Objective: It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). Design: Randomized, controlled clinical trial. Setting: Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: Espana Study). Patients: All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the PaO2/FIO2 remained 5c m H2O. In the Pflex/LTV group, tidal volume was 5‐8 mL/kg PBW and PEEP was set on day 1 at Pflex 2c m H2O. In both groups, FIO2 was set to maintain arterial oxygen saturation >90% and PaO2 70‐100 mm Hg, and respiratory rate was adjusted to maintain PaCO2 between 35 and 50 mm Hg. Measurements and Main Results: The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p .041), and ventilator-free days at day 28 (6.02 7.95 in control and 10.90 9.45 in Pflex/LTV, p .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001). Conclusions: A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS. (Crit Care Med 2006; 34:1311‐1318)

A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.

To better define the epidemiology of postinjury multiple organ failure (MOF), we prospectively evaluated 457 high-risk trauma patients who survived more than 48 hours. Overall, 70 (15%) developed MOF. In 27 (39%) patients, the occurrence was early, while in 43 (61%) patients the presentation was delayed. At presentation, early MOF had more cardiac dysfunction, while late MOF had greater hepatic failure. Indices of shock were more critical risk factors for early MOF, while advanced age was more important for late MOF. While early and late MOF had a similar high incidence of major infections, these appeared to be more important in precipitating late MOF. Finally, while mortality is similar, early MOF patients appear to succumb faster. In conclusion, postinjury MOF remains a significant challenge and appears to present in at least two patterns (i.e., early versus late). Better understanding of the relative roles of the dysfunctional inflammation and infections in early MOF versus late MOF may facilitate the development of new strategies for the prevention and treatment of morbid syndrome.

Postinjury multiple organ failure: a bimodal phenomenon.

A recent North-American-European Consensus Conference proposed new, uniform criteria for the definition of acute lung injury, in part to facilitate earlier identification of patients for clinical trials. However, these criteria have not been evaluated prospectively. We designed a prospective cohort study of 123 consecutive patients with acute lung injury prospectively identified on admission to the adult intensive care units of a tertiary care university hospital. The objectives were to determine if selection of patients using the new criteria for acute lung injury results in a significant change in the clinical characteristics, risk factors, or predictors of mortality when compared with prior studies of patients with adult respiratory distress syndrome (ARDS); and to determine if a quantitative index of the severity of acute lung injury has prognostic value in identifying nonsurvivors of acute lung injury. We used three methods: (1) prospective identification of patients with acute lung injury using a PaO2/FIO2 ratio < 300 and bilateral infiltrates on chest radiograph in the absence of left heart failure; (2) evaluation of the severity of lung injury using a four-point scoring system; and (3) stepwise logistic regression analysis to identify variables significantly associated with hospital mortality. Overall hospital mortality was 58%. Sepsis was the most common clinical disorder (50/123 or 41%) associated with the development of acute lung injury. Using the new definition for acute lung injury, 66 of the 123 patients were enrolled with a PaO2/FIO2 ratio between 150 and 299; 57 of the 123 patients had a PaO2/FIO2 < 150 at the time of entry into the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of patients with acute lung injury. Predictors of mortality.

While our understanding of the pathogenesis and management of acute respiratory distress syndrome (ARDS) has improved over the past decade, estimates of its incidence have been controversial. The goal of this study was to examine ARDS incidence and outcome under current lung protective ventilatory support practices before and after the diagnosis of ARDS. This was a 1-year prospective, multicenter, observational study in 13 geographical areas of Spain (serving a population of 3.55 million at least 18 years of age) between November 2008 and October 2009. Subjects comprised all consecutive patients meeting American-European Consensus Criteria for ARDS. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 255 mechanically ventilated patients fulfilled the ARDS definition, representing an incidence of 7.2/100,000 population/year. Pneumonia and sepsis were the most common causes of ARDS. At the time of meeting ARDS criteria, mean PaO2/FiO2 was 114 ± 40 mmHg, mean tidal volume was 7.2 ± 1.1 ml/kg predicted body weight, mean plateau pressure was 26 ± 5 cmH2O, and mean positive end-expiratory pressure (PEEP) was 9.3 ± 2.4 cmH2O. Overall ARDS intensive care unit (ICU) and hospital mortality was 42.7% (95%CI 37.7–47.8) and 47.8% (95%CI 42.8–53.0), respectively. This is the first study to prospectively estimate the ARDS incidence during the routine application of lung protective ventilation. Our findings support previous estimates in Europe and are an order of magnitude lower than those reported in the USA and Australia. Despite use of lung protective ventilation, overall ICU and hospital mortality of ARDS patients is still higher than 40%.

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The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation

ContextThe incidence of acute cor pulmonale (ACP), a frequent and usually lethal complication of acute respiratory distress syndrome (ARDS) during traditional respiratory support, has never been re-evaluated since protective ventilation gained acceptance.ObjectiveWe performed a longitudinal transeso

Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis

In order to examine the prognostic value of pulmonary arterial hypertension (PAH) in patients with moderate and severe acute respiratory failure (ARF), 225 patients with ARF who had been treated with mechanical ventilation and admitted to our ICU during a 3-yr period (January, 1983 to January, 1986) were prospectively studied. All 70 (31%) patients with moderate and severe ARF also had some form of hemodynamic or pulmonary instability, and were monitored with a pulmonary artery catheter. Of these 70 patients, 38 (54%) had PAH (mean BP 29 +/- 6 mm Hg); their mortality was 79% (30/38). The rest of the patients (n = 32) did not have PAH (mean BP was 15 +/- 3 mm Hg) and their mortality was 44% (14/32) (p less than .01). Thirty patients met all the criteria for adult respiratory distress syndrome (ARDS), and their mortality was 70% (21/30); all of them were included among the 38 PAH patients. ARDS patients who died had a significantly higher pulmonary vascular resistance and a significantly lower cardiac index than patients who survived (p less than .001). We conclude that PAH (present in all our ARDS patients) is a good predictor of mortality in ARF of diverse causes.

Miguel A. Blazquez

Papers

Pulmonary hypertension in acute respiratory failure.

Multiple system organ failure in acute respiratory failure