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  • Andersson, Emma, et al. (författare)
  • Acute-Phase Neurofilament Light and Glial Fibrillary Acidic Proteins in Cerebrospinal Fluid Predict Long-Term Outcome After Severe Traumatic Brain Injury
  • 2024
  • Ingår i: NEUROCRITICAL CARE. - 1541-6933 .- 1556-0961.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background This study investigated trajectory profiles and the association of concentrations of the biomarkers neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ventricular cerebrospinal fluid (CSF) with clinical outcome at 1 year and 10-15 years after a severe traumatic brain injury (sTBI).Methods This study included patients with sTBI at the Neurointensive Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. The injury was regarded as severe if patients had a Glasgow Coma Scale <= 8 corresponding to Reaction Level Scale >= 4. CSF was collected from a ventricular catheter during a 2-week period. Concentrations of NfL and GFAP in CSF were analyzed with enzyme-linked immunosorbent assay. The Glasgow Outcome Scale (GOS) was used to assess the 1-year and 10-15-year outcomes. After adjustment for age and previous neurological diseases, logistic regression was performed for the outcomes GOS 1 (dead) or GOS 2-5 (alive) and GOS 1-3 (poor) or GOS 4-5 (good) versus the independent continuous variables (NfL and GFAP).Results Fifty-three patients with sTBI were investigated; forty-seven adults are presented in the article, and six children (aged 7-18 years) are described in Supplement 1. The CSF concentrations of NfL gradually increased over 2 weeks post trauma, whereas GFAP concentrations peaked on days 3-4. Increasing NfL and GFAP CSF concentrations increased the odds of GOS 1-3 outcome 1 year after trauma (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80, p = 0.025; and OR 1.61, 95% CI 1.09-2.37, p = 0.016, respectively). Similarly, increasing CSF concentrations of NfL and GFAP increased the odds for GOS 1-3 outcome 10-15 years after trauma (OR 2.04, 95% CI 1.05-3.96, p = 0.035; and OR 1.60, 95% CI 1.02-2.00, p = 0.040).Conclusions This study shows that initial high concentrations of NfL and GFAP in CSF are both associated with higher odds for GOS 1-3 outcome 1 year and 10-15 years after an sTBI, implicating its potential usage as a prognostic marker in the future.
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  • Bentzer, Peter, et al. (författare)
  • Isolated Brain Trauma in Cats Triggers Rapid Onset of Hypovolemia
  • 2017
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 26:3, s. 450-456
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hemodynamic instability responsive to fluid resuscitation is common after a traumatic brain injury (TBI), also in the absence of systemic hemorrhage. The present study tests if an isolated severe TBI induces a decrease in plasma volume (PV). Methods: The study was performed in three groups of anesthetized and tracheostomized male cats (n = 21). In one group (n = 8), the cats were prepared with a cranial borehole (10 mm i.d) used to expose the brain to a fluid percussion brain injury (FPI) (1.90–2.20 bar), and two smaller cranial boreholes (4 mm i.d) for insertion of an intracranial pressure (ICP) and a microdialysis catheter. To differentiate the effect of FPI from that of the surgical preparation, a sham group was exposed to the same surgical preparation but no FPI trauma (n = 8). A control group had no brain trauma and no surgical preparation (n = 5). PV was determined by a 125I-albumin dilution technique. PV, electrolytes, pH, BE (base excess), hematocrit (Hct), PaO2, and PaCO2 were measured at baseline and after 3 h. Mean arterial pressure (MAP) was measured continuously. ICP was measured in the FPI and the sham group. Results: In the FPI group, PV decreased by 11.2 mL/kg from 31.7 mL/kg (p < 0.01) with a simultaneous increase in Hct and decrease in pH. In the sham group, PV decreased by 5.7 mL/kg from 32.7 mL/kg (p < 0.01). The control group showed no PV reduction. Conclusions: The results support that an isolated severe head trauma triggers a significant and rapid reduction in PV, most likely due to vascular leak.
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  • Böhm, Julia K., et al. (författare)
  • Extended Coagulation Profiling in Isolated Traumatic Brain Injury : A CENTER-TBI Analysis
  • 2022
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 36:3, s. 927-941
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury.METHODS: Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick's value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers.RESULTS: Patients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15-20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2.CONCLUSIONS: This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.
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  • Böhm, Julia K., et al. (författare)
  • Global Characterisation of Coagulopathy in Isolated Traumatic Brain Injury (iTBI) : A CENTER-TBI Analysis
  • 2020
  • Ingår i: Neurocritical Care. - : Encyclopedia of Global Archaeology/Springer Verlag. - 1541-6933 .- 1556-0961. ; 35:1, s. 184-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Trauma-induced coagulopathy in patients with traumatic brain injury (TBI) is associated with high rates of complications, unfavourable outcomes and mortality. The mechanism of the development of TBI-associated coagulopathy is poorly understood.Methods: This analysis, embedded in the prospective, multi-centred, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, aimed to characterise the coagulopathy of TBI. Emphasis was placed on the acute phase following TBI, primary on subgroups of patients with abnormal coagulation profile within 4 h of admission, and the impact of pre-injury anticoagulant and/or antiplatelet therapy. In order to minimise confounding factors, patients with isolated TBI (iTBI) (n = 598) were selected for this analysis.Results: Haemostatic disorders were observed in approximately 20% of iTBI patients. In a subgroup analysis, patients with pre-injury anticoagulant and/or antiplatelet therapy had a twice exacerbated coagulation profile as likely as those without premedication. This was in turn associated with increased rates of mortality and unfavourable outcome post-injury. A multivariate analysis of iTBI patients without pre-injury anticoagulant therapy identified several independent risk factors for coagulopathy which were present at hospital admission. Glasgow Coma Scale (GCS) less than or equal to 8, base excess (BE) less than or equal to − 6, hypothermia and hypotension increased risk significantly.Conclusion: Consideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management.
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  • Ceric, Ameldina, et al. (författare)
  • Cardiac Arrest Treatment Center Differences in Sedation and Analgesia Dosing During Targeted Temperature Management
  • 2023
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 38:1, s. 16-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sedation and analgesia are recommended during targeted temperature management (TTM) after cardiac arrest, but there are few data to provide guidance on dosing to bedside clinicians. We evaluated differences in patient-level sedation and analgesia dosing in an international multicenter TTM trial to better characterize current practice and clinically important outcomes. Methods: A total 950 patients in the international TTM trial were randomly assigned to a TTM of 33 °C or 36 °C after resuscitation from cardiac arrest in 36 intensive care units. We recorded cumulative doses of sedative and analgesic drugs at 12, 24, and 48 h and normalized to midazolam and fentanyl equivalents. We compared number of medications used, dosing, and titration among centers by using multivariable models, including common severity of illness factors. We also compared dosing with time to awakening, incidence of clinical seizures, and survival. Results: A total of 614 patients at 18 centers were analyzed. Propofol (70%) and fentanyl (51%) were most frequently used. The average dosages of midazolam and fentanyl equivalents were 0.13 (0.07, 0.22) mg/kg/h and 1.16 (0.49, 1.81) µg/kg/h, respectively. There were significant differences in number of medications (p < 0.001), average dosages (p < 0.001), and titration at all time points between centers (p < 0.001), and the outcomes of patients in these centers were associated with all parameters described in the multivariate analysis, except for a difference in the titration of sedatives between 12 and 24 h (p = 0.40). There were associations between higher dosing at 48 h (p = 0.003, odds ratio [OR] 1.75) and increased titration of analgesics between 24 and 48 h (p = 0.005, OR 4.89) with awakening after 5 days, increased titration of sedatives between 24 and 48 h with awakening after 5 days (p < 0.001, OR > 100), and increased titration of sedatives between 24 and 48 h with a higher incidence of clinical seizures in the multivariate analysis (p = 0.04, OR 240). There were also significant associations between decreased titration of analgesics and survival at 6 months in the multivariate analysis (p = 0.048). Conclusions: There is significant variation in choice of drug, dosing, and titration when providing sedation and analgesics between centers. Sedation and analgesia dosing and titration were associated with delayed awakening, incidence of clinical seizures, and survival, but the causal relation of these findings cannot be proven.
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  • Ceyisakar, Iris E., et al. (författare)
  • Can We Cluster ICU Treatment Strategies for Traumatic Brain Injury by Hospital Treatment Preferences?
  • 2022
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 36:3, s. 846-856
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In traumatic brain injury (TBI), large between-center differences in treatment and outcome for patients managed in the intensive care unit (ICU) have been shown. The aim of this study is to explore if European neurotrauma centers can be clustered, based on their treatment preference in different domains of TBI care in the ICU.METHODS: Provider profiles of centers participating in the Collaborative European Neurotrauma Effectiveness Research in TBI study were used to assess correlations within and between the predefined domains: intracranial pressure monitoring, coagulation and transfusion, surgery, prophylactic antibiotics, and more general ICU treatment policies. Hierarchical clustering using Ward's minimum variance method was applied to group data with the highest similarity. Heat maps were used to visualize whether hospitals could be grouped to uncover types of hospitals adhering to certain treatment strategies.RESULTS: Provider profiles were available from 66 centers in 20 different countries in Europe and Israel. Correlations within most of the predefined domains varied from low to high correlations (mean correlation coefficients 0.2-0.7). Correlations between domains were lower, with mean correlation coefficients of 0.2. Cluster analysis showed that policies could be grouped, but hospitals could not be grouped based on their preference.CONCLUSIONS: Although correlations between treatment policies within domains were found, the failure to cluster hospitals indicates that a specific treatment choice within a domain is not a proxy for other treatment choices within or outside the domain. These results imply that studying the effects of specific TBI interventions on outcome can be based on between-center variation without being substantially confounded by other treatments.TRIAL REGISTRATION: We do not report the results of a health care intervention.
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  • Engquist, Henrik, et al. (författare)
  • Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT
  • 2018
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 28:2, s. 143-151
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions.METHODS:Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0-3, 4-7, and 8-12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0-48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients.RESULTS:Twenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6-33.9) to 38.4 (IQR 27.0-41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time.CONCLUSIONS:HHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients.
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  • Engquist, Henrik, et al. (författare)
  • Temporal Dynamics of Cerebral Blood Flow During the Acute Course of Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT
  • 2019
  • Ingår i: Neurocritical Care. - : HUMANA PRESS INC. - 1541-6933 .- 1556-0961. ; 30:2, s. 280-290
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Compromised cerebral blood flow (CBF) is a crucial factor in delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Repeated measurement of CBF may improve our understanding of the temporal dynamics following SAH. The aim of this study was to assess CBF at different phases of the acute course in poor-grade SAH patients, hypothesizing more pronounced disturbances at day 4-7, and that the initial level of CBF determines the following course of CBF.Methods: Mechanically ventilated SAH patients were scheduled for bedside measurement of regional and global cortical CBF at day 0-3, 4-7, and 8-12, using xenon-enhanced computed tomography in a mobile setup. Patients were dichotomized depending on high or low initial global cortical CBF and cutoff level 30ml/100g/min.Results: Eighty-one patients were included, and 51 had measurements at day 0-3 and 4-7. In patients with high initial CBF, the level was unchanged at day 4-7; 37.7 (IQR 32.6-46.7) ml/100g/min versus 36.8 (IQR 29.5-44.8). The low-CBF group showed a slight increase from 23.6 (IQR 21.0-28.1) ml/100g/min to 28.4 (IQR 22.7-38.3) (P=0.025), still markedly lower than the high-CBF group (P=0.016). In the low-CBF group, CBF increased in patients who received hypertension, hypervolemia, and hemodilution (HHH therapy) but remained low in standard treated patients. For the subset of 27 patients examined also at day 8-12, the differences depending on initial CBF level were no longer statistically significant. Among patients with still low CBF at day 4-7, the proportion who had poor short-term outcome was 55% compared to 35% (n.s.) for patients with high CBF.Conclusions: CBF studied in poor-grade SAH patients at large did not show any statistically significant changes over time. Stratifying patients by high or low initial CBF and whether HHH therapy was given revealed an association between low initial CBF and persistent low CBF at day 4-7. These findings may be of clinical relevance in managing SAH patients with low early CBF.
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  • Fletcher-Sandersjoo, A, et al. (författare)
  • Time Course of Hemostatic Disruptions After Traumatic Brain Injury: A Systematic Review of the Literature
  • 2021
  • Ingår i: Neurocritical care. - : Springer Science and Business Media LLC. - 1556-0961 .- 1541-6933. ; 34:2, s. 635-656
  • Tidskriftsartikel (refereegranskat)abstract
    • Almost two-thirds of patients with severe traumatic brain injury (TBI) develop some form of hemostatic disturbance, which contributes to poor outcome. While the initial head injury often leads to impaired clot formation, TBI is also associated with an increased risk of thrombosis. Most likely there is a progression from early bleeding to a later prothrombotic state. In this paper, we systematically review the literature on the time course of hemostatic disruptions following TBI. A MEDLINE search was performed for TBI studies reporting the trajectory of hemostatic assays over time. The search yielded 5,049 articles, of which 4,910 were excluded following duplicate removal as well as title and abstract review. Full-text assessment of the remaining articles yielded 33 studies that were included in the final review. We found that the first hours after TBI are characterized by coagulation cascade dysfunction and hyperfibrinolysis, both of which likely contribute to lesion progression. This is then followed by platelet dysfunction and decreased platelet count, the clinical implication of which remains unclear. Later, a poorly defined prothrombotic state emerges, partly due to fibrinolysis shutdown and hyperactive platelets. In the clinical setting, early administration of the antifibrinolytic agent tranexamic acid has proved effective in reducing head-injury-related mortality in a subgroup of TBI patients. Further studies evaluating the time course of hemostatic disruptions after TBI are warranted in order to identify windows of opportunity for potential treatment options.
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  • Forssten, Maximilian Peter, 1996-, et al. (författare)
  • The Role of Glycerol-Containing Drugs in Cerebral Microdialysis : A Retrospective Study on the Effects of Intravenously Administered Glycerol
  • 2019
  • Ingår i: Neurocritical Care. - : Humana Press. - 1541-6933 .- 1556-0961. ; 30:3, s. 590-600
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cerebral microdialysis (CMD) is a valuable tool for monitoring compounds in the cerebral extracellular fluid (ECF). Glycerol is one such compound which is regarded as a marker of cell membrane decomposition. Notably, in some acutely brain-injured patients, CMD-glycerol levels rise without any other apparent indication of cerebral deterioration. The aim of this study was to investigate whether this could be due to an association between CMD-glycerol levels and the administration of glycerol-containing drugs.METHODS: Microdialysis data were retrospectively retrieved from the hospital's intensive care unit patient data management system (PDMS). All patients who were monitored with CMD for ≥ 96 h were included. Administered drug doses were retrieved from the PDMS and converted to exact doses of glycerol. Cross-correlation analyses were performed between the free, metabolized as well as total administered dose of glycerol and the detrended and differenced CMD-glycerol concentration. These analyses were repeated for two sets of subgroups based upon the individual catheter's graphical trend and its location in relation to the lesion.RESULTS: There was no significant correlation between the differenced CMD-glycerol levels and drug-administered glycerol. Furthermore, there was no significant correlation between CMD-glycerol and catheter location or graphical trend. However, if the CMD-glycerol levels were detrended, significant but clinically non-relevant correlations were identified (maximum correlation coefficient of 0.1 (0.04-0.15, 95% CI) at a lag of 7 h using the total administered dose of glycerol).CONCLUSIONS: Glycerol-containing drugs routinely administered intravenously in the clinical setting appear to have a minimal and clinically insignificant effect on levels of glycerol in the cerebral ECF.
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  • Hansen, Björn M., et al. (författare)
  • Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome : MISTIE II and CLEAR III
  • 2020
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 33:2, s. 516-524
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Objective: Intracerebral hemorrhage (ICH) patients commonly have concomitant white matter lesions (WML) which may be associated with poor outcome. We studied if WML affects hematoma expansion (HE) and post-stroke functional outcome in a post hoc analysis of patients from randomized controlled trials. Methods: In ICH patients from the clinical trials MISTIE II and CLEAR III, WML grade on diagnostic computed tomography (dCT) scan (dCT, < 24 h after ictus) was assessed using the van Swieten scale (vSS, range 0–4). The primary outcome for HE was > 33% or > 6 mL ICH volume increase from dCT to the last pre-randomization CT (< 72 h of dCT). Secondary HE outcomes were: absolute ICH expansion, > 10.4 mL total clot volume increase, and a subgroup analysis including patients with dCT < 6 h after ictus using the primary HE definition of > 33% or > 6 mL ICH volume increase. Poor functional outcome was assessed at 180 days and defined as modified Rankin Scale (mRS) ≥ 4, with ordinal mRS as a secondary endpoint. Results: Of 635 patients, 55% had WML grade 1–4 at dCT (median 2.2 h from ictus) and 13% had subsequent HE. WML at dCT did not increase the odds for primary or secondary HE endpoints (P ≥ 0.05) after adjustment for ICH volume, intraventricular hemorrhage volume, warfarin/INR > 1.5, ictus to dCT time in hours, age, diabetes mellitus, and thalamic ICH location. WML increased the odds for having poor functional outcome (mRS ≥ 4) in univariate analyses (vSS 4; OR 4.16; 95% CI 2.54–6.83; P < 0.001) which persisted in multivariable analyses after adjustment for HE and other outcome risk factors. Conclusions: Concomitant WML does not increase the odds for HE in patients with ICH but increases the odds for poor functional outcome. Clinical Trial Registration: http://www.clinicaltrials.gov trial-identifers: NCT00224770 and NCT00784134.
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  • Hägglund, Linda, et al. (författare)
  • Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage
  • 2022
  • Ingår i: Neurocritical Care. - : Humana Press. - 1541-6933 .- 1556-0961. ; 36:3, s. 993-1001
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: This study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored.METHODS: Patients with sTBI aged 15-70 years presenting with a Glasgow Coma Scale Score ≤ 8 were included. Brain and subcutaneous adipose tissue glycerol levels were measured through microdialysis in 48 patients, of whom 42 had complete data for analysis. Brain tissue damage was also evaluated by using the Rotterdam classification of brain computed tomography scans and the biochemical biomarkers S-100B and NSE.RESULTS: In 60% of the patients, a positive relationship in glycerolbrain/sc was observed. Patients with a positive correlation of glycerolbrain/sc had slightly higher brain glycerol levels compared with the group with a negative correlation. There was no significant association between the computed tomography Rotterdam score and glycerolbrain/sc. S-100B and NSE were associated with the profile of glycerolbrain/sc. Our results cannot be explained by the general severity of the trauma as measured by using the Injury Severity Score or Acute Physiology and Chronic Health Evaluation Score.CONCLUSIONS: We have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood-brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.
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  • Iaccarino, Corrado, et al. (författare)
  • Management of Antithrombotic Drugs in Patients with Isolated Traumatic Brain Injury : An Intersociety Consensus Document
  • 2024
  • Ingår i: Neurocritical Care. - : Springer Nature. - 1541-6933 .- 1556-0961. ; 40:1, s. 314-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAll available recommendations about the management of antithrombotic therapies (ATs) in patients who experienced traumatic brain injury (TBI) are mainly based on expert opinion because of the lack of strength in the available evidence-based medicine. Currently, the withdrawal and the resumption of AT in these patients is empirical, widely variable, and based on the individual assessment of the attending physician. The main difficulty is to balance the thrombotic and hemorrhagic risks to improve patient outcome.MethodsUnder the endorsement of the Neurotraumatology Section of Italian Society of Neurosurgery, the Italian Society for the Study about Haemostasis and Thrombosis, the Italian Society of Anaesthesia, Analgesia, Resuscitation, and Intensive Care, and the European Association of Neurosurgical Societies, a working group (WG) of clinicians completed two rounds of questionnaires, using the Delphi method, in a multidisciplinary setting. A table for thrombotic and bleeding risk, with a dichotomization in high risk and low risk, was established before questionnaire administration. In this table, the risk is calculated by matching different isolated TBI (iTBI) scenarios such as acute and chronic subdural hematomas, extradural hematoma, brain contusion (intracerebral hemorrhage), and traumatic subarachnoid hemorrhage with patients under active AT treatment. The registered indication could include AT primary prevention, cardiac valve prosthesis, vascular stents, venous thromboembolism, and atrial fibrillation.ResultsThe WG proposed a total of 28 statements encompassing the most common clinical scenarios about the withdrawal of antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients who experienced blunt iTBI. The WG voted on the grade of appropriateness of seven recommended interventions. Overall, the panel reached an agreement for 20 of 28 (71%) questions, deeming 11 of 28 (39%) as appropriate and 9 of 28 (32%) as inappropriate interventions. The appropriateness of intervention was rated as uncertain for 8 of 28 (28%) questions.ConclusionsThe initial establishment of a thrombotic and/or bleeding risk scoring system can provide a vital theoretical basis for the evaluation of effective management in individuals under AT who sustained an iTBI. The listed recommendations can be implemented into local protocols for a more homogeneous strategy. Validation using large cohorts of patients needs to be developed. This is the first part of a project to update the management of AT in patients with iTBI.
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  • Johansson Kostenniemi, Urban, 1987-, et al. (författare)
  • MeningiSSS : A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis
  • 2020
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 586-595
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Knowing the individual child’s risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors.Methods: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure.Results: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores’ results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson–Todd Scale (AUC = 0.79) was all associated with death.Conclusions: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.
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22.
  • Johnson, Ulf, et al. (författare)
  • Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx)
  • 2016
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 25:1, s. 47-55
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH.OBJECTIVE: To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI.METHODS: Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5 min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically.RESULTS: 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not.CONCLUSION: In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying.
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23.
  • Johnson, Ulf, et al. (författare)
  • Should the Neurointensive Care Management of Traumatic Brain Injury Patients be Individualized According to Autoregulation Status and Injury Subtype?
  • 2014
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 21:2, s. 259-265
  • Tidskriftsartikel (refereegranskat)abstract
    • The status of autoregulation is an important prognostic factor in traumatic brain injury (TBI), and is important to consider in the management of TBI patients. Pressure reactivity index (PRx) is a measure of autoregulation that has been thoroughly studied, but little is known about its variation in different subtypes of TBI. In this study, we examined the impact of PRx and cerebral perfusion pressure (CPP) on outcome in different TBI subtypes. 107 patients were retrospectively studied. Data on PRx, CPP, and outcome were collected from our database. The first CT scan was classified according to the Marshall classification system. Patients were assigned to "diffuse" (Marshall class: diffuse-1, diffuse-2, and diffuse-3) or "focal" (Marshall class: diffuse-4, evacuated mass lesion, and non-evacuated mass lesion) groups. 2 x 2 tables were constructed calculating the proportions of favorable/unfavorable outcome at different combinations of PRx and CPP. Low PRx was significantly associated with favorable outcome in the combined group (p = 0.002) and the diffuse group (p = 0.04), but not in the focal group (p = 0.06). In the focal group higher CPP values were associated with worse outcome (p = 0.02). In diffuse injury patients with disturbed autoregulation (PRx > 0.1), CPP > 70 mmHg was associated with better outcome (p = 0.03). TBI patients with diffuse injury may differ from those with mass lesions. In the latter higher levels of CPP may be harmful, possibly due to BBB disruption. In TBI patients with diffuse injury and disturbed autoregulation higher levels of CPP may be beneficial.
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24.
  • Koskinen, Lars-Owe D., et al. (författare)
  • Prostacyclin Affects the Relation Between Brain Interstitial Glycerol and Cerebrovascular Pressure Reactivity in Severe Traumatic Brain Injury
  • 2019
  • Ingår i: Neurocritical Care. - : Humana Press. - 1541-6933 .- 1556-0961. ; 31:3, s. 494-500
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cerebral injury may alter the autoregulation of cerebral blood flow. One index for describing cerebrovascular state is the pressure reactivity (PR). Little is known of whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. The aim of this investigation was to explore whether increased interstitial levels of glycerol, a marker of cell membrane damage, are associated with PR, and if prostacyclin, a membrane stabilizer and regulator of the microcirculation, may affect this association in a beneficial way.MATERIALS AND METHODS: ) during the 96-h sampling period were calculated. The mean PR was calculated as the ICP/mean arterial pressure (MAP) regression coefficient based on hourly mean ICP and MAP during the first 96 h.RESULTS: (ρ = 0.490, p = 0.015) levels in the placebo group only.CONCLUSIONS: PR is correlated to the glycerol level in patients suffering from sTBI, a relationship that is not seen in the group treated with prostacyclin. Glycerol has been associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakdown may impair the regulation of cerebrovascular PR.
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25.
  • Koskinen, Lars-Owe D., et al. (författare)
  • Prostacyclin Influences the Pressure Reactivity in Patients with Severe Traumatic Brain Injury Treated with an ICP-Targeted Therapy
  • 2015
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 22:1, s. 26-33
  • Tidskriftsartikel (refereegranskat)abstract
    • This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. Blunt head trauma patients, Glasgow coma scale a parts per thousand currency sign8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR a parts per thousand currency sign0. Mean PR over 96 h (PRtot) was 0.077 +/- A 0.168, in the prostacyclin group 0.030 +/- A 0.153 and in the placebo group 0.120 +/- A 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PRtot was 0.117 +/- A 0.182 in the unfavorable (GOSE 1-4) and 0.029 +/- A 0.140 in the favorable outcome group (GOSE 5-8). Area under the curve for prediction of death (ROC) was 0.742 and for favorable outcome 0.628. Prostacyclin influenced the PR in a direction of increased pressure stability and a lower PRtot was associated with improved outcome. The individual PR varied substantially over time. The predictive value of PRtot for outcome was not solid enough to be used in the clinical situation.
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26.
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27.
  • Lindgren, Cecilia, 1958-, et al. (författare)
  • ADMA Levels and Arginine/ADMA Ratios Reflect Severity of Disease and Extent of Inflammation After Subarachnoid Hemorrhage
  • 2014
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 21:1, s. 91-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome. Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0-240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3-5 and less severe clinical condition H&H 1-2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome. Compared to admission, 0-48 h after SAH, the following was observed 49-240 h after SAH; (a) ADMA was significantly increased at 97-240 h (highest 217-240 h), (b) CRP was significantly increased at 49-240 h (highest 73-96 h), (c) interleukin-6 (IL-6) was significantly lower at 97-240 h (highest 49-96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1-2 compared to patients with H&H 3-5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55 %) or without (45 %) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1-3 and patients with GOS 4-5. ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.
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28.
  • Lindgren, Cecilia, et al. (författare)
  • Frequency of non-convulsive Seizures and non-convulsive status Epilepticus in Subarachnoid Hemorrhage patients in need of controlled ventilation and sedation
  • 2012
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 17:3, s. 367-373
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Non-convulsive seizures (NCSZ) can be more prevalent than previously recognized among comatose neuro-intensive care patients. The aim of this study was to evaluate the frequency of NCSZ and non-convulsive status epilepticus (NCSE) in sedated and ventilated subarachnoid hemorrhage (SAH) patients.METHODS: Retrospective study at a university hospital neuro-intensive care unit, from January 2008 until June 2010. Patients were treated according to a local protocol, and were initially sedated with midazolam or propofol or combinations of these sedative agents. Thiopental was added for treatment of intracranial hypertension. No wake-up tests were performed. Using NicoletOne((R)) equipment (VIASYS Healthcare Inc., USA), continuous EEG recordings based on four electrodes and a reference electrode was inspected at full length both in a two electrode bipolar and a four-channel referential montage.RESULTS: Approximately 5,500 h of continuous EEG were registered in 28 SAH patients (33 % of the patients eligible for inclusion). The median Glasgow Coma scale was 8 (range 3-14) and the median Hunt and Hess score was 4 (range 1-4). During EEG registration, no clinical seizures were observed. In none of the patients inter ictal epileptiform activity was seen. EEG seizures were recorded only in 2/28 (7 %) patients. One of the patients experienced 4 min of an NCSZ and one had a 5 h episode of an NCSE.CONCLUSION: Continuous EEG monitoring is important in detecting NCSZ in sedated patients. Continuous sedation, without wake-up tests, was associated with a low frequency of subclinical seizures in SAH patients in need of controlled ventilation.
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29.
  • Marklund, Niklas, et al. (författare)
  • Neurointensive care management of raised intracranial pressure caused by severe valproic acid intoxication
  • 2007
  • Ingår i: Neurocritical care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 7:2, s. 160-164
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction We describe the neurointensive care (NIC) management of a patient with severe cerebral swelling and raised intracranial pressure (ICP) after severe sodium valproic acid (VPA) intoxication. A previously healthy 25-year old male with mild tonic-clonic epilepsy was found unconscious with serum VPA levels >10,000 mu mol/l. The patient deteriorated to Glasgow Motor Scale score (GMS) 2 and a CT scan showed signs of raised lCP. Early ICP was elevated, >50 mm Hg, and continuous EEG monitoring showed isoelectric readings. Methods The patient was treated with an ICP-guided protocol including mild hyperventilation, normovolemia, head elevation and intermittent doses of mannitol. Due to refractory elevations of ICP, high-dose pentobarbital infusion was initiated, and ICP gradually normalised. Results There were several systemic complications including coagulopathy, hypocalcemia and pancreatitis. The patient remained in a depressed level of consciousness for 2 months but gradually recovered, showing a good recovery with minor subjective cognitive deficits by 6 months. Conclusion We conclude that NIC may be an important treatment option in cases of severe intoxication causing cerebral swelling.
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30.
  • Mathieu, François, et al. (författare)
  • Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients : an Exploratory Analysis.
  • 2020
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 373-382
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI.METHODS: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses.RESULTS: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status.CONCLUSIONS: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.
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31.
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32.
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33.
  • Nielsen, T. H., et al. (författare)
  • Bedside Diagnosis of Mitochondrial Dysfunction After Malignant Middle Cerebral Artery Infarction
  • 2014
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 21:1, s. 35-42
  • Tidskriftsartikel (refereegranskat)abstract
    • The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.
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34.
  • Norberg, Erik, et al. (författare)
  • Impact of Acute Cardiac Complications After Subarachnoid Hemorrhage on Long-Term Mortality and Cardiovascular Events.
  • 2018
  • Ingår i: Neurocritical care. - : Springer Science and Business Media LLC. - 1556-0961 .- 1541-6933. ; 29:3, s. 404-412
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac complications frequently occur after subarachnoid hemorrhage (SAH) and are associated with an increased risk of neurological complications and poor outcomes. The aim of this study was to evaluate the impact of acute cardiac complications after SAH on long-term mortality and cardiovascular events.All patients admitted to our Neuro intensive care unit with verified SAH from January 2010 to April 2015, and electrocardiogram, echocardiogram, and troponin T or NTproBNP data obtained within 72h of admission were included in the study. Mortality data were obtained from the Swedish population register. Data regarding cause of death and hospitalization for cardiovascular events were obtained from the Swedish Board of Health and Welfare.A total of 455 patients were included in the study analysis. There were 102 deaths during the study period. Cardiac troponin release (HR 1.08, CI 1.02-1.15 per 100ng/l, p=0.019), NTproBNP (HR 1.05, CI 1.01-1.09 per 1000ng/l, p=0.018), and ST-T abnormalities (HR 1.53, CI 1.02-2.29, p=0.040) were independently associated with an increased risk of death. However, these associations were significant only during the first 3months after the hemorrhage. Cardiac events were observed in 25 patients, and cerebrovascular events were observed in 62 patients during the study period. ST-T abnormalities were independently associated with an increased risk of cardiac events (HR 5.52, CI 2.07-14.7, p<0.001), and stress cardiomyopathy was independently associated with an increased risk of cerebrovascular events (HR 3.65, CI 1.55-8.58, p=0.003).Cardiac complications after SAH are associated with an increased risk of short-term death. Patients with electrocardiogram abnormalities and stress cardiomyopathy need appropriate follow-up for the identification of cardiac disease or risk factors for cardiovascular disease.
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35.
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36.
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37.
  • Poulsen, Frantz R., et al. (författare)
  • Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis
  • 2015
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 22:2, s. 221-228
  • Tidskriftsartikel (refereegranskat)abstract
    • Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate that this technique may separate ischemia and non-ischemic mitochondrial dysfunction. The present study is a retrospective interpretation of biochemical data obtained in a series of patients with severe community-acquired meningitis. Cerebral energy metabolism was monitored in 15 patients with severe community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio > 30 with intracerebral pyruvate level < 70 A mu mol L-1. Non-ischemic mitochondrial dysfunction was defined as LP-ratio > 30 at a normal or increased interstitial concentration of pyruvate (a parts per thousand yen70 mu mol L-1). Patients with LP-ratios < 30 were classified as no mitochondrial dysfunction. The biochemical pattern was in 8 patients (10 microdialysis catheters) classified as no mitochondrial dysfunction, in 5 patients classified as non-ischemic mitochondrial dysfunction, and in 2 patients (3 catheters) classified as ischemia. In patients with severe community-acquired meningitis, compromised cerebral energy metabolism occurs frequently and was diagnosed in 7 out of 15 cases. A biochemical pattern of non-ischemic mitochondrial dysfunction appears to be a more common underlying condition than cerebral ischemia.
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38.
  • Prendergast, Virginia, et al. (författare)
  • Electric Versus Manual Tooth Brushing among Neuroscience ICU Patients: Is it Safe?
  • 2011
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 14:2, s. 281-286
  • Tidskriftsartikel (refereegranskat)abstract
    • Poor oral hygiene has been associated with ventilator-acquired pneumonia. Yet providing oral care for intubated patients is problematic. Furthermore, concerns that oral care could raise intracranial pressure (ICP) may cause nurses to use foam swabs to provide oral hygiene rather than tooth brushing as recommended by the American Association of Critical-Care Nurses. Evidence is needed to support the safety of toothbrushing during oral care. We therefore evaluated ICP and cerebral perfusion pressure (CPP) during oral care with a manual or electric toothbrush in intubated patients in a neuroscience intensive care unit (ICU). As part of a larger 2-year, prospective, randomized clinical trial, 47 adult neuroscience ICU patients with an ICP monitor received oral care with a manual or electric toothbrush. ICP and CPP were recorded before, during, and after oral care over the first 72 h of admission. Groups did not differ significantly in age, gender, or severity of injury. Of 807 ICP and CPP measurements obtained before, during, and after oral care, there were no significant differences in ICP (P = 0.72) or CPP (P = 0.68) between toothbrush methods. Analysis of pooled data from both groups revealed a significant difference across the three time points (Wilks' lambda, 12.56; P < 0.001; partial eta(2), 0.36). ICP increased significantly (mean difference, 1.7 mm Hg) from before to during oral care (P = 0.001) and decreased significantly (mean difference, 2.1 mm Hg) from during to after oral care (P < 0.001). In the absence of preexisting intracranial hypertension during oral care, tooth brushing, regardless of method, was safely performed in intubated neuroscience ICU patients.
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39.
  • Purins, Karlis, 1983-, et al. (författare)
  • Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model
  • 2012
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 16:3, s. 462-469
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (B(ti)pO(2)) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation- and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30). METHODS: B(ti)pO(2), L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved. RESULTS: Baseline level of B(ti)pO(2) was 22.9 ± 6.2 mmHg, the L/P ratio 17.7 ± 6.1 and CPP 73 ± 17 mmHg. B(ti)pO(2) and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30) when CPP decreased below 30 mmHg and B(ti)pO(2) to <10 mmHg. CONCLUSIONS: A severe increase of ICP leading to CPP below 30 mmHg and B(ti)pO(2) below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions.
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40.
  • Reinstrup, Peter, et al. (författare)
  • Cerebral Blood Flow and Transcranial Doppler Sonography Measurements of CO(2)-Reactivity in Acute Traumatic Brain Injured Patients.
  • 2014
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 20:1, s. 54-59
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements limits routine clinical use. An alternative approach is to measure the CBF velocity using bedside, non-invasive, and transcranial Doppler (TCD) sonography. This study was performed to investigate if TCD is a useful alternative to CBF in patients with severe TBI. METHOD: CBF and TCD flow velocity measurements and cerebrovascular reactivity to hypocapnia were simultaneously evaluated in 27 patients with acute TBI. Measurements were performed preoperatively during controlled normocapnia and hypocapnia in patients scheduled for hematoma evacuation under general anesthesia. MAIN FINDING AND CONCLUSION: Although the lack of statistical correlation between the calculated reactivity indices, there was a significant decrease in TCD-mean flow velocity and a decrease in CBF with hypocapnia. CBF and TCD do not seem to be directly interchangeable in determining CO(2)-reactivity in TBI, despite both methods demonstrating deviation in the same direction during hypocapnia. TCD and CBF measurements both provide useful information on cerebrovascular events which, although not interchangeable, may complement each other in clinical scenarios.
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41.
  • Reinstrup, Peter, et al. (författare)
  • Prostacyclin Infusion May Prevent Secondary Damage in Pericontusional Brain Tissue.
  • 2011
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 14, s. 441-446
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Prostacyclin is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation, and has been suggested as therapy for cerebral ischemia. A case of focal traumatic brain lesion that was monitored using intracerebral microdialysis, and bedside analysis and display is reported here. When biochemical signs of cerebral ischemia progressed, i.v. infusion of prostacyclin was started. METHODS: Two microdialysis catheters were placed in the penumbra zones surrounding evacuated focal brain contusions. The samples were analyzed for glucose, pyruvate, lactate, glutamate, and glycerol. RESULTS: When biochemical deterioration indicated progressive secondary ischemia (increase in lactate/pyruvate ratio, decrease in glucose, and increase in glutamate levels), continuous infusion of prostacyclin (0.5-1.0 ng kg(-1) min(-1) i.v.) was started. The treatment resulted in an improvement of the lactate/pyruvate ratios and a normalization of the interstitial levels of glucose and glutamate. The glycerol levels remained within normal limits indicating that degradation of cellular membranes had not occurred. CONCLUSION: The above case supports the view that new therapies directed toward protection of the sensitive biochemical penumbra zones surrounding focal brain lesions may be evaluated by intracerebral microdialysis.
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42.
  • Sader, N, et al. (författare)
  • Indomethacin for control of ICP
  • 2015
  • Ingår i: Neurocritical care. - : Springer Science and Business Media LLC. - 1556-0961 .- 1541-6933. ; 22:3, s. 437-449
  • Tidskriftsartikel (refereegranskat)
  •  
43.
  • Sjöberg, Rickard L., et al. (författare)
  • Blood Metabolomic Predictors of 1-Year Outcome in Subarachnoid Hemorrhage
  • 2015
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 23:2, s. 225-232
  • Tidskriftsartikel (refereegranskat)abstract
    • Delayed neurological deficit (DND) is the most important cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH) whose aneurysms have been secured. However, the methods currently used to predict the development of DND, such as trans-cranial Doppler or levels biochemical markers in blood and cerebrospinal fluid are not very accurate. Venous blood was drawn from 50 patients with SAH, admitted to the neurosurgical department UmeAyen University Hospital, at day 1-3 and day 7 after the bleed. The clinical status of the patients was followed up approximately 1 year after this episode and classified according to the Glasgow Outcome Score (GOS). Results showed considerable differences in blood metabolomic patterns between day 1-3 and 7 after the hemorrhage. Fifty-six out of 98 metabolites could be identified from our in-house library and 17 of these metabolites changed significantly from day 1-3 to 7 after the bleed. One of these, myo-inositol, was predictive of clinical outcome even after correction for multiple testing. An estimation of the diagnostic accuracy of high levels of this substance in predicting good outcome (GOS 4-5) yielded a sensitivity of .763 and a specificity of .5 at the optimal cut off point. SAH is an event with a profound effect on blood metabolomics profiles. Myo-inositol might be an interesting compound for future study to focus on in the search for metabolic markers in venous blood of delayed neurological deterioration in SAH patients.
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44.
  • Skoglund, Karin, 1964-, et al. (författare)
  • Effects of the neurological wake-up test on intracranial pressure and cerebral perfusion pressure in brain-injured patients
  • 2009
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 11:2, s. 135-142
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the effects of the neurological "wake-up test" (NWT), defined as interruption of continuous propofol sedation and evaluation of the patient's level of consciousness, on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with severe subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). METHODS: A total of 127 NWT procedures in 21 severely brain-injured adult patients with either TBI (n = 12) or SAH (n = 9) were evaluated. ICP and CPP levels prior to, during and after the NWT procedure were recorded. RESULTS: During the NWT, ICP increased from 13.4 +/- 6 mmHg at baseline to 22.7 +/- 12 (P < 0.05) and the CPP increased from 75.6 +/- 11 to 79.1 +/- 21 mmHg (P < 0.05) in TBI patients. Eight patients showed a reduced CPP during the NWT due to increased ICP. In SAH patients, ICP increased from 10.6 +/- 5 to 16.8 +/- 8 mmHg (P < 0.05) and the CPP increased from 76.9 +/- 13 to 84.6 +/- 15 mmHg (P < 0.05). CONCLUSION: When continuous propofol sedation was interrupted and NWT was performed in severely brain-injured patients, the mean ICP and CPP levels were modestly increased. A subset of patients showed more pronounced changes. To date, the role of the NWT in the neurointensive care of TBI and SAH patients is unclear. Although the NWT is safe in the majority of patients and may provide useful clinical information about the patient's level of consciousness, alternate monitoring methods are suggested in patients showing marked ICP and/or CPP changes during NWT.
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45.
  • Skoglund, Karin, et al. (författare)
  • The Neurological Wake-up Test Does not Alter Cerebral Energy Metabolism and Oxygenation in Patients with Severe Traumatic Brain Injury
  • 2014
  • Ingår i: Neurocritical Care. - New York : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 20:3, s. 413-426
  • Tidskriftsartikel (refereegranskat)abstract
    • The neurological wake-up test (NWT) is used to monitor the level of consciousness in patients with traumatic brain injury (TBI). However, it requires interruption of sedation and may elicit a stress response. We evaluated the effects of the NWT using cerebral microdialysis (MD), brain tissue oxygenation (PbtiO2), jugular venous oxygen saturation (SjvO(2)), and/or arterial-venous difference (AVD) for glucose, lactate, and oxygen in patients with severe TBI. Seventeen intubated TBI patients (age 16-74 years) were sedated using continuous propofol infusion. All patients received intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in addition to MD, PbtiO2 and/or SjvO(2). Up to 10 days post-injury, ICP, CPP, PbtiO2 (51 NWTs), MD (49 NWTs), and/or SjvO(2) (18 NWTs) levels during propofol sedation (baseline) and NWT were compared. MD was evaluated at a flow rate of 1.0 mu L/min (28 NWTs) or the routine 0.3 mu L/min rate (21 NWTs). The NWT increased ICP and CPP levels (p < 0.05). Compared to baseline, interstitial levels of glucose, lactate, pyruvate, glutamate, glycerol, and the lactate/pyruvate ratio were unaltered by the NWT. Pathological SjvO(2) (< 50 % or > 71 %; n = 2 NWTs) and PbtiO2 (< 10 mmHg; n = 3 NWTs) values were rare at baseline and did not change following NWT. Finally, the NWT did not alter the AVD of glucose, lactate, or oxygen. The NWT-induced stress response resulted in increased ICP and CPP levels although it did not negatively alter focal neurochemistry or cerebral oxygenation in TBI patients.
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46.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage : Relation to Neurointensive Care Targets
  • 2022
  • Ingår i: Neurocritical Care. - : Springer Nature. - 1541-6933 .- 1556-0961. ; 37:1, s. 281-292
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome. Methods In this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO2 was defined as CDO2 < 3.8 mL O-2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1-3) and vasospasm phase (day 4-14). Results Of 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R-2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions. Conclusions Systemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.
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47.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • High Arterial Glucose is Associated with Poor Pressure Autoregulation, High Cerebral Lactate/Pyruvate Ratio and Poor Outcome Following Traumatic Brain Injury
  • 2019
  • Ingår i: Neurocritical Care. - : HUMANA PRESS INC. - 1541-6933 .- 1556-0961. ; 31:3, s. 526-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Arterial hyperglycemia is associated with poor outcome in traumatic brain injury (TBI), but the pathophysiology is not completely understood. Previous preclinical and clinical studies have indicated that arterial glucose worsens pressure autoregulation. The aim of this study was to evaluate the relationship of arterial glucose to both pressure reactivity and cerebral energy metabolism. Method This retrospective study was based on 120 patients with severe TBI treated at the Uppsala University hospital, Sweden, 2008-2018. Data from cerebral microdialysis (glucose, pyruvate, and lactate), arterial glucose, and pressure reactivity index (PRx55-15) were analyzed the first 3 days post-injury. Results High arterial glucose was associated with poor outcome/Glasgow Outcome Scale-Extended at 6-month follow-up (r = - 0.201, p value = 0.004) and showed a positive correlation with both PRx55-15 (r = 0.308, p = 0.001) and cerebral lactate/pyruvate ratio (LPR) days 1-3 (r = 0. 244, p = 0.014). Cerebral lactate-to-pyruvate ratio and PRx55-15 had a positive association day 2 (r = 0.219, p = 0.048). Multivariate linear regression analysis showed that high arterial glucose predicted poor pressure autoregulation on days 1 and 2. Conclusions High arterial glucose was associated with poor outcome, poor pressure autoregulation, and cerebral energy metabolic disturbances. The latter two suggest a pathophysiological mechanism for the negative effect of arterial hyperglycemia, although further studies are needed to elucidate if the correlations are causal or confounded by other factors.
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48.
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49.
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50.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Temperature Changes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage : Relation to Injury Pattern, Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome
  • 2023
  • Ingår i: Neurocritical Care. - : Humana Press. - 1541-6933 .- 1556-0961. ; 39, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim was to study the course of body temperature in the acute phase of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) in relation to the primary brain injury, cerebral physiology, and clinical outcome.Methods: In this observational study, 166 patients with aSAH treated at the neurosurgery department at Uppsala University Hospital in Sweden between 2008 and2018 with temperature, intracranial pressure (ICP), and microdialysis (MD) monitoring were included. The first 10 days were divided into the early phase (days 1-3) and the vasospasm phase (days 4-10).Results: Normothermia (temperature = 36-38 degrees C) was most prevalent in the early phase. A lower mean temperature at this stage was univariately associated with a worse primary brain injury, with higher Fisher grade and higher MD glycerol concentration, as well as a worse neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the early phase. There was a transition toward an increased burden of hyperthermia (temperature > 38 degrees C) in the vasospasm phase. This was associated with concurrent infections but not with neurological or radiological injury severity at admission. Elevated temperature was associated with higher MD pyruvate concentration, lower rate of an MD pattern indicative of ischemia, and higher rate of poor neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the vasospasm phase. The associations between temperature and clinical outcome did not hold true in multiple logistic regression analyses.Conclusions: Spontaneously low temperature in the early phase reflected a worse primary brain injury and indicated a worse outcome prognosis. Hyperthermia was common in the vasospasm phase and was more related to infections than primary injury severity but also with a more favorable energy metabolic pattern with better substrate supply, possibly related to hyperemia.
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