score had long periods of hospitalization and eventually died (four patients), whereas those who had low Ga-67 scores had a short disease course and survived (five patients). It is concluded that Ga-67 imaging in ARDS patients is unable to detect lung infection; however, it may be useful in the assessment of patients' prognosis.