The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.

Acute respiratory distress syndrome: the Berlin Definition.

IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive ...

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Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)61069-2.pdf

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.

ContextIn the intensive care unit (ICU), delirium is a common yet underdiagnosed
form of organ dysfunction, and its contribution to patient outcomes is unclear.ObjectiveTo determine if delirium is an independent predictor of clinical outcomes,
including 6-month mortality and length of stay among ICU patients receiving
mechanical ventilation.Design, Setting, and ParticipantsProspective cohort study enrolling 275 consecutive mechanically ventilated
patients admitted to adult medical and coronary ICUs of a US university-based
medical center between February 2000 and May 2001. Patients were followed
up for development of delirium over 2158 ICU days using the Confusion Assessment
Method for the ICU and the Richmond Agitation-Sedation Scale.Main Outcome MeasuresPrimary outcomes included 6-month mortality, overall hospital length
of stay, and length of stay in the post-ICU period. Secondary outcomes were
ventilator-free days and cognitive impairment at hospital discharge.ResultsOf 275 patients, 51 (18.5%) had persistent coma and died in the hospital.
Among the remaining 224 patients, 183 (81.7%) developed delirium at some point
during the ICU stay. Baseline demographics including age, comorbidity scores,
dementia scores, activities of daily living, severity of illness, and admission
diagnoses were similar between those with and without delirium (P>.05 for all). Patients who developed delirium had higher 6-month
mortality rates (34% vs 15%, P = .03) and spent 10
days longer in the hospital than those who never developed delirium (P<.001). After adjusting for covariates (including age,
severity of illness, comorbid conditions, coma, and use of sedatives or analgesic
medications), delirium was independently associated with higher 6-month mortality
(adjusted hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.4-7.7; P = .008), and longer hospital stay (adjusted HR, 2.0;
95% CI, 1.4-3.0; P<.001). Delirium in the ICU
was also independently associated with a longer post-ICU stay (adjusted HR,
1.6; 95% CI, 1.2-2.3; P = .009), fewer median days
alive and without mechanical ventilation (19 [interquartile range, 4-23] vs
24 [19-26]; adjusted P = .03), and a higher incidence
of cognitive impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3-35.3; P = .002).ConclusionDelirium was an independent predictor of higher 6-month mortality and
longer hospital stay even after adjusting for relevant covariates including
coma, sedatives, and analgesics in patients receiving mechanical ventilation.

https://jamanetwork.com/journals/jama/articlepdf/198503/JCE30038.pdf

Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit

Background In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. Methods In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO 2 ) to the fraction of inspired oxygen (FiO 2 ) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. Results The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P = 0.04), after adjustment for both the baseline PaO 2 :FIO 2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P = 0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P = 0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. Conclusions In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique–Hopitaux de Marseille and the Programme Hospitalier de Recherche Clinique Regional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1005372

Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

Objectives
To re-examine the epidemiology of acute lung injury (ALI) in European intensive care units (ICUs).

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Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study.

Objectives: Primarily, to determine if respiratory variables, assessed on a daily basis on days 1–6 after ICU admission, were associated with mortality in non-ARDS and ARDS patients with respiratory failure requiring mechanical ventilation. Secondarily, to determine non-respiratory factors associated with mortality in ARDS and non-ARDS patients. Design: Prospective multicentre clinical study. Setting: Seventy-eight intensive care units in Sweden and Iceland. Patients: Five hundred twenty non-ARDS and 95 ARDS patients. Measurements and results: Potentially prognostic factors present at inclusion were tested against 90-day mortality using a Cox regression model. Respiratory variables (PaO2/FIO2, PEEP, mean airway pressure (MAP) and base excess (BE)) were tested against mortality using the model. Primary aim: in non-ARDS a low PaO2/FIO2 on day 1, RR (risk ratio) = 1.17, CI (95 % confidence interval) (1.00; 1.36), day 4, 1.24 (1.02; 1.50), day 5, 1.25 (1.02; 1.53) and a low MAP at baseline, 1.18 (1.00; 1.39), day 2, 1.24 (1.02; 1.52), day 3, 1.33 (1.06; 1.67), day 6, 2.38 (1.11; 5.73) were significantly associated with 90-day death. Secondary aim: in non-ARDS a low age, RR = 0.77 (0.67; 0.89), female gender, 0.85 (0.74; 0.98), and low APS (acute physiologic score), 0.85 (0.73; 0.99), were associated with survival; chronic disease, 1.31 (1.12; 1.52), and non-pulmonary origin to the respiratory failure, 1.27 (1.10; 1.47), with death. In ARDS low age, RR = 0.65 CI (0.46; 0.91), and low APS, 0.65 (0.46; 0.90), were associated with survival. Conclusions: No independent significant association was seen between 90-day mortality and degree of hypoxaemia, PEEP, MAP or BE for the first full week of ICU care in either ARDS or non-ARDS. In a sub-group of non-ARDS a lower PaO2/FIO2 and MAP tended to influence mortality where a significant association was seen for 3 of 7 study days. Age, gender, APS, presence of a chronic disease and a pulmonary/non-pulmonary reason for the respiratory failure were associated with mortality in non-ARDS, while only age and APS showed a similar association in ARDS.

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Adalbjörn Thorsteinsson

Papers

Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study.

The impact of respiratory variables on mortality in non-ARDS and ARDS patients requiring mechanical ventilation.