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The most effective timing for renal-replacement therapy in critically ill patients is unclear. In this randomized trial, patients with acute kidney injury who were assigned to an accelerated strategy did not have a lower risk of death at 90 days than those assigned to a standard strategy.

Background Hypotension following out-of-hospital cardiac arrest (OHCA) may cause secondary brain injury and increase mortality rates. Current guidelines recommend avoiding hypotension. However, the optimal blood pressure following OHCA is unknown. We hypothesised that exposure to hypotension and hypertension in the first 24 h in ICU would be associated with mortality following OHCA. Methods We conducted a retrospective analysis of OHCA patients included in the Intensive Care National Audit and Research Centre Case Mix Programme from 1 January 2010 to 31 December 2019. Restricted cubic splines were created following adjustment for important prognostic variables. We report the adjusted odds ratio for associations between lowest and highest mean arterial pressure (MAP) and systolic blood pressure (SBP) in the first 24 h of ICU care and hospital mortality. Results A total of 32,349 patients were included in the analysis. Hospital mortality was 56.2%. The median lowest and highest MAP and SBP were similar in survivors and non-survivors. Both hypotension and hypertension were associated with increased mortality. Patients who had a lowest recorded MAP in the range 60–63 mmHg had the lowest associated mortality. Patients who had a highest recorded MAP in the range 95–104 mmHg had the lowest associated mortality. The association between SBP and mortality followed a similar pattern to MAP. Conclusions We found an association between hypotension and hypertension in the first 24 h in ICU and mortality following OHCA. The inability to distinguish between the median blood pressure of survivors and non-survivors indicates the need for research into individualised blood pressure targets for survivors following OHCA. Graphical Abstract

In a large, blinded, randomized trial involving critically ill adults, no significant difference in 90-day mortality was noted between those who received red cells stored for a mean of 11.8 days and those who received red cells stored for a mean of 22.4 days.

Erythropoietin might have neurocytoprotective effects. In this trial, we studied its effect on neurological recovery, mortality, and venous thrombotic events in patients with traumatic brain injury. Erythropoietin in Traumatic Brain Injury (EPO-TBI) was a double-blind, placebo-controlled trial undertaken in 29 centres (all university-affiliated teaching hospitals) in seven countries (Australia, New Zealand, France, Germany, Finland, Ireland, and Saudi Arabia). Within 24 h of brain injury, 606 patients were randomly assigned by a concealed web-based computer-generated randomisation schedule to erythropoietin (40 000 units subcutaneously) or placebo (0·9% sodium chloride subcutaneously) once per week for a maximum of three doses. Randomisation was stratified by severity of traumatic brain injury (moderate vs severe) and participating site. With the exception of designated site pharmacists, the site dosing nurses at all sites, and the pharmacists at the central pharmacy in France, all study personnel, patients, and patients' relatives were masked to treatment assignment. The primary outcome, assessed at 6 months by modified intention-to-treat analysis, was improvement in the patients' neurological status, summarised as a reduction in the proportion of patients with an Extended Glasgow Outcome Scale (GOS-E) of 1–4 (death, vegetative state, and severe disability). Two equally spaced preplanned interim analyses were done (after 202 and 404 participants were enrolled). This study is registered with ClinicalTrials.gov, number NCT00987454. Between May 3, 2010, and Nov 1, 2014, 606 patients were enrolled and randomly assigned to erythropoietin (n=308) or placebo (n=298). Ten of these patients (six in the erythropoietin group and four in the placebo group) were lost to follow up at 6 months; therefore, data for the primary outcome analysis was available for 596 patients (302 in the erythropoietin group and 294 in the placebo group). Compared with placebo, erythropoietin did not reduce the proportion of patients with a GOS-E level of 1–4 (134 [44%] of 302 patients in the erythropoietin group vs 132 [45%] of 294 in the placebo group; relative risk [RR] 0·99 [95% CI 0·83–1·18], p=0·90). In terms of safety, erythropoietin did not significantly affect 6-month mortality versus placebo (32 [11%] of 305 patients had died at 6 months in the erythropoietin group vs 46 [16%] of 297 [16%] in the placebo group; RR 0·68 [95% CI 0·44–1·03], p=0·07) or increase the occurrence of deep venous thrombosis of the lower limbs (48 [16%] of 305 vs 54 [18%] of 298; RR 0·87 [95% CI 0·61–1·24], p=0·44). Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1–4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain. The National Health and Medical Research Council and the Transport Accident Commission.

The purpose of this work was to review and synthesise the evidence on the comparative effectiveness of neutralising monoclonal antibody (nMAB) therapies in individuals exposed to or infected with SARS-CoV-2 and at high risk of developing severe COVID-19. Outcomes of interest were mortality, healthcare utilisation, and safety. A rapid systematic review was undertaken to identify and synthesise relevant RCT evidence using a Bayesian Network Meta-Analysis. Relative treatment effects for individual nMABs (compared with placebo and one another) were estimated. Pooled effects for the nMAB class compared with placebo were estimated. Relative effects were combined with baseline natural history models to predict the expected risk reductions per 1000 patients treated. Eight articles investigating four nMABs (bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab) were identified. All four therapies were associated with a statistically significant reduction in hospitalisation (70–80% reduction in relative risk; absolute reduction of 35–40 hospitalisations per 1000 patients). For mortality, ICU admission, and invasive ventilation, the risk was lower for all nMABs compared with placebo with moderate to high uncertainty due to small event numbers. Rates of serious AEs and infusion reactions were comparable between nMABs and placebo. Pairwise comparisons between nMABs were typically uncertain, with broadly comparable efficacy. In conclusion, nMABs are effective at reducing hospitalisation among infected individuals at high-risk of severe COVID-19, and are likely to reduce mortality, ICU admission, and invasive ventilation rates; the effect on these latter outcomes is more uncertain. Widespread vaccination and the emergence of nMAB-resistant variants make the generalisability of these results to current patient populations difficult.

In this study, a consortium of intensive care units (ICUs) in Australia and New Zealand reported their experience with admissions associated with infection with the 2009 H1N1 virus. The overall rate of ICU admission was estimated to be 28.7 per million persons, approximately 15 times that in previous years. During the period of peak transmission in communities, the ICU bed-occupancy rate ranged from 8.9 to 19.0%. A consortium of ICUs in Australia and New Zealand report their experience with admissions associated with infection with the 2009 H1N1 virus. Infection with the 2009 pandemic influenza A (H1N1) virus emerged in Mexico toward the end of the 2008–2009 influenza season in the Northern Hemisphere. As of September 6, 2009, the World Health Organization had reported over 277,607 laboratory-confirmed cases of 2009 H1N1 influenza, with at least 3205 deaths. 1 From June through August 2009, Australia and New Zealand experienced the combined effect of the pandemic and winter in the Southern Hemisphere. The reported incidence of infection with the 2009 H1N1 virus during winter in Australia and New Zealand was 8 times that reported for the same period in the United States. . . .

Randomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities. This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations. We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful.

Background Obtaining informed consent can be challenging in emergency and critical care research due to the acute and severe nature of the patient’s condition. However, such research is urgently needed to inform practice and optimise patient outcomes. While alternative consent approaches have been commonly used, opinions may vary, particularly among diverse and underserved patient groups and in the context of the recent COVID-19 pandemic. The objective of this review was to assess views of alternative consent methods in emergency and critical care research. Methods We conducted a rapid systematic review to understand diverse opinions of alternative consent models used in emergency and critical care research with searches of MEDLINE, EMBASE, PsycINFO, Web of Science and CENTRAL carried out to July 31, 2024. We included quantitative and qualitative studies and summarised findings using narrative synthesis. We specifically investigated underserved groups and consent in the pandemic setting. Results From 9974 citations, we screened 289 full-text articles, and included 145 eligible studies from 26 countries. Consent methods included prospective informed consent, deferred consent, surrogate decision maker consent, healthcare professional consent and waived consent. Groups represented included previous trial participants, relatives of trial participants, patients, members of the general public, healthcare providers, researchers, site staff, and research ethics committees. It was recognised that prospective informed consent from the patient is not possible in all scenarios. In general, alternative consent models were acceptable, with emphasis on the inclusion of the patient and relatives in the decision-making process whenever possible. Acceptability of alternative consent models was influenced by previous research participation, experience of critical or emergency illness, perceived risk of participation, and invasiveness of the intervention. Study staff highlighted potential limitations of some alternative consent models, such as unavailability of relatives. Pandemic studies showed an increased need for alternative consent methods, and greater preparedness and engagement with ethics committees to facilitate implementation. Sub-analysis evaluating the views of underserved groups did not show consensus, and accommodations were largely not reported. Conclusion Alternative consent models used for emergency, critical care and pandemic research including deferred consent, relative/surrogate decision maker consent, and physician consent were generally acceptable. Trial registration PROSPERO CRD42023408305 (April 19, 2023).