Cost-effectiveness of Implementing Low-Tidal Volume Ventilation in Patients With Acute Lung Injury

Background: Despite widespread guidelines recommending the use of lung-protective ventilation (LPV) in patients with acute lung injury (ALI), many patients do not receive this lifesaving therapy. We sought to estimate the incremental clinical and economic outcomes associated with LPV and determined the maximum cost of a hypothetical intervention to improve adherence with LPV that remained cost-effective. Methods: Adopting a societal perspective, we developed a theoretical decision model to determine the cost-effectiveness of LPV compared to non-LPV care. Model inputs were derived from the literature and a large population-based cohort of patients with ALI. Cost-effectiveness was determined as the cost per life saved and the cost per quality-adjusted life-years (QALYs) gained. Results: Application of LPV resulted in an increase in QALYs gained by 15% (4.21 years for non-LPV vs 4.83 years for LPV), and an increase in lifetime costs of $7,233 per patient with ALI ($99,588 for non-LPV vs $106,821 for LPV). The incremental cost-effectiveness ratios for LPV were$22,566 per life saved at hospital discharge and $11,690 per QALY gained. The maximum, cost-effective, per patient investment in a hypothetical program to improve LPV adherence from 50 to 90$9,482. Results were robust to a wide range of economic and patient parameter assumptions. Conclusions: Even a costly intervention to improve adherence with low-tidal volume ventilation in patients with ALI reduces death and is cost-effective by current societal standards.NIH F32HL090220.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84154/1/Cooke - CEA LPV.pd

Year in review 2005: Critical Care – resource management

During 2005 Critical Care published several original papers dealing with resource management. Emphasis was placed on sepsis, especially the coagulation cascade, prognosis and resuscitation. The papers highlighted important aspects of the pathophysiology of coagulation and inflammation in sepsis, as well as dealing with the proper use of newly developed compounds. Several aspects of prognosis in critically ill patients were investigated, focusing on biological markers and clinical indexes. Resuscitation received great attention, dealing with the effects of fluid infusion in hemodynamics and the lung. The information obtained can be used to address unknown effects of established therapies, to enlighten current clinical discussion on controversial topics, and to introduce novel medical resources and strategies. Future clinical work will rely heavily on these preclinical and laboratory data

Risk Factors at Index Hospitalization Associated With Longer-term Mortality in Adult Sepsis Survivors

Importance: Sepsis survivors, defined as adult patients who survived to hospital discharge following a critical care unit admission for sepsis, are at increased risk of long-term mortality. Identifying factors independently associated with long-term mortality, known during critical care admission for sepsis, could inform targeted strategies to reduce this risk.Objective: To assess, in adult sepsis survivors, factors independently associated with long-term mortality, known during their index critical care admission for sepsis, meeting Third International Consensus Definitions for Sepsis and Septic Shock criteria.Design, Setting, and Participants: This cohort study included a nationally representative sample of 94 748 adult sepsis survivors from 192 critical care units in England. Participants were identified from consecutive critical care admissions between April 1, 2009, and March 31, 2014, with survival status ascertained as of March 31, 2015. Statistical analyses were completed in June 2017.Exposures: Generic patient characteristics (age, sex, ethnicity, severe comorbidities [defined using the Acute Physiology and Chronic Health Evaluation II method], dependency, surgical status, and acute illness severity [scored using the Acute Physiology and Chronic Health Evaluation II acute physiology component]) and sepsis-specific patient characteristics (site of infection, number of organ dysfunctions, and septic shock status) known during index critical care admission for sepsis.Main Outcomes and Measures: Long-term mortality in adult sepsis survivors with maximum follow-up of 6 years. Adjusted hazard ratios (HRs) were estimated using Cox regression for both generic and sepsis-specific patient characteristics.Results: Sepsis survivors had a mean (SD) age of 61.3 (17.0) years, 43 584 (46.0%) were female, and 86 056 (90.8%) were white. A total of 46.3% had respiratory site of infection. By 1 year from hospital discharge, 15% of sepsis survivors had died, with 6% to 8% dying per year over the subsequent 5 years. Age, sex, race/ethnicity, severe comorbidities, dependency, nonsurgical status, and site of infection were independently associated with long-term mortality. Compared with single-organ dysfunction, having 2 or 3 organ dysfunctions was associated with increased risk of long-term mortality (adjusted HR, 1.07; 95% CI, 1.01-1.13; and adjusted HR, 1.18; 95% CI, 1.03-1.14, respectively), while having 4 organ dysfunctions or more was not associated with increased risk. Unexpectedly, the Acute Physiology and Chronic Health Evaluation acute physiology component score had an incremental association with long-term mortality (adjusted HR, 1.11 for every 5-point increase; 95% CI, 1.08-1.13). The adjusted HR for septic shock was 0.89 (95% CI, 0.85-0.92).Conclusions and Relevance: This study suggests that generic and sepsis-specific risk factors, known during index critical care admission for sepsis, could identify a high-risk sepsis survivor population for biological characterization and designing interventions to reduce long-term mortality.</p

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)

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

Evidence for a causal link between sepsis and long-term mortality: a systematic review of epidemiologic studies

Background: In addition to acute hospital mortality, sepsis is associated with higher risk of death following hospital discharge. We assessed the strength of epidemiological evidence supporting a causal link between sepsis and mortality after hospital discharge by systematically evaluating the available literature for strength of association, bias, and techniques to address confounding. Methods: We searched Medline and Embase using the following ‘mp’ terms, MESH headings and combinations thereof - sepsis, septic shock, septicemia, outcome. Studies published since 1992 where one-year post-acute mortality in adult survivors of acute sepsis could be calculated were included. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms to assess risk of bias, confounding, and causality. The difference in proportion between cumulative one-year mortality and acute mortality was defined as post-acute mortality. Meta-analysis was done by sepsis definition categories with post-acute mortality as the primary outcome. Results: The literature search identified 11,156 records, of which 59 studies met our inclusion criteria and 43 studies reported post-acute mortality. In patients who survived an index sepsis admission, the post-acute mortality was 16.1 % (95 % CI 14.1, 18.1 %) with significant heterogeneity (p &lt; 0.001), on random effects meta-analysis. In studies reporting non-sepsis control arm comparisons, sepsis was not consistently associated with a higher hazard ratio for post-acute mortality. The additional hazard associated with sepsis was greatest when compared to the general population. Older age, male sex, and presence of comorbidities were commonly reported independent predictors of post-acute mortality in sepsis survivors, challenging the causality relationship. Sensitivity analyses for post-acute mortality were consistent with primary analysis. Conclusions: Epidemiologic criteria for a causal relationship between sepsis and post-acute mortality were not consistently observed. Additional epidemiologic studies with recent patient level data that address the pre-illness trajectory, confounding, and varying control groups are needed to estimate sepsis-attributable additional risk and modifiable risk factors to design interventional trials. </p

Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock

Introduction: In this study, we sought to determine the association between red blood cell (RBC) transfusion and outcomes in patients with acute lung injury (ALI), sepsis and shock.Methods: We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial (2000 to 2005) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria (mean arterial pressure (MAP) < 60 mmHg or vasopressor use) within 24 hours of randomization. Using multivariable logistic regression, we examined the association between RBC transfusion and 28-day mortality after adjustment for age, sex, race, randomization arm and Acute Physiology and Chronic Health Evaluation III score. Secondary end points included 90-day mortality and ventilator-free days (VFDs). Finally, we examined these end points among the subset of subjects meeting prespecified transfusion criteria defined by five simultaneous indicators: hemoglobin < 10.2 g/dL, central or mixed venous oxygen saturation < 70%, central venous pressure ≥ 8 mmHg, MAP ≥ 65 mmHg, and vasopressor use.Results: We identified 285 subjects with ALI, sepsis, shock and transfusion data. Of these, 85 also met the above prespecified transfusion criteria. Fifty-three (19%) of the two hundred eighty-five subjects with shock and twenty (24%) of the subset meeting the transfusion criteria received RBC transfusion within twenty-four hours of randomization. We found no independent association between RBC transfusion and 28-day mortality (odds ratio = 1.49, 95% CI (95% confidence interval) = 0.77 to 2.90; P = 0.23) or VFDs (mean difference = -0.35, 95% CI = -4.03 to 3.32; P = 0.85). Likewise, 90-day mortality and VFDs did not differ by transfusion status. Among the subset of patients meeting the transfusion criteria, we found no independent association between transfusion and mortality or VFDs.Conclusions: In patients with new-onset ALI, sepsis and shock, we found no independent association between RBC transfusion and mortality or VFDs. The physiological criteria did not identify patients more likely to be transfused or to benefit from transfusion. © 2011 Parsons et al. licensee BioMed Central Ltd