Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.

RATIONALE: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB). OBJECTIVES: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU. DESIGN: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting. METHODS: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance. RESULTS: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing. CONCLUSIONS: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status.

Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding - An Updated Meta-Analysis.

BACKGROUND: The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. METHODS: We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses. RESULTS: Twelve trials that enrolled 9533 patients were included. Proton-pump inhibitors were associated with a reduced incidence of clinically important upper gastrointestinal bleeding (relative risk [RR], 0.51 [95% confidence interval (CI), 0.34 to 0.76]; high certainty evidence). Proton-pump inhibitors may have little or no effect on mortality (RR, 0.99 [95% CI, 0.93 to 1.05]; low certainty). Within-trial subgroup analysis with intermediate credibility suggested that the effect of proton-pump inhibitors on mortality may differ based on disease severity. Subgroup results raise the possibility that proton-pump inhibitors may decrease 90-day mortality in less severely ill patients (RR, 0.89; 95% CI, 0.80 to 0.98) and may increase mortality in more severely ill patients (RR, 1.08; 95% CI, 0.96 to 1.20]. Proton-pump inhibitors may have no effect on pneumonia and little or no effect on Clostridioides difficile infection (low certainty). CONCLUSIONS: High certainty evidence supports the association of proton-pump inhibitors with decreased upper gastrointestinal bleeding. Proton-pump inhibitors may have little or no effect on mortality, although a decrease in mortality in less severely ill patients and an increase in mortality in more severely ill patients remain possible. (PROSPERO number CRD42023461695.).

Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation.

BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).

An international, multicenter, survey-based analysis of practice and management of acute liver failure.

Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and HE in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on the management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. A total of 267 physicians completed the survey, with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver-intensive or transplant-intensive care unit ( p < 0.001). The median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, 1 week in 37.6%, and more than 1 week in 9.6% ( p < 0.001). Deceased donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria, and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of patients with ALF, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring HE and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare, multicenter studies are valuable for identifying global practice.

Towards personalized medicine: a scoping review of immunotherapy in sepsis.

Despite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable. Subphenotypes are subgroups that can be reliably discriminated from other subgroup based on data-driven assessments. Included studies were randomized controlled trials and cohort studies investigating immunomodulatory therapies in adults with sepsis. Studies were identified by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov, from the first paper available until January 29th, 2024. The search resulted in 15,853 studies. Title and abstract screening resulted in 1409 studies (9%), assessed for eligibility; 771 studies were included, of which 282 (37%) were observational and 489 (63%) interventional. Treatment groups included were treatments targeting the innate immune response, the complement system, coagulation and endothelial dysfunction, non-pharmalogical treatment, pleiotropic drugs, immunonutrition, concomitant treatments, Traditional Chinese Medicine, immunostimulatory cytokines and growth factors, intravenous immunoglobulins, mesenchymal stem cells and immune-checkpoint inhibitors. A personalized approach was incorporated in 70 studies (9%). Enrichment was applied using cut-offs in temperature, laboratory, biomarker or genetic variables. Trials often showed conflicting results, possibly due to the lack of patient stratification or the potential influence of severity and timing on immunomodulatory therapy results. When a personalized approach was applied, trends of clinical benefit for several interventions emerged, which hold promise for future clinical trials using personalized immunotherapy.

Evidence related to a vegetarian diet and metabolic dysfunction-associated steatotic liver disease: protocol for a scoping review.

INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MASLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease worldwide. Given that there is no pharmacological treatment for MASLD, it is imperative to understand whether lifestyle modifications may improve biochemical and pathological outcomes. One commonly proposed dietary modification is the Mediterranean diet; however, vegetarianism may also be a promising intervention. Vegetarianism has been shown to be associated with reduced morbidity and mortality in metabolic syndrome outcomes in coronary artery disease and diabetes; however, the relationship between vegetarian diet and MASLD is less clear. In this scoping review, we will provide a comprehensive overview of the current body of evidence related to a vegetarian diet and MASLD. METHODS AND ANALYSIS: The aim of this scoping review is to describe and summarise the current body of evidence related to MASLD and a vegetarian diet. This review will be conducted using Arksey and O'Malley's framework. The literature review will be conducted using the following databases: SCOPUS, Web of Science, CINAHL-Plus, Cochrane Library and Medline. No restriction will be made on publication date. Included studies will encompass clinical trials and observational designs that examine effects or association of vegetarian diet in adults (≥16 years) and report on the incidence, prevalence or progression of MASLD. Grey literature, non-human studies and articles focusing on changes in a specific food or nutraceutical will be excluded. Articles must have an English-language abstract available to be considered for inclusion. Screening and data extraction will be conducted by two independent reviewers. The findings will be summarised with descriptive statistics. ETHICS AND DISSEMINATION: Approval from a medical ethics committee is not required for this review. Once the review is complete, the findings will be submitted to a peer-reviewed journal.

Adjudication of a primary trial outcome: Results of a calibration exercise and protocol for a large international trial.

Background: Ascertainment of the severity of the primary outcome of upper gastrointestinal (GI) bleeding is integral to stress ulcer prophylaxis trials. This protocol outlines the adjudication process for GI bleeding events in an international trial comparing pantoprazole to placebo in critically ill patients (REVISE: Re-Evaluating the Inhibition of Stress Erosions). The primary objective of the adjudication process is to assess episodes submitted by participating sites to determine which fulfil the definition of the primary efficacy outcome of clinically important upper GI bleeding. Secondary objectives are to categorize the bleeding severity if deemed not clinically important, and adjudicate the bleeding site, timing, investigations, and treatments. Methods: Research coordinators follow patients daily for any suspected clinically important upper GI bleeding, and submit case report forms, doctors' and nurses' notes, laboratory, imaging, and procedural reports to the methods center. An international central adjudication committee reflecting diverse specialty backgrounds conducted an initial calibration exercise to delineate the scope of the adjudication process, review components of the definition, and agree on how each criterion will be considered fulfilled. Henceforth, bleeding events will be stratified by study drug, and randomly assigned to adjudicator pairs (blinded to treatment allocation, and study center). Results: Crude agreement, chance-corrected agreement, or chance-independent agreement if data have a skewed distribution will be calculated. Conclusions: Focusing on consistency and accuracy, central independent blinded duplicate adjudication of suspected clinically important upper GI bleeding events will determine which events fulfil the definition of the primary efficacy outcome for this stress ulcer prophylaxis trial. Registration: NCT03374800 (REVISE: Re-Evaluating the Inhibition of Stress Erosions).

Patient-important upper gastrointestinal bleeding in the ICU: A mixed-methods study of patient and family perspectives.

INTRODUCTION: The objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial. DESIGN: This was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding. SETTING: Canada and the United States. PARTICIPANTS: 51 ICU survivors and family members of ICU patients. RESULTS: Participants considered gastrointestinal bleeding to be important if it resulted in death, disability, or prolonged hospitalization. The following also signaled patient-important upper gastrointestinal bleeding: blood transfusion, vasopressors, endoscopy, CT-angiography, or surgery. Whether an intervention evinced concern depended on its effectiveness, side-effects, invasiveness and accessibility; contextual influences included participant familiarity and knowledge of interventions and trust in the clinical team. CONCLUSIONS: Survivors of critical illness and family members described patient-important upper gastrointestinal bleeding differently than current definitions of clinically-important upper gastrointestinal bleeding.

Continuous renal replacement therapy and survival in acute liver failure: A systematic review and meta-analysis.

OBJECTIVE: Acute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia. Different therapies for hyperammonemia have been assessed including continuous renal replacement therapy (CRRT). We conducted a systematic review and meta-analysis to determine the efficacy of CRRT in ALF patients. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Cochrane Library, and Web of Science. Inclusion criteria included adult patients admitted to an ICU with ALF. Intervention was the use of CRRT for one or more indications with the comparator being standard care without the use of CRRT. Outcomes of interest were overall survival, transplant-free survival (TFS), mortality and changes in serum ammonia levels. RESULTS: In total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70-0.99, p-value 0.04, I2 = 50%] and improved TFS (RR 0.65, 95% CI 0.49-0.85, p-value 0.002, I2 = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84-1.81, p-value 0.28, I2 = 37%). Ammonia clearance data was unable to be pooled and was not analyzable. CONCLUSION: Use of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT.

Enhanced recovery after surgery protocols following emergency intra-abdominal surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to evaluate whether Enhanced Recovery After Surgery (ERAS) protocols for patients undergoing emergency intra-abdominal surgery improve postoperative outcomes as compared to conventional care. METHODS: MEDLINE, EMBASE, WoS, CENTRAL, and Pubmed were searched from inception to December 2022. Articles were eligible if they were randomized controlled trials (RCT) or non-randomized studies comparing ERAS protocols to conventional care for patients undergoing emergency intra-abdominal surgery. The outcomes included postoperative length of stay (LOS), postoperative morbidity, prolonged postoperative ileus (PPOI), and readmission. An inverse variance random effects meta-analysis was performed. A risk of bias was assessed with Cochrane tools. Certainty of evidence was assessed with GRADE. RESULTS: After screening 1018 citations, 20 studies with 1615 patients in ERAS programs and 1933 patients receiving conventional care were included. There was a reduction in postoperative LOS in the ERAS group for patients undergoing upper gastrointestinal (GI) surgery (MD3.35, 95% CI 2.52-4.17, p < 0.00001) and lower GI surgery (MD2.80, 95% CI 2.62-2.99, p < 0.00001). There was a reduction in postoperative morbidity in the ERAS group for patients undergoing upper GI surgery (RR0.56, 95% CI 0.30-1.02, p = 0.06) and lower GI surgery (RR 0.66, 95%CI 0.52-0.85, p = 0.001). In the upper and lower GI subgroup, there were nonsignificant reductions in PPOI in the ERAS groups (RR0.59, 95% CI 0.30-1.17, p = 0.13; RR0.49, 95% CI 0.21-1.14, p = 0.10). There was a nonsignificant increased risk of readmission in the ERAS group (RR1.60, 95% CI 0.57-4.50, p = 0.50). CONCLUSION: There is low-to-very-low certainty evidence supporting the use ERAS protocols for patients undergoing emergency intra-abdominal surgery. The currently available data are limited by imprecision.

A history of bariatric surgery before surgery for colorectal cancer may improve short-term postoperative outcomes: Analysis of the national inpatient sample 2015-2019.

BACKGROUND: Bariatric surgery is the most effective and sustainable form of weight loss. Bariatric surgery before elective operations for colorectal pathology may improve postoperative outcomes. To compare patients with and without prior bariatric surgery undergoing surgery for colorectal cancer in terms of postoperative morbidity and health care use. METHODS: Adult patients undergoing resection for colorectal cancer from 2015 to 2019 were identified from the National Inpatient Sample. Patients were stratified according to their history of bariatric surgery. Propensity score matching with 4:1 nearest-neighbor matching was performed according to demographic, operative, and hospital characteristics. The primary outcome was postoperative morbidity. Secondary outcomes included system-specific postoperative complications, postoperative mortality, postoperative length of stay, total admission health care cost, and post-discharge disposition. McNemar's test and Wilcoxon matched-pairs signed-rank test were performed. RESULTS: After propensity score matching, 1,197 patients without prior bariatric surgery and 376 patients with prior bariatric surgery were included. Patients with prior bariatric surgery had an absolute reduction of 6.5% in overall in-hospital postoperative morbidity (19.1% vs 25.6%, P < .0001), a $5,256 decrease in hospitalization cost ($70,344 vs $75,600, P = .034), and were more likely to be discharged home after their index operation (72.9% vs 63.9%, P < .0001). CONCLUSION: Bariatric surgery before surgery for colorectal cancer may be associated with decreased postoperative morbidity and health care use. Bariatric surgery and other forms of rapid and effective weight loss, such as very low-energy diets, should be evaluated further for the optimization of obese patients before nonbariatric abdominal surgery.

Enhanced Recovery After Surgery (ERAS) protocols following emergency intra-abdominal surgery: A systematic review and meta-analysis protocol.

OBJECTIVE: The aim of this systematic review and meta-analysis is to evaluate whether the implementation of Enhanced Recovery After Surgery (ERAS) protocols for adult patients undergoing emergency intra-abdominal surgery decreases postoperative length of stay, postoperative morbidity, and mortality compared to conventional perioperative care. METHODS: A systematic review and meta-analysis will be performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It has been registered on the International Prospective Register for Systematic Reviews (PROSPERO; CRD42023391709). A comprehensive, electronic search strategy will be used to identify studies published and indexed in MEDLINE, EMBASE, Web of Science, CENTRAL, and Pubmed databases since their inception. Trial registries and references of included studies and pertinent previous systematic reviews will also be searched. Studies will be included if they are randomized controlled trials or cohort studies evaluating adult patients undergoing emergency intra-abdominal surgery and comparing ERAS or modified ERAS protocols to conventional perioperative care and report one of the following outcomes: postoperative length of stay, overall 30-day morbidity, 30-day mortality, 30-day infectious morbidity, prolonged postoperative ileus, return of bowel function, and 30-day readmissions. A meta-analysis will be performed using a random effects model for all comparative data using Cochrane Review Manager 5.3 (London, United Kingdom). DISCUSSION: ERAS protocols have become standard of care for patients undergoing elective surgery. Their use in the setting of emergency surgery is far less common. The aim of this systematic review and meta-analysis is to assess whether there are benefits in patient important outcomes with the implementation of ERAS protocols for patients undergoing emergency intra-abdominal surgery. Ultimately, we hope to promote their use and further large randomized controlled trials evaluating emergency surgery ERAS programs. PROSPERO REGISTRATION NUMBER: CRD42023391709.

Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial.

BACKGROUND: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection. METHODS: The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection. DISCUSSION: Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research. TRIAL REGISTRATION: REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].

Very low energy diets prior to bariatric surgery may reduce postoperative morbidity: a systematic review and meta-analysis of randomized controlled trials.

Purpose: To optimize patients prior to bariatric surgery, very low energy diets (VLEDs) are often employed for 2-4 weeks preoperatively. They are known to result in preoperative weight loss, decrease liver volume, and decrease surgeon-perceived operative difficulty. Their impact on postoperative morbidity has been less extensively studied. We performed a focused systematic review and meta-analysis with the aim of comparing preoperative VLEDs prior to bariatric surgery with controls in terms of overall postoperative morbidity. Methods: MEDLINE, Embase, and CENTRAL were searched from database inception to February 2023. Articles were eligible for inclusion if they were randomized controlled trials (RCTs) comparing postoperative morbidity in adult patients (i.e., over the age of 18) receiving a VLED with liquid formulation to those receiving a non-VLED control prior to elective bariatric surgery. Outcomes included overall 30-day postoperative morbidity and preoperative weight loss. An inverse variance meta-analysis was performed with GRADE assessment of the quality of evidence. Results: After reviewing 2,525 citations, four RCTs with 294 patients receiving preoperative VLEDs with liquid formulation and 294 patients receiving a non-VLED control met inclusion. Patients receiving VLED experienced significantly more preoperative weight loss than patients receiving control (mean difference (MD) 3.38 kg, 95% confidence interval (CI) 1.06-5.70, p = 0.004, I2 = 95%). According to low certainty evidence, there was a non-significant reduction in 30-day postoperative morbidity in patients receiving VLED prior to bariatric surgery (risk ratio (RR) 0.67, 95%CI 0.39-1.17, p = 0.16, I2 = 0%). Conclusion: The impact of preoperative VLEDs on postoperative outcomes following bariatric surgery remains unclear. It is possible that VLEDs may contribute to decreased postoperative morbidity, but further larger prospective trials are required to investigate the signal identified in this study.

What counts as patient-important upper gastrointestinal bleeding in the ICU? A mixed-methods study protocol of patient and family perspectives.

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.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations

To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.