Extracellular brain pH with or without hypoxia is a marker of profound metabolic derangement and increased mortality after traumatic brain injury.
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ABSTRACT:
SUBMITTER: Timofeev I
PROVIDER: S-EPMC3587815 | biostudies-other | 2013 Mar
REPOSITORIES: biostudies-other
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Project description:Background: A major contributor to unfavorable outcome after traumatic brain injury (TBI) is secondary brain injury. Low brain tissue oxygen tension (PbtO2) has shown to be an independent predictor of unfavorable outcome. Although PbtO2 provides clinicians with an understanding of the ischemic and non-ischemic derangements of brain physiology, its value does not take into consideration systemic oxygenation that can influence patients' outcomes. This study analyses brain and systemic oxygenation and a number of related indices in TBI patients: PbtO2, partial arterial oxygenation pressure (PaO2), PbtO2/PaO2, ratio of PbtO2 to fraction of inspired oxygen (FiO2), and PaO2/FiO2. The primary aim of this study was to identify independent risk factors for cerebral hypoxia. Secondary goal was to determine whether any of these indices are predictors of mortality outcome in TBI patients. Materials and Methods: A single-centre retrospective cohort study of 70 TBI patients admitted to the Neurocritical Care Unit (NCCU) at Cambridge University Hospital in 2014-2018 and undergoing advanced neuromonitoring including invasive PbtO2 was conducted. Three hundred and three simultaneous measurements of PbtO2, PaO2, PbtO2/PaO2, PbtO2/FiO2, PaO2/FiO2 were collected and mortality at discharge from NCCU was considered as outcome. Generalized estimating equations were used to analyse the longitudinal data. Results: Our results showed PbtO2 of 28 mmHg as threshold to define cerebral hypoxia. PaO2/FiO2 found to be a strong and independent risk factor for cerebral hypoxia when adjusting for confounding factor of intracranial pressure (ICP) with adjusted odds ratio of 1.78, 95% confidence interval of (1.10-2.87) and p-value = 0.019. With respect to TBI outcome, compromised values of PbtO2, PbtO2/PaO2, PbtO2/FiO2, and PaO2/FiO2 were all independent predictors of mortality while considered individually and adjusting for confounding factors of ICP, age, gender, and cerebral perfusion pressure (CPP). However, when considering all the compromised values together, only PaO2/FiO2 became an independent predictor of mortality with adjusted odds ratio of 3.47 (1.20-10.04) and p-value = 0.022. Conclusions: Brain and Lung interaction in TBI patients is a complex interrelationship. PaO2/FiO2 seems to be a major determinant of cerebral hypoxia and mortality. These results confirm the importance of employing ventilator strategies to prevent cerebral hypoxia and improve the outcome in TBI patients.
| S-EPMC7426476 | biostudies-literature
Project description:Introduction:In the setting of cerebral injury, cerebral salt wasting (CSW) is a potential cause of hyponatremia, which contributes to adverse effects and mortality. Objective:The primary objective of this study was to evaluate the clinical outcomes of severe traumatic brain injury (TBI) patients complicated by CSW. Methods:A retrospective data analysis was performed on data collected from patients with TBI with an abbreviated injury scale (AIS) greater than 3. Data was divided into 2 groups of patients with CSW and those without. The primary endpoint was incidence of adverse effects of CSW in regard to injury severity score (ISS), hospital length of stay (HLOS), ventilator days, ICU length of stay (ICU LOS) and survival to discharge. Data was analyzed using a one-way analysis of variance (ANOVA). Results:A total of 310 consecutive patients with severe head injury (anatomic injury score 3 or greater) were evaluated over a 3-year period. A total of 125 of the 310 patients (40%) were diagnosed with cerebral salt wasting as defined by hyponatremia with appropriate urinary output and salt replacement. Patients with CSW had poorer outcomes in regard to ISS (21.8 vs 14.2, p<0.0001), HLOS (14.1 vs 3.5, p<0.0001), ventilator days (5.0 vs 0.45, p<0.0001), ICU LOS (8.5 vs 1.6, p<0.0001), and survival to discharge (88% vs 99%, p<0.0001). Discussion:Common adverse effects of CSW were noted in this study. Patients with TBI have a predilection towards development of CSW and consequently have poorer outcomes including increased morbidity and mortality. Data is sparse on the duration of CSW and degree of hyponatremia over time. Larger, comparative studies need to be performed to investigate the hyponatremic patient population and the clinical outcomes of those who present with CSW.
| S-EPMC7104213 | biostudies-literature
Project description:STUDY OBJECTIVESurvival is significantly reduced by either hypotension or hypoxia during the out-of-hospital management of major traumatic brain injury. However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. In patients with major traumatic brain injury, we evaluate the associations between mortality and out-of-hospital hypotension and hypoxia separately and in combination.METHODSAll moderate or severe traumatic brain injury cases in the preimplementation cohort of the Excellence in Prehospital Injury Care study (a statewide, before/after, controlled study of the effect of implementing the out-of-hospital traumatic brain injury treatment guidelines) from January 1, 2007, to March 31, 2014, were evaluated (exclusions: <10 years, out-of-hospital oxygen saturation ?10%, and out-of-hospital systolic blood pressure <40 or >200 mm Hg). The relationship between mortality and hypotension (systolic blood pressure <90 mm Hg) or hypoxia (saturation <90%) was assessed with multivariable logistic regression, controlling for Injury Severity Score, head region severity, injury type (blunt versus penetrating), age, sex, race, ethnicity, payer, interhospital transfer, and trauma center.RESULTSAmong the 13,151 patients who met inclusion criteria (median age 45 years; 68.6% men), 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the 4 study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios for death within the cohorts, using the patients with neither hypotension nor hypoxia as the reference, were 4.4 and 2.5, 6.6 and 3.0, and 13.2 and 6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects were additive on the log odds of death.CONCLUSIONIn this statewide analysis of major traumatic brain injury, combined out-of-hospital hypotension and hypoxia were associated with significantly increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the adjusted odds of death for patients with both hypotension and hypoxia were more than 2 times greater than for those with either hypotension or hypoxia alone. These findings seem supportive of the emphasis on aggressive prevention and treatment of hypotension and hypoxia reflected in the current emergency medical services traumatic brain injury treatment guidelines but clearly reveal the need for further study to determine their influence on outcome.
| S-EPMC5173421 | biostudies-literature
Project description:Extracellular acidification is an important feature of tumor microenvironments but has yet to be successfully exploited in cancer therapy. The reversal of the pH gradient across the plasma membrane in cells that regulate intracellular pH (pHi) has potential to drive the selective uptake of weak acids at low extracellular pH (pHe). Here, we investigate the dual targeting of low pHe and hypoxia, another key feature of tumor microenvironments. We prepared eight bioreductive prodrugs based on the benzotriazine di-oxide (BTO) nucleus by appending alkanoic or aminoalkanoic acid sidechains. The BTO acids showed modest selectivity for both low pHe (pH 6.5 versus 7.4, ratios 2 to 5-fold) and anoxia (ratios 2 to 8-fold) in SiHa and FaDu cell cultures. Related neutral BTOs were not selective for acidosis, but had greater cytotoxic potency and hypoxic selectivity than the BTO acids. Investigation of the uptake and metabolism of representative BTO acids confirmed enhanced uptake at low pHe, but lower intracellular concentrations than expected for passive diffusion. Further, the modulation of intracellular reductase activity and competition by the cell-excluded electron acceptor WST-1 suggests that the majority of metabolic reductions of BTO acids occur at the cell surface, compromising the engagement of the resulting free radicals with intracellular targets. Thus, the present study provides support for designing bioreductive prodrugs that exploit pH-dependent partitioning, suggesting, however, that that the approach should be applied to prodrugs with obligate intracellular activation.
| S-EPMC6680510 | biostudies-literature
Project description:The aim of this study is to describe the traumatic brain injury (TBI) population and causes and identify factors associated with TBI hospitalizations and mortality in California.This is a cross-sectional study of 61,188 patients with TBI from the California Hospital Discharge Data 2001 to 2009. We used descriptive, bivariate, and multivariate analyses in SAS version 9.3.TBI-related hospitalizations decreased by 14% and mortality increased by 19% from 2001 to 2009. The highest percentages of TBI hospitalizations were due to other causes (38.4%), falls (31.2%), being of age ?75 years old (37.2%), being a males (58.9%), and being of Medicare patients (44%). TBIs due to falls were found in those age ?4 years old (53.5%), ?75 years old (44.0%), and females (37.2%). TBIs due to assaults were more frequent in Blacks (29.0%). TBIs due to motor vehicle accidents were more frequent in 15-19 and 20-24 age groups (48.7% and 48.6%, resp.) and among Hispanics (27.8%). Higher odds of mortality were found among motor vehicle accident category (adjusted odds ratio (AOR): 1.27, 95% CI: 1.14-1.41); males (AOR: 1.36, 95% CI: 1.27-1.46); and the ?75-year-old group (AOR: 6.4, 95% CI: 4.9-8.4).Our findings suggest a decrease in TBI-related hospitalizations but an increase in TBI-related mortality during the study period. The majority of TBI-related hospitalizations was due to other causes and falls and was more frequent in the older, male, and Medicare populations. The higher likelihood of TBI-related mortalities was found among elderly male ?75 years old who had motor vehicle accidents. Our data can inform practitioners, prevention planners, educators, service sectors, and policy makers who aim to reduce the burden of TBI in the community. Implications for interventions are discussed.
| S-EPMC3845866 | biostudies-literature
Project description:Although alcohol exposure results in reduced mortality after traumatic brain injury (TBI) in animal models, clinical trials based on proposed mechanisms have been disappointing and have reported conflicting results. Methodological issues common to many of these clinical studies may have contributed to the spurious results. Our objective was to evaluate the association between blood alcohol concentration (BAC) and in-hospital mortality after TBI, and overcome methodological problems of prior studies. We conducted a retrospective cohort study on individuals treated for isolated TBI (n = 1,084) at the R Adams Cowley Shock Trauma Center (Baltimore, Maryland) from 1997 to 2012. We excluded individuals with injury to other body regions and examined multiple cutpoints of BAC. Our primary outcome was in-hospital mortality. In adjusted logistic regression models, the upper level of each blood alcohol categorization from 0.10 g/dL (odds ratio = 0.63, 95% confidence interval: 0.40, 0.97) through 0.30 g/dL (odds ratio = 0.25, 95% confidence interval: 0.08, 0.84) was associated with reduced risk of mortality after TBI compared with individuals with undetectable BAC. In sensitivity analyses among individuals without penetrating brain injuries (95% firearm-related) (n = 899), the protective association was eliminated. This study provides evidence that the observed protective association between BAC and in-hospital mortality after TBI resulted from bias introduced by inclusion of penetrating injuries.
| S-EPMC5860552 | biostudies-literature
Project description:Study Design Case report and review of the literature. Objectives Case report of a traumatic dissection of all major brain-supplying arteries resulting from a horseback-riding accident. Overview of the literature on diagnostic and therapeutic recommendations. Methods Case presentation. For the discussion, handpicked articles and PubMed database research with the keywords "dissection," "vertebral artery," "spine trauma," "computed tomography," "magnetic resonance imaging," and "angiography" were used. Results Despite high-energy induced acute lesion of all four cervical arteries, this 45-year-old patient did not demonstrate signs of microemboli nor suffer from stroke. Conclusion In case of high-energy trauma of the head and/or the neck, emergency physicians must consider traumatic cervical artery dissection (TCAD). Thus, emergency care algorithms should routinely include computed tomography angiography and magnetic resonance imaging. Although the incidence of TCAD-induced stroke is low, antiplatelet therapy is recommended in the presence of TCAD.
| S-EPMC4111942 | biostudies-other
Project description:Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Preventative measures reduce injury incidence and/or severity, yet one-third of hospitalized patients with TBI die from secondary pathological processes that develop during supervised care. Neutrophils, which orchestrate innate immune responses, worsen TBI outcomes via undefined mechanisms. We hypothesized that formation of neutrophil extracellular traps (NETs), a purported mechanism of microbial trapping, exacerbates acute neurological injury after TBI. NET formation coincided with cerebral hypoperfusion and tissue hypoxia after experimental TBI, while elevated circulating NETs correlated with reduced serum deoxyribonuclease-1 (DNase-I) activity in patients with TBI. Functionally, Toll-like receptor 4 (TLR4) and the downstream kinase peptidylarginine deiminase 4 (PAD4) mediated NET formation and cerebrovascular dysfunction after TBI. Last, recombinant human DNase-I degraded NETs and improved neurological function. Thus, therapeutically targeting NETs may provide a mechanistically innovative approach to improve TBI outcomes without the associated risks of global neutrophil depletion.
| S-EPMC7259928 | biostudies-literature
Project description:To determine the precise effects of post-traumatic seizure activity on hippocampal processes, we induced seizures at various intervals after traumatic brain injury (TBI) and analyzed plasticity at CA1 Schaffer collateral synapses.Rats were initially separated into two groups; one exposed solely to fluid percussion injury (FPI) at 2 Psi and the other only receiving kainic acid (KA)-induced seizures without FPI. Electrophysiological (ePhys) studies including paired-pulse stimulation for short-term presynaptic plasticity and long-term potentiation (LTP) of CA1 Schaffer collateral synapses of the hippocampus for post-synaptic function survey were followed at post-event 1 hour, 3 and 7 days respectively. Additional rats were exposed to three seizures at weekly intervals starting 1 week or 2 weeks after TBI and compared with seizures without TBI, TBI without seizures, and uninjured animals. An additional group placed under the same control variables were treated with levetiracetam prior to seizure induction. The ePhys studies related to post-TBI induced seizures were also followed in these additional groups.Seizures affected the short- and long-term synaptic plasticity of the hippocampal CA3-CA1 pathway. FPI itself suppressed LTP and field excitatory post synaptic potentials (fEPSP) in the CA1 Schaffer collateral synapses; KA-induced seizures that followed FPI further suppressed synaptic plasticity. The impairments in both short-term presynaptic and long-term plasticity were worse in the rats in which early post-TBI seizures were induced than those in which later post-TBI seizures were induced. Finally, prophylactic infusion of levetiracetam for one week after FPI reduced the synaptic plasticity deficits in early post-TBI seizure animals.Our data indicates that synaptic plasticity (i.e., both presynaptic and postsynaptic) suppression occurs in TBI followed by a seizure and that the interval between the TBI and seizure is an important factor in the severity of the resulting deficits. Furthermore, the infusion of prophylactic levetiracetam could partially reverse the suppression of synaptic plasticity.
| S-EPMC5837755 | biostudies-literature
Project description:IntroductionThe prevalence of hypoalbuminemia, early changes of plasma albumin (P-Alb) levels, and their effects on mortality in cardiogenic shock are unknown.Materials and methodsP-Alb was measured from serial blood samples in 178 patients from a prospective multinational study on cardiogenic shock. The association of hypoalbuminemia with clinical characteristics and course of hospital stay including treatment and procedures was assessed. The primary outcome was all-cause 90-day mortality.ResultsHypoalbuminemia (P-Alb < 34g/L) was very frequent (75%) at baseline in patients with cardiogenic shock. Patients with hypoalbuminemia had higher mortality than patients with normal albumin levels (48% vs. 23%, p = 0.004). Odds ratio for death at 90 days was 2.4 [95% CI 1.5-4.1] per 10 g/L decrease in baseline P-Alb. The association with increased mortality remained independent in regression models adjusted for clinical risk scores developed for cardiogenic shock (CardShock score adjusted odds ratio 2.0 [95% CI 1.1-3.8], IABP-SHOCK II score adjusted odds ratio 2.5 [95%CI 1.2-5.0]) and variables associated with hypoalbuminemia at baseline (adjusted odds ratio 2.9 [95%CI 1.2-7.1]). In serial measurements, albumin levels decreased at a similar rate between 0h and 72h in both survivors and nonsurvivors (ΔP-Alb -4.6 g/L vs. 5.4 g/L, p = 0.5). While the decrease was higher for patients with normal P-Alb at baseline (p<0.001 compared to patients with hypoalbuminemia at baseline), the rate of albumin decrease was not associated with outcome.ConclusionsHypoalbuminemia was a frequent finding early in cardiogenic shock, and P-Alb levels decreased during hospital stay. Low P-Alb at baseline was associated with mortality independently of other previously described risk factors. Thus, plasma albumin measurement should be part of the initial evaluation in patients with cardiogenic shock.Trial registrationNCT01374867 at ClinicalTrials.gov.
| S-EPMC6522037 | biostudies-literature