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Recent Bayesian reanalyses of prominent trials in critical illness have generated controversy by contradicting the initial conclusions based on conventional frequentist analyses. Many clinicians might be sceptical that Bayesian analysis, a philosophical and statistical approach that combines prior beliefs with data to generate probabilities, provides more useful information about clinical trials than the frequentist approach. In this Personal View, we introduce clinicians to the rationale, process, and interpretation of Bayesian analysis through a systematic review and reanalysis of interventional trials in critical illness. In the majority of cases, Bayesian and frequentist analyses agreed. In the remainder, Bayesian analysis identified interventions where benefit was probable despite the absence of statistical significance, where interpretation depended substantially on choice of prior distribution, and where benefit was improbable despite statistical significance. Bayesian analysis in critical care medicine can help to distinguish harm from uncertainty and establish the probability of clinically important benefit for clinicians, policy makers, and patients.

While early empiric antibiotic therapy is beneficial for patients presenting with sepsis, the presentation of sepsis from Clostridioides difficile (formerly Clostridium difficile) infection (CDI) has not been well studied in large cohorts. We sought to determine whether the combination of extreme leukocytosis and diarrhea was strongly predictive of CDI in a cohort of 8659 patients admitted to the intensive care unit. We found that CDI was present in 15.0% (95% CI, 12.1&ndash, 18.3%) of patients with extreme leukocytosis and diarrhea and that mortality for those with CDI, diarrhea, and extreme leukocytosis was 33.8% (95% CI, 23.2&ndash, 44.3%). These data support consideration of empiric treatment for CDI in unstable critically ill patients with extreme leukocytosis and diarrhea, along with treatment of other possible sources of sepsis as appropriate. Empiric treatment for CDI can usually be discontinued promptly, along with narrowing of other broad-spectrum antimicrobial coverage, if a sensitive C. difficile test is negative.

Diaphragmatic respiratory effort during mechanical ventilation is an important determinant of patient outcome, but direct measurement of diaphragmatic contractility requires specialized instrumentation and technical expertise. We sought to determine whether routinely collected clinical variables can predict diaphragmatic contractility and stratify the risk of diaphragm atrophy.We conducted a secondary analysis of a prospective cohort study on diaphragm ultrasound in mechanically ventilated subjects. Clinical variables, such as breathing frequency, ventilator settings, and blood gases, were recorded longitudinally. Machine learning techniques were used to identify variables predicting diaphragm contractility and stratifying the risk of diaphragm atrophy (10% decrease in thickness from baseline). Performance of the variables was evaluated in mixed-effects logistic regression and random-effects tree models using the area under the receiver operating characteristic curve.Measurements were available for 761 study days in 191 subjects, of whom 73 (38%) developed diaphragm atrophy. No routinely collected clinical variable, alone or in combination, could accurately predict either diaphragm contractility or the development of diaphragm atrophy (model area under the receiver operating characteristic curve 0.63-0.75). The risk of diaphragm atrophy was not significantly different according to the presence or absence of patient-triggered breaths (38.3% vs 38.6%; odds ratio 1.01, 95% CI 0.05-2.03). Diaphragm thickening fraction15% during either of the first 2 d of the study was associated with a higher risk of atrophy (44.6% vs 26.1%; odds ratio 2.28, 95% CI 1.05-4.95).Diaphragmatic contractility and the risk of diaphragm atrophy could not be reliably determined from routinely collected clinical variables and ventilator settings. A single measurement of diaphragm thickening fraction measured within 48 h of initiating mechanical ventilation can be used to stratify the risk of diaphragm atrophy during mechanical ventilation.

Background Treatment of hypoxemic respiratory failure (HRF) and ARDS is complex. Standardized management of HRF and ARDS may improve adherence to evidence-informed practice and improve outcomes. Research Question What is the effect of standardized treatment compared with usual care on survival of patients with HRF and ARDS? Study Design and Methods MEDLINE, EMBASE, Cochrane, CINAHL, Scopus, and Web-of-Science were searched (inception to 2018). Included studies were randomized clinical trials or quasi-experimental studies that examined the effect of standardized treatment (care-protocol, care-pathway, or bundle) compared with usual treatment among mechanically ventilated adult patients admitted to an ICU with HRF or ARDS. Study characteristics, pathway components, and patient outcomes were abstracted independently by two reviewers. Results From 15,932 unique citations, 14 studies were included in the systematic review (three randomized clinical trials and 11 quasi-experimental studies). Twelve studies (including 5,767 patients) were included in the meta-analysis. Standardized management of HRF was associated with a 23% relative reduction in mortality (relative risk, 0.77; 95% CI, 0.65-0.91; I2, 70%; P = .002). In studies targeting patients with ARDS (n = 8), a 21% pooled mortality reduction was observed (relative risk, 0.79; 95% CI, 0.71-0.88; I2, 3.1%). Standardized management was associated with increased 28-day ventilator-free days (weighted mean difference, 3.48 days; 95% CI, 2.43-4.54 days; P Interpretation When compared with usual treatment, standardized treatment of patients with HRF and ARDS is associated with increased ventilator-free days, lower tidal volume ventilation, and lower mortality. ICUs should consider the use of standardized treatment to improve the processes and outcomes of care for patients with HRF and ARDS. Clinical Trial Registration PROSPERO; No.: CRD42019099921; URL: www.crd.york.ac.uk/prospero/

Objectives There is conflicting evidence for the effectiveness of early rehabilitation in the intensive care and marked variation in rates of implementation in practice. We aimed to identify barriers and facilitators to early rehabilitation in mechanically ventilated patients and their relevance to practice, as perceived by key ICU clinicians across North America. Design A Delphi study using the Theoretical Domains Framework, consisting of an initial qualitative round and subsequent quantitative rounds, was conducted to gather clinician agreement and perceived importance of barriers and facilitators to early rehabilitation. The survey included questions on the range of individual, sociocultural, and broader organizational influence on behaviors. Setting Clinical practice in North America. Subjects Four clinician groups (intensive care physicians, nurses, therapists, and respiratory therapists). Interventions A three-round Delphi study. Measurements and main results Fifty of 74 (67%) of invited clinicians completed the study. Agreement and consensus with Delphi survey items were high in both rounds within and between professional groups. Agreement was highest for items related to the domain "Beliefs about Consequences" (e.g., mortality reduction) and lowest for items related to the domain "Behavioral Regulation" (e.g., team discussion of barriers). Beliefs expressed about improved mortality and improvements in a variety of other long-term outcomes were not consistent with the current evidence base. Individual agreement scores changed very little from Round 2 to Round 3 of the Delphi, suggesting stability of beliefs and existing consensus. Conclusions This study identified a wide range of beliefs about early rehabilitation that may influence provider behavior and the success and appropriateness of further implementation. The apparent inconsistency between the optimism of stakeholders regarding mortality reductions and a low level of implementation reported elsewhere represent the most major challenge to future implementation success. Other foci for future implementation work include planning, barriers, feedback, and education of staff.

Background Adjunctive strategies are an important part of the management of ARDS. However, their application in clinical practice remains inconsistent. Research Question We wished to determine the frequency and patterns of use of adjunctive strategies in patients with moderate to severe ARDS (Pa o 2/F io 2 [P/F ratio] Study Design and Methods The LUNG SAFE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in 2014 in 459 ICUs from 50 countries. The primary objective of this substudy was to determine the frequency of use of widely available (neuromuscular blockade, prone position) adjuncts vs adjuncts requiring specialized equipment (extracorporeal membrane oxygenation, inhaled vasodilators, high-frequency ventilation) in patients in the first 48 h of moderate to severe ARDS (P/F ratio Results Of 1,146 patients on invasive ventilation with moderate to severe ARDS, 811 patients (71%) received no adjunct within 48 h of ARDS onset. Of 335 (29%) that received adjunctive strategies, 252 (75%) received a single strategy, and 83 (25%) receiving more than one adjunct. Of ARDS nonsurvivors, 67% did not receive any adjunctive strategy in the first 48 h. Most patients (67%) receiving specialized adjuncts did not receive prone positioning or neuromuscular blockade. Patients that received adjuncts were more likely to have their ARDS recognized, be younger and sicker, have pneumonia, be more difficult to ventilate, and be in a European high-income country than those that did not receive adjuncts. Interpretation Three in 10 patients with moderate to severe ARDS, and only one-third of nonsurvivors, received adjunctive strategies over the first 48 h of ARDS. A more consistent and evidence-driven approach to adjunct use may reduce costs and improve outcomes in patients with moderate to severe ARDS. Trial Registry ClinicalTrials.gov; No.: NCT02010073 ; URL: www.clinicaltrials.gov

Objectives We sought to evaluate the impact of transitions of care among staff intensivists on the compliance with evidence-based processes of care. Design Cohort study using data from the Toronto Intensive Care Observational Registry. Setting Seven academic ICUs in Toronto, Ontario. Patients Critically ill mechanically ventilated adult patients. Interventions We explored the effects of the weekly transition of care among staff intensivists on compliance with three evidence-based processes of care (spontaneous breathing trials, lung-protective ventilation, and neuromuscular blocking agents). Two practices that are less guided by evidence (early discontinuation of antibiotics and extubation attempts) served as positive controls. We conducted the analysis using generalized estimating equations to account for clustering at the patient level. Measurements and main results The cohort consisted of 10,570 patients admitted between June 2014 and August 2018. Compliance varied for each practice (63.6%, 42.5%, and 21.1% for lung-protective ventilation, spontaneous breathing trials, and neuromuscular blockade, respectively). There was no effect of transitions of care on compliance with spontaneous breathing trials (odds ratio, 1.00; 95% CI, 0.95-1.07), lung-protective ventilation (odds ratio, 1.07, 95% CI, 0.90-1.26), or neuromuscular blockade use (odds ratio, 0.95; 95% CI, 0.75-1.20). However, early antibiotic discontinuation was more likely (odds ratio, 1.23; 95% CI, 1.06-1.42) and extubation attempts were less frequent (odds ratio, 0.77; 95% CI, 0.65-0.93) after a transition of care. Conclusions We observed no significant impact of transitions of care between individual staff physicians on evidence-based processes of care for mechanically ventilated adult patients. However, transitions were associated with a lower likelihood of extubation and higher odds of earlier discontinuation of antibiotics.

Key Points Question Could a prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors be developed using index sepsis illness characteristics as predictors? Findings In this cohort study of 94 748 patients in adult general critical care units in England, unplanned rehospitalization or death in the first year after hospital discharge occurred for 51% of patients in the derivation cohort and 53% of patients in the validation cohort. The prognostic score is calculated using 8 predictors: previous hospitalizations in the preceding year, age, socioeconomic status, preadmission dependence, number of comorbidities, admission type, site of infection, and admission blood hemoglobin level. Meaning This score provides clinically useful information for prognosis discussions and planning follow-up care for sepsis survivors., Importance The longer-term risk of rehospitalizations and death of adult sepsis survivors is associated with index sepsis illness characteristics. Objective To derive and validate a parsimonious prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors. Design, Setting, and Participants This cohort study used data from the Intensive Care National Audit & Research Centre Case Mix Programme database on adult sepsis survivors identified from consecutive critical care admissions to 192 adult general critical care units in England, United Kingdom, between April 1, 2009, and March 31, 2014 (94 748 patients in the derivation cohort), and between April 1, 2014, and March 31, 2015 (24 669 patients in the validation cohort). Statistical analysis was performed from July 5 to October 31, 2019. Generic characteristics (age, sex, race/ethnicity, 2015 Index of Multiple Deprivation [IMD2015] in England quintiles, preadmission dependence, previous hospitalizations in the year preceding index sepsis admission, comorbidity, admission type, Acute Physiology and Chronic Health Evaluation II physiology score, hospital length of stay, worst blood lactate and blood hemoglobin concentrations, and type of hospital) and sepsis-specific characteristics (site of infection, numbers of organ dysfunctions, and organ support) at the index sepsis admission were used as predictors. Main Outcomes and Measures Prognostic score derived and validated using multivariable logistic regression for the outcome of unplanned rehospitalization or death in the first year after hospital discharge of adult sepsis survivors, as well as clinical usefulness assessed using decision curve analysis. Prognostic score validation was performed for internal validation with bootstrapping and temporal cohort external validation. Results This cohort study included 94 748 patients (51 164 men [54.0%]; mean [SD] age, 61.3 [17.0] years) in the derivation cohort and 24 669 patients (13 255 men [53.7%]; mean [SD] age, 62.1 [16.8%]) in the validation cohort. Unplanned rehospitalization or death in the first year after hospital discharge occurred for 48 594 patients (51.3%) in the derivation cohort and 13 129 patients (53.2%) in the validation cohort. Eight independent predictors were identified and weighted to generate a prognostic score for every patient: previous hospitalizations, age in 10-year increments, IMD2015 in England quintiles, preadmission dependence, comorbidities, admission type, blood hemoglobin level, and site of infection. The total prognostic score ranged from 0 to 22 points, with lower scores indicating a lower risk of the outcome. The derivation and validation cohorts had similar rates of prognostic scores of 0 to 4 points (5088 of 16 684 patients [30.5%] and 471 of 1725 patients [27.3%]) and prognostic scores of 11 points or more (15 732 of 21 641 patients [72.7%] and 5753 of 7952 patients [72.3%]). The area under the receiver operating characteristic curve for the prognostic score was 0.675 (95% CI, 0.672-0.679). The decision curve analysis highlighted an optimal score cutoff of 7 points or more. Conclusions and Relevance The prognostic score reported in this study uses 8 internationally feasible predictors measured during the index sepsis admission and provides clinically useful information on sepsis survivors’ risk of unplanned rehospitalization or death in the first year after hospital discharge., This cohort study uses data from the Intensive Care National Audit & Research Centre Case Mix Programme database to derive and validate a parsimonious prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors.

We performed multivariable analysis of potential risk factors (including cytomegalovirus [CMV] reactivation) for clinical outcomes by day 28 (death or continued hospitalization, ventilator-free days, intensive care unit (ICU)-free days, hospital-free days) from pooled cohorts of 2 previous prospective studies of CMV-seropositive adults with sepsis. CMV reactivation at any level, >100 IU/mL, >1000 IU/mL, peak viral load, and area under the curve were independently associated with the clinical outcomes. We identified the potential effect size of CMV on outcomes that could be used as end points for future interventional trials of CMV prevention using antiviral prophylaxis in ICU patients with sepsis.

Conflicts of interest are a normal part of human social intercourse. They become problematic when there is a power differential between participants in the setting of relationships requiring a high degree of trust, as in healthcare. In this white paper we consider how these conflicts may be detected and mitigated. Following Medline search and reference chaining, we undertook a narrative review of the literature with iterative discussion. Conflicts of interest may be financial, professional or personal, and may operate at the level of the individual or the organisation. Unmanaged, they become a source of bias which places the interests of the professional or the organisation before those of the patient. Reported with increasing frequency, conflicts damage trust, harm patients, and defraud the health system. We make 15 recommendations for minimising conflicts of interest. Nationally funded open-access registries should be established to permit complete disclosure of financial, professional, and personal relationships with the potential for driving bias in research, clinical practice, or health management. Governance of disclosure should be the responsibility of employing organisations through annual staff appraisals, audited by national research integrity committees. Research fraud should incur suspension of the license to practice. Organisations should monitor staff perceptions of ethical climate to enhance awareness of staff behaviours and the potential for misconduct driven by academic pressures. Clear separation of advisory and voting roles is needed in best practice guideline panels. Professional societies and scientific journals should display conflict of interest policies for their own staff and officers as well as for speakers and authors. Undergraduates should not be exposed to pharmaceutical promotions masquerading as education. Undergraduate and postgraduate training programmes should include teaching about managing conflicts of interest and identifying research misconduct.

Background Few studies have investigated sleep in patients after intensive care despite the possibility that inadequate sleep might further complicate an acute illness impeding recovery. Aims To assess the quality and quantity of a patient's sleep on the ward by polysomnography (PSG) within a week of intensive care unit (ICU) discharge and to explore the prevalence of key in-ICU risk factors for persistent sleep fragmentation. Methods We enrolled 20 patients after they have been mechanically ventilated for at least 3 days and survived to ICU discharge. We included all patients over the age of 16 years and excluded patients with advanced cognitive impairment or who were unable to follow simple commands before their acute illness, primary admission diagnosis of neurological injury, uncontrolled psychiatric illness or not fluent in English. Results Twenty patients underwent an overnight PSG recording on day 7 after ICU discharge (SD, 1 day). ICU survivors provided 292.8 h of PSG recording time with median recording times of 16.8 h (Interquartile range (IQR), 15.0-17.2 h). The median total sleep time per patient was 5.3 h (IQR, 2.6-6.3 h). In a multivariable regression model, postoperative admission diagnosis (P = 0.04) and patient report of poor ICU sleep (P = 0.001) were associated with less slow-wave (restorative) sleep on the wards after ICU discharge. Conclusions Patients reported poor sleep while in the ICU, and a postoperative admission diagnosis may identify a high-risk subgroup of patients who may derive greater benefit from interventions to improve sleep hygiene.

Purpose:Nearly all sepsis trials report no statistically significant difference in mortality. The attributable fraction of deaths due to sepsis (AFsepsis) may be an important, yet overlooked consideration. We derived AFsepsis and explored the effect of incorporating AFsepsis into sample size calculations.Materials and Methods:We derived AFsepsis with a matched cohort study using consecutive admissions to adult general intensive care units (ICUs) in England (n=614,509). Cases were ICU patients with sepsis and the two controls were ICU-non-sepsis controls, matched for propensity to have sepsis and age-sex-matched general population. The primary exposure was sepsis. The primary outcome was hospital mortality. We generated sample size graphs, by varying control group mortality (10%-60%), relative risk reduction (0-1), for 80% power and 5% alpha. We then compared AFsepsis derived sample sizes with sample size calculations from published sepsis trials.Results:AFsepsis was 15%(95%CI:14%-16%) compared with propensity matched ICU-non- sepsis controls and 93%(95%CI:92%-93%) compared with age-sex-matched general population controls. When comparing AFsepsis derived sample sizes with sample size calculations from 18 trials meeting our selection criteria, these calculations assumed very high AFsepsis and/or very effective treatments.Conclusions:Estimating trial specific AFsepsis to inform sample size calculations could be an additional step in sepsis trial design.

Rationale: Diaphragm dysfunction worsens outcomes in mechanically ventilated patients, but the clinical impact of potentially preventable changes in diaphragm structure and function caused by mechanical ventilation is unknown.Objectives: To determine whether diaphragm atrophy developing during mechanical ventilation leads to prolonged ventilation.Methods: Diaphragm thickness was measured daily by ultrasound in adults requiring invasive mechanical ventilation; inspiratory effort was assessed by thickening fraction. The primary outcome was time to liberation from ventilation. Secondary outcomes included complications (reintubation, tracheostomy, prolonged ventilation, or death). Associations were adjusted for age, severity of illness, sepsis, sedation, neuromuscular blockade, and comorbidity.Measurements and Main Results: Of 211 patients enrolled, 191 had two or more diaphragm thickness measurements. Thickness decreased more than 10% in 78 patients (41%) by median Day 4 (interquartile range, 3–5). Developme...

Background Driving pressure (ΔP) is associated with mortality in patients with ARDS and with pulmonary complications in patients undergoing general anesthesia. Whether ΔP is associated with outcomes of patients without ARDS who undergo ventilation in the ICU is unknown. Our objective was to determine the independent association between ΔP and outcomes in mechanically ventilated patients without ARDS on day 1 of mechanical ventilation. Methods This was a retrospective analysis of a cohort of 622 mechanically ventilated adult patients without ARDS on day 1 of mechanical ventilation from five ICUs in a tertiary center in the United States. The primary outcome was hospital mortality. The presence of ARDS was determined using the minimum daily Pao 2 to Fio 2 (PF) ratio and an automated text search of chest radiography reports. The data set was validated by first testing the model in 543 patients with ARDS. Results In patients without ARDS on day 1 of mechanical ventilation, ΔP was not independently associated with hospital mortality (OR, 1.01; 95% CI, 0.97-1.05). The results of the primary analysis were confirmed in a series of preplanned sensitivity analyses. Conclusions In this cohort of patients without ARDS on day 1 of mechanical ventilation and within the limits of ventilatory settings normally used by clinicians, ΔP was not associated with hospital mortality. This study also confirms the association between ΔP and mortality in patients with ARDS not enrolled in a trial and in hypoxemic patients without ARDS.

By minimizing tidal lung strain and maintaining alveolar recruitment, high-frequency oscillatory ventilation (HFOV) may protect against ventilator-induced lung injury.To summarize the current evidence in support of the use of HFOV in adult patients with acute respiratory distress syndrome.We conducted a systematic review and meta-analysis of randomized trials comparing mortality rates with the use of HFOV versus conventional mechanical ventilation for adult patients with acute respiratory distress syndrome. Eligible trials were identified from previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapies were collected; effects were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology.Six trials were eligible for inclusion (total n = 1,715 patients). Four trials mandated lung-protective ventilation in the control group and one trial applied a higher positive end-expiratory pressure (PEEP) ventilation strategy in the control group. None of the trials were judged to be at high risk of bias, though all were unblinded. In trials that did not systematically employ any cointerventions with HFOV and that targeted low tidal volumes in the patients randomized to conventional ventilation (primary analysis), HFOV had no significant effect on mortality (three trials; risk ratio [RR], 1.14; 95% confidence interval [CI], 0.88 to 1.48; evidence grade = high). Pooled analysis of all six trials also did not suggest a significant mortality reduction (RR, 0.94; 95% CI, 0.71 to 1.24; evidence grade = low). The single trial that employed a conventional ventilation strategy with both lower tidal volumes and higher PEEP as control reported higher mortality in patients receiving HFOV (RR, 1.41; 95% CI, 1.12 to 1.79). HFOV was not associated with improved oxygenation after 24 hours (five trials; mean increase of 10 mm Hg; 95% CI, -16 to 37 mm Hg). Rates of barotrauma were not different between HFOV and conventional ventilation, although significant benefit or harm could not be excluded (RR, 1.15; 95% CI, 0.61 to 2.17).Published randomized trials suggest that HFOV is not associated with a mortality benefit, and may even be harmful in comparison to ventilation with low tidal volumes and higher levels of PEEP.

In patients with acute respiratory distress syndrome (ARDS), lung recruitment maneuvers (LRMs) may prevent ventilator-induced lung injury and improve survival.To summarize the current evidence in support of the use of LRMs in adult patients with ARDS and to inform the recently published American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline on mechanical ventilation in ARDS.We conducted a systematic review and meta-analysis of randomized trials comparing mechanical ventilation strategies with and without LRMs. Eligible trials were identified from among previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapy were collected, and results were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology.We screened 430 citations and previous systematic reviews and found six trials eligible for inclusion (n = 1,423 patients in total). The type of LRM varied widely between trials, and five of the trials involved a cointervention with a higher positive end-expiratory pressure (PEEP) ventilation strategy. Risk of bias was deemed high in one trial. In the primary analysis, the only trial without a cointervention showed that LRMs were associated with reduced mortality (one trial; risk ratio [RR], 0.62; 95% confidence interval [CI], 0.39-0.98; evidence grade = low). Meta-analysis of all six trials also suggested a significant mortality reduction (six trials; RR, 0.81; 95% CI, 0.69-0.95; evidence grade = moderate), and the use of a higher PEEP cointervention did not significantly modify the mortality effect (P = 0.27 for heterogeneity). LRMs were also associated with improved oxygenation after 24 hours (six trials; mean increase, 52 mm Hg; 95% CI, 23-81 mm Hg) and less frequent requirement for rescue therapy (three trials; RR, 0.65; 95% CI, 0.45-0.94). LRMs were not associated with an increased rate of barotrauma (four trials; RR, 0.84; 95% CI, 0.46-1.55). The rate of hemodynamic compromise was not significantly increased with LRMs (three trials; RR, 1.30; 95% CI, 0.92-1.78).Randomized trials suggest that LRMs in combination with a higher PEEP ventilation strategy reduce mortality, but confidence in this finding is limited. Further trials are required to confirm benefit from LRMs in adults with ARDS.

We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.

Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for

Rationale: Adoption and de-adoption of adjuvant strategies to mechanical ventilation for acute respiratory failure (ARF), and factors associated with their selection, have not been extensively evaluated.Objectives: To evaluate change in use of adjuvants to mechanical ventilation for ARF (2008–2013), the impact of landmark publications on adoption and de-adoption, and factors associated with use.Methods: Changes in use of four adjuvants for ARF from 2008 to 2013, the impact of landmark publications on use, and factors associated with use were evaluated with the Premier Database. Extracorporeal membrane oxygenation (ECMO), inhaled nitric oxide, inhaled epoprostenol, and continuous neuromuscular blockading agents (cNMBAs) in adult mechanically ventilated patients were identified on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification codes and billing data.Measurements and Main Results: Among 514,913 patients with ARF, 11,567 (2.3%) were treated with at least one adjuv...

Defining the severity of ARDS using PaO2/FIO2 , 150 as a surrogate for life-threatening edema is a promising approach. However, ARDS is a heterogeneous syndrome, and identifying a treatment-responsive hyperinflammatory subtype across the PaO2/FIO2 severity spectrum suggests the fundamental limitations of using physiological or anatomic variables alone to understand and treat the underlying mechanisms that lead to ARDS, let alone to stratify risk. We suspect that both approaches will be complementary and will require prospective evaluation for their predictive enrichment potential

Purpose Sepsis survivors have a higher risk of rehospitalisation and of long-term mortality. We assessed the rate, diagnosis, and independent predictors for rehospitalisation in adult sepsis survivors. Methods We searched for non-randomized studies and randomized clinical trials in MEDLINE, Cochrane Library, Web of Science, and EMBASE (OVID interface, 1992–October 2019). The search strategy used controlled vocabulary terms and text words for sepsis and hospital readmission, limited to humans, and English language. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms. Results The literature search identified 12,544 records. Among 56 studies (36 full and 20 conference abstracts) that met our inclusion criteria, all were non-randomised studies. Studies most often report 30-day rehospitalisation rate (mean 21.4%, 95% confidence interval [CI] 17.6–25.4%; N = 36 studies reporting 6,729,617 patients). The mean (95%CI) rehospitalisation rates increased from 9.3% (8.3–10.3%) by 7 days to 39.0% (22.0–59.4%) by 365 days. Infection was the most common rehospitalisation diagnosis. Risk factors that increased the rehospitalisation risk in sepsis survivors were generic characteristics such as older age, male, comorbidities, non-elective admissions, hospitalisation prior to index sepsis admission, and sepsis characteristics such as infection and illness severity, with hospital characteristics showing inconsistent associations. The overall certainty of evidence was moderate for rehospitalisation rates and low for risk factors. Conclusions Rehospitalisation events are common in sepsis survivors, with one in five rehospitalisation events occurring within 30 days of hospital discharge following an index sepsis admission. The generic and sepsis-specific characteristics at index sepsis admission are commonly reported risk factors for rehospitalisation. Registration PROSPERO CRD 42016039257, registered on 14-06-2016. Electronic supplementary material The online version of this article (10.1007/s00134-019-05908-3) contains supplementary material, which is available to authorized users.

PURPOSE OF REVIEW Sepsis and acute respiratory distress syndrome (ARDS) are two heterogenous acute illnesses where numerous RCTs have indeterminate results. We present a narrative review on the recent developments in enriching patient populations for future sepsis and ARDS trials. RECENT FINDINGS Many researchers are actively pursuing enrichment strategies to reduce heterogeneity to increase the sensitivity of future trials. Enrichment refers to the use of measurable patient characteristics, known before randomisation, to refine trial populations. Biomarkers could increase the diagnostic certainty of sepsis, whereas chest radiology training to enhance reliability of interpretation and stabilisation period of mechanical ventilation have been considered to increase the diagnostic certainty of ARDS. Clinical and biomarker data analyses identifies four to six sepsis clinical phenotypes and two ARDS clinical phenotypes. Similarly, leukocyte gene expression data identifies two to four sepsis molecular phenotypes. Use of a test-dose identifies ARDS subpopulations who are likely to benefit from higher PEEP. Early-phase trials report how a biomarker that is altered by the intervention, such as lymphocyte count for recombinant interleukin-7 therapy and higher check point inhibitor expression for anti-check point treatments in sepsis, could identify a higher treatment effect population for future trials. SUMMARY Enrichment reduces heterogeneity and will enhance the sensitivity of future trials. However, enrichment, even when it identifies more homogenous populations, may not be efficient to deploy in trials or clinical practice.

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

Background ICU survivors can experience both cognitive dysfunction and persistent sleep disturbances after hospitalization. Sleep disturbances have been linked with cognitive impairment in various patient populations, and the apolipoprotein E (APOE) genotype has been linked to sleep-related impairments in cognition. Research Question Is there an association between sleep, long-term cognition, and APOE status in ICU survivors? Study Design and Methods We enrolled 150 patients from five centers who had been mechanically ventilated for at least 3 days; 102 patients survived to ICU discharge. Actigraphy and cognitive testing were undertaken at 7 days, 6 months, and 12 months after ICU discharge, and sleep duration, quality, and timing were estimated by actigraphy. APOE single nucleotide polymorphisms were assessed for each patient. Results Actigraphy-estimated sleep fragmentation, but not total sleep time or interdaily stability (estimate of circadian rhythmicity), was associated with worse cognitive impairment at 7 days of ICU discharge. No actigraphy-estimated variable of sleep estimation at 7 days post-ICU discharge predicted cognitive impairment or persistent sleep abnormalities at 6 and 12 months of follow-up in subsequently assessed survivors. Possessing the APOE e4 allele was not significantly associated with sleep disturbances and its presence did not modify the risk of sleep-related cognitive impairment at follow-up. Interpretation Sleep fragmentation estimated by actigraphy was associated with worse cognitive performance in hospital, but not at later time intervals. Further research is needed to better delineate the relationship between persistent sleep disturbances and cognition in larger numbers of ICU survivors. Trial Registry ClinicalTrials.gov ; No.: NCT02086877; URL: www.clinicaltrials.gov

BACKGROUND: High rates of health care utilization at the end of life may be a marker of care that does not align with patient-stated preferences. We sought to describe trends in end-of-life care and factors associated with dying in hospital. METHODS: We conducted a population-level retrospective cohort study of adult decedents in Ontario between Apr. 1, 2004, and Mar. 31, 2015, using linked administrative data sets, including the Office of the Registrar General for Deaths database, the hospital Discharge Abstract Database, the National Ambulatory Care Reporting System and physicians’ billing claims (Ontario Health Insurance Plan). The primary outcome was place of death. To determine health care utilization and health care costs during the 6 months before death, we also identified admissions to hospital and to the intensive care unit, emergency department visits, and receipt of mechanical ventilation and palliative care. RESULTS: In the last 6 months of life, 77.3% of 962 462 decedents presented to an emergency department, 68.4% were admitted to hospital, 19.4% were admitted to an intensive care unit, and 13.9% received mechanical ventilation. Forty-five percent of all deaths occurred in hospital, a proportion that declined marginally over time, whereas receipt of palliative care increased during terminal hospital admissions (from 14.0% in fiscal year 2004/05 to 29.3% in 2014/15, p < 0.001) and in the last 6 months of life (from 28.1% in 2004/05 to 57.7% in 2014/15, p < 0.001). The proportion of decedents who presented to the emergency department, were admitted to hospital or were admitted to the intensive care unit in the last 6 months of life did not change over 11 years. The mean total health care costs in the last 6 months of life were highest among those dying in hospital, with most costs attributable to inpatient medical care. INTERPRETATION: Health care utilization in the last 6 months of life was substantial and did not decrease over time. It is possible that increased capacity for palliative, hospice and home care at the end of life may help to better align health system resources with the preferences of most patients, a topic that should be explored in future studies.

The purpose of this study was to use an objective measure to evaluate sleep quality on the ward after ICU discharge in survivors of critical illness.This was a prospective cohort study of 94 patients admitted to a multidisciplinary intensive care unit (ICU) between December 2013 and June 2017. Adult patients received ≥3 days of mechanical ventilation. Sleep quality was measured using multi-night sleep actigraphy. Baseline sleep quality (i.e. sleep prior to hospitalization) was evaluated using the Pittsburgh Sleep Quality Index.A total of 65% of patients had poor sleep quality measured with the PSQI. The average (SD) sleep time and sleep efficiency was 6.03 h (3.70 h) and 44% (27%), respectively. An admission diagnosis of sepsis was associated with shorter total sleep time (TST; p = .03) and reduced sleep efficiency (SE; p = .04) as were severity of illness and duration of sedative exposure (p = .12 and 0.03; p = .09 and 0.01; respectively for TST and SE). Weak correlations were seen between pro-inflammatory biomarkers and sleep quality.This study highlights the important role that future interventions might have in patients at high-risk of sleep disorders after critical illness.

To identify clinical and organizational factors associated with delays in antimicrobial therapy for septic shock.In a retrospective cohort of critically ill patients with septic shock.Twenty-four ICUs.A total of 6,720 patients with septic shock.None.Higher Acute Physiology Score (+24 min per 5 Acute Physiology Score points; p0.0001); older age (+16 min per 10 yr; p0.0001); presence of comorbidities (+35 min; p0.0001); hospital length of stay before hypotension: less than 3 days (+50 min; p0.0001), between 3 and 7 days (+121 min; p0.0001), and longer than 7 days (+130 min; p0.0001); and a diagnosis of pneumonia (+45 min; p0.01) were associated with longer times to antimicrobial therapy. Two variables were associated with shorter times to antimicrobial therapy: community-acquired infections (-53 min; p0.001) and higher temperature (-15 min per 1°C; p0.0001). After adjusting for confounders, admissions to academic hospitals (+52 min; p0.05), and transfers from medical wards (medical vs surgical ward admission; +39 min; p0.05) had longer times to antimicrobial therapy. Admissions from the emergency department (emergency department vs surgical ward admission, -47 min; p0.001) had shorter times to antimicrobial therapy.We identified clinical and organizational factors that can serve as evidence-based targets for future quality-improvement initiatives on antimicrobial timing. The observation that academic hospitals are more likely to delay antimicrobials should be further explored in future trials.

Many advances in health care fail to reach patients. Implementation science is the study of novel approaches to mitigate this evidence-to-practice gap.The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement on implementation science in pulmonary, critical care, and sleep medicine. The committee used an iterative consensus process to define implementation science and review the use of conceptual frameworks to guide implementation science for the pulmonary, critical care, and sleep community and to explore how professional medical societies such as the ATS can promote implementation science.The committee defined implementation science as the study of the mechanisms by which effective health care interventions are either adopted or not adopted in clinical and community settings. The committee also distinguished implementation science from the act of implementation. Ideally, implementation science should include early and continuous stakeholder involvement and the use of conceptual frameworks (i.e., models to systematize the conduct of studies and standardize the communication of findings). Multiple conceptual frameworks are available, and we suggest the selection of one or more frameworks on the basis of the specific research question and setting. Professional medical societies such as the ATS can have an important role in promoting implementation science. Recommendations for professional societies to consider include: unifying implementation science activities through a single organizational structure, linking front-line clinicians with implementation scientists, seeking collaborations to prioritize and conduct implementation science studies, supporting implementation science projects through funding opportunities, working with research funding bodies to set the research agenda in the field, collaborating with external bodies responsible for health care delivery, disseminating results of implementation science through scientific journals and conferences, and teaching the next generation about implementation science through courses and other media.Implementation science plays an increasingly important role in health care. Through support of implementation science, the ATS and other professional medical societies can work with other stakeholders to lead this effort.

The optimal timing of tracheostomy placement in acutely brain-injured patients, who generally require endotracheal intubation for airway protection rather than respiratory failure, remains uncertain. We systematically reviewed trials comparing early tracheostomy to late tracheostomy or prolonged intubation in these patients. We searched 5 databases (from inception to April 2015) to identify randomized controlled trials comparing early tracheostomy (≤10 days of intubation) with late tracheostomy (>10 days) or prolonged intubation in acutely brain-injured patients. We contacted the principal authors of included trials to obtain subgroup data. Two reviewers extracted data and assessed risk of bias. Outcomes included long-term mortality (primary), short-term mortality, duration of mechanical ventilation, complications, and liberation from ventilation without a tracheostomy. Meta-analyses used random-effects models. Ten trials (503 patients) met selection criteria; overall study quality was moderate to good. Early tracheostomy reduced long-term mortality (risk ratio [RR] 0.57. 95 % confidence interval (CI), 0.36–0.90; p = 0.02; n = 135), although in a sensitivity analysis excluding one trial, with an unclear risk of bias, the significant finding was attenuated (RR 0.61, 95 % CI, 0.32–1.16; p = 0.13; n = 95). Early tracheostomy reduced duration of mechanical ventilation (mean difference [MD] −2.72 days, 95 % CI, −1.29 to −4.15; p = 0.0002; n = 412) and ICU length of stay (MD −2.55 days, 95 % CI, −0.50 to −4.59; p = 0.01; n = 326). However, early tracheostomy did not reduce short-term mortality (RR 1.25; 95 % CI, 0.68–2.30; p = 0.47 n = 301) and increased the probability of ever receiving a tracheostomy (RR 1.58, 95 % CI, 1.24–2.02; 0

Key Points Question What are the characteristics of intensive care unit admissions identified by 2 proposed pandemic ventilator allocation triage guidelines using Sequential Organ Failure Assessment scores when applied retrospectively to critically ill US patients who received mechanical ventilation? Findings In this cohort study of 40 439 admissions to intensive care units that received mechanical ventilation, the New York State guideline identified 9% who would likely meet criteria for the lowest priority for ventilator allocation compared with 4% from the original White and Lo guideline. Only 655 admissions (1.6%) were in the lowest priority category for both guidelines, with 39% survival to hospital discharge for admissions identified as lowest priority using the New York State guideline compared with 56% for admissions identified using White and Lo. Meaning Two distinct approaches to triage for mechanical ventilation showed little agreement, suggesting that further clinical assessment of different potential criteria for triage decisions is important to ensure equitable allocation of resources., Importance In the current setting of the coronavirus disease 2019 pandemic, there is concern for the possible need for triage criteria for ventilator allocation; to our knowledge, the implications of using specific criteria have never been assessed. Objective To determine which and how many admissions to intensive care units are identified as having the lowest priority for ventilator allocation using 2 distinct sets of proposed triage criteria. Design, Setting, and Participants This retrospective cohort study conducted in spring 2020 used data collected from US hospitals and reported in the Philips eICU Collaborative Research Database. Adult admissions (N = 40 439) to 291 intensive care units from 2014 to 2015 who received mechanical ventilation and were not elective surgery patients were included. Exposures New York State triage criteria and original triage criteria proposed by White and Lo. Main Outcomes and Measures Sequential Organ Failure Assessment (SOFA) scores were calculated for admissions. The proportion of patients who met initial criteria for the lowest level of priority for mechanical ventilation using each set of criteria and their characteristics and outcomes were assessed. Agreement was compared between the 2 sets of triage criteria, recognizing differences in stated criteria aims. Results Among 40 439 intensive care unit admissions of patients who received mechanical ventilation, the mean (SD) age was 62.6 (16.6) years, 54.9% were male, and the mean (SD) SOFA score was 4.5 (3.7). Using the New York State triage criteria, 8.9% (95% CI, 8.7%-9.2%) were in the lowest priority category; these lowest priority admissions had a mean (SD) age of 62.9 (16.6) years, used a median (interquartile range) of 57.3 (20.1-133.5) ventilator hours each, and had a hospital survival rate of 38.6% (95% CI, 37.0%-40.2%). Using the White and Lo triage criteria, 4.3% (95% CI, 4.1%-4.5%) were in the lowest priority category; these admissions had a mean (SD) age of 68.6 (13.2) years, used a median (interquartile range) of 61.7 (24.3-142.8) ventilator hours each, and had a hospital survival rate of 56.2% (95% CI, 53.8%-58.7%). Only 655 admissions (1.6%) were in the lowest priority category for both guidelines, with the κ statistic for agreement equal to 0.20 (95% CI, 0.18-0.21). Conclusions and Relevance Use of 2 initially proposed ventilator triage guidelines identified approximately 1 in every 10 to 25 admissions as having the lowest priority for ventilator allocation, with little agreement. Clinical assessment of different potential criteria for triage decisions in critically ill populations is important to ensure valid and equitable allocation of resources., This cohort study compares the New York State Ventilator Allocation Guideline with the original triage criteria proposed by White and Lo to determine which and how many admissions to US intensive care units are identified as having the lowest priority for ventilator allocation.

Key Points Question Do anesthesiologists or other anesthesia professionals engage in discussions with patients regarding decisions with implications beyond the operating room? Findings In this systematic review of the literature on communication between patients and anesthesia professionals, limited data were found on communication regarding perioperative decisions with implications that reach beyond the operating room. These data suggest that communication between patients and anesthesia professionals during preoperative encounters is dominated by discussion of anesthetic planning and perioperative logistics, with variable discussion of risks vs benefits and infrequent discussion of postoperative care or elicitation of patient values and preferences. Meaning These findings suggest that patients who become critically ill following scheduled surgical interventions are unlikely to have had discussions with their anesthesiologist regarding values and preferences for navigating complex postoperative care decisions, such as prolonged invasive ventilation, protracted hospital stay with incomplete recovery, or end-of-life care., This systematic review studies the literature on communication between patients and anesthesia professionals, with a focus on discussions related to postoperative critical care., Importance Many patients are admitted to the intensive care unit following surgery, and some of them will experience incomplete recovery. For patients in this situation, preoperative discussions regarding patient values and preferences may direct care decisions. Existing literature shows that it is uncommon for surgeons to have these conversations preoperatively; it is unclear whether anesthesia professionals engage with patients on this topic prior to surgery. Objective To review the literature on communication between patients and anesthesia professionals, with a focus on discussions related to postoperative critical care. Evidence Review MEDLINE and Web of Science were searched using specific search criteria from January 1980 to April 2020. Studies describing encounters between patients and anesthesia professionals were selected, and data regarding study objectives, study design, methodology, measures, outcomes, patient characteristics, and clinical setting were extracted and collated. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Findings A total of 12 studies including 1284 individual patient encounters were eligible for inclusion in the review. These studies demonstrated that communication between patients and anesthesia professionals related to postoperative care is rare: only 2 studies reported communication regarding adverse postoperative events, and this communication behavior was reported in only 46 of 1284 consultations (3.6%) across all studies. Additional findings were that communication during these encounters is dominated by anesthetic planning and perioperative logistics, with variable discussion of perioperative risks vs benefits and infrequent elicitation of patient values and preferences. Some data suggest that patients wish to be involved in perioperative decision-making but are often limited by an incomplete understanding of risks and benefits. Conclusions and Relevance This systematic review found that communication in anesthesia is dominated by anesthetic planning and discussion of preoperative logistics, whereas postoperative critical care is rarely discussed. Most patients who are admitted to an intensive care unit after a major operation will not have had a discussion regarding goals of care specific to protracted recovery or prolonged intensive care with their anesthesiologist.

Importance Low diaphragm muscle mass at the outset of mechanical ventilation may predispose critically ill patients to poor clinical outcomes. Objective To determine whether lower baseline diaphragm thickness (Tdi) is associated with delayed liberation from mechanical ventilation and complications of acute respiratory failure (reintubation, tracheostomy, prolonged ventilation >14 days, or death in the hospital). Design, Setting, and Participants Secondary analysis (July 2018 to June 2019) of a prospective cohort study (data collected May 2013 to January 2016). Participants were 193 critically ill adult patients receiving invasive mechanical ventilation at 3 intensive care units in Toronto, Ontario, Canada. Exposures Diaphragm thickness was measured by ultrasonography within 36 hours of intubation and then daily. Patients were classified as having low or high diaphragm muscle mass according to the median baseline Tdi. Main Outcomes and Measures The primary outcome was time to liberation from ventilation accounting for the competing risk of death and adjusting for age, body mass index, severity of illness, sepsis, change in Tdi during ventilation, baseline comorbidity, and study center. Secondary outcomes included in-hospital death and complications of acute respiratory failure. Results A total of 193 patients were available for analysis; the mean (SD) age was 60 (15) years, 73 (38%) were female, and the median (interquartile range) Sequential Organ Failure Assessment score was 10 (8-13). Median (interquartile range) baseline Tdi was 2.3 (2.0-2.7) mm. In the primary prespecified analysis, baseline Tdi of 2.3 mm or less was associated with delayed liberation from mechanical ventilation (adjusted hazard ratio for liberation, 0.51; 95% CI, 0.36-0.74). Lower baseline Tdi was associated a higher risk of complications of acute respiratory failure (adjusted odds ratio, 1.77; 95% CI, 1.20-2.61 per 0.5-mm decrement) and prolonged weaning (adjusted odds ratio, 2.30; 95% CI, 1.42-3.74). Lower baseline Tdi was also associated with a higher risk of in-hospital death (adjusted odds ratio, 1.47; 95% CI, 1.00-2.16 per 0.5-mm decrement), particularly after discharge from the intensive care unit (adjusted odds ratio, 2.68; 95% CI, 1.35-5.32 per 0.5-mm decrement). Conclusions and Relevance In this study, low baseline diaphragm muscle mass in critically ill patients was associated with prolonged mechanical ventilation, complications of acute respiratory failure, and an increased risk of death in the hospital.

IMPORTANCE: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS). OBJECTIVE: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands. INTERVENTIONS: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484). MAIN OUTCOMES AND MEASURES: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax. RESULTS: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, –0.27 [95% CI, –1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [–1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; –0.60 [–3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55). CONCLUSIONS AND RELEVANCE: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02153294

International audience; Medical professionals are expected to prioritize patient interests, and most patients trust physicians to act in their best interest. However, a single patient is never a physician's sole concern. The competing interests of other patients, clinicians, family members, hospital administrators, regulators, insurers, and trainees are omnipresent. While prioritizing patient interests is always a struggle, it is especially challenging and important in the ICU setting where most patients lack the ability to advocate for themselves or seek alternative sources of care. This review explores factors that increase the risk, or the perception, that an ICU physician will reason, recommend, or act in a way that is not in their patient's best interest and discusses steps that could help minimize the impact of these factors on patient care.

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Summary Several mechanisms of diaphragm muscle injury (myotrauma) can result in ventilator-induced diaphragm dysfunction, including ventilator over-assistance, under-assistance, eccentric contractions, and end-expiratory shortening. In this Personal View, we summarise the evidence for the clinical relevance of these mechanisms, and present new data based on mediation analysis supporting the hypothesis that myotrauma due to ventilator over-assistance and under-assistance contribute, in part, to the effect of mechanical ventilation on clinical outcomes. The concept of diaphragmatic myotrauma has important implications for research and clinical practice.

This pooled cohort analysis assesses the association of quick Sequential (Sepsis-Related Organ Failure Assessment (qSOFA) score with excess hospital death among patients with suspected infection in low- to middle-income countries and compares the mortality association using qSOFA vs systemic inflammatory response syndrome (SIRS) criteria.

Objectives It is uncertain whether dedicated neurocritical care units are associated with improved outcomes for critically ill neurologically injured patients in the era of collaborative protocol-driven care. We examined the association between dedicated neurocritical care units and mortality and the effects of standardized management protocols for severe traumatic brain injury. Design We surveyed trauma medical directors from centers participating in the American College of Surgeons Trauma Quality Improvement Program to obtain information about ICU structure and processes of care. Survey data were then linked to the Trauma Quality Improvement Program registry, and random-intercept hierarchical multivariable modeling was used to evaluate the association between dedicated neurocritical care units, the presence of standardized management protocols and mortality. Setting Trauma centers in North America participating in Trauma Quality Improvement Program. Patients Data were analyzed from 9,773 adult patients with isolated severe traumatic brain injury admitted to 134 Trauma Quality Improvement Program centers between 2011 and 2013. Interventions None. Measurements and main results Only 50 ICUs (37%) were dedicated neurocritical care units, whereas 84 (63%) were general ICUs. Rates of standardized management protocols were similar comparing dedicated neurocritical care units and general ICUs. Among severe TBI patients admitted to trauma centers enrolled in Trauma Quality Improvement Program, care in a dedicated neurocritical care unit did not improve risk-adjusted in-hospital survival (odds ratio, 0.97; 95% CI, 0.80-1.19; p = 0.79). However, the presence of a standardized management protocol for these patients was associated with lower risk-adjusted in-hospital mortality (odds ratio, 0.77; 95% CI, 0.63-0.93; p = 0.009). Conclusions Compared with dedicated neurocritical care models, standardized management protocols for severe traumatic brain injured patients are process-targeted intervention strategies that may improve clinical outcomes.

Objectives: Radiographic criteria for acute respiratory distress syndrome have been criticized for poor reliability. Our objective was to test an educational intervention to improve the radiographic identification of acute respiratory distress syndrome by participants in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure study. Design: Randomized controlled trial. Settings: Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure study centers. Subjects: Study coordinators in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure study. Interventions: Participants were randomized to either an online training module followed by a test module (intervention) or test module followed by training module (control). Measurements and Main Results: The primary outcome was the number of radiographs correctly identified as meeting criteria for acute respiratory distress syndrome on an online test module (out of 11). Prespecified secondary analyses included a comparison of agreement between the groups and subgroup analyses by profession, age, years of experience, and stated familiarity with diagnostic criteria for acute respiratory distress syndrome. Four-hundred sixty-three study participants consented to participate. There was no effect of the intervention on correct answers by participants (proportion correct 58% [intervention] vs 56% [control]; p = 0.15), or in any subgroup analyses. Overall agreement between raters was 0.296 for the intervention and 0.272 for the control (p < 0.001). Conclusions: Participant recognition of radiographic criteria for acute respiratory distress syndrome was low, with poor agreement. This was not impacted by an educational intervention designed to improve accuracy of identification of radiographic criteria for acute respiratory distress syndrome

Background Despite a supportive evidence base and a push to implement, the uptake of early rehabilitation in critical care has been inconsistent. The objective of this study was to explore barriers and facilitators to early rehabilitation for critically ill patients receiving invasive mechanical ventilation. Methods Using the Theoretical Domains Framework (TDF) of behavior change, we conducted semi-structured interviews exploring barriers and facilitators to early rehabilitation among four purposively sampled ICU clinician groups (nurses, rehabilitation professionals, respiratory therapists, and physicians). The TDF is a comprehensive framework of 14 “construct domains,” synthesized from 33 theories of behavior that was developed to study determinants of behavior and to design interventions to improve evidence-based healthcare practice. A topic guide was developed and piloted based on the TDF and expert knowledge. Interviews were audio-recorded and transcribed verbatim. Transcripts were content analyzed by coding items into domains and then synthesized into more specific, over-arching themes or “beliefs.” An expert consensus group used structured decision rules to classify beliefs as high, moderate, or low in importance. Results We interviewed 40 stakeholders from the four clinician groups and identified 135 separate beliefs. Of these, 19 were classified as high, 40 as moderate, and 76 of low importance as barriers or facilitators. All beliefs classified as highly important fell within one of seven TDF domains: skills, social/professional role and identity, beliefs about capabilities, beliefs about consequences, environmental context/resources, social influences, and behavioral regulation. Beliefs of lower importance fell under the following seven domains: knowledge; optimism; reinforcement; intention; goals; memory, attention, and decision processes; and emotion. Quantitative differences in stated beliefs about early rehabilitation between professional groups were not common. Conclusions This study identified important barriers and facilitators to early rehabilitation in critical care patients. Domains identified as important should be considered when designing interventions to increase uptake of early rehabilitation. Electronic supplementary material The online version of this article (10.1186/s40560-018-0273-0) contains supplementary material, which is available to authorized users.