Designing a Bayesian adaptive clinical trial to evaluate novel mechanical ventilation strategies in acute respiratory failure using integrated nested Laplace approximations.

BACKGROUND: Adaptive trials usually require simulations to determine values for design parameters, demonstrate error rates, and establish the sample size. We designed a Bayesian adaptive trial comparing ventilation strategies for patients with acute hypoxemic respiratory failure using simulations. The complexity of the analysis would usually require computationally expensive Markov Chain Monte Carlo methods but this barrier to simulation was overcome using the Integrated Nested Laplace Approximations (INLA) algorithm to provide fast, approximate Bayesian inference. METHODS: We simulated two-arm Bayesian adaptive trials with equal randomization that stratified participants into two disease severity states. The analysis used a proportional odds model, fit using INLA. Trials were stopped based on pre-specified posterior probability thresholds for superiority or futility, separately for each state. We calculated the type I error and power across 64 scenarios that varied the probability thresholds and the initial minimum sample size before commencing adaptive analyses. Two designs that maintained a type I error below 5%, a power above 80%, and a feasible mean sample size were evaluated further to determine the optimal design. RESULTS: Power generally increased as the initial sample size and the futility threshold increased. The chosen design had an initial recruitment of 500 and a superiority threshold of 0.9925, and futility threshold of 0.95. It maintained high power and was likely to reach a conclusion before exceeding a feasible sample size. CONCLUSIONS: We designed a Bayesian adaptive trial to evaluate novel strategies for ventilation using the INLA algorithm to efficiently evaluate a wide range of designs through simulation.

An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months.

Importance: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. Design, Setting, and Participants: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P < .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P < .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

Outcomes Among Mechanically Ventilated Patients With Severe Pneumonia and Acute Hypoxemic Respiratory Failure From SARS-CoV-2 and Other Etiologies.

Importance: Early observations suggested that COVID-19 pneumonia had a higher mortality rate than other causes of pneumonia. Objective: To compare outcomes between mechanically ventilated patients with pneumonia due to COVID-19 (March 2020 to June 2021) and other etiologies (July 2016 to December 2019). Design, Setting, and Participants: This retrospective cohort study was conducted at the Johns Hopkins Healthcare System among adult patients (aged ≥18 years) with pneumonia who required mechanical ventilation in the first 2 weeks of hospitalization. Clinical, laboratory, and mechanical ventilation data were extracted from admission to hospital discharge or death. Exposures: Pneumonia due to COVID-19. Main Outcomes and Measures: The primary outcome was 90-day in-hospital mortality. Secondary outcomes were time to liberation from mechanical ventilation, hospital length of stay, static respiratory system compliance, and ventilatory ratio. Unadjusted and multivariable-adjusted logistic regression, proportional hazards regression, and doubly robust regression were used in propensity score-matched sets to compare clinical outcomes. Results: Overall, 719 patients (mean [SD] age, 61.8 [15.3] years; 442 [61.5%] were male; 460 [64.0%] belonged to a minoritized racial group and 253 [35.2%] were White) with severe COVID-19 pneumonia and 1127 patients (mean [SD] age, 60.9 [15.8] years; 586 [52.0%] were male; 459 [40.7%] belonged to a minoritized racial group and 655 [58.1%] were White) with severe non-COVID-19 pneumonia. In unadjusted analyses, patients with COVID-19 pneumonia had higher 90-day mortality (odds ratio, 1.21, 95% CI 1.04-1.41), longer time on mechanical ventilation (subdistribution hazard ratio 0.72, 95% CI 0.63-0.81), and lower compliance (32.0 vs 28.4 mL/kg PBW/cm H2O; P < .001) when compared with those with non-COVID-19 pneumonia. In propensity score-matched analyses, patients with COVID-19 pneumonia were equally likely to die within 90 days as those with non-COVID-19 pneumonia (odds ratio, 1.04; 95% CI, 0.81 to 1.35; P = .85), had similar respiratory system compliance (mean difference, 1.82 mL/cm H2O; 95% CI, -1.53 to 5.17 mL/cm H2O; P = .28) and ventilatory ratio (mean difference, -0.05; 95% CI, -0.22 to 0.11; P = .52), but had lower rates of liberation from mechanical ventilation (subdistribution hazard ratio, 0.81; 95% CI, 0.65 to 1.00) when compared with those with non-COVID-19 pneumonia. Patients with COVID-19 pneumonia had somewhat lower rates of being discharged from the hospital alive at 90 days (subdistribution hazard ratio, 0.83; 95% CI, 0.68 to 1.01) than those with non-COVID-19 pneumonia; however, this was not statistically significant. Conclusions and Relevance: In this study, mechanically ventilated patients with severe COVID-19 pneumonia had similar mortality rates as patients with other causes of severe pneumonia but longer times to liberation from mechanical ventilation. Mechanical ventilation use in COVID-19 pneumonia should follow the same evidence-based guidelines as for any pneumonia.

Laying the Groundwork for Physiology-Guided Precision Medicine in the Critically Ill.

Canonical critical care syndromes such as sepsis and acute respiratory distress syndrome (ARDS) include patients with markedly heterogeneous biology.1 This, paired with decades of randomized controlled trials (RCTs) that were traditionally viewed as "negative," has stalled progress in improving patient outcomes.2 However, emerging awareness of sub-phenotypes based on differences in biomarker profiles and resulting heterogeneous treatment effects have led to calls for precision medicine in which therapies are targeted to those most likely to benefit.3.

Comparing Prone Positioning Use in COVID-19 Versus Historic Acute Respiratory Distress Syndrome.

Use of prone positioning in patients with acute respiratory distress syndrome (ARDS) from COVID-19 may be greater than in patients treated for ARDS before the pandemic. However, the magnitude of this increase, sources of practice variation, and the extent to which use adheres to guidelines is unknown. OBJECTIVES: To compare prone positioning practices in patients with COVID-19 ARDS versus ARDS treated before the pandemic. DESIGN SETTING AND PARTICIPANTS: We conducted a multicenter retrospective cohort study of mechanically ventilated patients with early moderate-to-severe ARDS from COVID-19 (2020-2021) or ARDS from non-COVID-19 pneumonia (2018-2019) across 19 ICUs at five hospitals in Maryland. MAIN OUTCOMES AND MEASURES: The primary outcome was initiation of prolonged prone positioning (≥ 16 hr) within 48 hours of meeting oxygenation criteria. Comparisons were made between cohorts and within subgroups including academic versus community hospitals, and medical versus nonmedical ICUs. Other outcomes of interest included time to proning initiation, duration of prone sessions and temporal trends in proning frequency. RESULTS: Proning was initiated within 48 hours in 227 of 389 patients (58.4%) with COVID-19 and 11 of 123 patients (8.9%) with historic ARDS (49.4% absolute increase [95% CI for % increase, 41.7-57.1%]). Comparing COVID-19 to historic ARDS, increases in proning were similar in academic and community settings but were larger in medical versus nonmedical ICUs. Proning was initiated earlier in COVID-19 versus historic ARDS (median hours (hr) from oxygenation criteria, 12.9 vs 30.6; p = 0.002) and proning sessions were longer (median hr, 43.0 vs 28.0; p = 0.01). Proning frequency increased rapidly at the beginning of the pandemic and was sustained. CONCLUSIONS AND RELEVANCE: We observed greater overall use of prone positioning, along with shorter time to initiation and longer proning sessions in ARDS from COVID-19 versus historic ARDS. This rapid practice change can serve as a model for implementing evidence-based practices in critical care.

Causes and outcomes of ICU hospitalisations in patients with pulmonary arterial hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is a rare disease characterised by limited survival despite remarkable improvements in therapy. The causes, clinical burden and outcomes of patients admitted to the intensive care unit (ICU) remain poorly characterised. The aim of this study was to describe patient characteristics, causes of ICU hospitalisation, and risk factors for ICU and 1-year mortality. Methods: Data from patients enrolled in the Johns Hopkins Pulmonary Hypertension Registry were analysed for the period between January 2010 and December 2020. Clinical, functional, haemodynamic and laboratory data were collected. Measurements and main results: 102 adult patients with 155 consecutive ICU hospitalisations were included. The leading causes for admission were right heart failure (RHF, 53.3%), infection (17.4%) and arrhythmia (11.0%). ICU mortality was 27.1%. Mortality risk factors included Na <136 mEq·mL-1 (OR: 3.10, 95% CI: 1.41-6.82), elevated pro-B-type natriuretic peptide (proBNP) (OR: 1.75, 95% CI: 1.03-2.98), hyperbilirubinaemia (OR: 1.40, 95% CI: 1.09-1.80), hyperlactaemia (OR: 1.42, 95% CI: 1.05-1.93), and need for vasopressors/inotropes (OR: 5.29, 95% CI: 2.28-12.28), mechanical ventilation (OR: 3.76, 95% CI: 1.63-8.76) and renal replacement therapy (OR: 5.57, 95% CI: 1.25-24.76). Mortality rates at 3, 6 and 12 months were 17.5%, 27.6% and 39.0%, respectively. Connective tissue disease-associated PAH has lower 1-year survival compared to idiopathic PAH (51.4% versus 79.8%, log-rank test p=0.019). Conclusions: RHF is the most common cause for ICU admission. In-hospital and 1-year mortality remain exceedingly high despite improved ICU care. Recognising specific risk factors on admission can help identifying patients at risk for poor outcomes.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Characteristics and Outcomes of US Patients Hospitalized With COVID-19.

BACKGROUND: Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. OBJECTIVE: To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. METHODS: A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020. RESULTS: Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n = 262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services. CONCLUSIONS: In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.

Quality of Heart Failure Care in the Intensive Care Unit.

Patients with heart failure (HF) who are seen in an intensive care unit (ICU) manifest the highest-risk, most complex and most resource-intensive disease states. These patients account for a large relative proportion of days spent in an ICU. The paradigms by which critical care is provided to patients with HF are being reconsidered, including consideration of various multidisciplinary ICU staffing models and the development of acute-response teams. Traditional HF quality initiatives have centered on the peri- and postdischarge period in attempts to improve adherence to guideline-directed therapies and reduce readmissions. There is a compelling rationale for expanding high-quality efforts in treating patients with HF who are receiving critical care so we can improve outcomes, reduce preventable harm, improve teamwork and resource use, and achieve high health-system performance. Our goal is to answer the following question: For a patient with HF in the ICU, what is required for the provision of high-quality care? Herein, we first review the epidemiology of HF syndromes in the ICU and identify relevant critical care and quality stakeholders in HF. We next discuss the tenets of high-quality care for patients with HF in the ICU that will optimize critical care outcomes, such as ICU staffing models and evidence-based management of cardiac and noncardiac disease. We discuss strategies to mitigate preventable harm, improve ICU culture and conduct outcomes review, and we conclude with our summative vision of high-quality of ICU care for patients with HF; our vision includes clinical excellence, teamwork and ICU culture.

Higher PEEP for acute respiratory distress syndrome: a Bayesian meta-analysis of randomised clinical trials.

Objective: Benefit or harm of higher positive end expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) is controversial. We aimed to assess the impact of higher levels of PEEP in patients with ARDS under a Bayesian framework. Design: Systematic review and Bayesian meta-analysis of randomised clinical trials comparing higher to lower PEEP in adult patients with ARDS. Data sources: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from 1996 to 1 March 2020. Review methods: We extracted data from high quality randomised clinical trials comparing higher to lower levels of PEEP in adult patients, using low tidal volume in both arms, and conducted a Bayesian meta-analysis using aggregate data from these studies. Results: Eight clinical trials including 3703 patients (n = 1833 for higher PEEP, n = 1870 for lower PEEP) were included. Under a minimally informative prior, the posterior probability of benefit with higher PEEP was 65% (relative risk, 0.97 [95% credible interval, 0.78-1.14]). In patients with moderate-to- severe ARDS, the posterior probability of benefit with higher PEEP was 77% (relative risk, 0.94 [95% credible interval, 0.77-1.13]). Down-weighting studies that employed a maximum recruitment strategy by 100% increased the posterior probability of benefit to 92% under a minimally informative prior. Conclusions: The probability of benefit or harm from routine use of higher PEEP for patients with ARDS ranges from 27% to 86%, and from 14% to 73% depending on one's prior, suggesting continued uncertainty and equipoise regarding the benefit of PEEP If data from trials using a maximum recruitment strategy is discounted to some extent because of uncertainty over the appropriateness of this approach, the available evidence suggests that higher PEEP could be beneficial for moderate-to-severe ARDS. However, well powered randomised clinical trials are needed to confirm these findings.

Current and evolving standards of care for patients with ARDS.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards - treatments that have a solid evidence base and are well established as targets for usual care - and also evolving standards - treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate sub-phenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.

Lung- and Diaphragm-Protective Ventilation.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.

Mean Airway Pressure As a Predictor of 90-Day Mortality in Mechanically Ventilated Patients.

OBJECTIVES: To determine the association between mean airway pressure and 90-day mortality in patients with acute respiratory failure requiring mechanical ventilation and to compare the predictive ability of mean airway pressure compared with inspiratory plateau pressure and driving pressure. DESIGN: Prospective observational cohort. SETTING: Five ICUs in Lima, Peru. SUBJECTS: Adults requiring invasive mechanical ventilation via endotracheal tube for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of potentially eligible participants (n = 1,500), 65 (4%) were missing baseline mean airway pressure, while 352 (23.5%) were missing baseline plateau pressure and driving pressure. Ultimately, 1,429 participants were included in the analysis with an average age of 59 ± 19 years, 45% female, and a mean PaO2/FIO2 ratio of 248 ± 147 mm Hg at baseline. Overall, 90-day mortality was 50.4%. Median baseline mean airway pressure was 13 cm H2O (interquartile range, 10-16 cm H2O) in participants who died compared to a median mean airway pressure of 12 cm H2O (interquartile range, 10-14 cm H2O) in participants who survived greater than 90 days (p < 0.001). Mean airway pressure was independently associated with 90-day mortality (odds ratio, 1.38 for difference comparing the 75th to the 25th percentile for mean airway pressure; 95% CI, 1.10-1.74) after adjusting for age, sex, baseline Acute Physiology and Chronic Health Evaluation III, baseline PaO2/FIO2 (modeled with restricted cubic spline), baseline positive end-expiratory pressure, baseline tidal volume, and hospital site. In predicting 90-day mortality, baseline mean airway pressure demonstrated similar discriminative ability (adjusted area under the curve = 0.69) and calibration characteristics as baseline plateau pressure and driving pressure. CONCLUSIONS: In a multicenter prospective cohort, baseline mean airway pressure was independently associated with 90-day mortality in mechanically ventilated participants and predicts mortality similarly to plateau pressure and driving pressure. Because mean airway pressure is readily available on all mechanically ventilated patients and all ventilator modes, it is a potentially more useful predictor of mortality in acute respiratory failure.

Searching for the optimal positive end-expiratory pressure for lung protective ventilation.

PURPOSE OF REVIEW: The optimal strategy for setting positive end-expiratory pressure (PEEP) has not been established. This review examines different approaches for setting PEEP to achieve lung-protective ventilation. RECENT FINDINGS: PEEP titration strategies commonly focus either on achieving adequate arterial oxygenation or reducing ventilator-induced lung injury from repetitive alveolar opening and closing, referred to as the open lung approach. Five recent trials of higher versus lower PEEP have not shown benefit with higher PEEP, and one of the five trials showed increased harm for patients treated with the open lung strategy. Evidence suggests that some patients may respond beneficially to higher PEEP by recruiting lung, whereas other patients do not recruit lung and merely overdistend previously open alveoli when higher PEEP is applied. A PEEP titration approach that differentiates PEEP responders from nonresponders and provides higher or lower PEEP accordingly has not been prospectively tested. SUMMARY: When compared, no method for setting PEEP has been proven superior to another. Based on recent studies, higher compared with lower PEEP has not improved clinical outcomes and worsened mortality in one study. Future research should focus on identifying feasible methods for assessing lung recruitability in response to PEEP to enrich future trials of PEEP strategies.

Performance of Critical Care Outcome Prediction Models in an Intermediate Care Unit.

BACKGROUND: Intermediate care units (IMCUs) are heterogeneous in design and operation, which makes comparative effectiveness studies challenging. A generalizable outcome prediction model could improve such comparisons. However, little is known about the performance of critical care outcome prediction models in the intermediate care setting. The purpose of this study is to evaluate the performance of the Acute Physiology and Chronic Health Evaluation version II (APACHE II), Simplified Acute Physiology Score version II (SAPS II) and version 3 (SAPS 3), and Mortality Probability Model version III (MPM0III) in patients admitted to a well-characterized IMCU. MATERIALS AND METHODS: In the IMCU of an academic medical center (July to December 2012), the discrimination and calibration of each outcome prediction model were evaluated using the area under the receiver-operating characteristic and Hosmer-Lemeshow goodness-of-fit test, respectively. Standardized mortality ratios (SMRs) were also calculated. RESULTS: The cohort included data from 628 unique IMCU admissions with an inpatient mortality rate of 8.3%. All models exhibited good discrimination, but only the SAPS II and MPM0III were well calibrated. While the APACHE II and SAPS 3 both markedly overestimated mortality, the SMR for the SAPS II and MPM0III were 0.91 and 0.91, respectively. CONCLUSIONS: The SAPS II and MPM0III exhibited good discrimination and calibration, with slight overestimation of mortality. Each model should be further evaluated in multicenter studies of patients in the intermediate care setting.