Multicenter International Cohort Validation of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-sedation Scale.

OBJECTIVE: In a multicenter, international cohort, we aimed to validate a modified Sequential Organ Failure Assessment (mSOFA) using the Richmond Agitation-Sedation Scale, hypothesized as comparable to the Glasgow Coma Scale (GCS)-based Sequential Organ Failure Assessment (SOFA). SUMMARY BACKGROUND DATA: The SOFA score, whose neurologic component is based on the GCS, can predict intensive care unit (ICU) mortality. But, GCS is often missing in lieu of other assessments, such as the also reliable and validated Richmond Agitation Sedation Scale (RASS). Single-center data suggested an RASS-based SOFA (mSOFA) predicted ICU mortality. METHODS: Our nested cohort within the prospective 2016 Fourth International Study of Mechanical Ventilation contains 4120 ventilated patients with daily RASS and GCS assessments (20,023 patient-days, 32 countries). We estimated GCS from RASS via a proportional odds model without adjustment. ICU mortality logistic regression models and c-statistics were constructed using SOFA (measured GCS) and mSOFA (measured RASS-estimated GCS), adjusted for age, sex, body-mass index, region (Europe, USA-Canada, Latin America, Africa, Asia, Australia-New Zealand), and postoperative status (medical/surgical). RESULTS: Cohort-wide, the mean SOFA=9.4+/-2.8 and mean mSOFA = 10.0+/-2.3, with ICU mortality = 31%. Mean SOFA and mSOFA similarly predicted ICU mortality (SOFA: AUC = 0.784, 95% CI = 0.769-0.799; mSOFA: AUC = 0.778, 95% CI = 0.763-0.793, P = 0.139). Across models, other predictors of mortality included higher age, female sex, medical patient, and African region (all P < 0.001). CONCLUSIONS: We present the first SOFA modification with RASS in a "real-world" international cohort. Estimating GCS from RASS preserves predictive validity of SOFA to predict ICU mortality. Alternative neurologic measurements like RASS can be viably integrated into severity of illness scoring systems like SOFA.

Weaning Outcomes in Patients with Brain Injury.

BACKGROUND: Despite the need for specific weaning strategies in neurological patients, evidence is generally insufficient or lacking. We aimed to describe the evolution over time of weaning and extubation practices in patients with acute brain injury compared with patients who are mechanically ventilated (MV) due to other reasons. METHODS: We performed a secondary analysis of three prospective, observational, multicenter international studies conducted in 2004, 2010, and 2016 in adults who had need of invasive MV for more than 12 h. We collected data on baseline characteristics, variables related to management ventilator settings, and complications while patients were ventilated or until day 28. RESULTS: Among the 20,929 patients enrolled, we included 12,618 (60%) who started the weaning from MV, of whom 1722 (14%) were patients with acute brain injury. In the acutely brain-injured cohort, 538 patients (31%) did not undergo planned extubation, defined as the need for a tracheostomy without an attempt of extubation, accidental extubation, and death. Among the 1184 planned extubated patients with acute brain injury, 202 required reintubation (17%). Patients with acute brain injury had a higher odds for unplanned extubation (odds ratio [OR] 1.35, confidence interval for 95% [CI 95%] 1.19-1.54; p < 0.001), a higher odds of failure after the first attempt of weaning (spontaneous breathing trial or gradual reduction of ventilatory support; OR 1.14 [CI 95% 1.01-1.30; p = 0.03]), and a higher odds for reintubation (OR 1.41 [CI 95% 1.20-1.66; p < 0.001]) than patients without brain injury. Patients with hemorrhagic stroke had the highest odds for unplanned extubation (OR 1.47 [CI 95% 1.22-1.77; p < 0.001]), of failed extubation after the first attempt of weaning (OR 1.28 [CI 95% 1.06-1.55; p = 0.009]), and for reintubation (OR 1.49 [CI 95% 1.17-1.88; p < 0.001]). In relation to weaning evolution over time in patients with acute brain injury, the risk for unplanned extubation showed a downward trend; the risk for reintubation was not associated to time; and there was a significant increase in the percentage of patients who underwent extubation after the first attempt of weaning from MV. CONCLUSIONS: Patients with acute brain injury, compared with patients without brain injury, present higher odds of undergoing unplanned extubated after weaning was started, lower odds of being extubated after the first attempt, and a higher risk of reintubation.

Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease.

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Machine learning predicts mortality based on analysis of ventilation parameters of critically ill patients: multi-centre validation.

BACKGROUND: Mechanical Ventilation (MV) is a complex and central treatment process in the care of critically ill patients. It influences acid-base balance and can also cause prognostically relevant biotrauma by generating forces and liberating reactive oxygen species, negatively affecting outcomes. In this work we evaluate the use of a Recurrent Neural Network (RNN) modelling to predict outcomes of mechanically ventilated patients, using standard mechanical ventilation parameters. METHODS: We performed our analysis on VENTILA dataset, an observational, prospective, international, multi-centre study, performed to investigate the effect of baseline characteristics and management changes over time on the all-cause mortality rate in mechanically ventilated patients in ICU. Our cohort includes 12,596 adult patients older than 18, associated with 12,755 distinct admissions in ICUs across 37 countries and receiving invasive and non-invasive mechanical ventilation. We carry out four different analysis. Initially we select typical mechanical ventilation parameters and evaluate the machine learning model on both, the overall cohort and a subgroup of patients admitted with respiratory disorders. Furthermore, we carry out sensitivity analysis to evaluate whether inclusion of variables related to the function of other organs, improve the predictive performance of the model for both the overall cohort as well as the subgroup of patients with respiratory disorders. RESULTS: Predictive performance of RNN-based model was higher with Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.72 (± 0.01) and Average Precision (AP) of 0.57 (± 0.01) in comparison to RF and LR for the overall patient dataset. Higher predictive performance was recorded in the subgroup of patients admitted with respiratory disorders with AUC of 0.75 (± 0.02) and AP of 0.65 (± 0.03). Inclusion of function of other organs further improved the performance to AUC of 0.79 (± 0.01) and AP 0.68 (± 0.02) for the overall patient dataset and AUC of 0.79 (± 0.01) and AP 0.72 (± 0.02) for the subgroup with respiratory disorders. CONCLUSION: The RNN-based model demonstrated better performance than RF and LR in patients in mechanical ventilation and its subgroup admitted with respiratory disorders. Clinical studies are needed to evaluate whether it impacts decision-making and patient outcomes. TRIAL REGISTRATION: NCT02731898 ( https://clinicaltrials.gov/ct2/show/NCT02731898 ), prospectively registered on April 8, 2016.

Invasive Mechanical Ventilation in Chronic Obstructive Pulmonary Disease Exacerbations.

Chronic obstructive pulmonary disease (COPD) continues to be an important cause of morbidity, mortality, and health care costs worldwide. Although there exist some heterogeneity between patients, the course of COPD is characterized by recurrent acute exacerbations, which are among the most common causes of medical admission to hospital. Patients with frequent exacerbations have accelerated lung function decline, worse quality of life, and greater mortality. Therefore, interest is growing in assessing the effectiveness of interventions used to treat exacerbations. The present review summarizes the current evidence regarding the use of ventilatory management to treat COPD and the implementation of novel cost-effective strategies, such as high-flow oxygenation or extracorporeal carbon dioxide removal to improve clinical outcomes and functional recovery in this disease and to reduce the associated costs.

Invasive aspergillosis in critically ill patients: An autopsy study.

Autopsy studies show that IA is among the most commonly missed diagnoses in critically ill patients. And, because of lack of unequivocal diagnostic criteria, a timely diagnosis remains challenging. We investigate the epidemiology of and the clinical risk factors for IA in critically ill patients. We conducted a retrospective, observational study of all consecutive ICU patients with evidence of IA in the postmortem examination. During the period of the study (25 years), 893 postmortem examinations were performed in the ICU. Twenty-five patients (2.8%) were diagnosed with IA in autopsy. Only ten (40%) were classified as IA ante-mortem, based on the initiation of antifungal treatment. The most common comorbid conditions were corticosteroid treatment (n = 14, 56%), chronic obstructive pulmonary disease (COPD) (n = 11, 44%), immunosuppression (n = 6, 24%) and haematological malignancy (n = 5, 20%). Twenty-three patients (92%) had three or more risk factors for IA. Critically ill patients with pulmonary infiltrates, treated with high doses intravenous corticosteroids (even for a short period of time), particularly COPD patients who developed worsening respiratory insufficiency despite appropriate treatment were at the highest risk of IA.

Prediction and Outcome of Intensive Care Unit-Acquired Paresis.

BACKGROUND: Intensive care unit-acquired paresis (ICUAP) is associated with poor outcomes. Our objective was to evaluate predictors for ICUAP and the short-term outcomes associated with this condition. METHODS: A secondary analysis of a prospective study including 4157 mechanically ventilated adults in 494 intensive care units from 39 countries. After sedative interruption, patients were screened for ICUAP daily, which was defined as the presence of symmetric and flaccid quadriparesis associated with decreased or absent deep tendon reflexes. A multinomial logistic regression was used to create a predictive model for ICUAP. Propensity score matching was used to estimate the relationship between ICUAP and short-term outcomes (ie, weaning failure and intensive care unit [ICU] mortality). RESULTS: Overall, 114 (3%) patients had ICUAP. Variables associated with ICUAP were duration of mechanical ventilation (relative risk ratio [RRR] per day, 1.10; 95% confidence interval [CI] 1.08-1.12), steroid therapy (RRR 1.8; 95% CI, 1.2-2.8), insulin therapy (RRR 1.8; 95% CI 1.2-2.7), sepsis (RRR 1.9; 95% CI: 1.2 to 2.9), acute renal failure (RRR 2.2; 95% CI 1.5-3.3), and hematological failure (RRR 1.9; 95% CI: 1.2-2.9). Coefficients were used to generate a weighted scoring system to predict ICUAP. ICUAP was significantly associated with both weaning failure (paired rate difference of 22.1%; 95% CI 9.8-31.6%) and ICU mortality (paired rate difference 10.5%; 95% CI 0.1-24.0%). CONCLUSIONS: Intensive care unit-acquired paresis is relatively uncommon but is significantly associated with weaning failure and ICU mortality. We constructed a weighted scoring system, with good discrimination, to predict ICUAP in mechanically ventilated patients at the time of awakening.

Predictors of diffuse alveolar damage in patients with acute respiratory distress syndrome: a retrospective analysis of clinical autopsies.

BACKGROUND: Although diffuse alveolar damage (DAD) is considered the typical histological pattern of acute respiratory distress syndrome (ARDS), only half of patients exhibit this morphological hallmark. Patients with DAD may have higher mortality than those without DAD. Therefore, we aimed to identify the factors associated with DAD in patients with ARDS. METHODS: We analyzed autopsy samples of 356 patients who had ARDS at the time of death. DAD was assessed by two pathologists, and ARDS criteria were evaluated by two intensivists. Criteria for severe ARDS included the degree of hypoxemia and the ancillary variables of the current Berlin definition assessed within 48 h before death: radiographic severity, high positive end-expiratory pressure (PEEP) level, and physiological variables (i.e., altered respiratory system compliance and large anatomic dead space). RESULTS: After multivariable analysis, high PEEP levels, physiological variables, and opacities involving only three quadrants on chest radiographs were not associated with DAD. The four markers independently associated with DAD were (1) duration of evolution (OR 3.29 [1.95-5.55] for patients with ARDS ≥ 3 days, p < 0.001), (2) degree of hypoxemia (OR 3.92 [1.48-10.3] for moderate ARDS and 6.18 [2.34-16.3] for severe ARDS, p < 0.01 for both), (3) increased dynamic driving pressure (OR 1.06 [1.04-1.09], p = 0.007), and (4) radiographic severity (OR 2.91 [1.47-5.75] for patients with diffuse opacities involving the four quadrants, p = 0.002). DAD was found in two-thirds of patients with a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤ 100 mmHg and opacities involving the four quadrants. CONCLUSIONS: In addition to severe hypoxemia, diffuse opacities involving the four quadrants were a strong marker of DAD.

Outcome of acute respiratory distress syndrome in university and non-university hospitals in Germany.

BACKGROUND: This study investigates differences in treatment and outcome of ventilated patients with acute respiratory distress syndrome (ARDS) between university and non-university hospitals in Germany. METHODS: This subanalysis of a prospective, observational cohort study was performed to identify independent risk factors for mortality by examining: baseline factors, ventilator settings (e.g., driving pressure), complications, and care settings-for example, case volume of ventilated patients, size/type of intensive care unit (ICU), and type of hospital (university/non-university hospital). To control for potentially confounding factors at ARDS onset and to verify differences in mortality, ARDS patients in university vs non-university hospitals were compared using additional multivariable analysis. RESULTS: Of the 7540 patients admitted to 95 ICUs from 18 university and 62 non-university hospitals in May 2004, 1028 received mechanical ventilation and 198 developed ARDS. Although the characteristics of ARDS patients were very similar, hospital mortality was considerably lower in university compared with non-university hospitals (39.3% vs 57.5%; p = 0.012). Treatment in non-university hospitals was independently associated with increased mortality (OR (95% CI): 2.89 (1.31-6.38); p = 0.008). This was confirmed by additional independent comparisons between the two patient groups when controlling for confounding factors at ARDS onset. Higher driving pressures (OR 1.10; 1 cmH2O increments) were also independently associated with higher mortality. Compared with non-university hospitals, higher positive end-expiratory pressure (PEEP) (mean ± SD: 11.7 ± 4.7 vs 9.7 ± 3.7 cmH2O; p = 0.005) and lower driving pressures (15.1 ± 4.4 vs 17.0 ± 5.0 cmH2O; p = 0.02) were applied during therapeutic ventilation in university hospitals, and ventilation lasted twice as long (median (IQR): 16 (9-29) vs 8 (3-16) days; p < 0.001). CONCLUSIONS: Mortality risk of ARDS patients was considerably higher in non-university compared with university hospitals. Differences in ventilatory care between hospitals might explain this finding and may at least partially imply regionalization of care and the export of ventilatory strategies to non-university hospitals.

Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial.

IMPORTANCE: Studies of mechanically ventilated critically ill patients that combine populations that are at high and low risk for reintubation suggest that conditioned high-flow nasal cannula oxygen therapy after extubation improves oxygenation compared with conventional oxygen therapy. However, conclusive data about reintubation are lacking. OBJECTIVE: To determine whether high-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy for preventing reintubation in mechanically ventilated patients at low risk for reintubation. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial conducted between September 2012 and October 2014 in 7 intensive care units (ICUs) in Spain. Participants were 527 adult critical patients at low risk for reintubation who fulfilled criteria for planned extubation. Low risk for reintubation was defined as younger than 65 years; Acute Physiology and Chronic Health Evaluation II score less than 12 on day of extubation; body mass index less than 30; adequate secretions management; simple weaning; 0 or 1 comorbidity; and absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, and prolonged mechanical ventilation. INTERVENTIONS: Patients were randomized to undergo either high-flow or conventional oxygen therapy for 24 hours after extubation. MAIN OUTCOMES AND MEASURES: The primary outcome was reintubation within 72 hours, compared with the Cochran-Mantel-Haenszel χ2 test. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis and multiorgan failure, ICU and hospital length of stay and mortality, adverse events, and time to reintubation. RESULTS: Of 527 patients (mean age, 51 years [range, 18-64]; 62% men), 264 received high-flow therapy and 263 conventional oxygen therapy. Reintubation within 72 hours was less common in the high-flow group (13 patients [4.9%] vs 32 [12.2%] in the conventional group; absolute difference, 7.2% [95% CI, 2.5% to 12.2%]; P = .004). Postextubation respiratory failure was less common in the high-flow group (22/264 patients [8.3%] vs 38/263 [14.4%] in the conventional group; absolute difference, 6.1% [95% CI, 0.7% to 11.6%]; P = .03). Time to reintubation was not significantly different between groups (19 hours [interquartile range, 12-28] in the high-flow group vs 15 hours [interquartile range, 9-31] in the conventional group; absolute difference, -4 [95% CI, -54 to 46]; P = .66]. No adverse effects were reported. CONCLUSIONS AND RELEVANCE: Among extubated patients at low risk for reintubation, the use of high-flow nasal cannula oxygen compared with conventional oxygen therapy reduced the risk of reintubation within 72 hours. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01191489.

Management and outcome of mechanically ventilated patients after cardiac arrest.

INTRODUCTION: The aim of this study was to describe and compare the changes in ventilator management and complications over time, as well as variables associated with 28-day hospital mortality in patients receiving mechanical ventilation (MV) after cardiac arrest. METHODS: We performed a secondary analysis of three prospective, observational multicenter studies conducted in 1998, 2004 and 2010 in 927 ICUs from 40 countries. We screened 18,302 patients receiving MV for more than 12 hours during a one-month-period. We included 812 patients receiving MV after cardiac arrest. We collected data on demographics, daily ventilator settings, complications during ventilation and outcomes. Multivariate logistic regression analysis was performed to calculate odds ratios, determining which variables within 24 hours of hospital admission were associated with 28-day hospital mortality and occurrence of acute respiratory distress syndrome (ARDS) and pneumonia acquired during ICU stay at 48 hours after admission. RESULTS: Among 812 patients, 100 were included from 1998, 239 from 2004 and 473 from 2010. Ventilatory management changed over time, with decreased tidal volumes (VT) (1998: mean 8.9 (standard deviation (SD) 2) ml/kg actual body weight (ABW), 2010: 6.7 (SD 2) ml/kg ABW; 2004: 9 (SD 2.3) ml/kg predicted body weight (PBW), 2010: 7.95 (SD 1.7) ml/kg PBW) and increased positive end-expiratory pressure (PEEP) (1998: mean 3.5 (SD 3), 2010: 6.5 (SD 3); P <0.001). Patients included from 2010 had more sepsis, cardiovascular dysfunction and neurological failure, but 28-day hospital mortality was similar over time (52% in 1998, 57% in 2004 and 52% in 2010). Variables independently associated with 28-day hospital mortality were: older age, PaO2 <60 mmHg, cardiovascular dysfunction and less use of sedative agents. Higher VT, and plateau pressure with lower PEEP were associated with occurrence of ARDS and pneumonia acquired during ICU stay. CONCLUSIONS: Protective mechanical ventilation with lower VT and higher PEEP is more commonly used after cardiac arrest. The incidence of pulmonary complications decreased, while other non-respiratory organ failures increased with time. The application of protective mechanical ventilation and the prevention of single and multiple organ failure may be considered to improve outcome in patients after cardiac arrest.

Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy.

RATIONALE: A revised definition of clinical criteria for acute respiratory distress syndrome (ARDS), the Berlin definition, was recently established to classify patients according to their severity. OBJECTIVE: To evaluate the accuracy of these clinical criteria using diffuse alveolar damage (DAD) at autopsy as the reference standard. METHODS: All patients who died and had a clinical autopsy in our intensive care unit over a 20-year period (1991-2010) were included. Patients with clinical criteria for ARDS were identified from the medical charts and were classified as mild, moderate, or severe according to the Berlin definition using PaO2/FiO2 oxygenation criteria. Microscopic analysis from each pulmonary lobe was performed by two pathologists. MEASUREMENTS AND MAIN RESULTS: Among 712 autopsies analyzed, 356 patients had clinical criteria for ARDS at time of death, classified as mild (n = 49, 14%), moderate (n = 141, 40%), and severe (n = 166, 46%). Sensitivity was 89% and specificity 63% to identify ARDS using the Berlin definition. DAD was found in 159 of 356 (45%) patients with clinical criteria for ARDS (in 12, 40, and 58% of patients with mild, moderate, and severe ARDS, respectively). DAD was more frequent in patients who met clinical criteria for ARDS during more than 72 hours and was found in 69% of those with severe ARDS for 72 hours or longer. CONCLUSIONS: Histopathological findings were correlated to severity and duration of ARDS. Using clinical criteria the revised Berlin definition for ARDS allowed the identification of severe ARDS of more than 72 hours as a homogeneous group of patients characterized by a high proportion of DAD.

Evolution of mortality over time in patients receiving mechanical ventilation.

RATIONALE: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES: To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS: Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS: We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

Frailty in severe COVID-19 survivors after ICU admission. A prospective and multicenter study in Mexico.

OBJECTIVE: To analyze the presence of frailty in survivors of severe COVID-19 admitted in the Intensive Care Unit (ICU) and followed six months after discharge. DESIGN: An observational, prospective and multicenter, nation-wide study. SETTING: Eight adult ICU across eight academic acute care hospitals in Mexico. PATIENTS: All consecutive adult COVID-19 patients admitted in the ICU with acute respiratory failure between March 8, 2020 to February 28, 2021 were included. Frailty was defined according to the FRAIL scale, and was obtained at ICU admission and 6-month after hospital discharge. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: The primary endpoint was the frailty status 6-months after discharge. A regression model was used to evaluate the predictors during ICU stay associated with frailty. RESULTS: 196 ICU survivors were evaluated for basal frailty at ICU admission and were included in this analysis. After 6-months from discharge, 164 patients were evaluated for frailty: 40 patients (20.4%) were classified as non-frail, 67 patients (34.2%) as pre-frail and 57 patients (29.1%) as frail. After adjustment, the need of invasive mechanical ventilation was the only factor independently associated with frailty at 6 month follow-up (Odds Ratio [OR] 3.70, 95% confidence interval 1.40-9.81, P = .008). CONCLUSIONS: Deterioration of frailty was reported frequently among ICU survivors with severe COVID-19 at 6-months. The need of invasive mechanical ventilation in ICU survivors was the only predictor independently associated with frailty.

The effect of age on clinical outcomes in critically ill brain-injured patients.

PURPOSE: We studied the impact of age on survival and functional recovery in brain-injured patients. METHODS: We performed an observational cohort study of all consecutive adult patients with brain injury admitted to ICU in 8 years. To estimate the optimal cut-off point of the age associated with unfavorable outcomes (mRS 3-6), receiver operating characteristic (ROC) curve analyses were used. Multivariate logistic regression analyses were performed to identify prognostic factors for unfavorable outcomes. RESULTS: We included 619 brain-injured patients. We identified 60 years as the cut-off point at which the probability of unfavorable outcomes increases. Patients ≥ 60 years had higher severity scores at ICU admission, longer duration of mechanical ventilation, longer ICU and hospital stays, and higher mortality. Factors identified as associated with unfavorable outcomes (mRS 3-6) were an advanced age (≥ 60 years) [Odds ratio (OR) 4.59, 95% confidence interval (CI) 2.73-7.74, p < 0.001], a low GCS score (≤ 8 points) [OR 3.72, 95% CI 1.95-7.08, p < 0.001], the development of intracranial hypertension [OR 5.52, 95% CI 2.70-11.28, p < 0.001], and intracerebral hemorrhage as the cause of neurologic disease [OR 3.87, 95% CI 2.34-6.42, p < 0.001]. CONCLUSION: Mortality and unfavorable functional outcomes in critically ill brain-injured patients were associated with older age (≥ 60 years), higher clinical severity (determined by a lower GCS score at admission and the development of intracranial hypertension), and an intracerebral hemorrhage as the cause of neurologic disease.

Effect of a low versus intermediate tidal volume strategy on pulmonary complications in patients at risk of acute respiratory distress syndrome-a randomized clinical trial.

Introduction: There is no consensus on whether invasive ventilation should use low tidal volumes (VT) to prevent lung complications in patients at risk of acute respiratory distress syndrome (ARDS). The purpose of this study is to determine if a low VT strategy is more effective than an intermediate VT strategy in preventing pulmonary complications. Methods: A randomized clinical trial was conducted in invasively ventilated patients with a lung injury prediction score (LIPS) of >4 performed in the intensive care units of 10 hospitals in Spain and one in the United States of America (USA) from 3 November 2014 to 30 August 2016. Patients were randomized to invasive ventilation using low VT (≤ 6 mL/kg predicted body weight, PBW) (N = 50) or intermediate VT (> 8 mL/kg PBW) (N = 48). The primary endpoint was the development of ARDS during the first 7 days after the initiation of invasive ventilation. Secondary endpoints included the development of pneumonia and severe atelectases; the length of intensive care unit (ICU) and hospital stay; and ICU, hospital, 28- and 90-day mortality. Results: In total, 98 patients [67.3% male], with a median age of 65.5 years [interquartile range 55-73], were enrolled until the study was prematurely stopped because of slow recruitment and loss of equipoise caused by recent study reports. On day 7, five (11.9%) patients in the low VT group and four (9.1%) patients in the intermediate VT group had developed ARDS (risk ratio, 1.16 [95% CI, 0.62-2.17]; p = 0.735). The incidence of pneumonia and severe atelectasis was also not different between the two groups. The use of a low VT strategy did neither affect the length of ICU and hospital stay nor mortality rates. Conclusions: In patients at risk for ARDS, a low VT strategy did not result in a lower incidence of ARDS than an intermediate VT strategy.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02070666.

Cross-cultural adaptation of the FRAIL scale for critically ill patients in Spain.

AIM: To translate and culturally adapt the FRAIL scale into Spanish and perform a preliminary test of diagnostic accuracy in patients admitted to intensive care units. DESIGN: Cross-sectional diagnostic study. METHODS: Five intensive care units (ICU) in Spain were participated. Stage 1: Three native Spanish-speaking bilingual translators familiar with the field of critical care translated the scale from English into Spanish. Stage 2: Three native English-speaking bilingual translators familiar with critical care medicine. Stage 3: Authors of the original scale compared the English original and back-translated versions of the scale. Stage 4: Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the comprehension and relevance of each of the items of the Spanish version in 30 patients of 3 different age ranges (<50, 50-65 and >65 years). RESULTS: The FRAIL scale was translated and adapted cross-culturally for patients admitted to intensive care units in Spain. The process consisted of four stages: translation, back translation, comparison and pilot test. There was good correspondence between the original scale and the Spanish version in 100% of the items. The participating patients assessed the relevance (content validity) and comprehensibility (face validity) of each of the items of the first Spanish version. The relevance of some of the items scored low when the scale was used in patients younger than 65 years. CONCLUSIONS: We have cross-culturally adapted the FRAIL scale, originally in English, to Spanish for its use in the critical care medical setting in Spanish-speaking countries. IMPLICATIONS FOR PROFESSIONALS: Physicians and nurses can apply the new scale to all patients admitted to the intensive care units. Nursing care can be adapted according to frailty, trying to reduce the side effects of admission to these units for the most fragile patients. REPORTING METHOD: The manuscript's authors have adhered to the EQUATOR guidelines, using the COSMIN reporting guideline for studies on the measurement properties of patient-reported outcome measures. PATIENT OR PUBLIC CONTRIBUTION: In a pilot clinical study, we applied the first version of the FRAIL-Spain scale to intensive care unit (ICU) patients. Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the relevance (content validity) and comprehensibility (face validity) of the five items of the first Spanish version. Relevance was assessed using a 4-point Likert scale ranging from 1 (no relevance) to 4 (high relevance), and comprehensibility was assessed as poor, acceptable or good. Each health professional applied the scale to three patients (total number of patients = 30) of three different age ranges (<50, 50-65 and >65 years) and recorded the time of application of the scale to each patient. Although the frailty scales were initially created by geriatricians to be applied to the elders, there is little experience with their application in critically ill patients of any age. Therefore, more information is needed to determine the relevance of using this scale in critical care patients. In this pilot study, we considered that nurses and critical care physicians should evaluate frailty using this adapted scale in adult patients admitted to the Intensive Care Units.

Clinical diagnoses and autopsy findings: discrepancies in critically ill patients*.

OBJECTIVES: To determine the proportion of clinical errors by comparing clinical and pathological diagnoses, and to evaluate changes of errors over time. DESIGN: We conducted a prospective study of all consecutive autopsies performed on patients who died in the intensive care unit of the Hospital Universitario de Getafe, Madrid, Spain, between January 1982 and December 2007. The diagnostic errors were classified in two categories: class I errors that were major misdiagnoses with direct impact on therapy, and class II diagnostic errors which comprised major unexpected findings that probably would not have changed therapy. MAIN RESULTS: Of 2,857 deaths during the study period, autopsies were performed in 866 patients (30.3%). Autopsy reports were available in 834 patients, of whom 63 (7.5%) had class I errors and 95 (11.4%) had type II errors. The most frequently missed diagnoses were pulmonary embolism, pneumonia, secondary peritonitis, invasive aspergillosis, endocarditis and myocardial infarction. The autopsy did not determine the cause of death in 22 patients (2.6%). Our rate of diagnostic discrepancy remained relatively constant over time, and the conditions leading to discrepancies have slightly changed, with pneumonia showing a decline in diagnostic accuracy in the last years. CONCLUSIONS: This study found significant discrepancies in 18.5% of patients who underwent autopsy, 7.5% of them were diagnoses with impact on therapy and outcome. This reinforces the importance of the postmortem examination in confirming diagnostic accuracy and improving the quality of care of critically ill patients.

Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation.

RATIONALE: A new classification of patients based on the duration of liberation of mechanical ventilation has been proposed. OBJECTIVES: To analyze outcomes based on the new weaning classification in a cohort of mechanically ventilated patients. METHODS: Secondary analysis included 2,714 patients who were weaned and underwent scheduled extubation from a cohort of 4,968 adult patients mechanically ventilated for more than 12 hours. MEASUREMENTS AND MAIN RESULTS: Patients were classified according to a new weaning classification: 1,502 patients (55%) as simple weaning,1,058 patients (39%) as difficult weaning, and 154 (6%) as prolonged weaning.Variables associated with prolonged weaning(.7d)were: severity at admission (odds ratio [OR] per unit of Simplified Acute Physiology Score II, 1.01; 95% confidence interval [CI], 1.001­1.02), duration of mechanical ventilation before first attempt of weaning (OR per day, 1.10; 95% CI, 1.06­1.13), chronic pulmonary disease other than chronic obstructive pulmonary disease (OR,13.23; 95% CI, 3.44­51.05), pneumonia as the reason to start mechanical ventilation (OR, 1.82; 95% CI, 1.07­3.08), and level of positive end-expiratory pressure applied before weaning (OR per unit,1.09; 95% CI, 1.04­1.14). The prolonged weaning group had a nonsignificant trend toward a higher rate of reintubation (P » 0.08),tracheostomy (P » 0.15), and significantly longer length of stay and higher mortality in the intensive care unit (OR for death, 1.97;95%CI, 1.17­3.31). The adjusted probability of death remained constant until Day 7, at which point it increased to 12.1%.

Severe acute respiratory failure secondary to acute fibrinous and organizing pneumonia requiring mechanical ventilation: a case report and literature review.

A 27-year-old woman was admitted to our ICU with acute hypoxemic respiratory failure and criteria for ARDS. Despite an F(IO(2)) of 1.0 and a lung protective strategy, the patient died on day 15 without any improvement. The relatives gave consent for post-mortem analysis. The histopathologic study of the lung showed findings typical of an acute fibrinous and organizing pneumonia. Apropos of this case we performed a PubMed search. We found 13 articles, including a total of 29 patients. Acute fibrinous and organizing pneumonia is an unusual cause of acute lung injury. The diagnostic criterion is histopathologic. There is little information regarding the pathophysiology of this illness. Important questions remain regarding this disease, including predisposing factors and management. Patients who require mechanical ventilation have poor outcomes.