Obtaining informed consent from patients in intensive care units (ICUs) prior to enrolment in a study is practically and ethically complex. Decisions about the participation of critically ill patients in research often involve substitute decision makers (SDMs), such as a patient\'s relatives or doctors. We explored the perspectives of different stakeholder groups towards these consent procedures.
Mixed-methods study comprising surveys completed by ICU patients, their relatives and healthcare practitioners in 14 English ICUs, followed by qualitative interviews with a subset of survey participants. Empirical bioethics informed the analysis and synthesis of the data. Survey data were analysed using descriptive statistics of Likert responses, and analysis of interview data was informed by thematic reflective approaches.
Analysis included 1409 survey responses (ICU patients n=333, relatives n=488, healthcare practitioners n=588) and 60 interviews (ICU patients n=13, relatives n=30, healthcare practitioners n=17). Most agreed with relatives acting as SDMs based on the perception that relatives often know the patient well enough to reflect their views. While the practice of doctors serving as SDMs was supported by most survey respondents, a quarter (25%) disagreed. Views were more positive at interview and shifted markedly depending on particularities of the study. Participants also wanted reassurance that patient care was prioritised over research recruitment. Findings lend support for adaptations to consent procedures, including collaborative decision-making to correct misunderstandings of the implications of research for that patient. This empirical evidence is used to develop good practice guidance that is to be published separately.
Participants largely supported existing consent procedures, but their perspectives on these consent procedures depended on their perceptions of what the research involved and the safeguards in place. Findings point to the importance of explaining clearly what safeguards are in place to protect the patient.

Spontaneous hyperventilation (SHV) is common in aneurysmal subarachnoid haemorrhage (aSAH). The reduction in arterial partial pressure of carbon dioxide (PaCO2) may change the brain physiology, such as haemodynamics, oxygenation, metabolism and may lead to secondary brain injury. However, how to correct SHV safely and effectively in patients with aSAH has not been well investigated. The aim of this study is to investigate the efficacy and safety of remifentanil dose titration to correct hyperventilation in aSAH, as well as the effect of changes in PaCO2 on cerebral blood flow (CBF).
This study is a prospective, single-centre, physiological study in patients with aSAH. The patients who were mechanically ventilated and who meet with SHV (tachypnoea combined with PaCO2 <35 mm Hg and pH >7.45) will be enrolled. The remifentanil will be titrated to correct the SHV. The predetermined initial dose of remifentanil is 0.02 μg/kg/min and will be maintained for 30 min, and PaCO2 and CBF will be measured. After that, the dose of remifentanil will be sequentially increased to 0.04, 0.06, and 0.08 μg/kg/min, and the measurements for PaCO2 and CBF will be repeated 30 min after each dose adjustment and will be compared with their baseline values.
This study has been approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (KY 2021-006-02) and has been registered at ClinicalTrials.gov. The results of this study will be disseminated through peer-reviewed publications and conference presentations.
NCT04940273.

Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma.
TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO2 of 94%. The liberal group receives 12-15 L O2/min or FiO2=0.6-1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group.
TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal.
EudraCT 2021-000556-19; NCT05146700.

Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19.
In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro® device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T0) then after 24, 48 hours, then on day 5 and 7 (T1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury.
Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals.
NCT05218369; Clinicaltrials.gov.

Rapid sequence intubation (RSI) is an advanced airway technique to perform endotracheal intubation in patients at high risk of aspiration. Although RSI is recognised as a life-saving technique and performed by many physicians in various settings (emergency departments, intensive care units), there is still a lack of consensus on various features of the procedure, most notably patient positioning. Previously, experts have commented on the unique drawbacks and benefits of various positions and studies have been published comparing patient positions and how it can affect endotracheal intubation in the context of RSI. The purpose of this systematic review is to compile the existing evidence to understand and compare how different patient positions can potentially affect the success of RSI.
We will use MEDLINE, EMBASE and the Cochrane Library to source studies from 1946 to 2021 that evaluate the impact of patient positioning on endotracheal intubation in the context of RSI. We will include randomised control trials, case-control studies, prospective/retrospective cohort studies and mannequin simulation studies for consideration in this systematic review. Subsequently, we will generate a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram to display how we selected our final studies for inclusion in the review. Two independent reviewers will complete the study screening, selection and extraction, with a third reviewer available to address any conflicts. The reviewers will extract this data in accordance with our outcomes of interest and display it in a table format to highlight patient-relevant outcomes and difficulty airway management outcomes. We will use the Risk of Bias tool and the Newcastle-Ottawa Scale to assess included studies for bias.
This systematic review does not require ethics approval, as all patient-centred data will be reported from published studies.
CRD42022289773.