Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Treatment-limiting decisions in patients with severe traumatic brain injury in the Netherlands.

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.

Personalized decision-making for aneurysm treatment of aneurysmal subarachnoid hemorrhage: development and validation of a clinical prediction tool.

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.

Mastering the brain in critical conditions: an update.

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.

Fluid therapy in the acute brain injured patient.

Adequate fluid therapy in the acute brain injured (ABI) patient is essential for maintaining an adequate brain and systemic physiology and preventing intra- and extracranial complications. The target of euvolemia, implying avoidance of both hypovolemia and fluid overloading (or "hypervolemia," by definition associated with fluid extravasation leading to tissue edema) is of key importance. Primary brain injury can be aggravated by secondary brain injury and systemic deterioration through diverse pathways which can challenge appropriate fluid management, e.g. neuroendocrine and electrolyte disorders, stress cardiomyopathy (also known as cardiac stunning) and neurogenic pulmonary edema. This is an updated expert opinion aiming to provide a practical overview on fluid therapy in the ABI patient, partly based on more recent work and stressing the fact that intravenous fluids should be regarded as drugs, with their inherent potential for both benefit and (unintended) harm.

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial.

BACKGROUND: The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae. METHODS: This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization. RESULTS: The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73-1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18-0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12-1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29-1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22-2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study. CONCLUSIONS: Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov (#NCT03628391), October 9, 2017.

Effect of a music intervention on anxiety in adult critically ill patients: a multicenter randomized clinical trial.

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.

Haloperidol for the treatment of delirium in critically ill patients: an updated systematic review with meta-analysis and trial sequential analysis.

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; I2 = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I2 = 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.

Comparative Effectiveness of Mannitol Versus Hypertonic Saline in Patients With Traumatic Brain Injury: A CENTER-TBI Study.

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.

Sustained adherence to a delirium guideline five years after implementation in an intensive care setting: A retrospective cohort study.

OBJECTIVE: To explore the level of sustained adherence to a delirium guideline in a university intensive care unit setting five years after cessation of a multifaceted implementation program conducted between April 2012 and February 2015. RESEARCH METHODOLOGY/DESIGN: A quantitative retrospective cohort study was conducted using the medical records of all eligible patients admitted to the intensive care unit from November 2019 to February 2020. SETTING: Four adult intensive care units in a university hospital. MAIN OUTCOME MEASURES: Primary outcome is adherence to seven performance indicators indicated in the guideline being: light sedation days, mobilisation, physical therapy, analgesics use, delirium and sedation screening and avoiding benzodiazepines. Clinical patient outcomes such as Intensive care unit stay and prevalence of delirium were also collected. Data were compared with the results of the original implementation study's using descriptive statistics and Kruskal-wallis and Chi-square tests. RESULTS: Data of 236 patients were included. The most notable decrease in adherence concerned 'number of light sedation days' (-28 %). Adherence to three indicators had increased: 'number of days receiving out-of-bed mobilisation' (+11 %); 'number of days receiving physical therapy' (+9%); and 'use of analgesics' (+12 %). Comparison of clinical outcomes showed an increased intensive care unit length-of-stay from 3 to 5 days (P < 0.001). Prevalence of delirium increased over five years from 41 % to 43 % of patients while delirium duration decreased from a median of 3 days to a median of 2 days. CONCLUSION: Five years after ceasing of implementation efforts regarding the delirium guideline, partial sustainability has been achieved. The decrease in adherence to 'number of light sedation days' could have contributed to the increased length-of-stay on the intensive care unit. IMPLICATIONS FOR CLINICAL PRACTICE: After implementation, routine monitoring of performance indicators is required to evaluate the level of sustainment. Further, revisiting reasons for decrease in guideline adherence when contextual changes occur. Reassessment of the perceived barriers and facilitators can guide adaptations to sustain, or even improve, adherence.

TRansfusion strategies in Acute brain INjured patients (TRAIN): a prospective multicenter randomized interventional trial protocol.

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.

Tackling Neuroinflammation After Traumatic Brain Injury: Complement Inhibition as a Therapy for Secondary Injury.

Traumatic brain injury (TBI) is a leading cause of mortality, sensorimotor morbidity, and neurocognitive disability. Neuroinflammation is one of the key drivers causing secondary brain injury after TBI. Therefore, attenuation of the inflammatory response is a potential therapeutic goal. This review summarizes the most important neuroinflammatory pathophysiology resulting from TBI and the clinical trials performed to attenuate neuroinflammation. Studies show that non-selective attenuation of the inflammatory response, in the early phase after TBI, might be detrimental and that there is a gap in the literature regarding pharmacological trials targeting specific pathways. The complement system and its crosstalk with the coagulation system play an important role in the pathophysiology of secondary brain injury after TBI. Therefore, regaining control over the complement cascades by inhibiting overshooting activation might constitute useful therapy. Activation of the complement cascade is an early component of neuroinflammation, making it a potential target to mitigate neuroinflammation in TBI. Therefore, we have described pathophysiological aspects of complement inhibition and summarized animal studies targeting the complement system in TBI. We also present the first clinical trial aimed at inhibition of complement activation in the early days after brain injury to reduce the risk of morbidity and mortality following severe TBI.

Brain stem encephalitis is a rare complication of COVID-19.

Here, we describe the clinical phenotype of SARS-CoV-2-related CNS disease and evaluate the SARS-CoV-2 antibody index as a tool to differentiate between a direct (viral) and indirect etiology. Out of >4000 hospitalized patients with COVID-19, we included 13 patients with neurological symptoms with suspicion of neuroinflammation. On clinical grounds, eight were classified as having a possible/probable relationship between neurological symptoms and COVID-19. A clinically distinctive phenotype of brainstem and cerebellar symptoms was seen in 6/8 patients. As we found a positive SARS-CoV-2 antibody index in 3/5 patients, indicating specific intrathecal SARS-CoV-2 IgG production, a direct link with SARS-CoV-2 is likely.

Prognostic significance of delirium subtypes in critically ill medical and surgical patients: a secondary analysis of a prospective multicenter study.

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.

Endovascular versus neurosurgical aneurysm treatment: study protocol for the development and validation of a clinical prediction tool for individualised decision making.

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.

Hemodynamic management of acute brain injury caused by cerebrovascular diseases: a survey of the European Society of Intensive Care Medicine.

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.