Background Recent studies report a global shift in the demographics of individuals sustaining a traumatic brain injury (TBI). An increasingly higher proportion of older adults now experience TBIs, falls have overtaken transport-related accidents as the leading cause of injury, and there is high prevalence of TBIs classified as mild. However, it remains unclear whether these demographic and clinical shifts are also occurring in Australia. This study aimed to examine the clinical characteristics of patients hospitalised following TBI and assess whether similar trends were evident. Methods A retrospective cohort study was conducted in a metropolitan hospital in Sydney. Data from 260 patients were extracted and analysed. Results A total of 50% of patients hospitalised following a TBI were aged >60 years. Falls were the leading mechanism of injury (64%) for younger and older adults, and severe TBI cases (43%) were most frequently encountered. Males dominated the sample, except among adults aged >75 years, where distribution of cases was comparable for males and females. Conclusions Results indicated that demographic trends in this Australian sample broadly reflect those reported globally, with older adults and falls predominating. Future research should focus on examining whether these findings are observed across diverse settings while improving recruitment of underrepresented populations.

OBJECTIVE:A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN:Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING:Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS:A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS:A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS:A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.

INTRODUCTION:Patients often experience sleep disruption in hospital, which may prolong recovery and healing. Previous studies focusing on behavior change have ignored specific context implementation factors, resulting in limited improvements in patient sleep. OBJECTIVES:The aim of this study was to improve patient sleep through the implementation of a standardized patient self-report sleep assessment scale, together with a comprehensive evidence-based nocturnal sleep guideline for patients. METHODS:This study was conducted in two acute care wards in a 500-bed public tertiary referral hospital in Sydney, Australia. The study used the seven-phase JBI Evidence Implementation Framework, which is grounded in an audit and feedback process. Data were gathered through assessment of patients' self-reported sleep and semi-structured interviews with nurses and doctors. The resulting data and the Behaviour Change Wheel (BCW) informed the context-specific implementation strategy. A follow-up audit was then used to measure the effectiveness of the implementation strategy. RESULTS:Patients' self-reported quality of sleep remained unchanged; however, their perception of sound levels was lower post-implementation (median 49.0 [20.5] versus 23.0 [16.2-54.0]). Use of the sleep assessment scale was low. The main barrier was that nurses perceived documentation as a burden. Doctors reported that they were unaware of the sleep assessment scale and guideline post-implementation. CONCLUSIONS:Despite there being little uptake of the sleep assessment scale, there was evidence of some changes in practice relevant to sound reduction, which is key to improving sleep quality in hospitals. Documentation burden was a barrier for the uptake of the sleep assessment scale. SPANISH ABSTRACT:http://links.lww.com/IJEBH/A581.

Background Core outcome measurement sets (COMS) enhance the consistency and comparability of outcome reporting in clinical research. However, their effectiveness depends on the selection of valid, reliable, and feasible measurement instruments. Core outcome sets (COS) and COMS have been developed for specific intensive care unit (ICU) patient subgroups. The aim of this study is to establish a standardised approach to outcome measurement and operationalisation for adults acutely admitted to the ICU who are participating in clinical trials and other clinical research.Methods This protocol describes the development of a COMS for adults acutely admitted to the ICU, the CoreMS-ICU, consisting of six core outcomes: survival, free of life support, free of delirium, out of hospital, health-related quality of life, and cognitive function. We will follow the Consensus-based Standards for the Selection of Health Measurement Instruments guideline and report according to the Core Outcome Set-STAndardised Protocol Items guideline. The development of the CoreMS-ICU will follow five predefined steps: (1) conceptual considerations for the six core outcomes; (2) systematic searches for outcome measurement instruments, including consideration of existing COMS; (3) quality assessment of relevant outcome measurement instruments; (4) consensus-based selection of outcome measurement instruments; and (5) recommendations and guidance on how to operationalise and report the measurement of the six core outcomes. We will involve research panels consisting of key stakeholders: patients, family members, healthcare professionals, and researchers in steps 1 and 4.Conclusions We aim to develop a COMS for adults acutely admitted to ICU patients to facilitate the consistent use of outcomes in trials and enhance the translation of research findings into clinical practice.

Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer. To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest. The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively. Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 °C). The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT). Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, −0.02 [95% CI, −0.67 to 0.63]; SDMT: mean difference, −0.09 [95% CI, −0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, −2.00 to −1.50]; P < .001; 6 to 24 months: n = 1606 [95% CI, −0.50 to <0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months. Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery. ClinicalTrials.gov Identifier: NCT02908308

Importance:Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer. Objectives:To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest. Design, Setting, and Participants:The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively. Intervention:Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 °C). Main Outcomes and Measures:The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT). Results:Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, -0.02 [95% CI, -0.67 to 0.63]; SDMT: mean difference, -0.09 [95% CI, -0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, -2.00 to -1.50]; P < .001; 6 to 24 months: n = 1606 [95% CI, -0.50 to <0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months. Conclusions and Relevance:Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery. Trial Registration:ClinicalTrials.gov Identifier: NCT02908308.

OBJECTIVE:The aim of this study was to investigate the association between socioeconomic status (SES) and sepsis survival in Australian intensive care unit (ICU) admissions. METHODS:We conducted a retrospective cohort study of adult sepsis ICU admissions between 2018 and 2023, using ICU registry and national death data. SES was derived using the Australian Bureau of Statistics Index of Relative Socioeconomic Advantage and Disadvantage deciles mapped from residential postcodes and categorised as low, middle, or high. Unadjusted survival to 180 days and in-hospital 30-day survival were described using Kaplan-Meier estimates. Cox proportional hazard models, adjusted for age, sex, organ failure, ICU admission source, elective surgical status, chronic conditions, admission year, study site, and the presence of septic shock, were used to determine associations between SES and survival. RESULTS:Of 794,756 admissions, 80,422 (10.1%) were sepsis admissions; 180-day mortality was 7570 of 31,528 (24·0%) in low SES admissions compared to 5109 of 22262 (22.9%) and 6009 of 26,088 (23·0%) in middle and high SES admissions, respectively. In-hospital 30-day mortality was 4662 of 31,613 (14·7%) in low SES admissions compared to 3079 of 22348 (13.7%) and 3695 of 26,221 (14·1%) in middle and high SES admissions, respectively. In adjusted Cox regression models, high SES was associated with greater 180-day and in-hospital 30-day survival (adjusted hazard ratio: 0·86, 95% confidence interval: 0·83-0·90; p < 0·001 and adjusted hazard ratio: 0·88, 95% confidence interval: 0·84-0·93; p < 0·001, respectively). CONCLUSION:People living in areas of socioeconomic disadvantage had lower survival to day 180 after an ICU admission for sepsis than people living in other areas.

Background:Data on long-term survival after intensive care unit (ICU) admission for sepsis and septic shock are limited. This study aimed to evaluate survival over five years among critically ill sepsis or septic shock patients discharged alive from hospital. Methods:This retrospective cohort study of adults who survived to hospital discharge after non-elective ICU admission (2018-2024) used Australian and New Zealand Intensive Care Society Adult Patient Database. Sepsis, septic shock, or non-sepsis patients were classified using diagnostic codes and physiological/laboratory criteria during first 24-h of ICU admission. Mixed-effects Cox models with time-varying covariate effects were used, adjusting for demographics, comorbidities, frailty, illness severity, and ICU interventions. Findings:Of 557,538 hospital survivors, 7.3% had sepsis without shock, 11.5% septic shock, and 81.2% non-sepsis conditions. At five-years, unadjusted survival was lowest for septic shock (68.0%, 95% confidence interval/CI = 67.6-68.4%), sepsis without shock (74.2%, 73.7-74.6%), and non-sepsis (78.2%, 78.1-78.3%). After adjustment, hazards ratio/HR for sepsis without shock remained at or below the null relative to non-sepsis; 0-1 year: HR = 0.95, 0.92-0.98; 1-3 years: 0.96, 0.93-1.00; 3-5 years: 1.03, 0.97-1.08, while septic shock showed persistent independent excess mortality; 0-1 year: HR = 1.05,1.03-1.08; 1-3 years: 1.03, 1.00-1.06; and 3-5 years:1.09,1.05-1.14. Major predictors of mortality included age, frailty, comorbidities, and organ support. Interpretation:Septic shock was associated with persistent independent excess mortality over five years after hospital discharge, whereas in sepsis without shock, this was largely explained by pre-existing comorbidity and frailty. Funding:Medical Research Future Fund.

BACKGROUND:Guidelines discourage prediction of neurological outcome in comatose patients within the first 72 h after cardiac arrest. Increasing evidence suggests that patients with the most severe brain injury and those with no or minimal brain injury may be identified before 72 h using novel methods. We present a protocol for the EARLY-NEURO study, which aims to evaluate whether good and poor outcomes can be reliably predicted already from 24 h after cardiac arrest using the most commonly available methods. METHODS:Protocol for a prospective international multicenter substudy within the Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial where adults post-arrest are randomized to minimal or deep sedation, fever treatment with or without a temperature management device and to two different targets of mean arterial blood pressure. Patients sedated or still unconscious at 24 h are examined with head computed tomography (CT) and electroencephalogram (EEG). Blood samples are collected at 24 h after randomization, and stored for analysis of the brain injury marker neurofilament light. CT and EEG examinations will be centrally evaluated for signs of a likely poor or good outcome applying standardized criteria by raters blinded to treatment allocations and patient outcomes. Intensive care treatment, neurological prognostication, and criteria for withdrawal of care will be according to the STEPCARE protocol. Timepoint and reasons for withdrawal of life-sustaining therapy (WLST) will be recorded. WLST prior to 72 h after randomization based on a presumed futile neurological prognosis is strongly discouraged. Primary outcome will be good or poor functional outcome, assessed by the modified Rankin Scale (dichotomized as 0-3 versus 4-6) at 6 months. Results will be reported in accordance with the Standards for Reporting Diagnostic Accuracy (STARD). CONCLUSIONS:Earlier prognostication aims to balance the avoidance of premature treatment withdrawal in patients with favorable potential against the prevention of unnecessary intervention in patients with a definitely poor prognosis.

Sepsis is a major cause of mortality in intensive care unit (ICU) patients. Significant temporal improvements in survival were observed in Australia and New Zealand (ANZ) from 2000 to 2012. Whether this has continued remains uncertain, and current sepsis-related mortality in ANZ ICUs is unknown. We studied adult ICU patients admitted with sepsis (based on the 3rd international consensus definition for sepsis and septic shock), between January 2000 and June 2023. Data were obtained from 219 ICUs that contributed to the ANZ Intensive Care Society Adult Patient Database. We used logistic regression models to study changes in in-hospital mortality over time. Among 2,975,149 ICU admissions, 303,389 patients had sepsis. In-hospital mortality was 28

International clinical practice guidelines addressing corticosteroid treatment for patients hospitalised with non-viral community-acquired pneumonia (CAP) are inconsistent. We conducted a systematic review of randomized controlled trials (RCTs) evaluating the use of corticosteroids in hospitalised adult patients with suspected or probable CAP. We performed random effects pairwise, Bayesian, and dose–response meta-analyses using the restricted maximum likelihood (REML) heterogeneity estimator. We assessed certainty of evidence using GRADE methodology. We identified 30 eligible RCTs, including a total of 7519 patients. The prednisone-equivalent doses ranged between 29 mg/day and 100 mg/day. Corticosteroids probably reduced short-term (28–30 days) mortality (RR 0.82 [95

Sepsis is a syndrome of life-threatening organ dysfunction that results from dysregulated host response to infection, with septic shock defined as persistent hypotension despite fluid resuscitation, a serum lactate > 2 mmol/L and the need for a vasopressor infusion to maintain a mean arterial pressure of at least 65 mmHg. Approximately, 49 million cases of sepsis are recorded worldwide annually, with 11 million sepsis-related deaths, the majority occurring in patients with septic shock. A substantial proportion of survivors suffer from moderate to severe functional limitations including physical, cognitive and psychological disability, exacerbation of pre-existing chronic conditions and a high incidence of re-hospitalisation in the first 12 months after the initial diagnosis. Optimal management of patients with septic shock requires prompt and reliable recognition of patients with sepsis who require additional haemodynamic support. Initially, patients will need judicious intravenous fluids and consideration of the need for vasopressors such as norepinephrine. Administration of appropriate antibiotics and consideration for control of the source of infection are also required. In the optimisation phase, depending on patients’ comorbidities and response to therapy, the balance of fluid therapy, vasopressors and potentially the addition of an inotropic agent will need to be adjusted, based on clinical findings and haemodynamic and biochemical parameters. For those patients who do not respond to initial therapy, more intensive monitoring may be required with consideration of adjunctive therapies such as corticosteroids, vasopressin, angiotensin II or other rescue therapies to achieve cardiovascular stability. Once stability has been achieved, clinicians need to consider strategies to ameliorate the potential long-term effects on survivors, while keeping in mind the perspective and experience of their patients.

BACKGROUND:The international multi-center randomized controlled STEPCARE-trial will investigate optimal management of sedation, temperature, and mean arterial pressure (MAP) during intensive care in out-of-hospital cardiac arrest (OHCA) patients due to various etiologies. The primary outcome is mortality at 6 months. This protocol describes an extended follow-up sub-study of the STEPCARE-trial with the main objective to provide detailed long-term outcomes for survivors and caregivers. It will focus on potential neuroprotection and improved recovery for different targets of sedation, temperature, and MAP management at 6 and 12 months post-OHCA. METHODS:All survivors and one caregiver per survivor at selected STEPCARE sites will be invited to participate. Randomization is stratified by site. This sub-study extends the main STEPCARE follow-up at 6 months by undertaking detailed assessments, face-to-face meetings, inclusion of a caregiver, and repeating the assessments at 12 months. Our main outcome for survivors is cognitive function measured by the Montreal Cognitive Assessment, and for caregivers, the caregiver burden measured by the Zarit Burden Interview. Additional outcomes include symptoms of anxiety, depression, post-traumatic stress disorder, fatigue, physical function, life satisfaction, and life impact (disability), assessed by psychometrically robust measures. The estimated sample size is 600. Efforts to improve interrater reliability and decrease missing data are integral to the study design. CONCLUSION:These detailed long-term outcomes will explore the possible benefits or risks of fever, sedation, and blood pressure management in post-OHCA survivors. Additionally, this study will explore survivorship after cardiac arrest from various perspectives, including different causes of arrest. CLINICALTRIALS:gov: NCT0207942.

OBJECTIVES:Randomized clinical trials informing clinical practice (e.g., like large, pragmatic, and late-phase trials) should ideally mostly use harmonized outcomes that are important to patients, family members, clinicians, and researchers. Core outcome sets for specific subsets of ICU patients exist, for example, respiratory failure, delirium, and COVID-19, but not for ICU patients in general. Accordingly, we aimed to develop a core outcome set for adult general ICU patients. DESIGN:We developed a core outcome set in Denmark following the Core Outcome Measures in Effectiveness Trials Handbook. We used a modified Delphi consensus process with multiple methods design, including literature review, survey, semi-structured interviews, and discussions with initially five Danish research panels. The core outcome set was internationally validated and revised based on feedback from research panels in all countries. SETTING:There were five Danish research panels and 17 panels in 13 other countries. Interviews and the three-round Delphi survey was conducted in Denmark, followed by validation of the core outcome set across 14 countries in Europe, Australasia, and India. SUBJECTS:Adult ICU survivors, family members, clinicians, and researchers. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We identified 329 published outcomes, of which 50 were included in the 264 participant Delphi survey. In semi-structured interviews of 82, no additional outcomes were added. The first Delphi survey round was completed by 249 (94%) participants, and 202 (82%) contributed to the third and final round. The initial core outcome set comprised six outcomes. International validation involved 217 research panel members and resulted in the final core outcome set comprising survival, free of life support, free of delirium, out of hospital, health-related quality of life, and cognitive function. CONCLUSIONS:We developed and internationally validated a core outcome set with six core outcomes to be used in research, specifically clinical trials involving adult general ICU patients.

This study assessed the accuracy of three International Classification of Diseases (ICD) codes methods derived from Global Burden of Disease (GBD) sepsis study (modified GBD method) in identifying sepsis, compared to the Angus method. Sources of errors in these methods were also reported. Prospective multicentre, observational, study. Emergency Department patients aged ≥ 16 years with high sepsis risk from nine hospitals in NSW, Australia were screened for clinical sepsis using Sepsis 3 criteria and coded as having sepsis or not using the modified GBD and Angus methods. The three modified GBD methods were: Explicit—sepsis-specific ICD code recorded; Implicit—sepsis-specific code or infection as primary ICD code plus organ dysfunction code; Implicit plus—as for Implicit but infection as primary or secondary ICD code. Agreement between clinical sepsis and ICD coding methods was assessed using Cronbach alpha (α). For false positive cases (ICD-coded sepsis but not clinically diagnosed), the ICD codes leading to those errors were documented. For false negatives (clinically diagnosed sepsis but ICD-coded), uncoded sources of infection and organ dysfunction were documented. Of 6869 screened patients, 450 (median age 72.4 years, 48.9

To determine whether there is an interaction between baseline serum chloride concentration and pH and treatment effects in Intensive Care Unit (ICU) patients receiving intravenous fluid therapy with balanced solution versus 0.9

Background:There are theoretical reasons why beta-lactam antibiotics may be more effective in treating severe infections if administered by continuous infusion, rather than short intermittent infusions. The Beta-Lactam Infusion Group (BLING) III trial was a multinational randomised clinical trial (RCT) which tested this hypothesis in participants with sepsis who were cared for in an intensive care unit (ICU). The United Kingdom (UK) findings are reported here. Methods:The global trial was an open-label RCT conducted in the UK, Australia, New Zealand, Belgium, France, Sweden and Malaysia. Participants were critically ill adults being treated with meropenem or piperacillin/tazobactam due to a confirmed or presumed infection. Participants were randomised to receive the antibiotic by either continuous infusion or short intermittent infusion at equivalent daily doses as selected by the treating team. The primary outcome was 90-day all-cause mortality; secondary outcomes included clinical cure up to 14 days after randomisation, new infection and acquisition of resistant organisms, ICU and in hospital mortality. Results:Overall, 7202 participants were randomised, with 2900 from the UK. The UK cohort had very similar baseline characteristics and outcomes to the global trial. For continuous versus intermittent infusion, the global trial showed 24.9% versus 26.8% participants had died by 90 days (odds ratio 0.91, 95% CI: 0.81-1.01, p = 0.08); and in the UK 26.7% versus 29.3% participants had died (odds ratio 0.88, 95% CI: 0.75-1.04, p = 0.13). Although not statistically significant, all outcomes showed point estimates in favour of continuous infusion. Conclusions:The findings in the UK cohort are consistent with the conclusions drawn from the global BLING III trial. It seems reasonable to conclude the finding are applicable to the UK.