SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Stocchetti Nino) "

Search: WFRF:(Stocchetti Nino)

  • Result 1-43 of 43
Sort/group result
   
EnumerationReferenceCoverFind
1.
  • Akerlund, Cecilia A., I, et al. (author)
  • Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI) : a multicentre observational cohort study
  • 2024
  • In: Lancet Neurology. - : Elsevier BV. - 1474-4422 .- 1474-4465. ; 23:1, s. 71-80
  • Journal article (peer-reviewed)abstract
    • Background Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. Methods We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. Findings Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E <= 4) was improved. Interpretation First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice.
  •  
2.
  • Chesnut, Randall, et al. (author)
  • A Consensus-based Interpretation of the BEST TRIP ICP Trial.
  • 2015
  • In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 32:22, s. 1722-1724
  • Journal article (peer-reviewed)abstract
    • Widely varying published and presented analyses of the BEST TRIP randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi-method-based approach employed iterative pre-meeting polling to codify the groups general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of > 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83-100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that this study: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation and avoid "collateral damage".
  •  
3.
  • Chesnut, Randall, et al. (author)
  • A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring : the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
  • 2020
  • In: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 46:5, s. 919-929
  • Journal article (peer-reviewed)abstract
    • Background: Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.Methods: Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting.Results: We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms.Conclusions: These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.
  •  
4.
  • Chesnut, Randall M., et al. (author)
  • Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury : A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations
  • 2023
  • In: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 93:2, s. 399-408
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion.METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression.RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations.CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.
  •  
5.
  • Childs, Charmaine, et al. (author)
  • Report of a consensus meeting on human brain temperature after severe traumatic brain injury : Its measurement and management during pyrexia
  • 2010
  • In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; NOV
  • Journal article (peer-reviewed)abstract
    • Temperature disturbances are common in patients with severe traumatic brain injury. The possibility of an adaptive, potentially beneficial role for fever in patients with severe brain trauma has been dismissed, but without good justification. Fever might, in some patients, confer benefit. A cadre of clinicians and scientists met to debate the clinically relevant, but often controversial issue about whether raised brain temperature after human traumatic brain injury (TBI) should be regarded as "good or bad" for outcome. The objective was to produce a consensus document of views about current temperature measurement and pyrexia treatment. Lectures were delivered by invited speakers with National and International publication track records in thermoregulation, neuroscience, epidemiology, measurement standards and neurocritical care. Summaries of the lectures and workshop discussions were produced from transcriptions of the lectures and workshop discussions. At the close of meeting, there was agreement on four key issues relevant to modern temperature measurement and management and for undergirding of an evidence-based practice, culminating in a consensus statement. There is no robust scientific data to support the use of hypothermia in patients whose intracranial pressure is controllable using standard therapy. A randomized clinical trial is justified to establish if body cooling for control of pyrexia (to normothermia) vs moderate pyrexia leads to a better patient outcome for TBI patients.
  •  
6.
  • Citerio, Giuseppe, et al. (author)
  • Management of arterial partial pressure of carbon dioxide in the first week after traumatic brain injury : results from the CENTER-TBI study
  • 2021
  • In: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 47:9, s. 961-973
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To describe the management of arterial partial pressure of carbon dioxide (PaCO2) in severe traumatic brain-injured (TBI) patients, and the optimal target of PaCO2 in patients with high intracranial pressure (ICP).METHODS: Secondary analysis of CENTER-TBI, a multicentre, prospective, observational, cohort study. The primary aim was to describe current practice in PaCO2 management during the first week of intensive care unit (ICU) after TBI, focusing on the lowest PaCO2 values. We also assessed PaCO2 management in patients with and without ICP monitoring (ICPm), and with and without intracranial hypertension. We evaluated the effect of profound hyperventilation (defined as PaCO2 < 30 mmHg) on long-term outcome.RESULTS: We included 1100 patients, with a total of 11,791 measurements of PaCO2 (5931 lowest and 5860 highest daily values). The mean (± SD) PaCO2 was 38.9 (± 5.2) mmHg, and the mean minimum PaCO2 was 35.2 (± 5.3) mmHg. Mean daily minimum PaCO2 values were significantly lower in the ICPm group (34.5 vs 36.7 mmHg, p < 0.001). Daily PaCO2 nadir was lower in patients with intracranial hypertension (33.8 vs 35.7 mmHg, p < 0.001). Considerable heterogeneity was observed between centers. Management in a centre using profound hyperventilation (HV) more frequently was not associated with increased 6 months mortality (OR = 1.06, 95% CI = 0.77-1.45, p value = 0.7166), or unfavourable neurological outcome (OR 1.12, 95% CI = 0.90-1.38, p value = 0.3138).CONCLUSIONS: Ventilation is manipulated differently among centers and in response to intracranial dynamics. PaCO2 tends to be lower in patients with ICP monitoring, especially if ICP is increased. Being in a centre which more frequently uses profound hyperventilation does not affect patient outcomes.
  •  
7.
  • Cnossen, Maryse C., et al. (author)
  • Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury : a survey in 66 neurotrauma centers participating in the CENTER-TBI study
  • 2017
  • In: Critical Care. - : Springer. - 1364-8535 .- 1466-609X. ; 21:1
  • Journal article (peer-reviewed)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.
  •  
8.
  • Conte, Valeria, et al. (author)
  • TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice
  • 2008
  • In: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 26:1, s. 45-56
  • Journal article (peer-reviewed)abstract
    • PURPOSE: The ability of brain-derived neurotrophic factor (BDNF) to attenuate secondary damage and influence behavioral outcome after experimental traumatic brain injury (TBI) remains controversial. Because TBI can result in decreased expression of the trkB receptor, thereby preventing BDNF from exerting potential neuroprotective effects, the contribution of both BDNF and its receptor trkB to hippocampal neuronal loss and cognitive dysfunction were evaluated. METHODS: Full-length trkB was overexpressed in the left hippocampus of adult C57Bl/6 mice using recombinant adeno-associated virus serotype 2/5 (rAAV 2/5). EGFP (enhanced green fluorescent protein) expression was present at two weeks after AAV-EGFP injection and remained sustained up to four weeks after the injection. At 2 weeks following gene transduction, mice were subjected to parasagittal controlled cortical impact (CCI) brain injury, followed by either BDNF or PBS infusion into the hippocampus. RESULTS: No differences were observed in learning ability at two weeks post-injury or in motor function from 48 hours to two weeks among treatment groups. The number of surviving pyramidal neurons in the CA2-CA3 region of the hippocampus was also not different among treatment groups. CONCLUSIONS: These data suggest that neither overexpression of trkB, BNDF infusion or their combination affects neuronal survival or behavioral outcome following experimental TBI in mice.
  •  
9.
  • Dijkland, Simone A., et al. (author)
  • Outcome Prediction after Moderate and Severe Traumatic Brain Injury : External Validation of Two Established Prognostic Models in 1742 European Patients
  • 2021
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:10, s. 1377-1388
  • Journal article (peer-reviewed)abstract
    • The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS ≤12, age ≥14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS ≤14, age ≥16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment.
  •  
10.
  • Hawryluk, Gregory W. J., et al. (author)
  • A management algorithm for patients with intracranial pressure monitoring : the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
  • 2019
  • In: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 45:12, s. 1783-1794
  • Journal article (peer-reviewed)abstract
    • Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based.Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations.Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination.Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.
  •  
11.
  • Huijben, Jilske A, et al. (author)
  • Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe : a CENTER-TBI analysis
  • 2020
  • In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 46:5, s. 995-1004
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers.METHODS: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers.RESULTS: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13-15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatments (MOR = 2.9, p < 0.001); and smaller in 6-month outcome (MOR = 1.2, p = 0.01).CONCLUSIONS: Half of contemporary TBI patients at the ICU have mild to moderate head injury. Substantial between-center variations exist in ICU stay and treatment policies, and less so in outcome. It remains unclear whether admission of short-stay patients represents appropriate prudence or inappropriate use of clinical resources.
  •  
12.
  • Huijben, Jilske A., et al. (author)
  • Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury
  • 2019
  • In: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 23
  • Journal article (peer-reviewed)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.
  •  
13.
  • Huijben, Jilske A., et al. (author)
  • Use and impact of high intensity treatments in patients with traumatic brain injury across Europe : a CENTER-TBI analysis
  • 2021
  • In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 25:1
  • Journal article (peer-reviewed)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 (< 35 °C), intensive hyperventilation (PaCO2 < 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP.RESULTS: 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0-2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome.CONCLUSION: Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies.TAKE HOME MESSAGE: Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments.TRIAL REGISTRATION: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, https://clinicaltrials.gov/ct2/show/NCT02210221?id=NCT02210221&draw=1&rank=1 and with Resource Identification Portal (RRID: SCR_015582).
  •  
14.
  • Huijben, Jilske A., et al. (author)
  • Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit : A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study
  • 2017
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:2, s. 323-332
  • Journal article (peer-reviewed)abstract
    • Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.
  •  
15.
  • Huijben, Jilske A., et al. (author)
  • Variation in general supportive and preventive intensive care management of traumatic brain injury : a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study
  • 2018
  • In: Critical Care. - : Springer. - 1364-8535 .- 1466-609X. ; 22:1
  • Journal article (peer-reviewed)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) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%).CONCLUSIONS: Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.
  •  
16.
  • Hutchinson, Peter J, et al. (author)
  • Consensus statement from the 2014 International Microdialysis Forum
  • 2015
  • In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
  • Journal article (peer-reviewed)abstract
    • Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
  •  
17.
  •  
18.
  • Picetti, Edoardo, et al. (author)
  • WSES consensus conference guidelines: monitoring and management of severe adult traumatic brain injury patients with polytrauma in the first 24 hours
  • 2019
  • In: World Journal of Emergency Surgery. - : BioMed Central (BMC). - 1749-7922. ; 14:1
  • Research review (peer-reviewed)abstract
    • The acute phase management of patients with severe traumatic brain injury (TBI) and polytrauma represents a major challenge. Guidelines for the care of these complex patients are lacking, and worldwide variability in clinical practice has been documented in recent studies. Consequently, the World Society of Emergency Surgery (WSES) decided to organize an international consensus conference regarding the monitoring and management of severe adult TBI polytrauma patients during the first 24 hours after injury. A modified Delphi approach was adopted, with an agreement cut-off of 70%. Forty experts in this field (emergency surgeons, neurosurgeons, and intensivists) participated in the online consensus process. Sixteen recommendations were generated, with the aim of promoting rational care in this difficult setting. 
  •  
19.
  • Rass, Verena, et al. (author)
  • The Effect of Temperature Increases on Brain Tissue Oxygen Tension in Patients with Traumatic Brain Injury : A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Substudy
  • 2021
  • In: Therapeutic Hypothermia and Temperature Management. - : Mary Ann Liebert. - 2153-7658 .- 2153-7933. ; 11:2, s. 122-131
  • Journal article (peer-reviewed)abstract
    • Fever may aggravate secondary brain injury after traumatic brain injury (TBI). The aim of this study was to identify episodes of temperature increases through visual plot analysis and algorithm supported detection, and to describe associated patterns of changes in on brain tissue oxygen tension (PbtO2). Data derive from the high-resolution cohort of the multicenter prospective Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Temperature increases (≥0.5°C) were visually identified in 33 patients within the first 11 days of monitoring. Generalized estimating equations were used to detect significant changes of systemic and neuromonitoring parameters from baseline to the highest temperature. Patients were median 50 (interquartile range [IQR], 35–62) years old, and presented with a Glasgow Coma Scale (GCS) of 8 (IQR, 4–10). In 202 episodes of temperature increases, mean temperature rose by 1.0°C ± 0.5°C within 4 hours. Overall, PbtO2 slightly increased (ΔPbtO2 = 0.9 ± 6.1 mmHg, p = 0.022) during temperature increases. PbtO2 increased in 35% (p < 0.001), was stable in 49% (p = 0.852), and decreased in 16% (p < 0.001) of episodes. During episodes of temperature increases and simultaneous drops in PbtO2, cerebral perfusion pressure (CPP) decreased (ΔCPP −6.3 ± 11.5 mmHg; p < 0.001). Brain tissue hypoxia (PbtO2 <20 mmHg) developed during 27/164 (17%) episodes of effervescences, in the remaining 38/202 episodes baseline PbtO2 was already <20 mmHg. Comparable results were found when using algorithm-supported detection of temperature increases. In conclusion, during effervescences, PbtO2 was mostly stable or slightly increased. A decrease of PbtO2 was observed in every sixth episode, where it was associated with a decrease in CPP. Our data highlight the need for special attention to CPP monitoring and maintenance during episodes of fever.
  •  
20.
  • Riemann, Lennart, et al. (author)
  • Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury : a CENTER-TBI study
  • 2020
  • In: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 24:1
  • Journal article (peer-reviewed)abstract
    • Background: After traumatic brain injury (TBI), brain tissue can be further damaged when cerebral autoregulation is impaired. Managing cerebral perfusion pressure (CPP) according to computed "optimal CPP" values based on cerebrovascular reactivity indices might contribute to preventing such secondary injuries. In this study, we examined the discriminative value of a low-resolution long pressure reactivity index (LPRx) and its derived "optimal CPP" in comparison to the well-established high-resolution pressure reactivity index (PRx).Methods: Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset, the association of LPRx (correlation between 1-min averages of intracranial pressure and arterial blood pressure over a moving time frame of 20 min) and PRx (correlation between 10-s averages of intracranial pressure and arterial blood pressure over a moving time frame of 5 min) to outcome was assessed and compared using univariate and multivariate regression analysis. "Optimal CPP" values were calculated using a multi-window algorithm that was based on either LPRx or PRx, and their discriminative ability was compared.Results: LPRx and PRx were both significant predictors of mortality in univariate and multivariate regression analysis, but PRx displayed a higher discriminative ability. Similarly, deviations of actual CPP from "optimal CPP" values calculated from each index were significantly associated with outcome in univariate and multivariate analysis. "Optimal CPP" based on PRx, however, trended towards more precise predictions.Conclusions: LPRx and its derived "optimal CPP" which are based on low-resolution data were significantly associated with outcome after TBI. However, they did not reach the discriminative ability of the high-resolution PRx and its derived "optimal CPP." Nevertheless, LPRx might still be an interesting tool to assess cerebrovascular reactivity in centers without high-resolution signal monitoring.Trial registration: ClinicalTrials.gov Identifier: NCT02210221. First submitted July 29, 2014. First posted August 6, 2014.
  •  
21.
  • Robba, Chiara, et al. (author)
  • Incidence, Risk Factors, and Effects on Outcome of Ventilator-Associated Pneumonia in Patients With Traumatic Brain Injury : Analysis of a Large, Multicenter, Prospective, Observational Longitudinal Study
  • 2020
  • In: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 158:6, s. 2292-2303
  • Journal article (peer-reviewed)abstract
    • Background: No large prospective data, to our knowledge, are available on ventilator-associated pneumonia (VAP) in patients with traumatic brain injury (TBI).Research Question: To evaluate the incidence, timing, and risk factors of VAP after TBI and its effect on patient outcome.Study Design and Methods: This analysis is of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury data set, from a large, multicenter, prospective, observational study including patients with TBI admitted to European ICUs, receiving mechanical ventilation for ≥ 48 hours and with an ICU length of stay (LOS) ≥ 72 hours. Characteristics of patients with VAP vs characteristics of patients without VAP were compared, and outcome was assessed at 6 months after injury by using the Glasgow Outcome Scale Extended.Results: The study included 962 patients: 196 (20.4%) developed a VAP at a median interval of 5 days (interquartile range [IQR], 3-7 days) after intubation. Patients who developed VAP were younger (median age, 39.5 [IQR, 25-55] years vs 51 [IQR, 30-66] years; P < .001), with a higher incidence of alcohol abuse (36.6% vs 27.6%; P = .026) and drug abuse (10.1% vs 4.2%; P = .009), more frequent thoracic trauma (53% vs 43%; P = .014), and more episodes of respiratory failure during ICU stay (69.9% vs 28.1%; P < .001). Age (hazard ratio [HR], 0.99; 95% CI, 0.98-0.99; P = .001), chest trauma (HR, 1.4; 95% CI, 1.03-1.90; P = .033), histamine-receptor antagonist intake (HR, 2.16; 95% CI, 1.37-3.39; P = .001), and antibiotic prophylaxis (HR, 0.69; 95% CI, 0.50-0.96; P = .026) were associated with the risk of VAP. Patients with VAP had a longer duration of mechanical ventilation (median, 15 [IQR, 10-22] days vs 8 [IQR, 5-14] days; P < .001) and ICU LOS (median, 20 [IQR, 14-29] days vs 13 [IQR, 8-21] days; P < .001). However, VAP was not associated with increased mortality or worse neurological outcome. Overall mortality at 6 months was 22%.Interpretation: VAP occurs less often than previously described in patients after TBI and has a detrimental effect on ICU LOS but not on mortality and neurological outcome.Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02210221; URL: www.clinicaltrials.gov
  •  
22.
  • Robba, Chiara, et al. (author)
  • Tracheostomy practice and timing in traumatic brain-injured patients : a CENTER-TBI study
  • 2020
  • In: Intensive Care Medicine. - : Springer Berlin/Heidelberg. - 0342-4642 .- 1432-1238. ; 46, s. 983-994
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients' characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients' outcomes.METHODS: We selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay ≥ 72 h. Tracheostomy was defined as early (≤ 7 days from admission) or late (> 7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score.RESULTS: Of the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR = 1.04, 95% CI = 1.01-1.07, p = 0.003), Glasgow coma scale ≤ 8 (HR = 1.70, 95% CI = 1.22-2.36 at 7; p < 0.001), thoracic trauma (HR = 1.24, 95% CI = 1.01-1.52, p = 0.020), hypoxemia (HR = 1.37, 95% CI = 1.05-1.79, p = 0.048), unreactive pupil (HR = 1.76, 95% CI = 1.27-2.45 at 7; p < 0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9-50.2%) and timing (early 0-17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR = 1.69, 95% CI = 1.07-2.67, p = 0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p = 0.003).CONCLUSIONS: Tracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven.
  •  
23.
  • Sarigul, Buse, et al. (author)
  • Prognostication and Goals of Care Decisions in Severe Traumatic Brain Injury : A Survey of The Seattle International Severe Traumatic Brain Injury Consensus Conference Working Group
  • 2023
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:15-16, s. 1707-1717
  • Journal article (peer-reviewed)abstract
    • Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.
  •  
24.
  • Sewalt, Charlie Aletta, et al. (author)
  • Primary versus early secondary referral to a specialized neurotrauma center in patients with moderate/severe traumatic brain injury : a CENTER TBI study
  • 2021
  • In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central (BMC). - 1757-7241. ; 29:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Prehospital care for patients with traumatic brain injury (TBI) varies with some emergency medical systems recommending direct transport of patients with moderate to severe TBI to hospitals with specialist neurotrauma care (SNCs). The aim of this study is to assess variation in levels of early secondary referral within European SNCs and to compare the outcomes of directly admitted and secondarily transferred patients.METHODS: Patients with moderate and severe TBI (Glasgow Coma Scale < 13) from the prospective European CENTER-TBI study were included in this study. All participating hospitals were specialist neuroscience centers. First, adjusted between-country differences were analysed using random effects logistic regression where early secondary referral was the dependent variable, and a random intercept for country was included. Second, the adjusted effect of early secondary referral on survival to hospital discharge and functional outcome [6 months Glasgow Outcome Scale Extended (GOSE)] was estimated using logistic and ordinal mixed effects models, respectively.RESULTS: A total of 1347 moderate/severe TBI patients from 53 SNCs in 18 European countries were included. Of these 1347 patients, 195 (14.5%) were admitted after early secondary referral. Secondarily referred moderate/severe TBI patients presented more often with a CT abnormality: mass lesion (52% vs. 34%), midline shift (54% vs. 36%) and acute subdural hematoma (77% vs. 65%). After adjusting for case-mix, there was a large European variation in early secondary referral, with a median OR of 1.69 between countries. Early secondary referral was not associated with functional outcome (adjusted OR 1.07, 95% CI 0.78-1.69), nor with survival at discharge (1.05, 0.58-1.90).CONCLUSIONS: Across Europe, substantial practice variation exists in the proportion of secondarily referred TBI patients at SNCs that is not explained by case mix. Within SNCs early secondary referral does not seem to impact functional outcome and survival after stabilisation in a non-specialised hospital. Future research should identify which patients with TBI truly benefit from direct transportation.
  •  
25.
  • Steyerberg., Ewout W, et al. (author)
  • Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI : a European prospective, multicentre, longitudinal, cohort study
  • 2019
  • In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:10, s. 923-934
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI.METHODS: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582).FINDINGS: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]).INTERPRETATION: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes.FUNDING: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.
  •  
26.
  • Stocchetti, Nino, et al. (author)
  • Clinical applications of intracranial pressure monitoring in traumatic brain injury
  • 2014
  • In: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 156:8, s. 1615-1622
  • Journal article (peer-reviewed)abstract
    • Intracranial pressure (ICP) monitoring has been for decades a cornerstone of traumatic brain injury (TBI) management. Nevertheless, in recent years, its usefulness has been questioned in several reports. A group of neurosurgeons and neurointensivists met to openly discuss, and provide consensus on, practical applications of ICP in severe adult TBI. A consensus conference was held in Milan on October 5, 2013, putting together neurosurgeons and intensivists with recognized expertise in treatment of TBI. Four topics have been selected and addressed in pro-con presentations: 1) ICP indications in diffuse brain injury, 2) cerebral contusions, 3) secondary decompressive craniectomy (DC), and 4) after evacuation of intracranial traumatic hematomas. The participants were asked to elaborate on the existing published evidence (without a systematic review) and their personal clinical experience. Based on the presentations and discussions of the conference, some drafts were circulated among the attendants. After remarks and further contributions were collected, a final document was approved by the participants. The group made the following recommendations: 1) in comatose TBI patients, in case of normal computed tomography (CT) scan, there is no indication for ICP monitoring; 2) ICP monitoring is indicated in comatose TBI patients with cerebral contusions in whom the interruption of sedation to check neurological status is dangerous and when the clinical examination is not completely reliable. The probe should be positioned on the side of the larger contusion; 3) ICP monitoring is generally recommended following a secondary DC in order to assess the effectiveness of DC in terms of ICP control and guide further therapy; 4) ICP monitoring after evacuation of an acute supratentorial intracranial hematoma should be considered for salvageable patients at increased risk of intracranial hypertension with particular perioperative features.
  •  
27.
  • Timmers, Marjolein, et al. (author)
  • How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? : Experiences from the CENTER-TBI study
  • 2020
  • In: BMC Medical Ethics. - : BioMed Central (BMC). - 1472-6939. ; 21:1
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
28.
  • van Veen, Ernest, et al. (author)
  • Brain death and postmortem organ donation : report of a questionnaire from the CENTER-TBI study.
  • 2018
  • In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 22:1
  • Journal article (peer-reviewed)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.
  •  
29.
  • van Veen, Ernest, et al. (author)
  • End-of-life practices in traumatic brain injury patients : Report of a questionnaire from the CENTER-TBI study
  • 2020
  • In: Journal of critical care. - : Elsevier. - 0883-9441 .- 1557-8615. ; 58, s. 78-88
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
30.
  • van Veen, Ernest, et al. (author)
  • Occurrence and timing of withdrawal of life-sustaining measures in traumatic brain injury patients : a CENTER-TBI study
  • 2021
  • In: Intensive Care Medicine. - : Springer Science+Business Media B.V.. - 0342-4642 .- 1432-1238. ; 47:10, s. 1115-1129
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
31.
  • Volovici, Victor, et al. (author)
  • Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring : a CENTER-TBI study
  • 2022
  • In: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 164:7, s. 1693-1705
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)-driven treatment.METHODS: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with "center" as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome.RESULTS: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36-1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34-2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs.CONCLUSION: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor-guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group.
  •  
32.
  • Volovici, Victor, et al. (author)
  • Variation in Guideline Implementation and Adherence Regarding Severe Traumatic Brain Injury Treatment : A CENTER-TBI Survey Study in Europe
  • 2019
  • In: World Neurosurgery. - : Elsevier. - 1878-8750 .- 1878-8769. ; 125, s. e515-e520
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Guidelines may reduce practice variation and optimize patient care. We aimed to study differences in guideline use in the management of traumatic brain injury (TBI) patients and analyze reasons for guideline non-adherence.METHODS: As part of a prospective, observational, multicenter European cohort study, participants from 68 centers in 20 countries were asked to complete 72-item questionnaires regarding their management of severe TBI. Six questions with multiple sub-questions focused on guideline use and implementation.RESULTS: Questionnaires were completed by 65 centers. Of these, 49 (75%) reported use of the Brain Trauma Foundation guidelines for the medical management of TBI or related institutional protocols, 11 (17%) used no guidelines, and 5 used other guidelines (8%). Of 54 centers reporting use of any guidelines, 41 (75%) relied on written guidelines. Four centers of the 54 (7%) reported no formal implementation efforts. Structural attention to the guidelines during daily clinical rounds was reported by 21 centers (38%). The most often reported reasons for non-adherence were "every patient is unique" and the presence of extracranial injuries, both for centers that did and did not report the use of guidelines.CONCLUSIONS: There is substantial variability in the use and implementation of guidelines in neurotrauma centers in Europe. Further research is needed to strengthen the evidence underlying guidelines and to overcome implementation barriers.
  •  
33.
  • Wiegers, Eveline Janine Anna, et al. (author)
  • Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI) : a prospective, multicentre, comparative effectiveness study
  • 2021
  • In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:8, s. 627-638
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes.METHODS: We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable.FINDINGS: 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1·48 L (IQR 1·12 to 2·09) to 4·23 L (3·78 to 4·94) across centres. The median of the mean daily fluid balance ranged from -0·85 L (IQR -1·51 to -0·49) to 1·13 L (0·99 to 1·37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1·10 [95% CI 1·07 to 1·12] per 0·1 L increase) and worse functional outcome (1·04 [1·02 to 1·05] per 0·1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1·05 [1·03 to 1·06] per 0·1 L increase) and worse functional outcome (1·04 [1·03 to 1·04] per 1-point decrease of the GOSE per 0·1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1·17 [95% CI 1·05 to 1·29]) and worse functional outcome (1·07 [1·02 to 1·13]), but higher fluid input was not associated with ICU mortality (OR 0·95 [0·90 to 1·00]) or worse functional outcome (1·01 [0·98 to 1·03]).INTERPRETATION: In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome.
  •  
34.
  • Zeiler, Frederick A., et al. (author)
  • Association between Physiological Signal Complexity and Outcomes in Moderate and Severe Traumatic Brain Injury : A CENTER-TBI Exploratory Analysis of Multi-Scale Entropy
  • 2021
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:2, s. 272-282
  • Journal article (peer-reviewed)abstract
    • In traumatic brain injury (TBI), preliminary retrospective work on signal entropy suggests an association with global outcome. The goal of this study was to provide multi-center validation of the association between multi-scale entropy (MSE) of cardiovascular and cerebral physiological signals, with six-month outcome. Using the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we selected patients with a minimum of 72 h of physiological recordings and a documented six-month Glasgow Outcome Scale Extended (GOSE) score. The 10-sec summary data for heart rate (HR), mean arterial pressure (MAP), intracranial pressure (ICP), and pulse amplitude of ICP (AMP) were derived across the first 72 h of data. The MSE complexity index (MSE-Ci) was determined for HR, MAP, ICP, and AMP, with the association between MSE and dichotomized six-month outcomes assessed using Mann-Whitney U testing and logistic regression analysis. A total of 160 patients had a minimum of 72 h of recording and a documented outcome. Decreased HR MSE-Ci (7.3 [interquartile range (IQR) 5.4 to 10.2] vs. 5.1 [IQR 3.1 to 7.0]; p = 0.002), lower ICP MSE-Ci (11.2 [IQR 7.5 to 14.2] vs. 7.3 [IQR 6.1 to 11.0]; p = 0.009), and lower AMP MSE-Ci (10.9 [IQR 8.0 to 13.7] vs. 8.7 [IQR 6.6 to 11.0]; p = 0.022), were associated with death. Similarly, lower HR MSE-Ci (8.0 [IQR 6.2 to 10.9] vs. 6.2 [IQR 3.9 to 8.7]; p = 0.003) and lower ICP MSE-Ci (11.4 [IQR 8.6 to 14.4)] vs. 9.2 [IQR 6.0 to 13.5]), were associated with unfavorable outcome. Logistic regression analysis confirmed that lower HR MSE-Ci and ICP MSE-Ci were associated with death and unfavorable outcome at six months. These findings suggest that a reduction in cardiovascular and cerebrovascular system entropy is associated with worse outcomes. Further work in the field of signal complexity in TBI multi-modal monitoring is required.
  •  
35.
  • Zeiler, Frederick A, et al. (author)
  • Brain tissue oxygen and cerebrovascular reactivity in traumatic brain injury : a collaborative european neurotrauma effectiveness research in traumatic brain injury exploratory analysis of insult burden
  • 2020
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:17, s. 1854-1863
  • Journal article (peer-reviewed)abstract
    • Pressure reactivity index (PRx) and brain tissue oxygen (PbtO2) are associated with outcome in traumatic brain injury (TBI). This study explores the relationship between PRx and PbtO2 in adult moderate/severe TBI. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution intensive care unit (ICU) sub-study cohort, we evaluated those patients with archived high-frequency digital intraparenchymal intracranial pressure (ICP) and PbtO2 monitoring data of, a minimum of 6 h in duration, and the presence of a 6 month Glasgow Outcome Scale -Extended (GOSE) score. Digital physiological signals were processed for ICP, PbtO2, and PRx, with the % time above/below defined thresholds determined. The duration of ICP, PbtO2, and PRx derangements was characterized. Associations with dichotomized 6-month GOSE (alive/dead, and favorable/unfavorable outcome; ≤ 4 = unfavorable), were assessed. A total of 43 patients were included. Severely impaired cerebrovascular reactivity was seen during elevated ICP and low PbtO2 episodes. However, most of the acute ICU physiological derangements were impaired cerebrovascular reactivity, not ICP elevations or low PbtO2 episodes. Low PbtO2 without PRx impairment was rarely seen. % time spent above PRx threshold was associated with mortality at 6 months for thresholds of 0 (area under the curve [AUC] 0.734, p = 0.003), > +0.25 (AUC 0.747, p = 0.002) and > +0.35 (AUC 0.745, p = 0.002). Similar relationships were not seen for % time with ICP >20 mm Hg, and PbtO2 < 20 mm Hg in this cohort. Extreme impairment in cerebrovascular reactivity is seen during concurrent episodes of elevated ICP and low PbtO2. However, the majority of the deranged cerebral physiology seen during the acute ICU phase is impairment in cerebrovascular reactivity, with most impairment occurring in the presence of normal PbtO2 levels. Measures of cerebrovascular reactivity appear to display the most consistent associations with global outcome in TBI, compared with ICP and PbtO2.
  •  
36.
  • Zeiler, Frederick A., et al. (author)
  • Diffuse intracranial injury patterns are associated with impaired cerebrovascular reactivity in adult traumatic brain injury : a CENTER-TBI validation study
  • 2020
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:4, s. 1597-1608
  • Journal article (peer-reviewed)abstract
    • Recent single-center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intracranial injury and worse cerebrovascular reactivity. The goal of this study was to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high-resolution intensive care unit (HR ICU) data set. Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher) and the presence of a digital admission CT scan. Physiological signals were processed for pressure reactivity index (PRx) and both the percent (%) time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH), and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere-Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased percent (%) time and hourly dose above PRx threshold of 0, +0.25, and +0.35 (p < 0.02 for all). Logistic regression analysis displayed an association between deep peri-contusional edema and mean PRx above a threshold of +0.25. These results suggest that diffuse injury patterns, consistent with acceleration/deceleration forces, are associated with impaired cerebrovascular reactivity. Diffuse admission intracranial injury patterns appear to be consistently associated with impaired cerebrovascular reactivity, as measured through PRx. This is in keeping with the previous single-center retrospective literature on the topic. This study provides multi-center validation for those results, and provides preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern.
  •  
37.
  • Zeiler, Frederick A., et al. (author)
  • Evaluation of the relationship between slow-waves of intracranial pressure, mean arterial pressure and brain tissue oxygen in TBI : a CENTER-TBI exploratory analysis
  • 2021
  • In: Journal of clinical monitoring and computing. - : Springer Berlin/Heidelberg. - 1387-1307 .- 1573-2614. ; 35:4, s. 711-722
  • Journal article (peer-reviewed)abstract
    • Brain tissue oxygen (PbtO2) monitoring in traumatic brain injury (TBI) has demonstrated strong associations with globaloutcome. Additionally, PbtO2 signals have been used to derive indices thought to be associated with cerebrovascular reactivityin TBI. However, their true relationship to slow-wave vasogenic fuctuations associated with cerebral autoregulation remainsunclear. The goal of this study was to investigate the relationship between slow-wave fuctuations of intracranial pressure(ICP), mean arterial pressure (MAP) and PbtO2 over time. Using the Collaborative European NeuroTrauma EfectivenessResearch in Traumatic Brain Injury (CENTER-TBI) high resolution ICU sub-study cohort, we evaluated those patients withrecorded high-frequency digital intra-parenchymal ICP and PbtO2 monitoring data of a minimum of 6 h in duration. Digitalphysiologic signals were processed for ICP, MAP, and PbtO2 slow-waves using a moving average flter to decimate the highfrequency signal. The frst 5 days of recording were analyzed. The relationship between ICP, MAP and PbtO2 slow-wavesover time were assessed using autoregressive integrative moving average (ARIMA) and vector autoregressive integrativemoving average (VARIMA) modelling, as well as Granger causality testing. A total of 47 patients were included. The ARIMAstructure of ICP and MAP were similar in time, where PbtO2 displayed diferent optimal structure. VARIMA modellingand IRF plots confrmed the strong directional relationship between MAP and ICP, demonstrating an ICP response to MAPimpulse. PbtO2 slow-waves, however, failed to demonstrate a defnite response to ICP and MAP slow-wave impulses. Theseresults raise questions as to the utility of PbtO2 in the derivation of cerebrovascular reactivity measures in TBI. There isa reproducible relationship between slow-wave fuctuations of ICP and MAP, as demonstrated across various time-seriesanalytic techniques. PbtO2 does not appear to reliably respond in time to slow-wave fuctuations in MAP, as demonstratedon various VARIMA models across all patients. These fndings suggest that PbtO2 should not be utilized in the derivationof cerebrovascular reactivity metrics in TBI, as it does not appear to be responsive to changes in MAP in the slow-waves.These fndings corroborate previous results regarding PbtO2 based cerebrovascular reactivity indices. 
  •  
38.
  • Zeiler, Frederick A., et al. (author)
  • Patient-specific ICP Epidemiologic Thresholds in Adult Traumatic Brain Injury : A CENTER-TBI Validation Study
  • 2019
  • In: Journal of Neurosurgical Anesthesiology. - : Wolters Kluwer. - 0898-4921 .- 1537-1921.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Patient-specific epidemiologic intracranial pressure (ICP) thresholds in adult traumatic brain injury (TBI) have emerged, using the relationship between pressure reactivity index (PRx) and ICP, displaying stronger association with outcome over existing guideline thresholds. The goal of this study was to explore this relationship in a multi-center cohort in order to confirm the previous finding.METHODS: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit cohort, we derived individualized epidemiologic ICP thresholds for each patient using the relationship between PRx and ICP. Mean hourly dose of ICP was calculated for every patient for the following thresholds: 20, 22 mm Hg and the patient's individual ICP threshold. Univariate logistic regression models were created comparing mean hourly dose of ICP above thresholds to dichotomized outcome at 6 to 12 months, based on Glasgow Outcome Score-Extended (GOSE) (alive/dead-GOSE≥2/GOSE=1; favorable/unfavorable-GOSE 5 to 8/GOSE 1 to 4, respectively).RESULTS: Individual thresholds were identified in 65.3% of patients (n=128), in keeping with previous results (23.0±11.8 mm Hg [interquartile range: 14.9 to 29.8 mm Hg]). Mean hourly dose of ICP above individual threshold provides superior discrimination (area under the receiver operating curve [AUC]=0.678, P=0.029) over mean hourly dose above 20 mm Hg (AUC=0.509, P=0.03) or above 22 mm Hg (AUC=0.492, P=0.035) on univariate analysis for alive/dead outcome at 6 to 12 months. The AUC for mean hourly dose above individual threshold trends to higher values for favorable/unfavorable outcome, but fails to reach statistical significance (AUC=0.610, P=0.060). This was maintained when controlling for baseline admission characteristics.CONCLUSIONS: Mean hourly dose of ICP above individual epidemiologic ICP threshold has stronger associations with mortality compared with the dose above Brain Trauma Foundation defined thresholds of 20 or 22 mm Hg, confirming prior findings. Further studies on patient-specific epidemiologic ICP thresholds are required.
  •  
39.
  • Zeiler, Frederick Adam, et al. (author)
  • Statistical cerebrovascular reactivity signal properties after secondary decompressive craniectomy in traumatic brain injury : a CENTER-TBI pilot analysis
  • 2020
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:11, s. 1306-1314
  • Journal article (peer-reviewed)abstract
    • Decompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity metrics and slow-wave relationships were impacted after DC, as such information would allow us to comment on whether vascular reactivity monitoring remains reliable after craniectomy. Using the CENTER-TBI high-resolution intensive care unit (ICU) cohort, we selected those secondary DC patients with high-frequency physiologic data for both: at least 24 hours before DC, and more than 48 hours post-DC. Data for all physiology measures was separated into: the 24 hours before DC, the first 48 hours post DC, and beyond 48 hours post-DC. We produced slow-wave data sheets for intra-cranial pressure (ICP) and mean arterial pressure (MAP) per patient. We also derived pressure reactivity index (PRx) as continuous cerebrovascular reactivity metrics updated every minute. The time-series behavior of PRx was modeled for each time period per patient. Finally, the relationship between ICP and MAP during these 3 time periods was assessed using time-series vector autoregressive integrative moving average (VARIMA) models, impulse response function (IRF) plots, and Granger causality testing. Ten patients were included in this study. Mean PRx and proportion of time above PRx thresholds were not affected by craniectomy. Similarly, PRx time-series structure was not affected by DC, when assessed in each individual patient. This was confirmed with Granger causality testing, and VARIMA IRF plotting for the MAP/ICP slow-wave relationship. PRx metrics and statistical time-series behavior appears not to be substantially influenced by DC. Similarly, there is little change in the relationship between slow-waves of ICP and MAP before and after DC. This may suggest that cerebrovascular reactivity monitoring in the setting of DC may still provide valuable information regarding autoregulation. Keywords: cerebrovascular reactivity, decompressive craniectomy, DC, PRx, TBI.
  •  
40.
  • Zeiler, Frederick Adam, et al. (author)
  • Systemic Markers of Injury and Injury Response are not Associated with Impaired Cerebrovascular Reactivity in Adult TBI : A CENTER-TBI Study
  • 2021
  • In: Journal of Neurotrauma. - : Mary Ann Liebert Inc.. - 0897-7151 .- 1557-9042. ; 38:7, s. 870-878
  • Journal article (peer-reviewed)abstract
    • The role of extra-cranial injury burden on cerebrovascular response in traumatic brain injury (TBI) is poorly documented. This study preliminarily assesses the association between admission features of extra-cranial injury burden on cerebrovascular reactivity. Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital intra-parenchymal ICP monitoring data of a minimum of 6 hours in duration, and the presence of a digital copy of their admission CT scan. Digital physiologic signals were processed for pressure reactivity index (PRx) and both the % time above defined PRx thresholds and mean hourly dose above threshold. This was conducted for both the first 72 hours and entire duration of recording. Admission extra-cranial injury characteristics and CT injury scores were obtained from the database, with quantitative contusion, edema, intraventricular hemorrhage (IVH) and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission extra-cranial markers of injury and PRx metrics was conducted using Mann-U testing, and logistic regression techniques, adjusting for known CT injury metrics associated with impaired PRx. A total of 165 patients were included. Evaluating the entire ICU recording period, there was limited association between metrics of extra-cranial injury burden and impaired cerebrovascular reactivity. Using the first 72 hours of recording, admission temperature (p=0.042) and white blood cell % (WBC %) (p=0.013) were statistically associated with impaired cerebrovascular reactivity on Mann-U and univariate logistic regression. After adjusting for admission age, pupillary status, GCS motor score, pre-hospital hypoxia/hypotension and intra-cranial CT characteristics associated with impaired reactivity, temperature (p=0.021) and WBC % (p=0.013) remained significantly associated with mean PRx values above +0.25 and +0.35, respectively. Markers of extra-cranial injury burden do not appear to be strongly associated with impaired cerebrovascular reactivity in TBI, during both the initial and entire ICU stay. Keywords: autoregulation, cerebrovascular reactivity, extra-cranial injury, injury burden, TBI
  •  
41.
  •  
42.
  • Åkerlund, Cecilia, 1983-, et al. (author)
  • Clustering identifies endotypes of traumatic brain injury in an intensive care cohort : a CENTER-TBI study
  • 2022
  • In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 26:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as 'mild', 'moderate' or 'severe' based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights.METHODS: We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (< 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation.RESULTS: Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with 'moderate' TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with 'severe' GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p < 0.001).CONCLUSIONS: Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care. 
  •  
43.
  • Åkerlund, Cecilia, et al. (author)
  • Impact of duration and magnitude of raised intracranial pressure on outcome after severe traumatic brain injury : A CENTER-TBI high-resolution group study
  • 2020
  • In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:12
  • Journal article (peer-reviewed)abstract
    • Magnitude of intracranial pressure (ICP) elevations and their duration have been associated with worse outcomes in patients with traumatic brain injuries (TBI), however published thresholds for injury vary and uncertainty about these levels has received relatively little attention. In this study, we have analyzed high-resolution ICP monitoring data in 227 adult patients in the CENTER-TBI dataset. Our aim was to identify thresholds of ICP intensity and duration associated with worse outcome, and to evaluate the uncertainty in any such thresholds. We present ICP intensity and duration plots to visualize the relationship between ICP events and outcome. We also introduced a novel bootstrap technique to evaluate uncertainty of the equipoise line. We found that an intensity threshold of 18 ± 4 mmHg (2 standard deviations) was associated with worse outcomes in this cohort. In contrast, the uncertainty in what duration is associated with harm was larger, and safe durations were found to be population dependent. The pressure and time dose (PTD) was also calculated as area under the curve above thresholds of ICP. A relationship between PTD and mortality could be established, as well as for unfavourable outcome. This relationship remained valid for mortality but not unfavourable outcome after adjusting for IMPACT core variables and maximum therapy intensity level. Importantly, during periods of impaired autoregulation (defined as pressure reactivity index (PRx)>0.3) ICP events were associated with worse outcomes for nearly all durations and ICP levels in this cohort and there was a stronger relationship between outcome and PTD. Whilst caution should be exercised in ascribing causation in observational analyses, these results suggest intracranial hypertension is poorly tolerated in the presence of impaired autoregulation. ICP level guidelines may need to be revised in the future taking into account cerebrovascular autoregulation status considered jointly with ICP levels.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-43 of 43
Type of publication
journal article (41)
other publication (1)
research review (1)
Type of content
peer-reviewed (42)
other academic/artistic (1)
Author/Editor
Stocchetti, Nino (43)
Menon, David K. (25)
Citerio, Giuseppe (24)
Koskinen, Lars-Owe D ... (22)
Ercole, Ari (21)
Brorsson, Camilla (19)
show more...
Maas, Andrew I. R. (17)
Sundström, Nina (14)
Lingsma, Hester F. (13)
Smielewski, Peter (12)
Steyerberg, Ewout W. (11)
Nelson, David (9)
Menon, David (8)
Orešič, Matej, 1967- (7)
Huijben, Jilske A. (7)
Sahuquillo, Juan (7)
Büki, Andras, 1966- (6)
Videtta, Walter (6)
Manley, Geoffrey (6)
Servadei, Franco (6)
Cnossen, Maryse C. (6)
Meyfroidt, Geert (5)
Robertson, Claudia (5)
Diringer, Michael (5)
Cooper, D. Jamie (5)
Gao, Guoyi (5)
Oddo, Mauro (5)
Rubiano, Andres M. (5)
Chesnut, Randall M. (5)
Lecky, Fiona (5)
Holst, Anders (4)
Okonkwo, David O. (4)
Hutchinson, Peter (4)
Taccone, Fabio Silvi ... (4)
Mayer, Stephan (4)
Aguilera, Sergio (4)
Figaji, Anthony (4)
Ghajar, Jamshid (4)
Harris, Odette (4)
Hoffer, Alan (4)
Joseph, Mathew (4)
Kitagawa, Ryan (4)
Michael, Daniel B. (4)
Rosenfeld, Jeffrey V ... (4)
Shutter, Lori (4)
Ullman, Jamie S. (4)
Vespa, Paul (4)
Wright, David W. (4)
Zammit, Christopher (4)
Hawryluk, Gregory W. ... (4)
show less...
University
Umeå University (32)
Karolinska Institutet (30)
Örebro University (12)
Royal Institute of Technology (4)
Uppsala University (2)
Lund University (2)
Language
English (43)
Research subject (UKÄ/SCB)
Medical and Health Sciences (43)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view