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Background Traumatic brain injury (TBI) is associated with an increased risk of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). We aimed to identify predictors and develop models for the prediction of depression and PTSD symptoms at 6 months post-TBI.Methods We analysed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. We used linear regression to model the relationship between predictors and depression (Patient Health Questionnaire-9) and PTSD symptoms (PTSD Checklist for Diagnostic and Statistical Manual for Mental Health Disorders Fifth Edition). Predictors were selected based on Akaike’s Information Criterion. Additionally, we fitted logistic models for the endpoints ‘probable MDD’ and ‘probable PTSD’. We also examined the incremental prognostic value of 2–3 weeks of symptoms.Results We included 2163 adults (76% Glasgow Coma Scale=13–15). Depending on the scoring criteria, 7–18% screened positive for probable MDD and about 10% for probable PTSD. For both outcomes, the selected models included psychiatric history, employment status, sex, injury cause, alcohol intoxication and total injury severity; and for depression symptoms also preinjury health and education. The performance of the models was modest (proportion of explained variance=R2 8% and 7% for depression and PTSD, respectively). Symptoms assessed at 2–3 weeks had a large incremental prognostic value (delta R2=0.25, 95% CI 0.24 to 0.26 for depression symptoms; delta R2=0.30, 95% CI 0.29 to 0.31 for PTSD).Conclusion Preinjury characteristics, such as psychiatric history and unemployment, and injury characteristics, such as violent injury cause, can increase the risk of mental health problems after TBI. The identification of patients at risk should be guided by early screening of mental health.

Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p

IntroductionThe COVID-19 pandemic brought unprecedented challenges to healthcare systems worldwide, particularly the often challenging physical recovery from critical illness. Among the myriad complications faced by these patients, ICU-acquired weakness (ICU-AW) stands out due to its significant impact on patient outcomes. ICU-AW, characterized by skeletal muscle atrophy and weakness, is linked to critical illness polyneuropathy (CIN), myopathy (CIM), and muscle atrophy. Notably, fasciculations, or involuntary muscle twitches, have been observed in patients with ICU-AW, suggesting altered muscle fiber excitability. This study aimed to describe the pattern of fasciculations in critically ill mechanically ventilated COVID-19 patients, assess clinical features associated with fasciculations, and evaluate their prognostic significance.MethodsThe study enrolled patients admitted to the Intensive Care Unit (ICU) with COVID-19 infection requiring intubation and mechanical ventilation. Quadriceps muscles were assessed using muscle skeletal (MSK) ultrasound and Phase Angle (PhA) through multifrequency segmental bioelectrical impedance analysis (MFBIA) every 72 h. PhA is considered a marker of cell membrane integrity and function, with lower PhA values indicating reduced skeletal muscle quality and increased risk of sarcopenia. Fasciculations were classified based on their appearance and frequency.ResultsA total of 35 intubated patients were studied, with 15 patients (43%) displaying scattered fasciculations exclusively in the vastus intermedius muscles. Upon admission, the study found no significant difference in PhA between the fasciculation and non-fasciculation groups. However, PhA decreased significantly from admission to discharge ICU only in the fasciculation group. Patients with fasciculations exhibited higher mortality rates, though not statistically significant, and this correlated with prolonged ICU and hospital lengths of stay.DiscussionThis study is the first to report scattered fasciculations in the vastus intermedius muscles of multiple patients with SARS-CoV-2 infection identified with MSK ultrasound. The findings suggest that the combination of impaired muscle cellular function (PhA) and the onset of fasciculations could serve as a potential biomarker of adverse outcomes and ICU-related muscle dysfunction and muscle loss.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

Abstract Background In patients with aneurysmal subarachnoid hemorrhage suitable for endovascular coiling and neurosurgical clip-reconstruction, the aneurysm treatment decision-making process could be improved by considering heterogeneity of treatment effect and durability of treatment. We aimed to develop and validate a tool to predict individualized treatment benefit of endovascular coiling compared to neurosurgical clip-reconstruction. Methods We used randomized data (International Subarachnoid Aneurysm Trial, n = 2143) to develop models to predict 2-month functional outcome and to predict time-to-rebleed-or-retreatment. We modeled for heterogeneity of treatment effect by adding interaction terms of treatment with prespecified predictors and with baseline risk of the outcome. We predicted outcome with both treatments and calculated absolute treatment benefit. We described the patient characteristics of patients with ≥ 5% point difference in the predicted probability of favorable functional outcome (modified Rankin Score 0–2) and of no rebleed or retreatment within 10 years. Model performance was expressed with the c-statistic and calibration plots. We performed bootstrapping and leave-one-cluster-out cross-validation and pooled cluster-specific c-statistics with random effects meta-analysis. Results The pooled c-statistics were 0.72 (95% CI: 0.69–0.75) for the prediction of 2-month favorable functional outcome and 0.67 (95% CI: 0.63–0.71) for prediction of no rebleed or retreatment within 10 years. We found no significant interaction between predictors and treatment. The average predicted benefit in favorable functional outcome was 6% (95% CI: 3–10%) in favor of coiling, but 11% (95% CI: 9–13%) for no rebleed or retreatment in favor of clip-reconstruction. 134 patients (6%), young and in favorable clinical condition, had negligible functional outcome benefit of coiling but had a ≥ 5% point benefit of clip-reconstruction in terms of durability of treatment. Conclusions We show that young patients in favorable clinical condition and without extensive vasospasm have a negligible benefit in functional outcome of endovascular coiling – compared to neurosurgical clip-reconstruction – while at the same time having a substantially lower probability of retreatment or rebleeding from neurosurgical clip-reconstruction – compared to endovascular coiling. The SHARP prediction tool ( https://sharpmodels.shinyapps.io/sharpmodels/ ) could support and incentivize a multidisciplinary discussion about aneurysm treatment decision-making by providing individualized treatment benefit estimates.

Abstract Acute brain injuries, such as traumatic brain injury and ischemic and hemorragic stroke, are a leading cause of death and disability worldwide. While characterized by clearly distict primary events—vascular damage in strokes and biomechanical damage in traumatic brain injuries—they share common secondary injury mechanisms influencing long-term outcomes. Growing evidence suggests that a more personalized approach to optimize energy substrate delivery to the injured brain and prognosticate towards families could be beneficial. In this context, continuous invasive and/or non-invasive neuromonitoring, together with clinical evaluation and neuroimaging to support strategies that optimize cerebral blood flow and metabolic delivery, as well as approaches to neuroprognostication are gaining interest. Recently, the European Society of Intensive Care Medicine organized a 2-day course focused on a practical case-based clinical approach of acute brain-injured patients in different scenarios and on future perspectives to advance the management of this population. The aim of this manuscript is to update clinicians dealing with acute brain injured patients in the intensive care unit, describing current knowledge and clinical practice based on the insights presented during this course.

Abstract Background Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium. Methods This is an updated systematic review with meta-analysis and trial sequential analysis of randomised clinical trials investigating haloperidol versus placebo or any comparator in critically ill patients with delirium. We adhered to the Cochrane handbook, the PRISMA guidelines and the grading of recommendations assessment, development and evaluation statements. The primary outcomes were all-cause mortality and proportion of patients with one or more serious adverse events or reactions (SAEs/SARs). Secondary outcomes were days alive without delirium or coma, delirium severity, cognitive function and health-related quality of life. Results We included 11 RCTs with 15 comparisons (n = 2200); five were placebo-controlled. The relative risk for mortality with haloperidol versus placebo was 0.89; 96.7% CI 0.77 to 1.03; I 2 = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I 2 = 18% (low-certainty evidence). We found no difference in days alive without delirium or coma (moderate-certainty evidence). We found sparse data for other secondary outcomes and other comparators than placebo. Conclusions Haloperidol may reduce mortality and likely result in little to no change in the occurrence of SAEs/SARs compared with placebo in critically ill patients with delirium. However, the results were not statistically significant and more trial data are needed to provide higher certainty for the effects of haloperidol in these patients. Trial registration: CRD42017081133, date of registration 28 November 2017.

Abstract Background Previous studies show positive effect of music on reducing anxiety, pain, and medication requirement. Anxiety has become a more pertinent issue in the intensive care unit (ICU) since wakefulness is preferred according to recent guidelines. Nevertheless, evidence on the effect of music in ICU patients is scarce. Therefore, we studied the effect of music intervention on anxiety in ICU patients. Methods A multicenter randomized clinical trial was conducted between August 2020 and December 2021 in ICU’s at an academic medical centre and two regional hospitals. Adult critically ill patients were eligible when hemodynamically stable and able to communicate (Richmond agitation-sedation scale (RASS) of at least − 2). Patients in the intervention arm were offered music twice daily during three days for at least 30 min per session. Patients in the control group received standard care. The primary outcome was anxiety level assessed with the visual analogue scale for anxiety [VAS-A; range 0–10] twice daily (morning and evening). Secondary outcomes included; 6-item state-trait anxiety inventory (STAI-6), sleep quality, delirium, heart rate, mean arterial pressure, pain, RASS, medication, ICU length of stay, patients’ memory and experience of ICU stay. Results 94 patients were included in the primary analysis. Music did not significantly reduce anxiety (VAS-A in the intervention group; 2.5 (IQR 1.0–4.5), 1.8 (0.0–3.6), and 2.5 (0.0–3.6) on day 1, 2, and 3 vs. 3.0 (0.6–4.0), 1.5 (0.0–4.0), and 2.0 (0.0–4.0) in the control group; p > 0.92). Overall median daily VAS-A scores ranged from 1.5 to 3.0. Fewer patients required opioids (21 vs. 29, p = 0.03) and sleep quality was lower in the music group on study day one [5.0 (4.0–6.0) vs. 4.5 (3.0–5.0), p = 0.03]. Other outcomes were similar between groups. Conclusions Anxiety levels in this ICU population were low, and music during 3 days did not decrease anxiety. This study indicates that efficacy of music is context and intervention-dependent, given previous evidence showing decreased anxiety. Trial registration Netherlands Trial Register: NL8595, Registered, 1 April 2020. ClinicalTrials.gov ID: NCT04796389, Registered retrospectively, 12 March 2021

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.

Abstract Background Although blood transfusions can be lifesaving in severe hemorrhage, they can also have potential complications. As anemia has also been associated with poor outcomes in critically ill patients, determining an optimal transfusion trigger is a real challenge for clinicians. This is even more important in patients with acute brain injury who were not specifically evaluated in previous large randomized clinical trials. Neurological patients may be particularly sensitive to anemic brain hypoxia because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue oxygen demand. Methods We described herein the methodology of a prospective, multicenter, randomized, pragmatic trial comparing two different strategies for red blood cell transfusion in patients with acute brain injury: a “liberal” strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL and a “restrictive” approach in which the aim is to maintain Hb concentrations greater than 7 g/dL. The target population is patients suffering from traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH). The primary outcome is the unfavorable neurological outcome, evaluated using the extended Glasgow Outcome Scale (eGOS) of 1–5 at 180 days after the initial injury. Secondary outcomes include, among others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the occurrence of extra-cerebral organ dysfunction/failure, and the development of any infection or thromboembolic events. The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome from 50 to 39% between groups (397 patients in each arm). The study was initiated in 2016 in several ICUs and will be completed in December 2022. Discussion This trial will assess the impact of a liberal versus conservative strategy of blood transfusion in a large cohort of critically ill patients with a primary acute brain injury. The results of this trial will help to improve blood product and transfusion use in this specific patient population and will provide additional data in some subgroups of patients at high risk of brain ischemia, such as those with intracranial hypertension or cerebral vasospasm. Trial registration ClinicalTrials.gov NCT02968654.

Abstract Background The prognostic implication of delirium subtypes in critically ill medical and surgical patients is scarcely investigated. The objective was to determine how delirium subtypes are associated with hospital mortality and other clinical outcomes. Methods We performed a secondary analysis on data from a prospective multicenter study aimed at implementation of delirium-oriented measures, conducted between 2012 and 2015 in The Netherlands. We included adults (≥ 18 years) admitted to the medical or surgical intensive care unit (ICU). Exclusion criteria were neurological admission diagnosis, persistent coma or ICU readmissions. Delirium was assessed using the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist, and delirium subtypes (hypoactive, hyperactive, or mixed) were classified using the Richmond Agitation–Sedation Scale. The main outcome was hospital mortality. Secondary outcomes were ICU mortality, ICU length of stay, coma, mechanical ventilation, and use of antipsychotics, sedatives, benzodiazepines and opioids. Results Delirium occurred in 381 (24.4%) of 1564 patients (52.5% hypoactive, 39.1% mixed, 7.3% hyperactive). After case-mix adjustment, patients with mixed delirium had higher hospital mortality than non-delirious patients (OR 3.09, 95%CI 1.79–5.33, p = 0.001), whereas hypoactive patients did not (OR 1.34, 95%CI 0.71–2.55, p = 0.37). Similar results were found for ICU mortality. Compared to non-delirious patients, both subtypes had longer ICU stay, more coma, increased mechanical ventilation frequency and duration, and received more antipsychotics, sedatives, benzodiazepines and opioids. Except for coma and benzodiazepine use, the most unfavourable outcomes were observed in patients with mixed delirium. Conclusions Patients with mixed delirium had the most unfavourable outcomes, including higher mortality, compared with no delirium. These differences argue for distinguishing delirium subtypes in clinical practice and future research. Trial registration ClinicalTrials.gov NCT01952899.

Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p

Abstract Background The optimal hemodynamic targets and management of patients with acute brain injury are not completely elucidated, but recent evidence points to important impact on clinical outcomes. We performed an international survey with the aim to investigate the practice in the hemodynamic targets, monitoring, and management of patients with acute ischemic stroke (AIS), intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Methods This survey was endorsed by the European Society of Intensive Care (ESICM). An electronic questionnaire of 76 questions divided in 4 sections (general information, AIS, ICH, SAH specific questions) was available between January 2022 to March 2022 on the ESICM website. Results One hundred fifty-four healthcare professionals from 36 different countries and at least 98 different institutions answered the survey. Routine echocardiography is routinely performed in 37% of responders in AIS, 34% in ICH and 38% in SAH. Cardiac output monitoring is used in less than 20% of cases by most of the responders. Cardiovascular complications are the main reason for using advanced hemodynamic monitoring, and norepinephrine is the most common drug used to increase arterial blood pressure. Most responders target fluid balance to neutral (62% in AIS, 59% in ICH,44% in SAH), and normal saline is the most common fluid used. Large variability was observed regarding the blood pressure targets. Conclusions Hemodynamic management and treatment in patients with acute brain injury from cerebrovascular diseases vary largely in clinical practice. Further research is required to provide clear guidelines to physicians for the hemodynamic optimization of this group of patients.

Abstract Background Our randomized clinical trial on induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was halted prematurely due to unexpected slow recruitment rates. This raised new questions regarding recruitment feasibility. As our trial can therefore be seen as a feasibility trial, we assessed the reasons for the slow recruitment, aiming to facilitate the design of future randomized trials in aSAH patients with DCI or other critically ill patient categories. Methods Efficiency of recruitment and factors influencing recruitment were evaluated, based on the patient flow in the two centers that admitted most patients during the study period. We collected numbers of patients who were screened for eligibility, provided informed consent, and developed DCI and who eventually were randomized. Results Of the 862 aSAH patients admitted in the two centers during the course of the trial, 479 (56%) were eligible for trial participation of whom 404 (84%) were asked for informed consent. Of these, 188 (47%) provided informed consent, of whom 50 (27%) developed DCI. Of these 50 patients, 12 (24%) could not be randomized due to a logistic problem or a contraindication for induced hypertension emerging at the time of randomization, and four (8%) were missed for randomization. Eventually, 34 patients were randomized and received intervention or control treatment. Conclusions Enrolling patients in a randomized trial on a treatment strategy for DCI proved unfeasible: only 1 out of 25 admitted and 1 out of 14 eligible patients could eventually be randomized. These rates, caused by a large proportion of ineligible patients, a small proportion of patients providing informed consent, and a large proportion of patients with contraindications for treatment, can be used to make sample size calculations for future randomized trials in DCI or otherwise critically ill patients. Facilitating informed consent through improved provision of information on risks, possible benefits, and study procedures may result in improved enrolment. Trial registration The original trial was prospectively registered with ClinicalTrials.gov (NCT01613235), date of registration 07-06-2012.

Abstract Background Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) often receive delayed or no aneurysm treatment, although recent studies suggest that functional outcome following early aneurysm treatment has improved. We aimed to systematically review and meta-analyze early predictors of functional outcome in poor-grade aSAH patients. Methods We included studies investigating the association of early predictors and functional outcome in adult patients with confirmed poor-grade aSAH, defined as World Federation of Neurological Surgeons (WFNS) grade or Hunt and Hess (H–H) grade IV-V. Studies had to use multivariable regression analysis to estimate independent predictor effects of favorable functional outcome measured with the Glasgow Outcome Scale or modified Rankin Scale. We calculated pooled adjusted odds ratios (aOR) and 95% confidence intervals (CI) with random effects models. Results We included 27 studies with 3287 patients. The likelihood of favorable outcome increased with WFNS grade or H–H grade IV versus V (aOR 2.9, 95% CI 1.9–4.3), presence of clinical improvement before aneurysm treatment (aOR 3.3, 95% CI 2.0–5.3), and intact pupillary light reflex (aOR 2.9, 95% CI 1.6–5.1), and decreased with older age (aOR 0.7, 95% CI 0.5–1.0, per decade), increasing modified Fisher grade (aOR 0.4, 95% CI 0.3–0.5, per grade), and presence of intracerebral hematoma on admission imaging (aOR 0.4, 95% CI 0.2–0.8). Conclusions We present a summary of early predictors of functional outcome in poor-grade aSAH patients that can help to discriminate between patients with favorable and with unfavorable prognosis and may aid in selecting patients for early aneurysm treatment.

The aims of this study are to describe the use of pharmaceutical venous thromboembolism (pVTE) prophylaxis in patients with traumatic brain injury (TBI) in Europe and study the association of pVTE prophylaxis with outcome. We included 2006 patients ?18 years of age admitted to the intensive care unit from the CENTER-TBI study. VTE events were recorded based on clinical symptoms. Variation between 54 centers in pVTE prophylaxis use was assessed with a multi-variate random-effect model and quantified with the median odds ratio (MOR). The association between pVTE prophylaxis and outcome (Glasgow Outcome Scale-Extended at 6 months) was assessed at center level with an instrumental variable analysis and at patient level with a multi-variate proportional odds regression analysis and a propensity-matched analysis. A time-dependent Cox survival regression analysis was conducted to determine the effect of pVTE prophylaxis on survival during hospital stay. The association between VTE prophylaxis and computed tomography (CT) progression was assessed with a logistic regression analysis. Overall, 56 patients (2%) had a VTE during hospital stay. The majority, 1279 patients (64%), received pVTE prophylaxis, with substantial between-center variation (MOR, 2.7; p?0.001). A moderate association with improved outcome was found at center level (odds ratio [OR], 1.2 [0.7?2.1]) and patient level (multi-variate adjusted OR, 1.4 [1.1?1.7], and propensity adjusted OR, 1.5 [1.1?2.0]), with similar results in subgroup analyses. Survival was higher with the use of pVTE prophylaxis (p?

Abstract Background Traumatic brain injury (TBI) is a major cause of death and disability across all ages. After the primary impact, the pathophysiologic process of secondary brain injury consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system could therefore be a therapeutic target in TBI. Objective To study the safety and efficacy of C1-inhibitor (C1-INH) compared to placebo in patients with TBI. By temporarily blocking the complement system, we hypothesize a decrease in the posttraumatic neuroinflammatory response resulting in a less unfavorable clinical outcome for TBI patients. Methods CIAO@TBI is a multicenter, randomized, blinded, phase II placebo-controlled trial. Adult TBI patients with GCS < 13 requiring intracranial pressure (ICP) monitoring will be randomized, using block randomization, within 12 h after trauma to one dose 6000 IU C1-INH or placebo. A total of 106 patients will be included, and follow-up will occur up to 12 months. The primary endpoints are (1) Therapy Intensity Level (TIL) Scale, (2) Glasgow Outcome Scale-Extended (GOSE) at 6 months, and (3) complication rate during hospitalization. Outcomes will be determined by a trial nurse blinded for the treatment allocation. Analyses will be conducted in an intention-to-treat analysis. Discussion We expect that C1-INH administration will be safe and potentially effective to improve clinical outcomes by reducing neuroinflammation in TBI patients. Trial registration ClinicalTrials.gov NCT04489160. Registered on 27 July 2020. EudraCT 2020-000140-58

Introduction Treatment decisions for aneurysmal subarachnoid haemorrhage patients should be supported by individualised predictions of the effects of aneurysm treatment. We present a study protocol and analysis plan for the development and external validation of models to predict benefit of neurosurgical versus endovascular aneurysm treatment on functional outcome and durability of treatment.Methods and analysis We will use data from the International Subarachnoid Aneurysm Trial for model development. The outcomes are functional outcome, measured with modified Rankin Scale at 12 months, and any retreatment or rebleed of the target aneurysm during follow-up. We will develop an ordinal logistic regression model and Cox regression model, considering age, World Federation of Neurological Surgeons grade, Fisher grade, vasospasm at presentation, aneurysm lumen size, aneurysm neck size, aneurysm location and time-to-aneurysm-treatment as predictors. We will test for interactions with treatment and with baseline risk and derive individualised predicted probabilities of treatment benefit. A benefit of ≥5% will be considered clinically relevant. Discriminative performance of the outcome predictions will be assessed with the c-statistic. Calibration will be assessed with calibration plots. Discriminative performance of the benefit predictions will be assessed with the c-for benefit. We will assess internal validity with bootstrapping and external validity with leave-one-out internal-external cross-validation.Ethics and dissemination The medical ethical research committee of the Erasmus MC University Medical Center Rotterdam approved the study protocol under the exemption category and waived the need for written informed consent (MEC-2020-0810). We will disseminate our results through an open-access peer-reviewed scientific publication and with a web-based clinical prediction tool.

ObjectiveSpine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).MethodsData from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.ResultsA total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.ConclusionRates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.

Abstract Purpose To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). Methods We studied high TIL treatments (metabolic suppression, hypothermia (

The contribution of neurological symptomatology to morbidity and mortality after infection with Severe Acute Respiratory Syndrome-associated Coronavirus (SARS CoV II) is ill-defined. We hereby present a case of a 57-year old male patient, in excellent physical condition, who was admitted to the Intensive Care Unit (ICU), with respiratory distress duo to SARS CoV II-induced bilateral pneumonia. After 2 weeks at the ICU, with respiratory conditions improving, the patient developed lethal cerebral edema. This case advocates regular wake-up calls in Coronavirus disease 2019 patients for neurological (radiological) evaluation to provide rapid diagnosis and a therapeutic window for fulminant central nervous system complications.

Abstract Background The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement. Methods Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10. Results A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p

Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR ​= ​1.35, 95% CI: 1.14–1.60, p ​

Introduction Anxiety is common in critically ill patients and has likely become more prevalent in the recent decade due to the imperative of the recent Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients (PADIS) to use low levels of sedation and strive for wakefulness. However, management of anxiety has not been included in the PADIS guidelines, and there is lack of evidence to treat it in spite of its growing importance. Administration of sedative and analgesic medication is often chosen to reduce anxiety, especially when associated with agitation. Sedatives are associated with prolonged mechanical ventilation, delirium and muscle wasting and are therefore preferably minimised. Previous studies have suggested positive effects of music interventions on anxiety in the critically ill. Therefore, we aim to study the effect of music intervention on anxiety in adult critically ill patients.Methods and design A multicentre randomised controlled trial was designed to study the effect of a music intervention on the level of anxiety experienced by adult patients admitted to the intensive care unit (ICU). One hundred and four patients will be included in three centres in the Netherlands. Patient recruitment started on 24-08-2020 and is ongoing in three hospitals. The primary outcome is self-reported anxiety measured on the visual analogue scale. Secondary outcomes include anxiety measured using the six-item State-Trait Anxiety Inventory, sleep quality, agitation and sedation level, medication requirement, pain, delirium, complications, time spend on mechanical ventilation, physical parameters and ICU memory and experience.Ethics and dissemination The Medical Ethics Review Board of Erasmus MC University Medical Centre Rotterdam, The Netherlands, has approved this protocol. The study is being conducted in accordance with the Declaration of Helsinki. Results of this trial will be published in peer-reviewed scientific journals and conference presentations.Trial registration number NCT04796389.

Abstract Background We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators. Methods A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool. Results The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N = 24, 48%) and neurosurgeons (N = 7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N = 49, 98%) and indicated routine measurement in registries (N = 41, 82%), benchmarking (N = 42, 84%), and quality improvement programs (N = 41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N = 48, 98%). Conclusions This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.

An amendment to this paper has been published and can be accessed via the original article.

Objective Sleep disruption occurs frequently in hospitalised patients. Given the potential of music intervention as a non-pharmacological measure to improve sleep quality, we aimed to assess and quantify current literature on the effect of recorded music interventions on sleep quality and quantity in the adult critical care and surgical populations.Design Systematic review and meta-analysis.Data sources Embase, MEDLINE Ovid, Cochrane Central, Web of Science and Google Scholar.Eligibility criteria for studies Randomised controlled trials assessing the effect of music on sleep quality in critically ill and surgical patients.Methods The electronic databases were systematically searched from 1 January 1981 to 27 January 2020. Data were screened, extracted and appraised by two independent reviewers. Primary outcomes were sleep quality and quantity, assessed with validated tools. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Random effects meta-analysis was performed, and pooled standardised mean differences (SMDs) with 95% CIs were reported.Results Five studies (259 patients) were included in qualitative (risk of bias) and quantitative analysis (meta-analysis). Pooled data showed a significant effect of recorded music on subjective sleep quality in the critical care and surgical population (SMD=1.21 (95% CI 0.50 to 1.91), p

Introduction Delirium in critically ill adults is associated with prolonged hospital stay, increased mortality and greater cognitive and functional decline. Current practice guideline recommendations advocate the use of non-pharmacological strategies to reduce delirium. The routine use of scheduled haloperidol to treat delirium is not recommended given a lack of evidence regarding its ability to resolve delirium nor improve relevant short-term and longer-term outcomes. This study aims to evaluate the efficacy and safety of haloperidol for the treatment of delirium in adult critically ill patients to reduce days spent with coma or delirium.Methods and analysis EuRIDICE is a prospective, multi-centre, randomised, double-blind, placebo-controlled trial. Study population consists of adult intensive care unit (ICU) patients without acute neurological injury who have delirium based on a positive Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method for the ICU (CAM-ICU) assessment. Intervention is intravenous haloperidol 2.5 mg (or matching placebo) every 8 hours, titrated daily based on ICDSC or CAM-ICU positivity to a maximum of 5 mg every 8 hours, until delirium resolution or ICU discharge. Main study endpoint is delirium and coma-free days (DCFD) up to 14 days after randomisation. Secondary endpoints include (1) 28-day and 1-year mortality, (2) cognitive and functional performance at 3 and 12 months, (3) patient and family delirium and ICU experience, (4) psychological sequelae during and after ICU stay, (4) safety concerns associated with haloperidol use and (5) cost-effectiveness. Differences in DCFDs between haloperidol and placebo group will be analysed using Poisson regression analysis. Study recruitment started in February 2018 and continues.Ethics and dissemination The study has been approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam (MEC2017-511) and by the Institutional Review Boards of the participating sites. Its results will be disseminated via peer-reviewed publication and conference presentations.Trial registration NCT03628391

Objective We aimed to explore: the exposure of healthcare workers to a delirium guidelines implementation programme; effects on guideline adherence at intensive care unit (ICU) level; impact on knowledge and barriers, and experiences with the implementation.Design A mixed-methods process evaluation of a prospective multicentre implementation study.Setting Six ICUs.Participants 4449 adult ICU patients and 500 ICU professionals approximately.Intervention A tailored implementation programme.Main outcome measure Adherence to delirium guidelines recommendations at ICU level before, during and after implementation; knowledge and perceived barriers; and experiences with the implementation.Results Five of six ICUs were exposed to all implementation strategies as planned. More than 85% followed the required e-learnings; 92% of the nurses attended the clinical classroom lessons; five ICUs used all available implementation strategies and perceived to have implemented all guideline recommendations (>90%). Adherence to predefined performance indicators (PIs) at ICU level was only above the preset target (>85%) for delirium screening. For all other PIs, the inter-ICU variability was between 34% and 72%. The implementation of delirium guidelines was feasible and successful in resolving the majority of barriers found before the implementation. The improvement was well sustained 6 months after full guideline implementation. Knowledge about delirium was improved (from 61% to 65%). The implementation programme was experienced as very successful.Conclusions Multifaceted implementation can improve and sustain adherence to delirium guidelines, is feasible and can largely be performed as planned. However, variability in delirium guideline adherence at individual ICUs remains a challenge, indicating the need for more tailoring at centre level.

Abstract Background We aimed to investigate the extent of the agreement on practices around brain death and postmortem organ donation. Methods Investigators from 67 Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study centers completed several questionnaires (response rate: 99%). Results Regarding practices around brain death, we found agreement on the clinical evaluation (prerequisites and neurological assessment) for brain death determination (BDD) in 100% of the centers. However, ancillary tests were required for BDD in 64% of the centers. BDD for nondonor patients was deemed mandatory in 18% of the centers before withdrawing life-sustaining measures (LSM). Also, practices around postmortem organ donation varied. Organ donation after circulatory arrest was forbidden in 45% of the centers. When withdrawal of LSM was contemplated, in 67% of centers the patients with a ventricular drain in situ had this removed, either sometimes or all of the time. Conclusions This study showed both agreement and some regional differences regarding practices around brain death and postmortem organ donation. We hope our results help quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation.

Abstract Background Accurate prediction of delirium in the intensive care unit (ICU) may facilitate efficient use of early preventive strategies and stratification of ICU patients by delirium risk in clinical research, but the optimal delirium prediction model to use is unclear. We compared the predictive performance and user convenience of the prediction model for delirium (PRE-DELIRIC) and early prediction model for delirium (E-PRE-DELIRIC) in ICU patients and determined the value of a two-stage calculation. Methods This 7-country, 11-hospital, prospective cohort study evaluated consecutive adults admitted to the ICU who could be reliably assessed for delirium using the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist. The predictive performance of the models was measured using the area under the receiver operating characteristic curve. Calibration was assessed graphically. A physician questionnaire evaluated user convenience. For the two-stage calculation we used E-PRE-DELIRIC immediately after ICU admission and updated the prediction using PRE-DELIRIC after 24 h. Results In total 2178 patients were included. The area under the receiver operating characteristic curve was significantly greater for PRE-DELIRIC (0.74 (95% confidence interval 0.71–0.76)) compared to E-PRE-DELIRIC (0.68 (95% confidence interval 0.66–0.71)) (z score of − 2.73 (p

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP)

Haloperidol is considered the first-line treatment for delirium in critically ill patients. However, clinical evidence of efficacy is lacking and no pharmacokinetic studies have been performed in intensive care unit (ICU) patients. The aim of this study was to establish a pharmacokinetic model to describe the PK in this population to improve insight into dosing. One hundred and thirty-nine samples from 22 patients were collected in a single-center study in adults with ICU delirium who were treated with low-dose intravenous haloperidol (3–6 mg per day). We conducted a population pharmacokinetic analysis using Nonlinear Mixed Effects Modelling (NONMEM). A one-compartment model best described the data. The mean population estimates were 51.7 L/h (IIV 42.1%) for clearance and 1490 L for the volume of distribution. The calculated half-life was around 22 h (12.3–29.73 h) for an average patient. A negative correlation between C-Reactive Protein (CRP) and haloperidol clearance was observed, where clearance decreased significantly with increasing CRP up to a CRP concentration of 100 mg/L. This is the first step towards haloperidol precision dosing in ICU patients and our results indicate a possible role of inflammation.

Abstract Background In Bangladesh, most patients with Guillain-Barré syndrome (GBS) cannot afford standard treatment with intravenous immunoglobulin (IVIG) or a standard plasma exchange (PE) course, which partly explains the high rate of mortality and residual disability associated with GBS in this country. Small volume plasma exchange (SVPE) is an affordable and potentially effective alternative form of plasma exchange. SVPE is the repeated removal of small volumes of supernatant plasma over several days via sedimentation of patient whole blood. The aim of this study is to define the clinical feasibility and safety of SVPE in patients with GBS in resource poor settings. Methods A total of 20 adult patients with GBS will be enrolled for SVPE at a single center in Bangladesh. Six daily sessions of whole blood sedimentation and plasma removal will be performed in all patients with GBS with a target to remove an overall volume of at least 8 liters (L) of plasma over a total of 8 days. Serious adverse events (SAE) are defined as the number of patients developing severe sepsis associated with the central venous catheter or deep venous thrombosis in the limb where the catheter is placed for SVPE. Based upon a predictive success rate of 75%, the SVPE procedure will be considered safe if less than 5 of 20 SVPE-treated GBS patients have a SAE. The procedure will be considered feasible if 8 L of plasma can be removed in at least 15 of 20 patients with GBS who receive SVPE. In addition, detailed clinical and neurological outcome assessments will be performed until discharge of the patient from the hospital and up to 4 weeks after study entry. Discussion This is the first clinical study to evaluate the feasibility and safety of SVPE as a potential alternative low-cost treatment for the patients with GBS in resource poor settings. Trial registration Clinicaltrials.gov NCT02780570

Abstract Background No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI. Methods A 29-item survey on ICP monitoring and treatment was developed on the basis of literature and expert opinion, and it was pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Results The survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately 90% of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomographic abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as using a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%). Conclusions Substantial variation was found regarding monitoring and treatment policies in patients with TBI and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research.