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Purpose Functional status and chronic health status are important baseline characteristics of critically ill patients. The assessment of frailty on admission to the intensive care unit (ICU) may provide objective, prognostic information on baseline health. To determine the impact of frailty on the outcome of critically ill patients, we performed a systematic review and meta-analysis comparing clinical outcomes in frail and non-frail patients admitted to ICU. Methods We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, CINAHL, and Clinicaltrials.gov. All study designs with the exception of narrative reviews, case reports, and editorials were included. Included studies assessed frailty in patients greater than 18 years of age admitted to an ICU and compared outcomes between fit and frail patients. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were hospital and long-term mortality. We also determined the prevalence of frailty, the impact on other patient-centered outcomes such as discharge disposition, and health service utilization such as length of stay. Results Ten observational studies enrolling a total of 3030 patients (927 frail and 2103 fit patients) were included. The overall quality of studies was moderate. Frailty was associated with higher hospital mortality [relative risk (RR) 1.71; 95% CI 1.43, 2.05; p  < 0.00001; I 2  = 32%] and long-term mortality (RR 1.53; 95% CI 1.40, 1.68; p  < 0.00001; I 2  = 0%). The pooled prevalence of frailty was 30% (95% CI 29–32%). Frail patients were less likely to be discharged home than fit patients (RR 0.59; 95% CI 0.49, 0.71; p  < 0.00001; I 2  = 12%). Conclusions Frailty is common in patients admitted to ICU and is associated with worsened outcomes. Identification of this previously unrecognized and vulnerable ICU population should act as the impetus for investigating and implementing appropriate care plans for critically ill frail patients. Registration: PROSPERO (ID: CRD42016053910).

Appropriate end points are crucial for the successful interpretation of clinical trials. Choosing end points for therapeutic trials of ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) requires careful consideration, because they are complications of critical illness. It may be difficult to distinguish the consequences of VAP and HAP from manifestations of the underlying illnesses, and it is important to determine their incremental magnitude, to plan for possible treatment effects and, thus, sample size calculations. In this article, we discuss mortality, attributable mortality, and time to clinical events as possible end points for HAP and/or VAP trials. Because of the paucity of evidence on HAP, we focus predominantly on VAP. In a systematic review of applicable trials, VAP appears to have slight intensive care unit and low hospital-attributable mortality. VAP is associated with prolonged durations of intensive care unit stay, hospital stay, and mechanical ventilation. Because of these findings, superiority trials of VAP treatment that use mortality as a primary end point are not possible. Equivalency studies are possible, but there are sample size implications. The use of time to clinical event end points, especially when combined with mortality, may be the best option for trial in the future.

This trial involving critically ill adults with multiorgan failure who were receiving mechanical ventilation showed that early provision of glutamine and antioxidants did not improve clinical outcomes. Furthermore, the use of glutamine appeared to increase mortality. Critically ill patients have oxidative stress. The most seriously ill patients in intensive care units (ICUs) have increased mediators of oxidant stress and a higher incidence of multiorgan failure than less seriously ill patients. 1 – 5 Meta-analyses of randomized trials suggest that glutamine and antioxidant supplementation in critically ill patients may be associated with improved survival. 6 , 7 However, recent large studies have not confirmed such an effect. 8 , 9 The objective of the present trial was to evaluate the effect of early glutamine and antioxidant supplementation in critically ill patients. Our a priori hypothesis was that supplementation with these nutrients would reduce . . .

IntroductionObstructive lung diseases (OLDs) such as asthma and chronic obstructive pulmonary disease are major global sources of morbidity and mortality. Current treatments broadly include bronchodilators such as beta agonists/antimuscarinics and anti-inflammatory agents such as steroids. Despite therapy patients still experience exacerbations of their diseases and overall decline over time. Nebulised furosemide may have a novel use in the treatment of OLD. Multiple small studies have shown improvement in pulmonary function as well as dyspnoea. This systematic review will aim to summarise and analyse the existing literature on nebulised furosemide use in OLD to guide treatment and future studies.Methods and analysisWe will identify all experimental studies using nebulised/inhaled furosemide in patients with asthma or chronic obstructive pulmonary disease that report any outcome. Databases will include EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment and the NHS Economic Evaluation Database (1995–2015). We will also search ClinicalTrials.gov and the WHO-International Clinical Trials Registry Platform. Two reviewers will independently determine trial eligibility. For each included trial, we will perform duplicate independent data extraction, risk of bias assessment and evaluation of the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.Ethics and disseminationEthical approval will not be applicable to this systematic review. The results of the study will be communicated through publication in peer-reviewed journals.PROSPERO registration numberCRD42021284680.

The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use.

Purpose Increasingly, very old patients are admitted to Intensive Care Units (ICUs). The objective of this study was to describe 12-month outcomes of these patients and determine which characteristics are associated with a return to baseline physical function 1 year later. Methods In this prospective cohort study in 22 Canadian hospitals, we recruited 610 patients aged 80 years or older who were admitted to ICU for at least 24 h. At baseline, we completed a comprehensive geriatric assessment and followed patients to determine 12-month survival and physical function. Our primary outcome was physical recovery from critical illness at 12 months, defined as being alive with Short Form-36 physical function score of at least 10 points, and not 10 or more points below baseline. We used regression analysis to examine factors associated with physical recovery. Results Patients were on average 84 years old (range 80–99). Mortality was 14 % in ICU, 26 % in hospital and 44 % at 12 months after admission. Of 505 patients evaluable at 12 months, 26 % achieved physical recovery. In the multivariable model, physical recovery was significantly associated with younger age, lower APACHE II score, lower Charlson comorbidity score, lower frailty index, lower baseline physical function score, and specific admission diagnoses. Conclusions One-quarter of patients aged 80 years or older who are admitted to ICU survived and returned to baseline levels of physical function at 1 year. Routine assessment of baseline physical function and frailty status could aid in prognostication and informed decision-making for very old critically ill patients. (ClinicalTrials.gov number NCT01293708).

New-onset atrial fibrillation is a common problem in critically ill patients, with reported incidence ranging from 5% to 46%. It is associated with significant morbidity and mortality. The present review summarizes studies investigating new-onset atrial fibrillation conducted in the critical care setting, focusing on the etiology, management of the hemodynamically unstable patient, rate versus rhythm control, ischemic stroke risk and anticoagulation. Recommendations for an approach to management in the intensive care unit are drawn from the results of these studies.

To describe pre-ICU frailty in critically ill patients using the Clinical Frailty Scale (CFS). We included patients ≥18years admitted to 2 ICUs in Hamilton, Canada. The ICU Research Coordinator (RC) generated 3 CFS scores using: 1) chart review, 2) family interview, 3) patient interview. Subsequently, an overall impression was captured in a final score. Mean differences were calculated to assess the RC intra-rater reliability and inter-rater reliability of chart reviews by the RC, Occupational Therapist (OT), and Geriatrics Resident (GR). Scores were also compared between younger and older patients. We also analyzed the relationship between CFS scores and mortality. We prospectively enrolled 150 patients (mean age 63.8 [SD 15.3] years, APACHE II score 21 [SD 7.3]). CFS were similar between RC, OT, and GR chart reviews (p>0.05 for all comparisons). There was no difference between RC chart review and RC final score, or between RC patient interview and RC final score. Scores following the RC family interview and the RC final score were significantly different (−0.24, 95% CI −0.38, −0.09, p<0.01). Each 1-point increase in the final CFS scored by the RC was weakly associated with ICU mortality (odds ratio 1.18, 95% CI 0.84–1.66, p=0.33), and hospital mortality (OR 1.19, 95% CI 0.89, −1.59, p=0.24). CFS scores can be generated using medical chart review and can be reliably completed by ICU clinicians and research staff. •Using the Clinical Frailty Scale is feasible in the ICU.•Frailty scores are similar across ages despite higher illness severity in older patients.•Chart review and interviews yield similar frailty scores.

To test the hypothesis that poor brain tissue oxygenation (BtO2) during the first 24h of critical illness correlates with the proportion of time spent delirious. We also sought to define the physiological determinants of BtO2. Adult patients admitted to the ICU within the previous 24h were considered eligible for enrollment if they required mechanical ventilation, and/or vasopressor support. BtO2 was measured using near-infrared spectroscopy, for 24h after enrollment. Hourly vital signs and clinically ordered arterial and central venous blood gases were collected throughout BtO2 monitoring. Patients were screened daily for delirium with the confusion assessment method for the intensive care unit (CAM-ICU). BtO2 and the proportion of time spent delirious did not result in a significant correlation (p=0.168). However, critically ill patients who spent the majority of their ICU stay delirious had significantly lower mean BtO2 compared to non-delirious patients, (p=0.017). BtO2 correlated positively with central venous pO2 (p=0.00003) and hemoglobin concentration (p=0.001). Logistic regression indicated that lower BtO2, higher narcotic doses and a history of alcohol abuse were independent risk factors for delirium. Poor cerebral oxygenation during the first 24 hours of critical illness contributes to the development of delirium. This trial is registered on clinicaltrials.gov (Identifier: NCT02344043), retrospectively registered January 8, 2015. •Low BtO2 is an independent risk factor for the subsequent development of delirium.•BtO2 and the proportion of time spent delirious were not significantly correlated.•BtO2 was positively associated with central vpO2 and hemoglobin concentration.•Other delirium risk factors: higher narcotic doses and a history of alcohol abuse

IntroductionClinically important upper gastrointestinal bleeding is conventionally defined as bleeding accompanied by haemodynamic changes, requiring red blood cell transfusions or other invasive interventions. However, it is unclear if this clinical definition reflects patient values and preferences. This protocol describes a study to elicit views from patients and families regarding features, tests, and treatments for upper gastrointestinal bleeding that are important to them.Methods and analysisThis is a sequential mixed-methods qualitative-dominant multi-centre study with an instrument-building aim. We developed orientation tools and educational materials in partnership with patients and family members, including a slide deck and executive summary. We will invite intensive care unit (ICU) survivors and family members of former ICU patients to participate. Following a virtual interactive presentation, participants will share their perspectives in an interview or focus group. Qualitative data will be analysed using inductive qualitative content analysis, wherein codes will be derived directly from the data rather than using preconceived categories. Concurrent data collection and analysis will occur. Quantitative data will include self-reported demographic characteristics. This study will synthesise the values and perspectives of patients and family members to create a new trial outcome for a randomised trial of stress ulcer prophylaxis. This study is planned for May 2022 to August 2023. The pilot work was completed in Spring 2021.Ethics and disseminationThis study has ethics approval from McMaster University and the University of Calgary. Findings will be disseminated via manuscript and through incorporation as a secondary trial outcome on stress ulcer prophylaxis.Trial registration numberNCT05506150.