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The noise produced by oscillatory movements of secretions in oropharynx, hypopharynx and trachea during inspiration and expiration in unconscious terminal patients is often described as 'the death rattle'. The reported incidence of death rattle in terminally ill patients varied between six and 92%. It is most commonly reported in patients dying from pulmonary malignancies, primary brain tumours or brain metastases, and predicts death within 48 hours in 75% of the patients. Clinical studies demonstrate that hyoscine hydrobromide is effective at improving symptoms. After withdrawal of artificial ventilation on the intensive care unit, excessive respiratory secretions resulting in rattling breathing, during the last hours of life, is not uncommon. Physicians and nurses experience considerable difficulties and frustrations in treating the death rattle. The distressing experience and negative influence in the bereavement process indicates an ethical demand to treat this symptom from the perspective of others merely than that of the patient. This article provides practical and ethical considerations in the management of this near-death symptom. The fact that relatives were relieved in almost all cases, in which a positive effect was obtained, makes treatment in anticipation of death rattle an ethical demand. In practice, injectable scopolamine is the reference drug for symptomatic treatment of death rattle. [ABSTRACT FROM AUTHOR]

Objective: To describe a case of deliberate termination of life (euthanasia) in intensive care.Design: Case report and review of the literature.Patient: A 56-yr-old man experienced a bilateral hemorrhage in the pontine structures and the medulla oblongata, resulting in a locked-in syndrome. The patient was taught to communicate by eye opening. On day 10 after the hemorrhage, he was informed about his diagnosis and prognosis. He was asked if he wished prolonged care, but this was refused. He was offered withdrawal of fluids and ventilation under sedation or deliberate termination of life (euthanasia). He chose euthanasia.Interventions: The patient was admitted to the intensive care unit and was mechanically ventilated. The patient was euthanized 33 days after the diagnosis by the injection of 30 mg of midazolam, discontinuation of ventilation, and injection of 1.4 g of thiopentone.Main Results: The tetraplegic aphonic patient was declared competent. His refusal of prolonged care was taken seriously. The requirements of due care according to the Dutch euthanasia act were met in this case.Conclusions: Euthanasia is an option in terminal illness in the Netherlands, but it is very rarely performed in intensive care. This case demonstrates that euthanasia is possible in a conscious patient who is unable to speak or write and who is mechanically ventilated. [ABSTRACT FROM AUTHOR]

Introduction: Severely injured patients are often incapacitated to provide informed consent for clinical studies. Deferred consent could facilitate unbiased enrollment in studies involving these patients. Little is known about how healthcare professionals (HCPs) perceive deferred consent and how this impacts patient enrollment. The aim of this study was to identify factors that could influence HCPs decision-making during recruitment of patients for interventional studies in (pre)hospital emergency trauma research., Methods: This was a qualitative study in which physicians and nurses working in prehospital or in-hospital care were interviewed using a semi-structured interview guide. Interviews were audio-recorded, transcribed, and analyzed according to thematic analysis as described by Braun and Clarke., Results: Ten semi-structured interviews were conducted with six physicians and four nurses. Eight themes were identified as being relevant consent related factors influencing HCPs' decision-making during patient recruitment in studies using deferred consent: (1) HCPs' lack of knowledge; (2) Patients' and proxies' inability to be informed; (3) Practical (im)possibilities for informed consent; (4) Nature of intervention; (5) HCPs' personal beliefs; (6) Importance of emergency care research; (7) HCPs' trust in legal base; and (8) Communication and collaboration., Conclusions: Eight consent-related factors influencing HCPs' decision making were identified. Insufficient knowledge about consent procedures among HCPs leads to significant negative attitudes towards deferred consent., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Treatment-limiting decisions (TLDs) can be inevitable severe traumatic brain injury (s-TBI) patients, but data on their use remain scarce., Research Question: To investigate the prevalence, timing and considerations of TLDs in s-TBI patients., Material and Methods: s-TBI patients between 2008 and 2017 were analysed retrospecively. Patient data, timing, location, involvement of proxies, and reasons for TLDs were collected. Baseline characteristics and in-hospital outcomes were compared between s-TBI patients with and without TLDs., Results: TLDs were reported in 117 of 270 s-TBI patients (43.3%) and 95.9% of deaths after s-TBI were preceded by a TLD. The majority of TLDs (68.4%) were categorized as withdrawal of therapy, of which withdrawal of organ-support in 64.1%. Neurosurgical intervention was withheld in 29.9%. The median time from admission to TLD was 2 days [IQR, 0-8] and 50.4% of TLDs were made within 3 days of admission. The main reason for a TLD was that the patients were perceived as unsalvageable (66.7%). Nearly all decisions were made multidisciplinary (99.1%) with proxies involvement (75.2%). The predicted mortality (CRASH-score) between patients with and without TLDs were 72.6 vs. 70.6%. The percentage of TLDs in s-TBI patients increased from 20.0% in 2008 to 42.9% in 2012 and 64.3% in 2017., Discussion and Conclusion: TLDs occurred in almost half of s-TBI patients and were instituted more frequently over time. Half of TLDs were made within 3 days of admission in spite of baseline prognosis between groups being similar. Future research should address whether prognostic nihilism contributes to self-fulfilling prophecies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wilco Peul reports a relationship with The 10.13039/501100000780European Union seventh Framework Program (grant 602,150) for Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) that includes: funding grants. Wilco Peul reports a relationship with 10.13039/501100008358Hersenstichting Nederland (Dutch Brain Foundation) that includes: funding grants. Thomas van Essen reports a relationship with Niels Stensen Fellowship. that includes: funding grants., (© 2024 The Authors.)

Background: The negative impact on long-term health-related outcomes among relatives of critically ill patients in the intensive care unit (ICU) has been well described. High-quality ICU specialized follow-up care, which is easily accessible with digital innovation and which is designed by and with relevant stakeholders (i.e., ICU patients' relatives and nurses), should be considered to reduce these impairments in the psychological and social domains., Aim: The programme's aim is to develop and test an e-health intervention in a follow-up service to support ICU patients' relatives. Here, the protocol for the overall study programme will be described., Study Design: The overall study comprises a mixed-methods, multicentre research design with qualitative and quantitative study parts. The study population is ICU patients' adult relatives and ICU nurses. The main outcomes are the experiences of these stakeholders with the newly developed e-health intervention. There will be no predefined selection based on age, gender, and level of education to maximize diversity throughout the study programme. After the participants provide informed consent, data will be gathered through focus groups (n = 5) among relatives and individual interviews (n = 20) among nurses exploring the needs and priorities of a digital follow-up service. The findings will be explored further for priority considerations among members of the patient/relative organization (aiming n = 150), which will serve as a basis for digital prototypes of the e-health intervention. Assessment of the intervention will be followed during an iterative process with investigator-developed questionnaires. Finally, symptoms of anxiety and depression will be measured with the 14-item Dutch version of the 'Hospital Anxiety and Depression Scale', and symptoms of posttraumatic stress will be measured with the 21-item Dutch version of the 'Impact of Events Scale-Revised' to indicate the effectiveness of digital support among ICU patients' relatives., Relevance to Clinical Practice: The e-health intervention to be developed during this research programme can possibly bridge the gap in integrated ICU follow-up care by providing relevant information, self-monitoring and stimulating self-care among ICU patients' relatives., (© 2023 The Authors. Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

In a thought-provoking article - or how she herself named it, 'a thought experiment' - the philosopher-medical ethicist Anna Smajdor analyzed in this journal the idea of whole-body gestational donation (WBGD) in brain-dead female patients, as an alternative means of gestation for prospective women who cannot or prefer not to become pregnant themselves. We have serious legal, economical, medical and ethical concerns about this proposal. First, consent for eight months of ICU treatment can never be assumed to be derived from consent for post-mortem organ donation; these two are of an incomparable and entirely different medical and ethical order. Moreover, the brain-dead woman is very likely to be medically unfit for high-tech surrogacy and the brain-dead state poses a high risk for deficient embryo/fetal development. Second, from a scarcity perspective, occupying an ICU bed for eight months appears to be unjust. The costs for eight months of ICU treatment are far too high compared to the costs of surrogacy for a living, selected, and healthy woman. Neither insurance companies nor prospective parents will want to pay these exceptionally high costs for a dead woman if a living surrogate mother can be hired for a considerably lower amount. Third, there is an increased risk for harm of the child to be in WBGD. And finally, WBGD risks violating the brain-dead woman's dignity and harming the interests of her loved ones. In short, there is simply no need for brain-dead women as surrogates., (© 2023. The Author(s).)

Increased intracranial pressure (ICP) is one of the most important modifiable and immediate threats to critically ill patients suffering from traumatic brain injury (TBI). Two hyperosmolar agents (HOAs), mannitol and hypertonic saline (HTS), are routinely used in clinical practice to treat increased ICP. We aimed to assess whether a preference for mannitol, HTS, or their combined use translated into differences in outcome. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study is a prospective multi-center cohort study. For this study, patients with TBI, admitted to the intensive care unit (ICU), treated with mannitol and/or HTS, and aged ≥16 years were included. Patients and centers were differentiated based on treatment preference with mannitol and/or HTS based on structured, data-driven criteria such as first administered HOA in the ICU. We assessed influence of center and patient characteristics in the choice of agent using adjusted multi-variate models. Further, we assessed the influence of HOA preference on outcome using adjusted ordinal and logistic regression models, and instrumental variable analyses. In total, 2056 patients were assessed. Of these, 502 (24%) patients received mannitol and/or HTS in the ICU. The first received HOA was HTS for 287 (57%) patients, mannitol for 149 (30%) patients, or both mannitol and HTS on the same day for 66 (13%) patients. Two unreactive pupils were more common in patients receiving both (13, 21%), compared with patients receiving HTS (40, 14%) or mannitol (22, 16%). Center, rather than patient characteristics, was independently associated with the preferred choice of HOA ( p -value <0.05). ICU mortality and 6-month outcome were similar between patients preferably treated with mannitol compared with HTS (odds ratio [OR] = 1.0, confidence interval [CI] = 0.4-2.2; OR = 0.9, CI = 0.5-1.6, respectively). Patients who received both also had a similar ICU mortality and 6-month outcome compared with patients receiving HTS (OR = 1.8, CI = 0.7-5.0; OR = 0.6, CI = 0.3-1.7, respectively). We found between-center variability regarding HOA preference. Moreover, we found that center is a more important driver of the choice of HOA than patient characteristics. However, our study indicates that this variability is an acceptable practice given absence of differences in outcomes associated with a specific HOA.

Most historical articles have named Johann Jacob Wepfer as the first author to describe a case of chronic subdural hematoma (CSDH). However, the question arises whether these cases truly describe CSDH. Two other names that appear in literature as the first authors to describe a case of CSDH are Thomas Willis and Giovanni Battista Morgagni. In our attempt to find the first description of a CSDH, we studied the original cases described by Willis, Wepfer, and Morgagni. The cases described by Willis and Wepfer cannot be interpreted as cases of CSDH. Willis's university scholar is more likely to have experienced venous infarction with an underlying septic thrombosis than a CSDH. Wepfer's cases seem to represent an intraparenchymal hemorrhage from the rupture of a branch or branches of the internal carotid artery, a subarachnoid hemorrhage complicated with hydrocephalus, and a hydrocephalus in tuberculous meningitis. Morgagni's case described in Letter III, Article 20 in the Sedibus in 1761 seems to be the first accurate historical description of a CSDH, and we believe it should be cited as such. With these early cases of alleged CSDH, we emphasize the importance of misquotation and blind copying of references, which are important citation errors.

Competing Interests: Declaration of interests No funding was provided specifically for this Commission paper; however, most authors are involved in the International Initiative for Traumatic Brain Injury Research (InTBIR) as a scientific participant or an investigator. This Commission would not have been possible without the indirect facilitation provided by the InTBIR network. AIRM declares consulting fees from PresSura Neuro, Integra Life Sciences, and NeuroTrauma Sciences. DKM reports research support, and educational and consulting fees from Lantmannen AB, GlaxoSmithKline, Calico, PresSura Neuro, NeuroTrauma Sciences, and Integra Neurosciences. GTM declares grants from the US National Institutes of Health-National Institute of Neurological Disorders and Stroke (grant U01NS086090), the US Department of Defense (grant W81XWH-14-2-0176, grant W81XWH-18-2-0042, and contract W81XWH-15-9-0001). MC reports licensing fees for ICM+ software from Cambridge Enterprise and was an honorary (unpaid) director for Medicam. PS reports licensing fees for ICM+ software from Cambridge Enterprise. MBS has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, Boehringer Ingelheim, Bionomics, BioXcel Therapeutics, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, and Roche/Genentech. MBS also has stock options in Oxeia Biopharmaceuticals and EpiVario and is paid for editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). KKWW holds stock options in Gryphon Bio. All other authors declare no competing interests.

Introduction: A decrease in short-term mortality of critically ill cancer patients with an unplanned intensive care unit (ICU) admission has been described. Few studies describe a change over time of 1-year mortality. Therefore, we examined the 1-year mortality of cancer patients (hematological or solid) with an unplanned ICU admission and we described whether the mortality changed over time. Methods: We used the National Intensive Care Evaluation (NICE) registry and extracted all patients with an unplanned ICU admission in the Netherlands between 2008 and 2017. The primary outcome was 1-year mortality, analyzed with a mixed-effects Cox proportional hazard regression. We compared the 1-year mortality of cancer patients to that of patients without cancer. Furthermore, we examined changes in mortality over the study period. Results: We included 470,305 patients: 10,401 with hematological cancer, 35,920 with solid cancer, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% respectively ( P < .01). Approximately 30% of the cancer patients surviving their hospital admission died within 1 year, this was 12% in patients without cancer. In hematological patients, 1-year mortality decreased between 2008 and 2011, after which it stabilized. In solid cancer patients, inspection showed neither an increasing nor decreasing trend over the inclusion period. For patients without cancer, 1-year mortality decreased between 2008 and 2013, after which it stabilized. A clear decrease in hospital mortality was seen within all three groups. Conclusion: The 1-year mortality of cancer patients with an unplanned ICU admission (hematological and solid) was higher than that of patients without cancer. About one-third of the cancer patients surviving their hospital admission died within 1 year after ICU admission. We found a decrease in 1-year mortality until 2011 in hematology patients and no decrease in solid cancer patients. Our results suggest that for many cancer patients, an unplanned ICU admission is still a way to recover from critical illness, and it does not necessarily lead to success in long-term survival. The underlying type of malignancy is an important factor for long-term outcomes in patients recovering from critical illness.

Background: In some acute care trials, immediate informed consent is not possible, but deferred consent is often considered problematic. We investigated the opinions of patients, proxies, and physicians about deferred consent in an acute stroke trial to gain insight into its acceptability and effects., Methods: Paper-based surveys were sent to patients who were randomly assigned in the Ultra-early Tranexamic Acid After Subarachnoid Hemorrhage (ULTRA) trial between 2015 and 2018 in two tertiary referral centers and to physicians of centers who agreed or declined to participate. The primary outcome measure was the proportion of respondents who agreed with deferral of consent in the ULTRA trial. Secondary outcomes included respondents' preferred consent procedure for the ULTRA trial, the effect of deferred consent on trust in physicians and scientific research, and the willingness to participate in future research., Results: Eighty-nine of 135 (66%) patients or proxies and 20 of 30 (67%) physicians completed the survey. Of these, 82 of 89 (92%) patients or proxies and 14 of 20 (70%) physicians agreed with deferral of consent in the ULTRA trial. When asked for their preferred consent procedure for the ULTRA trial, 31 of 89 (35%) patients or proxies indicated deferred consent, 15 of 89 (17%) preferred immediate informed consent, and 32 of 89 (36%) had no preference. None of the patients' or proxies' trust in physicians or scientific research had decreased because of the deferred consent procedure. Willingness to participate in future studies remained the same or increased in 84 of 89 (94%) patients or proxies., Conclusions: A large majority of the surveyed patients and proxies and a somewhat smaller majority of the surveyed physicians agreed with deferred consent in the ULTRA trial. Deferred consent may enable acute care trials in an acceptable manner without decreasing trust in medicine. Future research should investigate factors facilitating the responsible use of deferred consent, such as in-depth interviews, to study the minority of participants who agreed with deferred consent but still preferred immediate informed consent., (© 2021. The Author(s).)

Background: The rapidly increasing number of elderly (≥ 65 years old) with TBI is accompanied by substantial medical and economic consequences. An ASDH is the most common injury in elderly with TBI and the surgical versus conservative treatment of this patient group remains an important clinical dilemma. Current BTF guidelines are not based on high-quality evidence and compliance is low, allowing for large international treatment variation. The RESET-ASDH trial is an international multicenter RCT on the (cost-)effectiveness of early neurosurgical hematoma evacuation versus initial conservative treatment in elderly with a t-ASDH METHODS: In total, 300 patients will be recruited from 17 Belgian and Dutch trauma centers. Patients ≥ 65 years with at first presentation a GCS ≥ 9 and a t-ASDH > 10 mm or a t-ASDH < 10 mm and a midline shift > 5 mm, or a GCS < 9 with a traumatic ASDH < 10 mm and a midline shift < 5 mm without extracranial explanation for the comatose state, for whom clinical equipoise exists will be randomized to early surgical hematoma evacuation or initial conservative management with the possibility of delayed secondary surgery. When possible, patients or their legal representatives will be asked for consent before inclusion. When obtaining patient or proxy consent is impossible within the therapeutic time window, patients are enrolled using the deferred consent procedure. Medical-ethical approval was obtained in the Netherlands and Belgium. The choice of neurosurgical techniques will be left to the discretion of the neurosurgeon. Patients will be analyzed according to an intention-to-treat design. The primary endpoint will be functional outcome on the GOS-E after 1 year. Patient recruitment starts in 2022 with the exact timing depending on the current COVID-19 crisis and is expected to end in 2024., Discussion: The study results will be implemented after publication and presented on international conferences. Depending on the trial results, the current Brain Trauma Foundation guidelines will either be substantiated by high-quality evidence or will have to be altered., Trial Registration: Nederlands Trial Register (NTR), Trial NL9012 ., Clinicaltrials: gov, Trial NCT04648436 ., (© 2022. The Author(s).)

Background: Expectation of long-term outcome is an important factor in treatment decision-making after severe traumatic brain injury (sTBI). Conclusive long-term outcome data substantiating these decisions is nowadays lacking. This systematic review aimed to provide an overview of the scientific literature on long-term outcome after sTBI., Methods: A systematic search was conducted using PubMed from 2008 to 2020. Studies were included when reporting long-term outcome ≥ 2 years after sTBI (GCS 3-8 or AIS head score ≥ 4), using standardized outcome measures. Study quality and risk of bias were assessed using the QUIPS tool., Results: Twenty observational studies were included. Studies showed substantial variation in study objectives and study methodology. GOS-E (n = 12) and GOS (n = 8) were the most frequently used outcome measures. Mortality was reported in 46% of patients (range 18-75%). Unfavourable outcome rates ranged from 29 to 100% and full recovery was seen in 21-27% of patients. Most surviving patients reported SF-36 scores lower than the general population., Conclusion: Literature on long-term outcome after sTBI was limited and heterogeneous. Mortality and unfavourable outcome rates were high and persisting sequelae on multiple domains common. Nonetheless, a considerable proportion of survivors achieved favourable outcome. Future studies should incorporate standardized multidimensional and temporal long-term outcome measures to strengthen the evidence-base for acute and subacute decision-making., Highlights: 1. Expectation of long-term outcome is an important factor in treatment decision-making for patients with severe traumatic brain injury (sTBI). 2. Favourable outcome and full recovery after sTBI are possible, but mortality and unfavourable outcome rates are high. 3. sTBI survivors are likely to suffer from a wide range of long-term consequences, underscoring the need for long-term and multi-modality outcome assessment in future studies. 4. The quality of the scientific literature on long-term outcome after sTBI can and should be improved to advance treatment decision-making., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: In patients with severe brain injury, withdrawal of life-sustaining measures (WLSM) is common in intensive care units (ICU). WLSM constitutes a dilemma: instituting WLSM too early could result in death despite the possibility of an acceptable functional outcome, whereas delaying WLSM could unnecessarily burden patients, families, clinicians, and hospital resources. We aimed to describe the occurrence and timing of WLSM, and factors associated with timing of WLSM in European ICUs in patients with traumatic brain injury (TBI)., Methods: The CENTER-TBI Study is a prospective multi-center cohort study. For the current study, patients with traumatic brain injury (TBI) admitted to the ICU and aged 16 or older were included. Occurrence and timing of WLSM were documented. For the analyses, we dichotomized timing of WLSM in early (< 72 h after injury) versus later (≥ 72 h after injury) based on recent guideline recommendations. We assessed factors associated with initiating WLSM early versus later, including geographic region, center, patient, injury, and treatment characteristics with univariable and multivariable (mixed effects) logistic regression., Results: A total of 2022 patients aged 16 or older were admitted to the ICU. ICU mortality was 13% (n = 267). Of these, 229 (86%) patients died after WLSM, and were included in the analyses. The occurrence of WLSM varied between regions ranging from 0% in Eastern Europe to 96% in Northern Europe. In 51% of the patients, WLSM was early. Patients in the early WLSM group had a lower maximum therapy intensity level (TIL) score than patients in the later WLSM group (median of 5 versus 10) The strongest independent variables associated with early WLSM were one unreactive pupil (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.3-12.4) or two unreactive pupils (OR 5.8, CI 2.6-13.1) compared to two reactive pupils, and an Injury Severity Score (ISS) if over 41 (OR per point above 41 = 1.1, CI 1.0-1.1). Timing of WLSM was not significantly associated with region or center., Conclusion: WLSM occurs early in half of the patients, mostly in patients with severe TBI affecting brainstem reflexes who were severely injured. We found no regional or center influences in timing of WLSM. Whether WLSM is always appropriate or may contribute to a self-fulfilling prophecy requires further research and argues for reluctance to institute WLSM early in case of any doubt on prognosis., (© 2021. The Author(s).)

Background: Very few studies assessed the association between Intensive Care Unit (ICU) triage decisions and mortality. The aim of this study was to assess whether an association could be found between 30-day mortality, and ICU admission consultation conditions and triage decisions., Methods: We conducted a retrospective cohort study in two large referral university hospitals in the Netherlands. We identified all adult cancer patients for whom ICU admission was requested from 2016 to 2019. Via a multivariable logistic regression analysis, we assessed the association between 30-day mortality, and ICU admission consultation conditions and triage decisions., Results: Of the 780 cancer patients for whom ICU admission was requested, 332 patients (42.6%) were considered 'too well to benefit' from ICU admission, 382 (49%) patients were immediately admitted to the ICU and 66 patients (8.4%) were considered 'too sick to benefit' according to the consulting intensivist(s). The 30-day mortality in these subgroups was 30.1%, 36.9% and 81.8%, respectively. In the patient group considered 'too well to benefit', 258 patients were never admitted to the ICU and 74 patients (9.5% of the overall study population, 22.3% of the patients 'too well to benefit') were admitted to the ICU after a second ICU admission request (delayed ICU admission). Thirty-day mortality in these groups was 25.6% and 45.9%. After adjustment for confounders, ICU consultations during off-hours (OR 1.61, 95% CI 1.09-2.38, p-value 0.02) and delayed ICU admission (OR 1.83, 95% CI 1.00-3.33, p-value 0.048 compared to "ICU admission") were independently associated with 30-day mortality., Conclusion: The ICU denial rate in our study was high (51%). Sixty percent of the ICU triage decisions in cancer patients were made during off-hours, and 22.3% of the patients initially considered "too well to benefit" from ICU admission were subsequently admitted to the ICU. Both decisions during off-hours and a delayed ICU admission were associated with an increased risk of death at 30 days. Our study suggests that in cancer patients, ICU triage decisions should be discussed during on-hours, and ICU admission policy should be broadened, with a lower admission threshold for critically ill cancer patients., (© 2021. The Author(s).)

Background: Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer., Methods: This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer., Results: Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p < 0.001 and p = 0.62, respectively). In patients with concordant PECs, we found no evidence for a difference in time from admission until death (HR 1.02, 95% CI 0.60-1.72 and HR 0.87, 95% CI 0.49-1.54) and TLDs (HR 0.81, 95% CI 0.33-1.99 and HR 0.70, 95% CI 0.27-1.81) across subgroups. In patients without concordant PECs, we found differences between the time from admission until death (HR 2.23, 95% CI 1.58-3.15 and 1.66, 95% CI 1.28-2.15), without a corresponding increase in time until TLDs (NA, p = 0.3 and 0.7) across subgroups., Conclusions: The absence of a difference in time from admission until TLDs and death in patients with concordant PECs makes bias by ICU clinicians towards cancer patients unlikely. However, the differences between the time from admission until death, without a corresponding increase in time until TLDs, suggest prognostic unawareness, uncertainty or optimism in ICU clinicians who did not provide PECs, more specifically in patients with uncontrolled cancer. This study highlights the need to improve intra- and interdisciplinary ethical reflection and subsequent decision-making at the ICU., (© 2021. The Author(s).)

Introduction: Given clinicians' frequent concerns about unfavourable outcomes, Intensive Care Unit (ICU) triage decisions in acutely ill cancer patients can be difficult, as clinicians may have doubts about the appropriateness of an ICU admission. To aid to this decision making, we studied the survival and performance status of cancer patients 2 years following an unplanned ICU admission., Materials and Methods: This was a retrospective cohort study in a large tertiary referral university hospital in the Netherlands. We categorized all adult patients with an unplanned ICU admission in 2017 into two groups: patients with or without an active malignancy. Descriptive statistics, Pearson's Chi-square tests and the Mann-Whitney U tests were used to evaluate the primary objective 2-year mortality and performance status. A good performance status was defined as ECOG performance status 0 (fully active) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out light work). A multivariable binary logistic regression analysis was used to identify factors associated with 2-year mortality within cancer patients., Results: Of the 1046 unplanned ICU admissions, 125 (12%) patients had cancer. The 2-year mortality in patients with cancer was significantly higher than in patients without cancer (72% and 42.5%, P <0.001). The median performance status at 2 years in cancer patients was 1 (IQR 0-2). Only an ECOG performance status of 2 (OR 8.94; 95% CI 1.21-65.89) was independently associated with 2-year mortality., Conclusions: In our study, the majority of the survivors have a good performance status 2 years after ICU admission. However, at that point, three-quarter of these cancer patients had died, and mortality in cancer patients was significantly higher than in patients without cancer. ICU admission decisions in acutely ill cancer patients should be based on performance status, severity of illness and long-term prognosis, and this should be communicated in the shared decision making. An ICU admission decision should not solely be based on the presence of a malignancy., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Critical care medicine is a natural environment for machine learning approaches to improve outcomes for critically ill patients as admissions to ICUs generate vast amounts of data. However, technical, legal, ethical, and privacy concerns have so far limited the critical care medicine community from making these data readily available. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine have identified ICU patient data sharing as one of the priorities under their Joint Data Science Collaboration. To encourage ICUs worldwide to share their patient data responsibly, we now describe the development and release of Amsterdam University Medical Centers Database (AmsterdamUMCdb), the first freely available critical care database in full compliance with privacy laws from both the United States and Europe, as an example of the feasibility of sharing complex critical care data., Setting: University hospital ICU., Subjects: Data from ICU patients admitted between 2003 and 2016., Interventions: We used a risk-based deidentification strategy to maintain data utility while preserving privacy. In addition, we implemented contractual and governance processes, and a communication strategy. Patient organizations, supporting hospitals, and experts on ethics and privacy audited these processes and the database., Measurements and Main Results: AmsterdamUMCdb contains approximately 1 billion clinical data points from 23,106 admissions of 20,109 patients. The privacy audit concluded that reidentification is not reasonably likely, and AmsterdamUMCdb can therefore be considered as anonymous information, both in the context of the U.S. Health Insurance Portability and Accountability Act and the European General Data Protection Regulation. The ethics audit concluded that responsible data sharing imposes minimal burden, whereas the potential benefit is tremendous., Conclusions: Technical, legal, ethical, and privacy challenges related to responsible data sharing can be addressed using a multidisciplinary approach. A risk-based deidentification strategy, that complies with both U.S. and European privacy regulations, should be the preferred approach to releasing ICU patient data. This supports the shared Society of Critical Care Medicine and European Society of Intensive Care Medicine vision to improve critical care outcomes through scientific inquiry of vast and combined ICU datasets., Competing Interests: Dr. Sijbrands’ institution received funding from European Institute of Innovation and Technology (EIT) Health and Amgen. Drs. Kaplan and Bailey received funding from Society of Critical Care Medicine. Dr. Cecconi received funding from Directed Systems, Edwards Lifesciences, and Cheetah Medical. Dr. Churpek’s institution received funding from an EarlySense research grant; he is supported by National Institutes of Health (NIH) R01 (GM123193), and he has a patent pending for risk stratification algorithm for hospitalized patients (money from royalties from the University of Chicago). Dr. Clermont received funding from the NIH, Department of Defense, National Science Foundation, and NOMA AI. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Treatment limitation decisions (TLDs) on the ICU can be challenging, especially in patients with a malignancy. Up-to-date literature regarding TLDs in critically ill patients with a malignancy admitted to the ICU is scarce. The aim was to compare the incidence of written TLDs between patients with an active malignancy, patients with a malignancy in their medical history (complete remission, CR) and patients without a malignancy admitted unplanned to the ICU., Methods: We conducted a retrospective cohort study in a large university hospital in the Netherlands. We identified all unplanned admissions to the ICU in 2017 and categorized the patients in 3 groups: patients with an active malignancy (study population), with CR and without a malignancy. A TLD was defined as a written instruction not to perform life-saving treatments, such as CPR in case of cardiac arrest. A multivariate binary logistic regression analysis was used to identify whether having a malignancy was associated with TLDs., Results: Of the 1046 unplanned admissions, 125 patients (12%) had an active malignancy and 76 (7.3%) patients had CR. The incidence of written TLDs in these subgroups were 37 (29.6%) and 20 (26.3%). Age (OR 1.03; 95% CI 1.01 -1.04), SOFA score at ICU admission (OR 1.11; 95% CI 1.05 -1.18) and having an active malignancy (OR 1.75; 95% CI 1.04-2.96) compared to no malignancy were independently associated with written TLDs. SOFA scores on the day of the TLD were not significantly different in patients with and without a malignancy., Conclusions: This study shows that the presence of an underlying malignancy is independently associated with written TLDs during ICU stay. Patients with CR were not at risk of more written TLDs. Whether this higher incidence of TLDs in patients with a malignancy is justified, is at least questionable and should be evaluated in future research.

Health-care professionals and researchers have a legal and ethical responsibility to inform patients before carrying out diagnostic tests or treatment interventions as part of a clinical study. Interventional research in emergency situations can involve patients with some degree of acute cognitive impairment, as is regularly the case in traumatic brain injury and ischaemic stroke. These patients or their proxies are often unable to provide informed consent within narrow therapeutic time windows. International regulations and national laws are criticised for being inconclusive or restrictive in providing solutions. Currently accepted consent alternatives are deferred consent, exception from consent, or waiver of consent. However, these alternatives appear under-utilised despite being ethically permissible, socially acceptable, and regulatorily compliant. We anticipate that, when the requirements for medical urgency are properly balanced with legal and ethical conduct, the increased use of these alternatives has the potential to improve the efficiency and quality of future emergency interventional studies in patients with an inability to provide informed consent., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice., Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries., Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N = 426;20%) and deferred consent (N = 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%)., Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: We aimed to study variation regarding specific end-of-life (EoL) practices in the intensive care unit (ICU) in traumatic brain injury (TBI) patients., Materials and Methods: Respondents from 67 hospitals participating in The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study completed several questionnaires on management of TBI patients., Results: In 60% of the centers, ≤50% of all patients with severe neurological damage dying in the ICU, die after withdrawal of life-sustaining measures (LSM). The decision to withhold/withdraw LSM was made following multidisciplinary consensus in every center. Legal representatives/relatives played a role in the decision-making process in 81% of the centers. In 82% of the centers, age played a role in the decision to withhold/withdraw LSM. Furthermore, palliative therapy was initiated in 79% of the centers after the decision to withdraw LSM was made. Last, withholding/withdrawing LSM was, generally, more often considered after more time had passed, in a patient with TBI, who remained in a very poor prognostic condition., Conclusion: We found variation regarding EoL practices in TBI patients. These results provide insight into variability regarding important issues pertaining to EoL practices in TBI, which can be useful to stimulate discussions on EoL practices, comparative effectiveness research, and, ultimately, development of recommendations., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The high occurrence and acute and chronic sequelae of traumatic brain injury (TBI) cause major healthcare and socioeconomic challenges. This study aimed to describe outcome, in-hospital healthcare consumption and in-hospital costs of patients with TBI., Methods: We used data from hospitalised TBI patients that were included in the prospective observational CENTER-TBI study in three Dutch Level I Trauma Centres from 2015 to 2017. Clinical data was completed with data on in-hospital healthcare consumption and costs. TBI severity was classified using the Glasgow Coma Score (GCS). Patient outcome was measured by in-hospital mortality and Glasgow Outcome Score-Extended (GOSE) at 6 months. In-hospital costs were calculated following the Dutch guidelines for cost calculation., Results: A total of 486 TBI patients were included. Mean age was 56.1 ± 22.4 years and mean GCS was 12.7 ± 3.8. Six-month mortality (4.2%-66.7%), unfavourable outcome (GOSE ≤ 4) (14.6%-80.4%) and full recovery (GOSE = 8) (32.5%-5.9%) rates varied from patients with mild TBI (GCS13-15) to very severe TBI (GCS3-5). Length of stay (8 ± 13 days) and in-hospital costs (€11,920) were substantial and increased with higher TBI severity, presence of intracranial abnormalities, extracranial injury and surgical intervention. Costs were primarily driven by admission (66%) and surgery (13%)., Conclusion: In-hospital mortality and unfavourable outcome rates were rather high, but many patients also achieved full recovery. Hospitalised TBI patients show substantial in-hospital healthcare consumption and costs, even in patients with mild TBI. Because these costs are likely to be an underestimation of the actual total costs, more research is required to investigate the actual costs-effectiveness of TBI care.

Background: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency., Methods: We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe., Results: From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75-224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074)., Conclusion: We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.

Purpose: Apart from organizational issues, quality of inter-professional collaboration during ethical decision-making may affect the intention to leave one's job. To determine whether ethical climate is associated with the intention to leave after adjustment for country, ICU and clinicians characteristics., Methods: Perceptions of the ethical climate among clinicians working in 68 adult ICUs in 12 European countries and the US were measured using a self-assessment questionnaire, together with job characteristics and intent to leave as a sub-analysis of the Dispropricus study. The validated ethical decision-making climate questionnaire included seven factors: not avoiding decision-making at end-of-life (EOL), mutual respect within the interdisciplinary team, open interdisciplinary reflection, ethical awareness, self-reflective physician leadership, active decision-making at end-of-life by physicians, and involvement of nurses in EOL. Hierarchical mixed effect models were used to assess associations between these factors, and the intent to leave in clinicians within ICUs, within the different countries., Results: Of 3610 nurses and 1137 physicians providing ICU bedside care, 63.1% and 62.9% participated, respectively. Of 2992 participating clinicians, 782 (26.1%) had intent to leave, of which 27% nurses, 24% junior and 22.7% senior physicians. After adjustment for country, ICU and clinicians characteristics, mutual respect OR 0.77 (95% CI 0.66- 0.90), open interdisciplinary reflection (OR 0.73 [95% CI 0.62-0.86]) and not avoiding EOL decisions (OR 0.87 [95% CI 0.77-0.98]) were all associated with a lower intent to leave., Conclusion: This is the first large multicenter study showing an independent association between clinicians' intent to leave and the quality of the ethical climate in the ICU. Interventions to reduce intent to leave may be most effective when they focus on improving mutual respect, interdisciplinary reflection and active decision-making at EOL.