Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights.

BACKGROUND: Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. METHODS: We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. RESULTS: At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. CONCLUSIONS: Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

Impact of patient safety on outcomes. From prevention to the treatment of post-intensive care syndrome.

Survivors of critical illness may present physical, psychological, or cognitive symptoms after hospital discharge, encompassed within what is known as post-intensive care syndrome. These alterations result from both the critical illness itself and the medical interventions surrounding it. For its prevention, the implementation of the ABCDEF bundle (Assess/treat pain, Breathing/awakening trials, Choice of sedatives, Delirium reduction, Early mobility and exercise, Family) has been proposed, along with additional strategies grouped under the acronym GHIRN (Good communication, Handout materials, Redefined ICU architectural design, Respirator, Nutrition). In addition to these preventive measures during the ICU stay, high-risk patients should be identified for subsequent follow-up through multidisciplinary teams coordinated by Intensive Care Medicine Departments.

Effect of aggressive vs conservative screening and confirmatory test on time to extubation among patients at low or intermediate risk: a randomized clinical trial.

PURPOSE: This study aimed to determine the best strategy to achieve fast and safe extubation. METHODS: This multicenter trial randomized patients with primary respiratory failure and low-to-intermediate risk for extubation failure with planned high-flow nasal cannula (HFNC) preventive therapy. It included four groups: (1) conservative screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and positive end-expiratory pressure (PEEP) ≤ 8 cmH2O plus conservative spontaneous breathing trial (SBT) with pressure support 5 cmH2O + PEEP 0 cmH2O); (2) screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and PEEP ≤ 8 plus aggressive SBT with pressure support 8 + PEEP 5; (3) aggressive screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 8 + PEEP 5; (4) screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 5 + PEEP 0. Primary outcomes were time-to-extubation and simple weaning rate. Secondary outcomes included reintubation within 7 days after extubation. RESULTS: Randomization to the aggressive-aggressive group was discontinued at the interim analysis for safety reasons. Thus, 884 patients who underwent at least 1 SBT were analyzed (conservative-conservative group, n = 256; conservative-aggressive group, n = 267; aggressive-conservative group, n = 261; aggressive-aggressive, n = 100). Median time to extubation was lower in the groups with aggressive screening (p < 0.001). Simple weaning rates were 45.7%, 76.78% (205 patients), 71.65%, and 91% (p < 0.001), respectively. Reintubation rates did not differ significantly (p = 0.431). CONCLUSION: Among patients at low or intermediate risk for extubation failure with planned HFNC, combining aggressive screening with preventive PEEP and a conservative SBT reduced the time to extubation without increasing the reintubation rate.

Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients.

PURPOSE: Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia. METHODS: We carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations. RESULTS: Between 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT ≥ 0.12 ng/mL was associated with higher 90 days mortality. CONCLUSION: Our study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19.

Prevalence of post-intensive care syndrome in mechanically ventilated patients with COVID-19.

Coronavirus disease 19 (COVID-19) patients usually require long periods of mechanical ventilation and sedation, which added to steroid therapy, favours a predisposition to the development of delirium and subsequent mental health disorders, as well as physical and respiratory sequelae. The aim of this study was to determine the prevalence of post-intensive care syndrome (PICS) at 3 months after hospital discharge, in a cohort of mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ambispective, observational study was conducted in three hospitals with intensive care unit (ICU) follow-up clinics. We studied adults who survived a critical illness due to SARS-CoV-2 infection requiring invasive mechanical ventilation. A physical (muscle strength and pulmonary function), functional [12-Item Short Form Health Survey (SF-12), and Barthel score], psychological [hospital anxiety and depression (HADS) and posttraumatic stress disorder symptom severity scales], and cognitive [Montreal cognitive assessment (MoCA) test] assessment were performed. A total of 186 patients were evaluated at 88 days (IQR 68-121) after hospital discharge. Mean age was 59 ± 12 years old, 126 (68%) patients were men, and median length of mechanical ventilation was 14 days (IQR 8-31). About 3 out of 4 patients (n = 139, 75%) met PICS criteria. Symptoms of cognitive and psychiatric disorders were found in 59 (32%) and 58 (31%) patients, respectively. Ninety-one (49%) patients had muscle weakness. Pulmonary function tests in patients with no respiratory comorbidities showed a normal pattern in 93 (50%) patients, and a restrictive disorder in 62 (33%) patients. Also, 69 patients (37%) were on sick leave, while 32 (17%) had resumed work at the time of assessment. In conclusion, survivors of critical illness due to SARS-CoV-2 infection requiring mechanical ventilation have a high prevalence of PICS. Physical domain is the most frequently damaged, followed by cognitive and psychiatric disorders. ICU follow-up clinics enable the assistance of this vulnerable population.

Early Tracheostomy for Managing ICU Capacity During the COVID-19 Outbreak: A Propensity-Matched Cohort Study.

BACKGROUND: During the first wave of the COVID-19 pandemic, shortages of ventilators and ICU beds overwhelmed health care systems. Whether early tracheostomy reduces the duration of mechanical ventilation and ICU stay is controversial. RESEARCH QUESTION: Can failure-free day outcomes focused on ICU resources help to decide the optimal timing of tracheostomy in overburdened health care systems during viral epidemics? STUDY DESIGN AND METHODS: This retrospective cohort study included consecutive patients with COVID-19 pneumonia who had undergone tracheostomy in 15 Spanish ICUs during the surge, when ICU occupancy modified clinician criteria to perform tracheostomy in Patients with COVID-19. We compared ventilator-free days at 28 and 60 days and ICU- and hospital bed-free days at 28 and 60 days in propensity score-matched cohorts who underwent tracheostomy at different timings (≤ 7 days, 8-10 days, and 11-14 days after intubation). RESULTS: Of 1,939 patients admitted with COVID-19 pneumonia, 682 (35.2%) underwent tracheostomy, 382 (56%) within 14 days. Earlier tracheostomy was associated with more ventilator-free days at 28 days (≤ 7 days vs > 7 days [116 patients included in the analysis]: median, 9 days [interquartile range (IQR), 0-15 days] vs 3 days [IQR, 0-7 days]; difference between groups, 4.5 days; 95% CI, 2.3-6.7 days; 8-10 days vs > 10 days [222 patients analyzed]: 6 days [IQR, 0-10 days] vs 0 days [IQR, 0-6 days]; difference, 3.1 days; 95% CI, 1.7-4.5 days; 11-14 days vs > 14 days [318 patients analyzed]: 4 days [IQR, 0-9 days] vs 0 days [IQR, 0-2 days]; difference, 3 days; 95% CI, 2.1-3.9 days). Except hospital bed-free days at 28 days, all other end points were better with early tracheostomy. INTERPRETATION: Optimal timing of tracheostomy may improve patient outcomes and may alleviate ICU capacity strain during the COVID-19 pandemic without increasing mortality. Tracheostomy within the first work on a ventilator in particular may improve ICU availability.

Long-term survival of mechanically ventilated patients with severe COVID-19: an observational cohort study.

BACKGROUND: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality. METHODS: Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality. RESULTS: 868 patients were included (median age, 64 years [interquartile range [IQR], 56-71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50-63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56-62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age [Odds Ratio [OR] per 1-year increase 1.051, 95% CI 1.033-1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011-1.044), diabetes (OR 1.546, 95% CI 1.085-2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001-1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124-3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358-0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205-3.460). CONCLUSION: The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered).

Tracheostomy During the COVID-19 Pandemic: Comparison of International Perioperative Care Protocols and Practices in 26 Countries.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in critically ill patients requiring invasive mechanical ventilation, some of whom may benefit from tracheostomy. Decisions on if, when, and how to perform tracheostomy in patients with COVID-19 have major implications for patients, clinicians, and hospitals. We investigated the tracheostomy protocols and practices that institutions around the world have put into place in response to the COVID-19 pandemic. DATA SOURCES: Protocols for tracheostomy in patients with severe acute respiratory syndrome coronavirus 2 infection from individual institutions (n = 59) were obtained from the United States and 25 other countries, including data from several low- and middle-income countries, 23 published or society-endorsed protocols, and 36 institutional protocols. REVIEW METHODS: The comparative document analysis involved cross-sectional review of institutional protocols and practices. Data sources were analyzed for timing of tracheostomy, contraindications, preoperative testing, personal protective equipment (PPE), surgical technique, and postoperative management. CONCLUSIONS: Timing of tracheostomy varied from 3 to >21 days, with over 90% of protocols recommending 14 days of intubation prior to tracheostomy. Most protocols advocate delaying tracheostomy until COVID-19 testing was negative. All protocols involved use of N95 or higher PPE. Both open and percutaneous techniques were reported. Timing of tracheostomy changes ranged from 5 to >30 days postoperatively, sometimes contingent on negative COVID-19 test results. IMPLICATIONS FOR PRACTICE: Wide variation exists in tracheostomy protocols, reflecting geographical variation, different resource constraints, and limited data to drive evidence-based care standards. Findings presented herein may provide reference points and a framework for evolving care standards.

Tracheostomy in the COVID-19 era: global and multidisciplinary guidance.

Global health care is experiencing an unprecedented surge in the number of critically ill patients who require mechanical ventilation due to the COVID-19 pandemic. The requirement for relatively long periods of ventilation in those who survive means that many are considered for tracheostomy to free patients from ventilatory support and maximise scarce resources. COVID-19 provides unique challenges for tracheostomy care: health-care workers need to safely undertake tracheostomy procedures and manage patients afterwards, minimising risks of nosocomial transmission and compromises in the quality of care. Conflicting recommendations exist about case selection, the timing and performance of tracheostomy, and the subsequent management of patients. In response, we convened an international working group of individuals with relevant expertise in tracheostomy. We did a literature and internet search for reports of research pertaining to tracheostomy during the COVID-19 pandemic, supplemented by sources comprising statements and guidance on tracheostomy care. By synthesising early experiences from countries that have managed a surge in patient numbers, emerging virological data, and international, multidisciplinary expert opinion, we aim to provide consensus guidelines and recommendations on the conduct and management of tracheostomy during the COVID-19 pandemic.

Subglottic secretion drainage for preventing ventilator-associated pneumonia: an overview of systematic reviews and an updated meta-analysis.

Although several guidelines recommend subglottic secretion drainage as a strategy for prevention of ventilator-associated pneumonia (VAP), its use is not widespread. With the aim to assess the effectiveness of subglottic secretion drainage for preventing VAP and to improve other outcomes such as mortality, duration of mechanical ventilation and length of stay in the intensive care unit (ICU) or hospital, an electronic search of the Cochrane Library, MEDLINE, Web of Science and Embase was undertaken. Nine systematic reviews with meta-analysis (in the overview of reviews) and 20 randomised controlled trials (in the updated meta-analysis) were included.In the overview of reviews, all systematic reviews with meta-analysis included found a positive effect of subglottic secretion drainage in the reduction of incidence of VAP. In the updated meta-analysis, subglottic secretion drainage significantly reduced VAP incidence (risk ratio (RR) 0.56, 95% CI 0.48-0.63; I2=0%, p=0.841) and mortality (RR 0.88, 95% CI 0.80-0.97; I2=0%, p=0.888).This is the first study that has found a decrease of mortality associated with the use of subglottic secretion drainage. In addition, subglottic secretion drainage is an effective measure to reduce VAP incidence, despite not improving the duration of mechanical ventilation and ICU and/or hospital length of stay.

Limitation of life support techniques at admission to the intensive care unit: a multicenter prospective cohort study.

PURPOSE: To determine the frequency of limitations on life support techniques (LLSTs) on admission to intensive care units (ICU), factors associated, and 30-day survival in patients with LLST on ICU admission. METHODS: This prospective observational study included all patients admitted to 39 ICUs in a 45-day period in 2011. We recorded hospitals' characteristics (availability of intermediate care units, usual availability of ICU beds, and financial model) and patients' characteristics (demographics, reason for admission, functional status, risk of death, and LLST on ICU admission (withholding/withdrawing; specific techniques affected)). The primary outcome was 30-day survival for patients with LLST on ICU admission. Statistical analysis included multilevel logistic regression models. RESULTS: We recruited 3042 patients (age 62.5 ± 16.1 years). Most ICUs (94.8%) admitted patients with LLST, but only 238 (7.8% [95% CI 7.0-8.8]) patients had LLST on ICU admission; this group had higher ICU mortality (44.5 vs. 9.4% in patients without LLST; p < 0.001). Multilevel logistic regression showed a contextual effect of the hospital in LLST on ICU admission (median OR = 2.30 [95% CI 1.59-2.96]) and identified the following patient-related variables as independent factors associated with LLST on ICU admission: age, reason for admission, risk of death, and functional status. In patients with LLST on ICU admission, 30-day survival was 38% (95% CI 31.7-44.5). Factors associated with survival were age, reason for admission, risk of death, and number of reasons for LLST on ICU admission. CONCLUSIONS: The frequency of ICU admission with LLST is low but probably increasing; nearly one third of these patients survive for ≥ 30 days.

Neurally adjusted ventilatory assist in patients with acute respiratory failure: study protocol for a randomized controlled trial.

BACKGROUND: Patient-ventilator asynchrony is a common problem in mechanically ventilated patients with acute respiratory failure. It is assumed that asynchronies worsen lung function and prolong the duration of mechanical ventilation (MV). Neurally Adjusted Ventilatory Assist (NAVA) is a novel approach to MV based on neural respiratory center output that is able to trigger, cycle, and regulate the ventilatory cycle. We hypothesized that the use of NAVA compared to conventional lung-protective MV will result in a reduction of the duration of MV. It is further hypothesized that NAVA compared to conventional lung-protective MV will result in a decrease in the length of ICU and hospital stay, and mortality. METHODS/DESIGN: This is a prospective, multicenter, randomized controlled trial in 306 mechanically ventilated patients with acute respiratory failure from several etiologies. Only patients ventilated for less than 5 days, and who are expected to require prolonged MV for an additional 72 h or more and are able to breathe spontaneously, will be considered for enrollment. Eligible patients will be randomly allocated to two ventilatory arms: (1) conventional lung-protective MV (n = 153) and conventional lung-protective MV with NAVA (n = 153). Primary outcome is the number of ventilator-free days, defined as days alive and free from MV at day 28 after endotracheal intubation. Secondary outcomes are total length of MV, and ICU and hospital mortality. DISCUSSION: This is the first randomized clinical trial examining, on a multicenter scale, the beneficial effects of NAVA in reducing the dependency on MV of patients with acute respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov website ( NCT01730794 ). Registered on 15 November 2012.

Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Although much has evolved in our understanding of the pathogenesis and factors affecting outcome of patients with acute respiratory distress syndrome (ARDS), still there is no specific pharmacologic treatment for ARDS. Several clinical trials have evaluated the utility of corticoids but none of them has demonstrated a definitive benefit due to small sample sizes, selection bias, patient heterogeneity, and time of initiation of treatment or duration of therapy. We postulated that adjunctive treatment of persistent ARDS with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and a decrease in mortality. METHODS/DESIGN: This is a prospective, multicenter, randomized, controlled trial in 314 patients with persistent moderate/severe ARDS. Persistent ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 24 hours of routine intensive care. Eligible patients will be randomly allocated to two arms: (i) conventional treatment without dexamethasone, (ii) conventional treatment plus dexamethasone. Patients in the dexamethasone group will be treated with a daily dose of 20 mg iv from day 1 to day 5, and 10 mg iv from day 6 to day 10. Primary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after intubation. Secondary outcome is all-cause mortality at day 60 after enrollment. DISCUSSION: This study will be the largest randomized controlled clinical trial to assess the role of dexamethasone in patients with persistent ARDS. TRIAL REGISTRATION: Registered on 21 November 2012 as DEXA-ARDS at ClinicalTrials.gov website ( NCT01731795 ).

Common variants of NFE2L2 gene predisposes to acute respiratory distress syndrome in patients with severe sepsis.

INTRODUCTION: The purpose of this study was to investigate whether common variants across the nuclear factor erythroid 2-like 2 (NFE2L2) gene contribute to the development of the acute respiratory distress syndrome (ARDS) in patients with severe sepsis. NFE2L2 is involved in the response to oxidative stress, and it has been shown to be associated with the development of ARDS in trauma patients. METHODS: We performed a case-control study of 321 patients fulfilling international criteria for severe sepsis and ARDS who were admitted to a Spanish network of post-surgical and critical care units, as well as 871 population-based controls. Six tagging single-nucleotide polymorphisms (SNPs) of NFE2L2 were genotyped, and, after further imputation of additional 34 SNPs, association testing with ARDS susceptibility was conducted using logistic regression analysis. RESULTS: After multiple testing adjustments, our analysis revealed 10 non-coding SNPs in tight linkage disequilibrium (0.75 ≤ r (2) ≤ 1) that were associated with ARDS susceptibility as a single association signal. One of those SNPs (rs672961) was previously associated with trauma-induced ARDS and modified the promoter activity of the NFE2L2 gene, showing an odds ratio of 1.93 per T allele (95 % confidence interval, 1.17-3.18; p = 0.0089). CONCLUSIONS: Our findings support the involvement of NFE2L2 gene variants in ARDS susceptibility and reinforce further exploration of the role of oxidant stress response as a risk factor for ARDS in critically ill patients.

Relationship between volume and survival in closed intensive care units is weak and apparent only in mechanically ventilated patients.

BACKGROUND: Recent studies have found an association between increased volume and increased intensive care unit (ICU) survival; however, this association might not hold true in ICUs with permanent intensivist coverage. Our objective was to determine whether ICU volume correlates with survival in the Spanish healthcare system. METHODS: Post hoc analysis of a prospective study of all patients admitted to 29 ICUs during 3 months. At ICU discharge, the authors recorded demographic variables, severity score, and specific ICU treatments. Follow-up variables included ICU readmission and hospital mortality. Statistics include logistic multivariate analyses for hospital mortality according to quartiles of volume of patients. RESULTS: The authors studied 4,001 patients with a mean predicted risk of death of 23% (range at hospital level: 14-46%). Observed hospital mortality was 19% (range at hospital level: 11-35%), resulting in a standardized mortality ratio of 0.81 (range: 0.5-1.3). Among the 1,923 patients needing mechanical ventilation, the predicted risk of death was 32% (14-60%) and observed hospital mortality was 30% (12-61%), resulting in a standardized mortality ratio of 0.96 (0.5-1.7). The authors found no correlation between standardized mortality ratio and ICU volume in the entire population or in mechanically ventilated patients. Only mechanically ventilated patients in very low-volume ICUs had slightly worse outcome. CONCLUSION: In the currently studied healthcare system characterized by 24/7 intensivist coverage, the authors found wide variability in outcome among ICUs even after adjusting for severity of illness but no relationship between ICU volume and outcome. Only mechanically ventilated patients in very low-volume centers had slightly worse outcomes.