Pre-injury antithrombotic agents predict intracranial hemorrhagic progression, but not worse clinical outcome in severe traumatic brain injury.
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ABSTRACT: Background
The incidence of traumatic brain injury (TBI) patients of older age with comorbidities, who are pre-injury treated with antithrombotic agents (antiplatelets and/or anticoagulants), has increased. In this study, our aim was to investigate if pre-injury antithrombotic treatment was associated with worse intracranial hemorrhagic/injury progression and clinical outcome in patients with severe TBI.Methods
In this retrospective study, including 844 TBI patients treated at our neurointensive care at Uppsala University Hospital, Sweden, 2008-2018, 159 (19%) were pre-injury treated with antithrombotic agents. Demography, admission status, radiology, treatment, and outcome variables were evaluated. Significant intracranial hemorrhagic/injury evolution was defined as hemorrhagic progression seen on the second computed tomography (CT), emergency neurosurgery after the initial CT, or death following the initial CT.Results
Patients with pre-injury antithrombotics were significantly older and with a higher Charlson comorbidity index. They were more often injured by falls and more frequently developed acute subdural hematomas. Sixty-eight (8%) patients were pre-injury treated with monotherapy of antiplatelets, 67 (8%) patients with anticoagulants, and 24 (3%) patients with a combination of antithrombotics. Pre-injury anticoagulants, but not antiplatelets, were independently associated with significant intracranial hemorrhagic/injury evolution in a multiple regression analysis. However, neither anticoagulants nor antiplatelets were associated with mortality and unfavorable outcome in multiple regression analyses.Conclusions
Only anticoagulants were associated with intracranial hemorrhagic/injury progression, but no antithrombotic agent correlated with worse clinical outcome. Management, including early anticoagulant reversal, availability of emergency neurosurgery, and neurointensive care, may be important aspects for reducing the adverse effects of pre-injury antithrombotics.
SUBMITTER: Svedung Wettervik T
PROVIDER: S-EPMC8053649 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveWhile existing guidelines support the treatment of intracranial hypertension in severe traumatic brain injury (TBI), it is unclear when to suspect and initiate treatment for high intracranial pressure (ICP). The objective of this study was to derive a clinical decision rule that accurately predicts intracranial hypertension.MethodsUsing Delphi methods, the authors identified a set of potential predictors of intracranial hypertension and a clinical decision rule a priori by consensus among a group of 43 neurosurgeons and intensivists who have extensive experience managing severe TBI without ICP monitoring. To validate these predictors, the authors used data from a Latin American trial (n = 150; BEST TRIP). To report on the performance of the rule, they calculated sensitivity, specificity, and positive and negative predictive values with 95% confidence intervals. In a secondary analysis, the rule was validated using data from a North American trial (n = 131; COBRIT).ResultsThe final predictors and the clinical decision rule were approved by 97% of participants in the consensus working group. The predictors are divided into major and minor criteria. High ICP would be considered suspected in the presence of 1 major or ≥ 2 minor criteria. Major criteria are: compressed cisterns (CT classification of Marshall diffuse injury [DI] III), midline shift > 5 mm (Marshall DI IV), or nonevacuated mass lesion. Minor criteria are: Glasgow Coma Scale (GCS) motor score ≤ 4, pupillary asymmetry, abnormal pupillary reactivity, or Marshall DI II. The area under the curve for the logistic regression model that contains all the predictors was 0.86. When high ICP was defined as > 22 mm Hg, the decision rule performed with a sensitivity of 93.9% (95% CI 85.0%-98.3%), a specificity of 42.3% (95% CI 31.7%-53.6%), a positive predictive value of 55.5% (95% CI 50.7%-60.2%), and a negative predictive value of 90% (95% CI 77.1%-96.0%). The sensitivity of the clinical decision rule improved with higher ICP cutoffs up to a sensitivity of 100% when intracranial hypertension was defined as ICP > 30 mm Hg. Similar results were found in the North American cohort.ConclusionsA simple clinical decision rule based on a combination of clinical and imaging findings was found to be highly sensitive in distinguishing patients with severe TBI who would suffer intracranial hypertension. It could be used to identify patients who require ICP monitoring in high-resource settings or start ICP-lowering treatment in environments where resource limitations preclude invasive monitoring.Clinical trial registration no.: NCT02059941 (clinicaltrials.gov).
| S-EPMC6586526 | biostudies-literature
Project description:ImportanceIntracranial pressure (ICP) monitoring is a mainstay of therapy for children with traumatic brain injury (TBI), but its overall association with patient outcome is unclear.ObjectiveTo test the hypothesis that ICP monitoring is associated with improved functional survival of children with severe TBI.Design, setting, and participantsA propensity-weighted effectiveness analysis was conducted using 2 linked national databases with data from 30 US children's hospitals from January 1, 2007, to December 31, 2012, on 3084 children with severe TBI. Clinical events including neurosurgical procedures were identified using validated computable phenotypes. Data analysis was conducted from September 1, 2016, to March 1, 2017.ExposurePlacement of an ICP monitor.Main outcomes and measuresA composite of hospital mortality, discharge to hospice, or survival with placement of new tracheostomy and gastrostomy tubes.ResultsOf the 3084 children in the study (1128 girls and 1956 boys; mean [SD] age, 7.03 [5.44] years), 1002 (32.4%) underwent ICP monitoring, with substantial hospital variation (6% to 50% by hospital). Overall, 484 children (15.7%) experienced the primary composite outcome. A propensity approach using matching weights generated good covariate balance between those who did and those who did not undergo ICP monitoring. Using a propensity-weighted logistic regression model clustered by hospital, no statistically significant difference was found in functional survival between monitored and unmonitored patients (odds ratio of poor outcome among those who underwent ICP monitoring, 1.31; 95% CI, 0.99-1.74). In a prespecified secondary analysis, no difference in mortality was found (odds ratio, 1.16; 95% CI, 0.89-1.50). Prespecified subgroup analyses of children younger and older than 2 years of age and among those with unintentional and inflicted (intentional) injuries also showed no difference in outcome with ICP monitoring.Conclusions and relevanceWith the use of linked national data and validated computable phenotypes, no evidence was found of a benefit from ICP monitoring on functional survival of children with severe TBI. Intracranial pressure monitoring is a widely but inconsistently used technology with incompletely demonstrated effectiveness. A large prospective cohort study or randomized trial is needed.
| S-EPMC5710627 | biostudies-literature
Project description:BackgroundTraumatic brain injury (TBI) is the leading cause of death and disability in children, but effective tools for predicting outcome remain elusive. Although many pediatric patients receive early magnetic resonance imaging (MRI), data on its utility in prognostication are lacking. Diffuse axonal injury (DAI) is a hallmark of TBI detected on early MRI and was shown previously to improve prognostication in adult patients with TBI. In this exploratory study, we investigated whether DAI grade correlates with functional outcome and improves prognostic accuracy when combined with core clinical variables and computed tomography (CT) biomarkers in pediatric patients with moderate-severe TBI (msTBI).MethodsPediatric patients (≤ 19 years) who were admitted to two regional level one trauma centers with a diagnosis of msTBI (Glasgow Coma Scale [GCS] score < 13) between 2011 and 2019 were identified through retrospective chart review. Patients who underwent brain MRI within 30 days of injury and had documented clinical follow-up after discharge were included. Age, pupil reactivity, and initial motor GCS score were collected as part of the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. Imaging was reviewed to calculate the Rotterdam score (CT) and DAI grade (MRI) and to evaluate for presence of hypoxic-ischemic injury (MRI). The primary outcome measure was the Pediatric Cerebral Performance Category Scale (PCPCS) score at 6 months after TBI, with favorable outcome defined as PCPCS scores 1-3 and unfavorable outcome defined as PCPCS scores 4-6. The secondary outcome measure was discharge disposition to home versus to an inpatient rehabilitation facility.ResultOf 55 patients included in the study, 45 (82%) had severe TBI. The most common mechanism of injury was motor vehicle collision (71%). Initial head CT scans showed acute hemorrhage in 84% of patients. MRI was acquired a median of 5 days after injury, and hemorrhagic DAI lesions were detected in 87% of patients. Each 1-point increase in DAI grade increased the odds of unfavorable functional outcome by 2.4-fold. When controlling for core IMPACT clinical variables, neither the DAI grade nor the Rotterdam score was independently correlated with outcome and neither significantly improved outcome prediction over the IMPACT model alone.ConclusionsA higher DAI grade on early MRI is associated with worse 6-month functional outcome and with discharge to inpatient rehabilitation in children with acute msTBI in a univariate analysis but does not independently correlate with outcome when controlling for the GCS score. Addition of the DAI grade to the core IMPACT model does not significantly improve prediction of poor neurological outcome. Further study is needed to elucidate the utility of early MRI in children with msTBI.
| S-EPMC8405042 | biostudies-literature
Project description:PurposeAround 10-30 % of patients are dissatisfied with the results of their total knee arthroplasty (TKA). This review aimed to identify and evaluate the predictors of outcome measured by the three domains of health-related quality of life (pain, stiffness and function). The focus was on pre-operative psychological factors as related to other patient-related variables.MethodsA systematic search was performed using the following databases: MEDLINE, PubMed, AMED, CINAHL, PsychINFO, SciFinder, Scopus, EMBASE, Cochrane, Lilacs, Web of Science and ScienceDirect. The quality of identified studies was assessed using the Critical Appraisal Skills Programme Cohort checklist.ResultsTen studies met the eligibility criteria. From these, nine patient-related predictors of outcome were identified (depression, anxiety, age at surgery, gender (being female), medical co-morbidities, BMI, level of education, pre-operative pain severity and pre-operative knee function). Greater anxiety, pre-operative pain and function were the most significant factors to predict a poorer outcome of a TKA. The results of depression, gender (female), medical co-morbidities, BMI and level of education were variable among the included studies. There was very little evidence to support older age at operation as a predictor of poorer outcome.ConclusionPatients experiencing high levels of pain before surgery should be informed of the chances of improvement by having a TKA. A validated psychological screening tool that separates depression and anxiety is recommended as part of the pre-operative assessment stage. Patients presenting with symptoms of depression and anxiety should be identified and consulted before a TKA.Level of evidenceII.
| S-EPMC5644683 | biostudies-literature
Project description:The role of decompressive craniectomy in treating raised intracranial pressure (ICP) after traumatic brain injuries (TBI) is controversial. The aim of this study was to assess the differences in prognosis of patients initially treated by decompressive craniectomy, craniotomy, or conservatively.We conducted a single-center retrospective study on adult blunt TBI patients admitted to a neurosurgical intensive care unit during 2009-2012. Patients were divided into three groups based on their initial treatment - decompressive craniectomy, craniotomy, and conservative. Primary outcome was 6-month Glasgow Outcome Scale (GOS) dichotomized to favorable outcome (independent) and unfavorable outcome (dependent). The association between initial treatment and outcome was assessed using a logistic regression model adjusting for case-mix using known predictors of outcome.Of the 822 included patients, 58 patients were in the craniectomy group, 401 patients in the craniotomy group, and 363 patients in the conservatively treated group. Overall, 6-month unfavorable outcome was 48%. After adjusting for case-mix, patients in the decompressive craniectomy group had a statistical significantly higher risk for poor neurological outcome compared to patients in the conservative group (OR 3.06, 95% CI 1.45-6.42) and craniotomy group (OR 3.61, 95% CI 1.74-7.51).In conclusion, patients requiring primary decompressive craniectomy had a higher risk for poor neurological outcome compared to patients undergoing craniotomy or were conservatively treated. It is plausible that the poor prognosis is related to the TBI severity itself rather than the intervention. Further prospective randomized trials are required to establish the role of decompressive craniectomy in the treatment of patients with TBI.
| S-EPMC5523471 | biostudies-other
Project description:This study evaluates the correlation between injuries to deep gray matter nuclei, as quantitated by lesions in these nuclei on MR T2 Fast Spin Echo (T2 FSE) images, with 6-month neurological outcome after severe traumatic brain injury (TBI).Ninety-five patients (80 males, mean age = 36.7y) with severe TBI were prospectively enrolled. All patients underwent a MR scan within the 45 days after the trauma that included a T2 FSE acquisition. A 3D deformable atlas of the deep gray matter was registered to this sequence; deep gray matter lesions (DGML) were evaluated using a semi-quantitative classification scheme. The 6-month outcome was dichotomized into unfavorable (death, vegetative or minimally conscious state) or favorable (minimal or no neurologic deficit) outcome.Sixty-six percent of the patients (63/95) had both satisfactory registration of the 3D atlas on T2 FSE and available clinical follow-up. Patients without DGML had an 89% chance (P = 0.0016) of favorable outcome while those with bilateral DGML had an 80% risk of unfavorable outcome (P = 0.00008). Multivariate analysis based on DGML accurately classified patients with unfavorable neurological outcome in 90.5% of the cases.Lesions in deep gray matter nuclei may predict long-term outcome after severe TBI with high sensitivity and specificity.
| S-EPMC5667824 | biostudies-literature
Project description:Increasing evidence demonstrates that aging influences the brain's response to traumatic brain injury (TBI), setting the stage for neurodegenerative pathology like Alzheimer's disease (AD). This topic is often dominated by discussions of post-injury aging and inflammation, which can diminish the consideration of those same factors before TBI. In fact, pre-TBI aging and inflammation may be just as critical in mediating outcomes. For example, elderly individuals suffer from the highest rates of TBI of all severities. Additionally, pre-injury immune challenges or stressors may alter pathology and outcome independent of age. The inflammatory response to TBI is malleable and influenced by previous, coincident, and subsequent immune insults. Therefore, pre-existing conditions that elicit or include an inflammatory response could substantially influence the brain's ability to respond to traumatic injury and ultimately affect chronic outcome. The purpose of this review is to detail how age-related cellular and molecular changes, as well as genetic risk variants for AD affect the neuroinflammatory response to TBI. First, we will review the sources and pathology of neuroinflammation following TBI. Then, we will highlight the significance of age-related, endogenous sources of inflammation, including changes in cytokine expression, reactive oxygen species processing, and mitochondrial function. Heightened focus is placed on the mitochondria as an integral link between inflammation and various genetic risk factors for AD. Together, this review will compile current clinical and experimental research to highlight how pre-existing inflammatory changes associated with infection and stress, aging, and genetic risk factors can alter response to TBI.
| S-EPMC8790486 | biostudies-literature
Project description:BackgroundCompensatory-reserve-weighted intracranial pressure (wICP) has recently been suggested as a supplementary measure of intracranial pressure (ICP) in adult traumatic brain injury (TBI), with a single-center study suggesting an association with mortality at 6 months. No multi-center studies exist to validate this relationship. The goal was to compare wICP to ICP for association with outcome in a multi-center TBI cohort.MethodsUsing the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived ICP and wICP (calculated as wICP = (1 - RAP) × ICP; where RAP is the compensatory reserve index derived from the moving correlation between pulse amplitude of ICP and ICP). Various univariate logistic regression models were created comparing ICP and wICP to dichotomized outcome at 6 to 12 months, based on Glasgow Outcome Score-Extended (GOSE) (alive/dead-GOSE ≥ 2/GOSE = 1; favorable/unfavorable-GOSE 5 to 8/GOSE 1 to 4, respectively). Models were compared using area under the receiver operating curves (AUC) and p values.ResultswICP displayed higher AUC compared to ICP on univariate regression for alive/dead outcome compared to mean ICP (AUC 0.712, 95% CI 0.615-0.810, p = 0.0002, and AUC 0.642, 95% CI 0.538-746, p < 0.0001, respectively; no significant difference on Delong's test), and for favorable/unfavorable outcome (AUC 0.627, 95% CI 0.548-0.705, p = 0.015, and AUC 0.495, 95% CI 0.413-0.577, p = 0.059; significantly different using Delong's test p = 0.002), with lower wICP values associated with improved outcomes (p < 0.05 for both). These relationships on univariate analysis held true even when comparing the wICP models with those containing both ICP and RAP integrated area under the curve over time (p < 0.05 for all via Delong's test).ConclusionsCompensatory-reserve-weighted ICP displays superior outcome association for both alive/dead and favorable/unfavorable dichotomized outcomes in adult TBI, through univariate analysis. Lower wICP is associated with better global outcomes. The results of this study provide multi-center validation of those seen in a previous single-center study.
| S-EPMC6581920 | biostudies-literature
Project description:IntroductionThe aim of the current study was to evaluate the impact of increased blood lactate levels during cardiopulmonary bypass (CPB) on immediate results in patients who underwent open heart surgery.Materials and methodsWe performed a retrospective single-center study on 1290 patients. Adult cardiac surgical patients who underwent valve surgery, coronary artery bypass graft, combined procedure, adult congenital anomalies and aortic surgery were enrolled. Patients with associated comorbidities such as liver dysfunction, hemodynamic instability before surgery were excluded. Arterial blood lactate concentration was measured immediately after weaning from CPB and evaluated together with clinical data and outcomes including in hospital mortality. Patients were classified into 3 groups according to their peak arterial lactate level: group I [normal lactatemia, lactate ˂ 2 mmol/l (n = 749)], group II [mild hyperlactatemia, lactate 2-5 mmol/l (n = 489)], group III [severe hyperlactatemia, lactate ˃ 5 mmol/l (n = 52)].ResultsWhen comparing outcomes across the 3 groups, severe hyperlactatemia was correlated with worse outcomes including higher in-hospital mortality, low output cardiac syndrome, postoperative renal insufficiency, myocardial infarction, red blood cell transfusion (RBC) transfusion, prolonged mechanical ventilation and longer intensive care unit (ICU) stay hours.ConclusionBlood lactate level above 5 mmol/l and more during CPB is associated with higher in-hospital mortality rate and postoperative complications. More attention must be given to correct the common abnormalities conditions inherent of CPB in order to conduct adequate tissue perfusion and reduce the risk of hyperlactatemia.
| S-EPMC8767239 | biostudies-literature
Project description:Traumatic microbleeds are small foci of hypointensity seen on T2*-weighted MRI in patients following head trauma that have previously been considered a marker of axonal injury. The linear appearance and location of some traumatic microbleeds suggests a vascular origin. The aims of this study were to: (i) identify and characterize traumatic microbleeds in patients with acute traumatic brain injury; (ii) determine whether appearance of traumatic microbleeds predict clinical outcome; and (iii) describe the pathology underlying traumatic microbleeds in an index patient. Patients presenting to the emergency department following acute head trauma who received a head CT were enrolled within 48 h of injury and received a research MRI. Disability was defined using Glasgow Outcome Scale-Extended ≤6 at follow-up. All magnetic resonance images were interpreted prospectively and were used for subsequent analysis of traumatic microbleeds. Lesions on T2* MRI were stratified based on 'linear' streak-like or 'punctate' petechial-appearing traumatic microbleeds. The brain of an enrolled subject imaged acutely was procured following death for evaluation of traumatic microbleeds using MRI targeted pathology methods. Of the 439 patients enrolled over 78 months, 31% (134/439) had evidence of punctate and/or linear traumatic microbleeds on MRI. Severity of injury, mechanism of injury, and CT findings were associated with traumatic microbleeds on MRI. The presence of traumatic microbleeds was an independent predictor of disability (P < 0.05; odds ratio = 2.5). No differences were found between patients with punctate versus linear appearing microbleeds. Post-mortem imaging and histology revealed traumatic microbleed co-localization with iron-laden macrophages, predominately seen in perivascular space. Evidence of axonal injury was not observed in co-localized histopathological sections. Traumatic microbleeds were prevalent in the population studied and predictive of worse outcome. The source of traumatic microbleed signal on MRI appeared to be iron-laden macrophages in the perivascular space tracking a network of injured vessels. While axonal injury in association with traumatic microbleeds cannot be excluded, recognizing traumatic microbleeds as a form of traumatic vascular injury may aid in identifying patients who could benefit from new therapies targeting the injured vasculature and secondary injury to parenchyma.
| S-EPMC6821371 | biostudies-literature