Assessment of Clinical Criteria for Sepsis For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

IMPORTANCE: The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE: To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS AND POPULATION: Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES: Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES: For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS: In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75-0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome. CONCLUSIONS AND RELEVANCE: Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries

IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS:The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES:Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS

Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome: Insights from the LUNG SAFE Study

Abstract RATIONALE: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. OBJECTIVES: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. METHODS: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. MEASUREMENTS AND MAIN RESULTS: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159-1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg. CONCLUSIONS: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073)

Simvastatin for patients with Acute Respiratory Distress Syndrome: long term outcomes and cost-effectiveness from a randomised controlled trial

Background: Simvastatin therapy for patients with ARDS has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. Methods: A cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland. Five hundred and forty intubated and mechanically ventilated patients with acute respiratory distress syndrome were randomly assigned (1:1) to receive once-daily simvastatin (at a dose of 80 mg) or identical placebo tablets enterally for up to 28 days. Results: Mortality was lower in the simvastatin group (31.8%; 95% CI 26.1, 37.5) compared to the placebo group (37.3%; 95% CI 31.6, 43.0) at 12 months although this was not significant. Simvastatin was associated with statistically significant QALY gain (incremental QALYs 0.064, 95% CI 0.002, 0.127) compared to placebo. Simvastatin was also less costly (incremental total costs –£3601, 95% CI –8061, 859). At a willingness-to-pay threshold of £20,000 per QALY the probability of simvastatin being cost-effective was 99%. Sensitivity analyses indicated that the results were robust to changes in methodological assumptions with the probability of cost-effectiveness never dropping below 90%. Conclusion: Simvastatin was found to be cost-effective for the treatment of ARDS, being associated with both a significant QALY gain and a cost saving. There was no significant reduction in mortality at 12 months

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Patterns of use of adjunctive therapies in patients with early moderate- severe Acute Respiratory Distress syndrome: Insights from the LUNG SAFE Study

Background: Adjunctive strategies are an important part of the management of ARDS. However, their application in clinical practice remains inconsistent. Research Question: We wished to determine the frequency and patterns of use of adjunctive strategies in patients with moderate to severe ARDS (PaO2/FIO2 [P/F ratio] &lt; 150) enrolled into the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Study Design and Methods: The LUNG SAFE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in 2014 in 459 ICUs from 50 countries. The primary objective of this substudy was to determine the frequency of use of widely available (neuromuscular blockade, prone position) adjuncts vs adjuncts requiring specialized equipment (extracorporeal membrane oxygenation, inhaled vasodilators, high-frequency ventilation) in patients in the first 48 h of moderate to severe ARDS (P/F ratio &lt; 150). Results: Of 1,146 patients on invasive ventilation with moderate to severe ARDS, 811 patients (71%) received no adjunct within 48 h of ARDS onset. Of 335 (29%) that received adjunctive strategies, 252 (75%) received a single strategy, and 83 (25%) receiving more than one adjunct. Of ARDS nonsurvivors, 67% did not receive any adjunctive strategy in the first 48 h. Most patients (67%) receiving specialized adjuncts did not receive prone positioning or neuromuscular blockade. Patients that received adjuncts were more likely to have their ARDS recognized, be younger and sicker, have pneumonia, be more difficult to ventilate, and be in a European high-income country than those that did not receive adjuncts. Interpretation: Three in 10 patients with moderate to severe ARDS, and only one-third of nonsurvivors, received adjunctive strategies over the first 48 h of ARDS. A more consistent and evidence-driven approach to adjunct use may reduce costs and improve outcomes in patients with moderate to severe ARDS. Trial Registry: ClinicalTrials.gov; No.: NCT02010073; URL: www.clinicaltrials.go