Multimodal prediction of residual consciousness in the intensive care unit: the CONNECT-ME study.

Functional MRI (fMRI) and EEG may reveal residual consciousness in patients with disorders of consciousness (DoC), as reflected by a rapidly expanding literature on chronic DoC. However, acute DoC is rarely investigated, although identifying residual consciousness is key to clinical decision-making in the intensive care unit (ICU). Therefore, the objective of the prospective, observational, tertiary centre cohort, diagnostic phase IIb study 'Consciousness in neurocritical care cohort study using EEG and fMRI' (CONNECT-ME, NCT02644265) was to assess the accuracy of fMRI and EEG to identify residual consciousness in acute DoC in the ICU. Between April 2016 and November 2020, 87 acute DoC patients with traumatic or non-traumatic brain injury were examined with repeated clinical assessments, fMRI and EEG. Resting-state EEG and EEG with external stimulations were evaluated by visual analysis, spectral band analysis and a Support Vector Machine (SVM) consciousness classifier. In addition, within- and between-network resting-state connectivity for canonical resting-state fMRI networks was assessed. Next, we used EEG and fMRI data at study enrolment in two different machine-learning algorithms (Random Forest and SVM with a linear kernel) to distinguish patients in a minimally conscious state or better (≥MCS) from those in coma or unresponsive wakefulness state (≤UWS) at time of study enrolment and at ICU discharge (or before death). Prediction performances were assessed with area under the curve (AUC). Of 87 DoC patients (mean age, 50.0 ± 18 years, 43% female), 51 (59%) were ≤UWS and 36 (41%) were ≥ MCS at study enrolment. Thirty-one (36%) patients died in the ICU, including 28 who had life-sustaining therapy withdrawn. EEG and fMRI predicted consciousness levels at study enrolment and ICU discharge, with maximum AUCs of 0.79 (95% CI 0.77-0.80) and 0.71 (95% CI 0.77-0.80), respectively. Models based on combined EEG and fMRI features predicted consciousness levels at study enrolment and ICU discharge with maximum AUCs of 0.78 (95% CI 0.71-0.86) and 0.83 (95% CI 0.75-0.89), respectively, with improved positive predictive value and sensitivity. Overall, both machine-learning algorithms (SVM and Random Forest) performed equally well. In conclusion, we suggest that acute DoC prediction models in the ICU be based on a combination of fMRI and EEG features, regardless of the machine-learning algorithm used.

Multimodal Prediction of 3- and 12-Month Outcomes in ICU Patients with Acute Disorders of Consciousness.

BACKGROUND: In intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.e. CONNECT-ME; ClinicalTrials.gov identifier: NCT02644265) investigates ICU patients with acute DoC due to traumatic and nontraumatic brain injuries, using electroencephalography (EEG) (resting-state and passive paradigms), functional magnetic resonance imaging (fMRI) (resting-state) and systematic clinical examinations. METHODS: We previously presented results for a subset of patients (n = 87) concerning prediction of consciousness levels in the ICU. Now we report 3- and 12-month outcomes in an extended cohort (n = 123). Favorable outcome was defined as a modified Rankin Scale score ≤ 3, a cerebral performance category score ≤ 2, and a Glasgow Outcome Scale Extended score ≥ 4. EEG features included visual grading, automated spectral categorization, and support vector machine consciousness classifier. fMRI features included functional connectivity measures from six resting-state networks. Random forest and support vector machine were applied to EEG and fMRI features to predict outcomes. Here, random forest results are presented as areas under the curve (AUC) of receiver operating characteristic curves or accuracy. Cox proportional regression with in-hospital death as a competing risk was used to assess independent clinical predictors of time to favorable outcome. RESULTS: Between April 2016 and July 2021, we enrolled 123 patients (mean age 51 years, 42% women). Of 82 (66%) ICU survivors, 3- and 12-month outcomes were available for 79 (96%) and 77 (94%), respectively. EEG features predicted both 3-month (AUC 0.79 [95% confidence interval (CI) 0.77-0.82]) and 12-month (AUC 0.74 [95% CI 0.71-0.77]) outcomes. fMRI features appeared to predict 3-month outcome (accuracy 0.69-0.78) both alone and when combined with some EEG features (accuracies 0.73-0.84) but not 12-month outcome (larger sample sizes needed). Independent clinical predictors of time to favorable outcome were younger age (hazard ratio [HR] 1.04 [95% CI 1.02-1.06]), traumatic brain injury (HR 1.94 [95% CI 1.04-3.61]), command-following abilities at admission (HR 2.70 [95% CI 1.40-5.23]), initial brain imaging without severe pathological findings (HR 2.42 [95% CI 1.12-5.22]), improving consciousness in the ICU (HR 5.76 [95% CI 2.41-15.51]), and favorable visual-graded EEG (HR 2.47 [95% CI 1.46-4.19]). CONCLUSIONS: Our results indicate that EEG and fMRI features and readily available clinical data predict short-term outcome of patients with acute DoC and that EEG also predicts 12-month outcome after ICU discharge.

Endovascular treatment for cerebral venous sinus thrombosis - a single center study.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disorder. The majority of these patients respond favorably to systemic anticoagulation. However, a subset of patients will deteriorate clinically, despite optimal medical therapy. METHODS: Retrospective single center study of 28 consecutive CVST patients treated with systemic anticoagulation and additional endovascular therapy. RESULTS: Median age was 37.5 years (range 15-76 years), there were 21 (75%) women, and 20 (71%) had thrombosis involving ≥2 venous sinuses. Intracranial hemorrhage (ICH) was present at admission in 18 patients (64%). Endovascular therapy consisted of local thrombolysis in 26 (93%) patients; 9 patients (32%) had additional mechanical thrombectomy, and in 2 (7%) patients thrombectomy alone was performed. Complete recanalization at end of the final intervention was achieved in 15 patients (54%), partial recanalization in 11 patients (39%), whereas there was no recanalization in 2 patients (7%). On follow-up imaging, conducted between 3 and 6 months, recanalization further improved to 76%, 19% and 5%, respectively. A favorable outcome (mRS ≤ 2) was achieved in 63% of patients at 3 months, which improved to 79% at 6 months. Post-procedural ICH or volume expansion of preexisting ICH was seen in 9 patients (32%). In total 5 patients died (18%). CONCLUSIONS: Systemic anticoagulation with the addition of endovascular therapy with local thrombolysis and/or mechanical thrombectomy is a potential strategy to obtain recanalization in patients with CVST who deteriorate clinically despite medical therapy or are comatose. Endovascular therapy may increase the risk of ICH.

Delayed cerebral ischaemia in patients with aneurysmal subarachnoid haemorrhage: Functional outcome and long-term mortality.

INTRODUCTION: Delayed cerebral ischaemia (DCI) is one of the most frequent complications of aneurysmal subarachnoid haemorrhage (aSAH). The purpose of the present retrospective cohort study of patients with aSAH was to identify the association between DCI, functional outcome and 4-year mortality. METHODS: Patients admitted to the Neurointensive Care Unit at Rigshospitalet, Copenhagen, with aSAH from 1 January 2010, through 31 December 2013 were registered. Patients were categorized into 3 groups: (a) those with DCI, defined as either a decline in consciousness or focal neurological deficits lasting ≥1 hour without any other detectable cause, (b) those without DCI, or (c) those who were unassessable for DCI. Functional neurological outcome after 6 months, as measured by the modified Rankin Scale (mRS), was dichotomized into good (mRS 0-2) and poor (mRS 3-6). Kaplan-Meier survival curves were constructed, and incidence risk rates were calculated both to determine the association between DCI and mortality. RESULTS: Four hundred ninety-two cases of aSAH were recorded in the study period. DCI occurred in 23% of all patients, corresponding to 33% of assessable patients. Patients without DCI had the best functional outcome (mRS) compared to patients with DCI and patients who were unassessable; furthermore, the latter had worse outcomes than patients with DCI. Patients diagnosed with DCI had significantly higher mortality than those without DCI, even ignoring the first 14 days after admission. CONCLUSION: DCI may be associated with both short- and long-term morbidity and mortality in patients with aSAH.

Cardiac arrhythmias the first month after acute traumatic spinal cord injury.

OBJECTIVE: Cardiovascular complications including cardiac arrest and arrhythmias remain a clinical challenge in the management of acute traumatic spinal cord injury (SCI). Still, there is a lack of knowledge regarding the characteristics of arrhythmias in patients with acute traumatic SCI. The aim of this prospective observational study was to investigate the occurrence of cardiac arrhythmias and cardiac arrests in patients with acute traumatic SCI. METHODS: As early as possible after SCI 24-hour Holter monitoring was performed. Additional Holter recordings were performed 1, 2, 3, and 4 weeks after SCI. Furthermore, 12-lead electrocardiograms (ECGs) were obtained shortly after SCI and at 4 weeks. RESULTS: Thirty patients were included. Bradycardia (heart rate (HR) <50 b.p.m.) was present in 17-35% of the patients with cervical (C1-C8) SCI (n = 24) within the first 14 days. In the following 14 days, the occurrence was 22-32%. Bradycardia in the thoracic (Th1-Th12) SCI group (n = 6) was present in 17-33% during the observation period. The differences between the two groups were not statistically significant. The mean minimum HR was significantly lower in the cervical group compared with the thoracic group both on 12-lead ECGs obtained shortly after SCI (P = 0.030) and at 4 weeks (P = 0.041). CONCLUSION: Many patients with cervical SCI experience arrhythmias such as bradycardia, sinus node arrest, supraventricular tachycardia, and more rarely cardiac arrest the first month after SCI. Apart from sinus node arrests and limited bradycardia, no arrhythmias were seen in patients with thoracic SCI. Standard 12-lead ECGs will often miss the high prevalence these arrhythmias have.

Organ donation after circulatory death in Denmark.

Donation after circulatory death (DCD) is practiced in several countries to increase the number of organs for transplantation. This review summarises the key points in a new protocol which will introduce controlled DCD in Denmark as an option in seriously ill patients, in whom death is inevitable and the criteria for brain death is not met. It includes a no touch period of five minutes following circulatory arrest. Rapid procurement or normothermic regional perfusion may be applied depending on the organs to be transplanted. The introduction of DCD requires thorough training of involved health personnel.

Elderly trauma patients have high circulating noradrenaline levels but attenuated release of adrenaline, platelets, and leukocytes in response to increasing injury severity.

OBJECTIVE: High patient age is a strong predictor of poor outcome in trauma patients. The present study investigated the effect of age on mortality and biomarkers of sympathoadrenal activation, tissue, endothelial, and glycocalyx damage, coagulation activation/inhibition, fibrinolysis, and inflammation in trauma patients at admission. DESIGN: Prospective observational study. SETTING: Single level I trauma center. PATIENTS: Eighty adult trauma patients (≥18 yrs) who met criteria for full trauma team activation and had an arterial cannula. INTERVENTION: Blood sampling a median of 68 min (interquartile range 48-88) post injury. MEASUREMENTS: Data on demography, biochemistry, Injury Severity Score, and 30-day mortality were recorded and plasma/serum was analyzed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments, annexin V, thrombomodulin, syndecan-1), platelet activation (soluble CD40 ligand), coagulation activation/inhibition (prothrombin fragment 1.2, thrombin/antithrombin complex, antithrombin, protein C, activated protein C, protein S, soluble endothelial protein C receptor, tissue factor pathway inhibitor, von Willebrand factor, fibrinogen, factor XIII), fibrinolysis (D-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1), and inflammation (interleukin-6, terminal complement complex). Patients were stratified according to the median age (46 yrs) of the full cohort. RESULTS: Older trauma patients had markedly higher noradrenaline (p < .001) but an attenuated increase in adrenaline with increasing Injury Severity Score and lower platelets and leukocytes (both p < .05) compared to the younger patients. Older patients displayed a biomarker profile suggestive of enhanced release, activation, and consumption of the natural anticoagulants (low antithrombin, high activated protein C, protein S, and tissue factor pathway inhibitor) and hyperfibrinolysis (high tissue-type plasminogen activator) (all p < .05 vs. younger patients). Age was an independent predictor of mortality (hazard ratio 1.04 [95% confidence interval 1.01-1.07], p = .005) after adjusting for Injury Severity Score, prehospital Glasgow Coma Scale, and plasma catecholamines. CONCLUSIONS: In trauma patients, the association between age and mortality was confirmed. Older patients had high plasma noradrenaline but attenuated adrenaline release with higher Injury Severity Score, impaired platelet and leukocyte mobilization, enhanced consumption of anticoagulants, and hyperfibrinolysis, which may all contribute to the poor outcome in these patients.

Depression, anxiety and quality-of-life among relatives of patients with severe brain injury: the acute phase.

PRIMARY OBJECTIVE: To investigate the emotional well-being of relatives of patients with a severe brain injury in the acute setting, as well as risk factors associated with high anxiety and depression scores and impaired quality-of-life. RESEARCH DESIGN: Clinical convenience sample. METHODS AND PROCEDURES: Participants included 45 relatives of patients with severe brain injury recruited at a NICU. All relatives completed selected scales from the SCL-90-R and SF-36 ∼ 14 days after injury. Data concerning the condition of the patient were also collected. MAIN OUTCOME AND RESULTS: Of the relatives, 51% and 69% reported anxiety and depression, respectively, as well as significantly impaired quality-of-life compared to normal reference populations. Regression analysis revealed that up to 20% of the variance in depression and anxiety scores could be explained by the CRASH 2 Mortality prediction. CONCLUSIONS: The majority of the relatives had severely impaired quality-of-life and symptoms of anxiety and depression during the patient's NICU stay. Future research is required to explore stressors and evaluate effects of psychological intervention in the acute setting.

Cardiac arrhythmias six months following traumatic spinal cord injury.

OBJECTIVE: To investigate the incidence of cardiac arrhythmias at six months following traumatic spinal cord injury (SCI) and to compare the prevalence of arrhythmias between participants with cervical and thoracic SCI. DESIGN: A prospective observational study using continuous twenty-four-hour Holter monitoring. SETTING: Inpatient rehabilitation unit of a university research hospital and patient home setting. PARTICIPANTS: Fifty-five participants with acute traumatic SCI were prospectively included. For each participant, the SCI was characterized according to the International Standards for Neurological Classification of SCI by the neurological level and severity according to the American Spinal Injury Association Impairment Scale. OUTCOME MEASURES: Comparisons between demographic characteristics and arrhythmogenic occurrences as early as possible after SCI (4 ± 2 days) followed by 1, 2, 3, 4 weeks and 6 month time points of Holter monitoring. RESULTS: Bradycardia (heart rate [HR] <50 bpm) was present in 29% and 33% of the participants with cervical (C1-C8) and thoracic (T1-T12) SCI six months after SCI, respectively. The differences in episodes of bradycardia between the two groups were not significant (P < 0.54). The mean maximum HR increased significantly from 4 weeks to 6 months post-SCI (P < 0.001), however mean minimum and maximum HR were not significantly different between the groups at the six-month time point. There were no differences in many arrhythmias between recording periods or between groups at six months. CONCLUSIONS: At the six-month timepoint following traumatic SCI, there were no significant differences in occurrences of arrhythmias between participants with cervical and thoracic SCI compared to the findings observed in the first month following SCI.

Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study.

INTRODUCTION: It is debated whether early trauma-induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated the prevalence of overt DIC and ACoTS in trauma patients and characterized these conditions based on their biomarker profiles. METHODS: An observational study was carried out at a single Level I Trauma Center. Eighty adult trauma patients (≥18 years) who met criteria for full trauma team activation and had an arterial cannula inserted were included. Blood was sampled a median of 68 minutes (IQR 48 to 88) post-injury. Data on demography, biochemistry, injury severity score (ISS) and mortality were recorded. Plasma/serum was analyzed for biomarkers reflecting tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption (fibrinogen, FXIII), fibrinolysis (D-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1) and inflammation (interleukin (IL)-6, terminal complement complex (sC5b-9)). Comparison of patients stratified according to the presence or absence of overt DIC (International Society of Thrombosis and Hemostasis (ISTH) criteria) or ACoTS (activated partial thromboplastin time (APTT) and/or international normalized ratio (INR) above normal reference). RESULTS: No patients had overt DIC whereas 15% had ACoTS. ACoTS patients had higher ISS, transfusion requirements and mortality (all P < 0.01) and a biomarker profile suggestive of enhanced tissue, endothelial cell and glycocalyx damage and consumption coagulopathy with low protein C, antithrombin, fibrinogen and FXIII levels, hyperfibrinolysis and inflammation (all P < 0.05). Importantly, in non-ACoTS patients, apart from APTT/INR, higher ISS correlated with biomarkers of enhanced tissue, endothelial cell and glycocalyx damage, protein C activation, coagulation factor consumption, hyperfibrinolysis and inflammation, that is, resembling that observed in patients with ACoTS. CONCLUSIONS: ACoTS and non-ACoTS may represent a continuum of coagulopathy reflecting a progressive early evolutionarily adapted hemostatic response to the trauma hit and both are parts of TIC whereas DIC does not appear to be part of this early response.

Effect of an analgo-sedation protocol for neurointensive patients: a two-phase interventional non-randomized pilot study.

INTRODUCTION: Sedation protocols are needed for neurointensive patients. The aim of this pilot study was to describe sedation practice at a neurointensive care unit and to assess the feasibility and efficacy of a new sedation protocol. The primary outcomes were a shift from sedation-based to analgesia-based sedation and improved pain management. The secondary outcomes were a reduction in unplanned extubations and duration of sedation. METHODS: This was a two-phase (before-after), prospective controlled study at a university-affiliated, 14-bed neurointensive care unit in Denmark. The sample included patients requiring mechanical ventilation for at least 48 hours treated with continuous sedative and analgesic infusions or both. During the observation phase the participants (n = 106) were sedated as usual (non-protocolized), and during the intervention phase the participants (n = 109) were managed according to a new sedation protocol. RESULTS: Our study showed a shift toward analgo-sedation, suggesting feasibility of the protocol. We found a significant reduction in the use of propofol (P < .001) and midazolam (P = .001) and an increase in fentanyl (P < .001) and remifentanil (P = .003). Patients selected for daily sedation interruption woke up faster, and estimates of pain free patients increased from 56.8% to 82.7% (P < .001), suggesting efficacy of the protocol. The duration of sedation and unplanned extubations were unchanged. CONCLUSIONS: Our pilot study showed feasibility and partial efficacy of our protocol. Some neurointensive patients might not benefit from protocolized practice. We recommend an interdisciplinary effort to target patients requiring less sedation, as issues of oversedation and inadequate pain management still need more attention. TRIAL REGISTRATION: ISRCTN80999859.

Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, and endothelial damage in patients with traumatic brain injury.

It remains to be debated whether traumatic brain injury (TBI) induces a different coagulopathy than does non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy, and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients was sampled (median of 68 min [IQR 48-88] post-injury) upon admission to our trauma center. Plasma/serum were retrospectively analyzed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue factor pathway inhibitor, antithrombin, prothrombin fragment 1+2, thrombin/antithrombin complex, von Willebrand factor, factor XIII, d-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1), immunology (interleukin [IL]6), endothelial cell/glycocalyx damage (soluble thrombomodulin, syndecan-1), and vasculogenesis (angiopoietin-1, -2). Patients were stratified according to: (1) isolated severe head/neck injuries (Abbreviated injury score [AIS]-head/neck ≥ 3, AIS-other<3) (isoTBI); (2) severe head/neck and extracranial injuries (AIS-head/neck ≥ 3, AIS-other>3) (sTBI+other); and (3) injuries without significant head/neck injuries (AIS-head/neck<3, including all AIS-other scores) (non-TBI). Twenty-three patients presented with isoTBI, 15 with sTBI+other and 42 with non-TBI. Acute coagulopathy of trauma shock, defined as activated partial thromboplastin time (APTT) and/or international normalized ratio (INR)>35 sec and>1.2, was found in 13%, 47%, and 5%, respectively (p=0.000). sTBI+other had significantly higher plasma levels of adrenaline, noradrenaline, annexin V, d-dimer, IL-6, syndecan-1, soluble thrombomodulin, and reduced protein C and factor XIII levels (all p<0.05). No significant biomarker differences were found between isoTBI and non-TBI patients. Injury severity scale (ISS) rather than the presence or absence of head/neck injuries determined the hemostatic and biomarker response to the injury. The coagulopathy identified thus reflected the severity of injury rather than its localization.

High levels of soluble VEGF receptor 1 early after trauma are associated with shock, sympathoadrenal activation, glycocalyx degradation and inflammation in severely injured patients: a prospective study.

BACKGROUND: The level of soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is increased in sepsis and strongly associated with disease severity and mortality. Endothelial activation and damage contribute to both sepsis and trauma pathology. Therefore, this study measured sVEGFR1 levels in trauma patients upon hospital admission hypothesizing that sVEGFR1 would increase with higher injury severity and predict a poor outcome. METHODS: Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry, Injury Severity Score (ISS), transfusions and 30-day mortality were recorded and plasma/serum (sampled a median of 68 min (IQR 48-88) post-injury) was analyzed for sVEGFR1 and biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue injury (histone-complexed DNA fragments, hcDNA), endothelial activation and damage (von Willebrand Factor Antigen, Angiopoietin-2, soluble endothelial protein C receptor, syndecan-1, soluble thrombomodulin (sTM)), coagulation activation/inhibition and fibrinolysis (prothrombinfragment 1 + 2, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer) and inflammation (interleukin-6). Spearman correlations and regression analyses to identify variables associated with sVEGFR1 and its predictive value. RESULTS: Circulating sVEGFR1 correlated with injury severity (ISS, rho = 0.46), shock (SBE, rho = -0.38; adrenaline, rho = 0.47), tissue injury (hcDNA, rho = 0.44) and inflammation (IL-6, rho = 0.54) (all p < 0.01) but by multivariate linear regression analysis only lower SBE and higher adrenaline and IL-6 were independent predictors of higher sVEGFR1. sVEGFR1 also correlated with biomarkers indicative of endothelial glycocalyx degradation (syndecan-1, rho = 0.67), endothelial cell damage (sTM, rho = 0.66) and activation (Ang-2, rho = 0.31) and hyperfibrinolysis (tPA, rho = 0.39; D-dimer, rho = 0.58) and with activated protein C (rho = 0.31) (all p < 0.01). High circulating sVEGFR1 correlated with high early and late transfusion requirements (number of packed red blood cells (RBC) at 1 h (rho = 0.27, p = 0.016), 6 h (rho = 0.27, p = 0.017) and 24 h (rho = 0.31, p = 0.004) but was not associated with mortality. CONCLUSIONS: sVEGFR1 increased with increasing injury severity, shock and inflammation early after trauma but only sympathoadrenal activation, hypoperfusion, and inflammation were independent predictors of sVEGFR1 levels. sVEGFR1 correlated strongly with other biomarkers of endothelial activation and damage and with RBC transfusion requirements. Sympathoadrenal activation, shock and inflammation may be critical drivers of endothelial activation and damage early after trauma.

The prognostic value of thrombelastography in identifying neurosurgical patients with worse prognosis.

Coagulopathy in patients with intracranial haemorrhage or traumatic brain injury (TBI) is associated with clinical deterioration and worse outcome. Whole blood viscoelastic haemostatic assays, like thrombelastography (TEG), might aid conventional coagulation assays in identification of patients with worse prognosis. We performed a review of patients (totalling 78 patients) with primary acute intracranial haemorrhage or isolated TBI admitted to a neurointensive care unit (NICU) for more than 24 h during a period of 9 months, who had TEG analysis performed at admission. Primary outcome was all-cause 30-day mortality, whereas decline in Glasgow Coma Scale (GCS) score at 24 h after admission or death due to cerebral incarceration were secondary outcomes. Patients were defined as hypocoaguable if TEG reaction time was more than 8 min, angle less than 55° and/or maximal amplitude less than 51 mm. Patients were defined hypocoaguable according to conventional coagulation assays if international normalized ratio was more than 1.3, platelet counts less than 100×10/l and/or activated partial thromboplastine time more than 35 s. Eight patients were hypocoaguable by TEG on admission to NICU and had higher 30-day mortality (63% vs. 16%, P=0.008), more often declined in GCS (57% vs. 16%, P=0.02) and expired due to cerebral incarceration (50% vs. 6%, P=0.02). Hypocoagulability by TEG, lower admission GCS and subarachnoid haemorrhage were independently associated with higher 30-day mortality [TEG: odds ratio (OR) 14.8 (2.2-100.1), P=0.006; GCS: OR 1.3 (1.1-1.5), P=0.006; subarachnoid haemorrhage: OR: 5.3 (1.3-22.3), P=0.02]. Only two patients were hypocoaguable by both conventional coagulation assays and TEG. The current data indicate that hypocoagulability by TEG at admission to NICU predicts worse prognosis. Low concordance with conventional coagulation assays indicates that TEG might be valuable in identifying patients with clinically relevant coagulopathy.

[Neurointensive care of severe traumatic brain injury]. / Neurointensiv behandling af svaere traumatiske hjerneskader.

We present a Danish algorithm for the neurointensive care of patients with severe traumatic brain injury. The primary goal is to avoid cerebral ischaemia and hypoxia and secondarily brain injury. Patient evaluation by a neurosurgeon is mandatory, and decision-making concerning extended cerebral monitoring should take place immediately. Treatment aiming at diminishing increased intracranial pressure should be initiated early. Early critical care management of patients with severe traumatic brain injury should be performed in a teamwork comprising various specialties.

[Actively induced hypothermia following severe traumatic brain injury]. / Aktivt induceret hypotermi efter svaer traumatisk hjerneskade.

A Cochrane metaanalysis and a study performed on children have recently confirmed that therapeutic hypothermia does not improve outcome after severe traumatic brain injury (TBI). TBI is not comparable to a short episode of global ischemia, where therapeutic hypothermia has been shown to improve outcome. The difference may be explained by the fact that hypothermia-induced stress after a traumatic brain injury reduces cerebral perfusion in the penumbra zone, where local circulation is already reduced. Thus, to date there is no indication for therapeutic hypothermia in TBI patients.

[Organ donation from alcohol and opioid-abusing patient]. / Organdonation fra en patient med misbrugsproblematik.

A case of a 37-year old obese patient with alcohol, sedative and opioid abuse as well as previous admissions with chest pain is presented. The patient suffered from a large subarachnoid haemorrhage and the clinical diagnosis of brain death was made. He had substantial signs of organ failure. The patient was registered as a potential organ donor in the Danish Registry for Organ Donation, and his heart and kidneys were donated. Considering all brain dead patients as potential organ donors is important.

[What is intensive therapy? Neurointensive therapy]. / Hvad er intensiv terapi? Neurointensiv terapi.

The neurointensive care unit provides observation and treatment of acute, life-threatening disorders of and injuries to the central and peripheral nervous system. The primary aim of care is the prevention of secondary neuronal damage; this requires a highly multidisciplinary approach, involving neuromonitoring as well as management of systemic comorbidity and complications. This article presents major pathophysiological issues specific to neurointensive care, as well as recent advances in the management of the critically-ill neurosurgical and neurological patient.