Quality Indicators in Adult Critical Care Medicine.

Quality indicators are increasingly used in the intensive care unit (ICU) to compare and improve the quality of delivered healthcare. Numerous indicators have been developed and are related to multiple domains, most importantly patient safety, care timeliness and effectiveness, staff well-being, and patient/family-centered outcomes and satisfaction. In this review, we describe pertinent ICU quality indicators that are related to organizational structure (such as the availability of an intensivist 24/7 and the nurse-to-patient ratio), processes of care (such as ventilator care bundle), and outcomes (such as ICU-acquired infections and standardized mortality rate). We also present an example of a quality improvement project in an ICU indicating the steps taken to attain the desired changes in quality measures.

Practice and Predictors of Do-Not-Resuscitate Orders in a Tertiary-Care Intensive Care Unit in Saudi Arabia.

Introduction: The objective of this study was to describe Do-Not-Resuscitate (DNR) practices in a tertiary-care intensive care unit (ICU) in Saudi Arabia, and determine the predictors and outcomes of patients who had DNR orders. Methods: This retrospective cohort study was based on a prospectively collected database for a medical-surgicalIntensive CareDepartment in a tertiary-care center in Riyadh, Saudi Arabia (1999-2017). We compared patients who had DNR orders during the ICU stay with those with "full code." The primary outcome was hospital mortality. The secondary outcomes included ICU mortality, tracheostomy, duration of mechanical ventilation, and length of stay in the ICU and hospital. Results: Among 24790 patients admitted to the ICU over the 19-year study period, 3217 (13%) had DNR orders during the ICU stay. Compared to patients with "full code," patients with DNR orders were older (median 67 years [Q1, Q3: 55, 76] versus 57 years [Q1, Q3: 33, 71], p < 0.0001), were more likely to be females (43% versus 38%, p < 0.0001), had worse premorbid functional status (WHO performance status scores 4-5: 606[18.9%] versus 1894[8.8%], p < 0.0001), higher prevalence of comorbid conditions, and higher APACHE II score (median 28 [Q1, Q3: 23, 34] versus 19 [Q1, Q3: 13, 25], p < 0.0001) and were more likely to be mechanically ventilated (83% versus 55%, p < 0.0001). Patients had DNR orders were more likely to die in the ICU (67.8% versus 8.5%, p < 0.0001) and hospital (82.4% versus 18.1%, p < 0.0001). On multivariable logistic regression analysis, the following were associated with an increased likelihood of DNR status: increasing age (odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01-1.02), higher APACHE II score (OR 1.09, 95% CI 1.08-1.10), and worse WHO performance status score. Patients admitted in recent years (2012-2017 versus 2002-2005) were less likely to have DNR orders (OR 0.35, 95% CI 0.32-0.39, p < 0.0001). Patients with DNR orders had higher ICU mortality, more tracheostomies, longer duration of mechanical ventilation and length of ICU stay compared to patients with with "full code" but they had shorter length of hospital stay. Conclusion: In a tertiary-care hospital in Saudi Arabia, 13% of critically ill patients had DNR orders during ICU stay. This study identified several predictors of DNR orders, including the severity of illness and poor premorbid functional status.

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

European Society of Intensive Care Medicine clinical practice guideline on fluid therapy in adult critically ill patients. Part 1: the choice of resuscitation fluids.

PURPOSE: This is the first of three parts of the clinical practice guideline from the European Society of Intensive Care Medicine (ESICM) on resuscitation fluids in adult critically ill patients. This part addresses fluid choice and the other two will separately address fluid amount and fluid removal. METHODS: This guideline was formulated by an international panel of clinical experts and methodologists. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was applied to evaluate the certainty of evidence and to move from evidence to decision. RESULTS: For volume expansion, the guideline provides conditional recommendations for using crystalloids rather than albumin in critically ill patients in general (moderate certainty of evidence), in patients with sepsis (moderate certainty of evidence), in patients with acute respiratory failure (very low certainty of evidence) and in patients in the perioperative period and patients at risk for bleeding (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than albumin in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using albumin rather than crystalloids in patients with cirrhosis (very low certainty of evidence). The guideline provides conditional recommendations for using balanced crystalloids rather than isotonic saline in critically ill patients in general (low certainty of evidence), in patients with sepsis (low certainty of evidence) and in patients with kidney injury (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than balanced crystalloids in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using isotonic crystalloids rather than small-volume hypertonic crystalloids in critically ill patients in general (very low certainty of evidence). CONCLUSIONS: This guideline provides eleven recommendations to inform clinicians on resuscitation fluid choice in critically ill patients.

Family centeredness of care: a cross-sectional study in intensive care units part of the European society of intensive care medicine.

PURPOSE: To identify key components and variations in family-centered care practices. METHODS: A cross-sectional study, conducted across ESICM members. Participating ICUs completed a questionnaire covering general ICU characteristics, visitation policies, team-family interactions, and end-of-life decision-making. The primary outcome, self-rated family-centeredness, was assessed using a visual analog scale. Additionally, respondents completed the Maslach Burnout Inventory and the Ethical Decision Making Climate Questionnaire to capture burnout dimensions and assess the ethical decision-making climate. RESULTS: The response rate was 53% (respondents from 359/683 invited ICUs who actually open the email); participating healthcare professionals (HCPs) were from Europe (62%), Asia (9%), South America (6%), North America (5%), Middle East (4%), and Australia/New Zealand (4%). The importance of family-centeredness was ranked high, median 7 (IQR 6-8) of 10 on VAS. Significant differences were observed across quartiles of family centeredness, including in visitation policies availability of a waiting rooms, family rooms, family information leaflet, visiting hours, night visits, sleep in the ICU, and in team-family interactions, including daily information, routine day-3 conference, and willingness to empower nurses and relatives. Higher family centeredness correlated with family involvement in rounds, participation in patient care and end-of-life practices. Burnout symptoms (41% of respondents) were negatively associated with family-centeredness. Ethical climate and willingness to empower nurses were independent predictors of family centeredness. CONCLUSIONS: This study emphasizes the need to prioritize healthcare providers' mental health for enhanced family-centered care. Further research is warranted to assess the impact of improving the ethical climate on family-centeredness.

Protocol implementation during the COVID-19 pandemic: experiences from a randomized trial of stress ulcer prophylaxis.

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.

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).

The prevalence of acute kidney injury in patients with community-acquired pneumonia who required mechanical ventilation.

BACKGROUND: Community-acquired pneumonia (CAP) is a common reason for intensive care unit (ICU) admission and sepsis. Acute kidney injury (AKI) is a frequent complication of community-acquired pneumonia and is associated with increased short- and long-term morbidity and mortality and healthcare costs. OBJECTIVE: Describe the prevalence of AKI in patients with CAP requiring mechanical ventilation and evaluate its association with inhospital mortality. DESIGN: Retrospective cohort. SETTING: Intensive care unit. PATIENTS AND METHODS: We included patients with CAP on mechanical ventilation. Patients were categorized according to the development of AKI in the first 24 hours of ICU admission using the Kidney Disease Improving Global Outcomes (KDIGO) classification from no AKI, stage 1 AKI, stage 2 AKI, and stage 3 AKI. MAIN OUTCOME MEASURES: The primary outcome was hospital mortality. Secondary outcomes were ICU mortality, hospital and ICU length of stay, ventilation duration, tracheostomy, and renal replacement therapy requirement. RESULTS: Of 1536 patients included in the study, 829 patients (54%) had no AKI while 707 (46%) developed AKI. In-hospital mortality was 288/829 (34.8%) for patients with no AKI, 43/111 (38.7%) for stage 1 AKI, 86/216 (40%) for stage 2 AKI, and 196/380 (51.7%) for stage 3 AKI (P<.0001). Multivariate analysis revealed that stages 1, 2, or 3 AKI compared to no AKI were not independently associated with in-hospital mortality. Older age, vasopressor use; decreased Glasgow coma scale, PaO2/Fio2 ratio and platelet count, increased bilirubin, lactic acid and INR were associated with increased mortality while female sex was associated with reduced mortality. CONCLUSION: Among mechanically ventilated patients with CAP, AKI was common and was associated with higher crude mortality. The higher mortality could not be attributed alone to AKI, but rather appeared to be related to multi-organ dysfunction. LIMITATIONS: Single-center retrospective study with no data on baseline serum creatinine and the use of estimated baseline creatinine distributions based on the MDRD (Modification of Diet in Renal Disease)equation which may lead to an overestimation of AKI. Second, we did not have data on the microbiology of pneumonia, appropriateness of antibiotic therapy or the administration of other medications that have been demonstrated to be associated with AKI.

Durability of COVID-19 humoral immunity post infection and different SARS-COV-2 vaccines.

BACKGROUND: The global challenge posed by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been a major concern for the healthcare sector in recent years. Healthcare workers have a relatively high risk of encountering COVID-19 patients, making protective immunity against SARS-CoV-2 is a priority for them. This study aims to evaluate the longitudinal measurement of SARS-CoV-2 IgG spike protein antibodies in healthcare workers (HCWs) after COVID-19 infection and after receiving the first and second doses of SARS-CoV-2 vaccines, including Pfizer-BioNTech (BNT162b2) and Oxford-AstraZeneca (AZD1222). METHODS: This longitudinal cohort study involved 311 healthcare workers working in two tertiary hospitals in Saudi Arabia. All participants were followed between July 2020 and July 2022 after completing the study questionnaire. A total of 3 ml of the blood samples were collected at four intervals: before/after vaccination. RESULTS: HCWs post-infection had lower mean SARS-CoV-2 IgG levels three months post-infection than post-vaccination. 92.2% had positive IgG levels two weeks after the first dose and reached 100% after the second dose. Over 98% had positive antibodies nine months after the second dose, regardless of vaccine type. The number of neutralizing antibodies decreased and was around 50% at nine months after the second dose. CONCLUSION: The results show different antibody patterns between infected and vaccinated HCWs. A high proportion of participants had positive antibodies after vaccination, with high levels persisting nine months after the second dose. Neutralizing antibodies decreased over time, with only about 50% of participants having positive antibodies nine months after the second dose. These results contribute to our understanding of immunity in healthcare workers and highlight the need for the continuous monitoring and possible booster strategies.

Prognostic evaluation of quick sequential organ failure assessment score in ICU patients with sepsis across different income settings.

BACKGROUND: There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions. METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study. RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p < 0.001) and UMIC (p < 0.001) and not HIC (p = 0.220) countries/regions. Similarly, higher 90-day mortality was associated with increased qSOFA in LLMIC (p < 0.001) and UMIC (p < 0.001) only. In contrast, higher 3-day mortality with increasing qSOFA score was observed across all income countries/regions (p < 0.001). Multivariate analysis showed that qSOFA remained associated with 28-day mortality (adjusted RR 1.09 (1.00-1.18), p = 0.038) even after adjustments for covariates including APACHE II, SOFA, income country/region and administration of antibiotics within 3 h. CONCLUSIONS: qSOFA was independently associated with 28-day mortality in ICU patients admitted for sepsis. In LLMIC and UMIC countries/regions, qSOFA was associated with early to late mortality but only early mortality in HIC countries/regions.

A New Global Definition of Acute Respiratory Distress Syndrome.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Diagnosis and management of autoimmune diseases in the ICU.

Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.

Mechanical ventilation practices in Asian intensive care units: A multicenter cross-sectional study.

PURPOSE: This study investigated current practices of mechanical ventilation in Asian intensive care units, focusing on tidal volume, plateau pressure, and positive end-expiratory pressure (PEEP). MATERIALS AND METHODS: In this multicenter cross-sectional study, data on mechanical ventilation and clinical outcomes were collected. Predictors of mortality were analyzed by univariate and multivariable logistic regression. A scoring system was generated to predict 28-day mortality. RESULTS: A total of 1408 patients were enrolled. In 138 patients with acute respiratory distress syndrome (ARDS), 65.9% were on a tidal volume ≤ 8 ml/kg predicted body weight (PBW), and 71.3% were on sufficient PEEP. In 1270 patients without ARDS, 88.8% were on a tidal volume ≤ 10 ml/kg PBW. A plateau pressure < 30 cmH2O was measured in 92.2% of patients. Mortality rates increased from 13% to 74% as the generated predictive score increased from 5 to ≥8.5. Income classification, age, SOFA score, PaO2/FiO2 ratio, plateau pressure, number of vasopressors, and steroid use were associated with mortality. CONCLUSIONS: In Asia, low tidal volume ventilation and sufficient PEEP were underused in patients with ARDS. The majority of patients without ARDS were on intermediate tidal volumes. Country income, age, and severity of illness were associated with mortality.

Critical care bed capacity in Asian countries and regions before and during the COVID-19 pandemic: an observational study.

Background: The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of critical care. The aim of the current study was to compare the number of adult critical care beds in relation to population size in Asian countries and regions before (2017) and during (2022) the pandemic. Methods: This observational study collected data closest to 2022 on critical care beds (intensive care units and intermediate care units) in 12 middle-income and 7 high-income economies (using the 2022-2023 World Bank classification), through a mix of methods including government sources, national critical care societies, personal contacts, and data extrapolation. Data were compared with a prior study from 2017 of the same countries and regions. Findings: The cumulative number of critical care beds per 100,000 population increased from 3.0 in 2017 to 9.4 in 2022 (p = 0.003). The median figure for middle-income economies increased from 2.6 (interquartile range [IQR] 1.7-7.8) to 6.6 (IQR 2.2-13.3), and that for high-income economies increased from 11.4 (IQR 7.3-22.8) to 13.9 (IQR 10.7-21.7). Only 3 countries did not see a rise in bed capacity. Where data were available in 2022, 10.9% of critical care beds were in single rooms (median 5.0% in middle-income and 20.3% in high-income economies), and 5.3% had negative pressure (median 0.7% in middle-income and 18.5% in high-income economies). Interpretation: Critical care bed capacity in the studied Asian countries and regions increased close to three-fold from 2017 to 2022. Much of this increase was attributed to middle-income economies, but substantial heterogeneity exists. Funding: None.

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

BACKGROUND: The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. OBJECTIVE: To outline the statistical analysis plan for the REVISE trial. METHODS: REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. RESULTS: The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are 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 concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. CONCLUSIONS: This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT03374800. November 21, 2017.

Outcomes of patients admitted to the intensive care unit with community-acquired pneumonia in a tertiary care center in Riyadh, Saudi Arabia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of intensive care unit (ICU) morbidity and mortality. Despite extensive international epidemiological and clinical studies to improve those patients' outcomes, local statistics in Saudi Arabia are limited. The objective of this study is to describe the clinical characteristics and outcomes of patients admitted to the ICU with the diagnosis of CAP reflecting the experience of a tertiary center over an 18-year period. METHODS: A retrospective cohort study included all consecutive adult ICU patients diagnosed with CAP between 1999 and 2017. Baseline demographics, patients' risk factors, and initial admission laboratory investigations were compared between survivors and nonsurvivors. A multivariate regression model was used to predict mortality. RESULTS: During the study period, there were 3438 patients admitted to the ICU with CAP (median age 67 [Quartile 1, 3 (Q1, Q3) 51, 76] years) and 54.4% were males, of whom 1007 (29.2%) died. The survivors compared with nonsurvivors were younger (65 vs. 70 years), less likely to have chronic liver disease (2.4% vs. 10.5%), chronic renal failure (8.1% vs. 14.4%), and be immunocompromised (10.2% vs. 18.2%), and less frequently required mechanical ventilation or vasopressors (46.2% vs. 80.5% and 29.6% vs. 55.9%, respectively). Acute Physiology and Chronic Health Evaluation (APACHE) II score was significantly higher among nonsurvivors (median score 26 vs. 20) with a longer duration of mechanical ventilation and ICU stay. Using a multivariate regression model, age, APACHE II score, bilirubin level, vasopressors, and mechanical ventilation were significantly associated with increased mortality, while diabetes was associated with lower mortality. CONCLUSION: Around one-third of patients admitted to the ICU with CAP died. Mortality was significantly associated with age, APACHE II score, vasopressor use, and mechanical ventilation. A comprehensive national registry is needed to enhance epidemiological data and to guide initiatives for improving CAP patients' outcomes.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869

REVISE: Re-Evaluating the Inhibition of Stress Erosions in the ICU: a randomised trial protocol.

INTRODUCTION: The Re-Evaluating the Inhibition of Stress Erosions (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.