Respiratory Subsets in Patients with Moderate to Severe Acute Respiratory Distress Syndrome for Early Prediction of Death.

Introduction: In patients with acute respiratory distress syndrome (ARDS), the PaO2/FiO2 ratio at the time of ARDS diagnosis is weakly associated with mortality. We hypothesized that setting a PaO2/FiO2 threshold in 150 mm Hg at 24 h from moderate/severe ARDS diagnosis would improve predictions of death in the intensive care unit (ICU). Methods: We conducted an ancillary study in 1303 patients with moderate to severe ARDS managed with lung-protective ventilation enrolled consecutively in four prospective multicenter cohorts in a network of ICUs. The first three cohorts were pooled (n = 1000) as a testing cohort; the fourth cohort (n = 303) served as a confirmatory cohort. Based on the thresholds for PaO2/FiO2 (150 mm Hg) and positive end-expiratory pressure (PEEP) (10 cm H2O), the patients were classified into four possible subsets at baseline and at 24 h using a standardized PEEP-FiO2 approach: (I) PaO2/FiO2 ≥ 150 at PEEP < 10, (II) PaO2/FiO2 ≥ 150 at PEEP ≥ 10, (III) PaO2/FiO2 < 150 at PEEP < 10, and (IV) PaO2/FiO2 < 150 at PEEP ≥ 10. Primary outcome was death in the ICU. Results: ICU mortalities were similar in the testing and confirmatory cohorts (375/1000, 37.5% vs. 112/303, 37.0%, respectively). At baseline, most patients from the testing cohort (n = 792/1000, 79.2%) had a PaO2/FiO2 < 150, with similar mortality among the four subsets (p = 0.23). When assessed at 24 h, ICU mortality increased with an advance in the subset: 17.9%, 22.8%, 40.0%, and 49.3% (p < 0.0001). The findings were replicated in the confirmatory cohort (p < 0.0001). However, independent of the PEEP levels, patients with PaO2/FiO2 < 150 at 24 h followed a distinct 30-day ICU survival compared with patients with PaO2/FiO2 ≥ 150 (hazard ratio 2.8, 95% CI 2.2−3.5, p < 0.0001). Conclusions: Subsets based on PaO2/FiO2 thresholds of 150 mm Hg assessed after 24 h of moderate/severe ARDS diagnosis are clinically relevant for establishing prognosis, and are helpful for selecting adjunctive therapies for hypoxemia and for enrolling patients into therapeutic trials.

Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines.

PURPOSE: To determine the epidemiology and outcome of severe sepsis and septic shock after 9 years of the implementation of the Surviving Sepsis Campaign (SSC) and to build a mortality prediction model. METHODS: This is a prospective, multicenter, observational study performed during a 5-month period in 2011 in a network of 11 intensive care units (ICUs). We compared our findings with those obtained in the same ICUs in a study conducted in 2002. RESULTS: The current cohort included 262 episodes of severe sepsis and/or septic shock, and the 2002 cohort included 324. The prevalence was 14% (95% confidence interval: 12.5-15.7) with no differences to 2002. The population-based incidence was 31 cases/100 000 inhabitants/year. Patients in 2011 had a significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II; 21.9 ± 6.6 vs 25.5 ± 7.07), Logistic Organ Dysfunction Score (5.6 ± 3.2 vs 6.3 ± 3.6), and Sequential Organ Failure Assessment (SOFA) scores on day 1 (8 ± 3.5 vs 9.6 ± 3.7; P < .01). The main source of infection was intraabdominal (32.5%) although microbiologic isolation was possible in 56.7% of cases. The 2011 cohort had a marked reduction in 48-hour (7% vs 14.8%), ICU (27.2% vs 48.2%), and in-hospital (36.7% vs 54.3%) mortalities. Most relevant factors associated with death were APACHE II score, age, previous immunosuppression and liver insufficiency, alcoholism, nosocomial infection, and Delta SOFA score. CONCLUSION: Although the incidence of sepsis/septic shock remained unchanged during a 10-year period, the implementation of the SSC guidelines resulted in a marked decrease in the overall mortality. The lower severity of patients on ICU admission and the reduced early mortality suggest an improvement in early diagnosis, better initial management, and earlier antibiotic treatment.

A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation.

OBJECTIVES: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome. DESIGN: A secondary analysis of existing data from previously reported observational studies. SETTING: A network of ICUs. PATIENTS: We studied 778 patients with moderate to severe acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001). CONCLUSIONS: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.

Mortality Reduction and Long-Term Compliance with Surviving Sepsis Campaign: A Nationwide Multicenter Study.

PURPOSE: To determine the long-term degree of compliance with the Surviving Sepsis Campaign (SSC) bundles and related outcomes after an educational program in septic patients admitted to a network of intensive care units (ICU). METHODS: Prospective, observational, multicenter study in several ICUs during a 5-month period for evaluating the degree of compliance with the SSC bundles of resuscitation in the first 6 h (B6H) and management in the following 24 h (B24H). We compared the findings with those from a historical cohort at the same ICUs after an educational program (EDUSEPSIS) 5 years earlier. RESULTS: The study cohort comprised 231 episodes of severe sepsis and the historical cohort included 217. In the current cohort, we found a better compliance with B6H compared with the historical cohort (27.7% vs. 9.7%, P < 0.001), and lower compliance with B24H (4.3% vs. 12.9%, P < 0.001). ICU and in-hospital mortalities were reduced from 37.3% to 27.1% (P = 0.02) and from 45.3% to 36.7% (P = 0.06), respectively. This reduction occurred linearly with the number of B6H items completed (P for trend <0.001). All B6H measures were individually associated with lower ICU mortality. Measurement of plasma lactate, blood cultures, and administration of broad-spectrum antibiotics were associated with lower in-hospital mortality. No benefit was observed regarding B24H. CONCLUSIONS: Our study confirmed that an educational campaign aimed at early recognition and management of patients with severe sepsis improves compliance with management recommendations and hospital survival in the long term.

Assessment of PaO2/FiO2 for stratification of patients with moderate and severe acute respiratory distress syndrome.

OBJECTIVES: A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at ARDS onset. Since the proposal did not mandate PaO2/FiO2 calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO2/FiOv would not provide accurate assessment of lung injury severity. DESIGN: A prospective, multicentre, observational study. SETTING: A network of teaching hospitals. PARTICIPANTS: 478 patients with eligible criteria for moderate (100300). PRIMARY AND SECONDARY OUTCOMES: Group severity and hospital mortality. RESULTS: At ARDS onset, 173 patients had a PaO2/FiO2≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO2/FiO2 category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO2/FiO2 and non-standardised PaO2/FiO2 at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). CONCLUSIONS: Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the diagnosis and management of ARDS patients. TRIAL REGISTRATION NUMBERS: NCT00435110 and NCT00736892.