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Introduction: The R e- Ev aluating the I nhibition of S tress E rosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE., Methods and Analysis: REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial., Ethics and Dissemination: All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to - Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide., Trial Registration Number: NCT03374800., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Clinically 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 Analysis: This 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 Dissemination: This 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 Number: NCT05506150., Competing Interests: Competing interests: The following individuals are investigators for the randomised trial REVISE: DJC, JD, GG, WA, KEAB, JCM, JMu, SF, AMD, JMy, BR, IB, TM, DN, SE. We have no other conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Perioperative benzodiazepines are used because of their anxiolytic, sedative and amnestic effects. Evidence has demonstrated an association of benzodiazepines with adverse neuropsychiatric effects. Nonetheless, because of their potential benefits, perioperative benzodiazepines continue to be used routinely. We seek to evaluate the body of evidence of the risks and benefits of benzodiazepine use during the perioperative period., Methods and Analysis: We will search Cochrane CENTRAL, MEDLINE, EMBASE, PsychINFO, CINAHL and Web of Science from inception to March 2019 for randomised controlled trials (RCTs) and observational studies evaluating the administration of benzodiazepine medications as compared with all other medications (or nothing) in patients undergoing cardiac and non-cardiac surgery. We will exclude studies assessing the use of benzodiazepines for procedural sedation or day surgery. We will examine the impact of giving these medications before, during and after surgery. Outcomes of interest include the incidence of delirium, duration of delirium, postprocedure cognitive change, the incidence of intraoperative awareness, patient satisfaction/quality of life/quality of recovery, length-of-stay (LOS) in the intensive care unit (ICU), hospital LOS and in-hospital mortality.Reviewers will screen references and assess eligibility using predefined criteria independently and in duplicate. Two reviewers will independently collect data using prepiloted forms. We will present results separately for RCTs and observational studies. We will pool data using a random effect model and present results as relative risk with 95% CIs for dichotomous outcomes and mean difference with 95% CI for continuous outcomes. We will pool adjusted ORs for observational studies. We will assess risk of bias for individual studies using the Cochrane Collaboration tool for RCTs. For observational studies, we will use tools designed by the Clinical Advances through Research and Information Translation group. Quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach., Ethics and Dissemination: This systematic review involves no patient contact and no interaction with healthcare providers or systems. As such, we did not seek ethics board approval. We will disseminate the findings of our systematic review through the presentation at peer-reviewed conferences and by seeking publication in a peer-reviewed journal., Prospero Registration Number: CRD42019128144., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Endotracheal intubation and invasive mechanical ventilation are lifesaving interventions that are commonly performed in the intensive care unit (ICU). Laryngeal oedema is a known complication of intubation that may cause airway obstruction in a patient on extubation. To date, the only test available to predict this complication is the cuff leak test (CLT); however, its diagnostic accuracy and utility remains uncertain. Herein, we report the protocol for the CuffLeak and AirwayObstruction in MechanicallyVentilated ICU Patients (COMIC) pilottrial., Methods and Analysis: This will be a multicentred, pragmatic, pilot randomised controlled trial (RCT). We will enrol 100 mechanically ventilated patients in the ICU who are deemed ready for extubation. We will exclude patients at a high risk of laryngeal oedema. All enrolled patients will have a CLT done before extubation. In the intervention arm, the results of the CLT will be communicated to the bedside physician, and decision to extubate will be left to the treating team. In the control arm, respiratory therapist will not communicate the results of the CLT to the treating physician, and the patient will be extubated regardless of the CLT result. Randomisation will be done in a 1:1 allocation ratio, stratified by size of the endotracheal tube and duration of invasive mechanical ventilation.Although we will examine all clinical outcomes relevant for the future COMIC RCT, the primary outcomes of the COMIC pilottrial will be feasibility outcomes including: consent rate, recruitment rate and protocol adherence. Clinical outcomes include postextubation stridor, reintubation, emergency surgical airway, ICU mortality, in hospital mortality, duration of mechanical ventilation and ICU length of stay in days., Ethics and Dissemination: The Hamilton Integrated Research Ethics Board, Imam Abdulrahman Bin Faisal University Institutional Review Board and Bioethical Commission of the Jagiellonian University approved this study. The trial results will be disseminated via publication in peer-reviewed journals., Trial Registration Number: NCT03372707., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Diarrhoea is a frequent concern in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, increased length of ICU stay, skin breakdown and renal dysfunction. However, its prevalence, aetiology and prognosis in the critically ill have been poorly studied. The primary objectives of this study are to determine the incidence, risk factors and consequences of diarrhoea in critically ill adults. The secondary objectives are to estimate the incidence of Clostridium difficile- associated diarrhoea (CDAD) in ICU patients and to validate the Bristol Stool Chart and Bliss Stool Classification System characterising bowel movements in the ICU. Our primary outcome is the incidence of diarrhoea . Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay., Methods and Analysis: This international prospective cohort study will enrol patients over 10 weeks in 12 ICUs in Canada, the USA, Poland and Saudi Arabia. We will include all patients 18 years of age and older who are admitted to the ICU for at least 24 hours and follow them daily until ICU discharge. Our primary outcome is the incidence of diarrhoea based on the WHO definition, during the ICU stay. Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay. We will use logistic regression to identify factors associated with diarrhoea (as defined using WHO criteria) and the kappa statistic to measure agreement on diarrhoea rates between the WHO definition and the Bristol Stool Chart and Bliss Stool Classification System., Ethics and Dissemination: The protocol has been approved by the research ethics board of all participating centres. The diarrhoea interventions, consequences and epidemiology in the intensive care unit (DICE-ICU) study will generate evidence about diarrhoea and its frequency, predisposing factors and consequences, to inform critical care practice and future research., Lay Summary: Diarrhoea is a frequent clinical problem for hospitalised patients including those who are critically ill in the ICU. Diarrhoea can cause complications such as skin damage, dehydration and kidney problems. It is not clear how common diarrhoea is in the ICU, the factors that cause it or the best way for clinicians to assess it. The DICE-ICU study is an international prospective observational study to examine the frequency, risk factors and outcomes of diarrhoea during critical illness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Increased intracranial pressure (ICP) is a significant neurological issue that may lead to permanent neurological sequelae. When evaluating patients with traumatic brain injury, it is crucial to identify those with high ICP in order to expedite ICP lowering measures and maintain adequate cerebral perfusion. Several measures are used to recognise patients with increased ICP including CT scan, MRI, ICP monitor, and lumbar puncture (LP). However, these tests can be invasive, associated with radiation exposure, contraindicated, or not readily available. Ultrasonography measurement of the optic nerve sheath diameter (ONSD) is proposed as a non-invasive and quick measure to identify high ICP. The aim of this systematic review and meta-analysis will be to examine the accuracy of ONSD sonography for increased ICP diagnosis., Methods and Analyses: We will include published and unpublished randomised controlled trials, observational studies, and abstracts, with no publication type or language restrictions. Search strategies will be designed to peruse the MEDLINE, Embase, Web of Science, WHO Clinical Trials, ClinicalTrials.gov, CINAHL, and the Cochrane Library databases. We will also implement strategies to search grey literature. Two reviewers will independently complete data abstraction and conduct quality assessment. Included studies will be assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We will construct the hierarchical summary receiver operating characteristic curve for included studies and pool sensitivity and specificity using the bivariate model. We also plan to conduct prespecified subgroup analyses to explore heterogeneity. The overall quality of evidence will be rated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE)., Ethics and Dissemination: Research ethics board approval is not required for this study as it draws from published data and raises no concerns related to patient privacy. This review will provide a comprehensive assessment of the evidence on ONSD sonography diagnostic accuracy and is directed to a wide audience. Results from the review will be disseminated extensively through conferences and submitted to a peer-reviewed journal for publication., Prospero Registration Number: CRD42017055485., Clinical Trial Number: Trial registration number is NCT00783809., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Sepsis is associated with a dysregulated host response to infection and impaired endogenous corticosteroid metabolism. As such, therapeutic use of exogenous corticosteroids is a promising adjunctive intervention. Despite a large number of trials examining this research question, uncertainty persists regarding the effect of corticosteroids on survival in sepsis. Several large randomised controlled trials have been published recently prompting a re-evaluation of the available literature., Methods and Analysis: A rigorous and reproducible search and screening process from a Cochrane review on the same topic was comprehensive to October 2014. We will search MEDLINE, EMBASE, LILACS, the Cochrane trial registry and clinicaltrials.gov for eligible randomised controlled trials investigating the use of corticosteroids in patients with sepsis from September 2014. Outcomes have been chosen by a semi-independent guideline panel, created in the context of a parallel BMJ Rapid Recommendation on the topic. This panel includes clinicians, content experts, methodologists and patient representatives, who will help identify patient-important outcomes that are critical for deciding whether to use or not use corticosteroids in sepsis. Two reviewers will independently screen and identify eligible studies; a third reviewer will resolve any disagreements. We will use RevMan to pool effect estimates from included studies for each outcome using a random-effect model. We will present the results as relative risk with 95% CI for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95% CI. We will assess the certainty of evidence at the outcome level using the Grading of Recommendations, Assessment, Development and Evaluation approach. We will conduct a priori subgroup analyses, which have been chosen by the parallel BMJ Rapid Recommendation panel., Ethics and Dissemination: The aim of this systematic review is to summarise the updated evidence on the efficacy and safety of corticosteroids in patients with sepsis., Trial Registration Number: CRD42017058537., Competing Interests: Competing interests: BR and SO are supported by McMaster University Department of Medicine early career research awards., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Lumbar puncture is one of the oldest and most commonly performed procedures in medicine, used to diagnose and treat disease. Headache following lumbar puncture remains a frequent complication, causing significant patient discomfort and often requiring narcotic analgesia or invasive therapy. Needle tip design has been proposed to affect the incidence of headache postlumbar puncture, with pencil-point 'atraumatic' needles thought to reduce its incidence in comparison to bevelled 'traumatic' needles. Despite this, the use of atraumatic needles and knowledge of their existence remains significantly limited among clinicians. This study will systematically review the evidence on atraumatic lumbar puncture needles and compare them with traumatic needles across a variety of clinical outcomes., Methods and Analyses: We will include published randomised controlled trials (RCTs), observational studies and abstracts, with no publication type or language restrictions. Search strategies will be designed to peruse the MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CINAHL, WHO Clinical Trials Database and Cochrane Library databases. We will also implement strategies to search the grey literature. 3 reviewers will thoroughly and independently examine the search results, complete data abstraction and conduct quality assessment. Included RCTs will be assessed using the Cochrane risk of bias assessment tool and eligible observational studies will be examined using the Newcastle-Ottawa Scale. We will examine the outcomes of: headache and its type, intensity, duration and treatment; backache; success rate; hearing disturbance and nerve root irritation. The primary outcome will be the incidence of postdural puncture headache. We will calculate pooled estimates, relative risks for dichotomous outcomes and weighted mean differences for continuous outcomes, with corresponding 95% CIs. Statistical heterogeneity will be measured using Cochran's Q test and quantified using the I 2 statistic. We will also conduct prespecified subgroup and sensitivity analyses to examine if covariates exist and to explore potential heterogeneity., Ethics and Dissemination: Research ethics board approval is not required for this study as it draws from published data and raises no concerns related to patient privacy. This review will provide a comprehensive assessment of the evidence on atraumatic needles for lumbar puncture and is directed to a wide audience. Results from the review will be disseminated extensively through conferences and submitted to a peer-reviewed journal for publication., Trial Registration Number: CRD42016047546., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)