Anemia and brain oxygen after severe traumatic brain injury

Purpose: To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO2) after severe traumatic brain injury (TBI) and to examine its impact on outcome. Methods: This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO2 was monitored. The relationship between Hgb—categorized into four quartiles (≤9; 9-10; 10.1-11; >11g/dl)—and PbtO2 was analyzed using mixed-effects models. Anemia with compromised PbtO2 was defined as episodes of Hgb≤9g/dl with simultaneous PbtO211g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO2, PaCO2), Hgb≤9g/dl was the only Hgb level that was associated with lower PbtO2 (coefficient −6.53 (95% CI −9.13; −3.94), p<0.001). Anemia with simultaneous PbtO2<20mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95% CI 1.61; 24.22), p=0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score. Conclusions: In this cohort of severe TBI patients whose PbtO2 was monitored, a Hgb level no greater than 9g/dl was associated with compromised PbtO2. Anemia with simultaneous compromised PbtO2, but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severit

Evidence that a Panel of Neurodegeneration Biomarkers Predicts Vasospasm, Infarction, and Outcome in Aneurysmal Subarachnoid Hemorrhage

Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6–9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H

Brain Tissue Hypoxia is a Strong Predictor of Outcome after Severe Traumatic Brain Injury Independent from Elevated Intracranial Pressure

Introduction: Low brain tissue oxygen pressure (PbtO2) is associated with worse outcome in patients with severe traumatic brain injury (TBI). However, it is unclear whether brain tissue hypoxia is merely a marker of injury severity or a predictor of prognosis, independent from intracranial pressure (ICP) and injury severity. Hypothesis: We hypothesized that brain tissue hypoxia was an independent predictor of outcome in patients wih severe TBI, irrespective of elevated ICP and of the severity of cerebral and systemic injury. Methods: This observational study was conducted at the Neurological ICU, Hospital of the University of Pennsylvania, an academic level I trauma center. Patients admitted with severe TBI who had PbtO2 and ICP monitoring were included in the study. PbtO2, ICP, mean arterial pressure (MAP) and cerebral perfusion pressure (CPP = MAP-ICP) were monitored continuously and recorded prospectively every 30 min. Using linear interpolation, duration and cumulative dose (area under the curve, AUC) of brain tissue hypoxia (PbtO2 &lt; 15 mm Hg), elevated ICP &gt;20 mm Hg and low CPP &lt;60 mm Hg were calculated, and the association with outcome at hospital discharge, dichotomized as good (Glasgow Outcome Score [GOS] 4-5) vs. poor (GOS 1-3), was analyzed. Results: A total of 103 consecutive patients, monitored for an average of 5 days, was studied. Brain tissue hypoxia was observed in 66 (64%) patients despite ICP was &lt; 20 mm Hg and CPP &gt; 60 mm Hg (72 +/- 39% and 49 +/- 41% of brain hypoxic time, respectively). Compared with patients with good outcome, those with poor outcome had a longer duration of brain hypoxia (1.7 +/- 3.7 vs. 8.3 +/- 15.9 hrs, P&lt;0.01), as well as a longer duration (11.5 +/- 16.5 vs. 21.6 +/- 29.6 hrs, P=0.03) and a greater cumulative dose (56 +/- 93 vs. 143 +/- 218 mm Hg*hrs, P&lt;0.01) of elevated ICP. By multivariable logistic regression, admission Glasgow Coma Scale (OR, 0.83, 95% CI: 0.70-0.99, P=0.04), Marshall CT score (OR 2.42, 95% CI: 1.42-4.11, P&lt;0.01), APACHE II (OR 1.20, 95% CI: 1.03-1.43, P=0.03), and the duration of brain tissue hypoxia (OR 1.13; 95% CI: 1.01-1.27; P=0.04) were all significantly associated with poor outcome. No independent association was found between the AUC for elevated ICP and outcome (OR 1.01, 95% CI 0.97-1.02, P=0.11) in our prospective cohort. Conclusions: In patients with severe TBI, brain tissue hypoxia is frequent, despite normal ICP and CPP, and is associated with poor outcome, independent of intracranial hypertension and the severity of cerebral and systemic injury. Our findings indicate that PbtO2 is a strong physiologic prognostic marker after TBI. Further study is warranted to examine whether PbtO2-directed therapy improves outcome in severely head-injured patients

Time courses for 6 CSF neurodegeneration biomarkers in relation to functional outcome and the severity of cerebral vasospasm.

<p>Long-term outcome was dichotomized to either poor (closed circles: GOS-E  = 1–4; mRS  = 4–6) or good (open boxes: GOS-E  = 5–8; mRS  = 1–3), while angiographic vasospasm was categorized as either moderate/severe (closed circles) or absent/mild (open boxes) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028938#s2" target="_blank">Methods</a>. Mean CSF levels of each neurodegeneration biomarker at the indicated times post-aneurysm rupture (in days) are shown with the standard error of the mean. Statistically significant between-group differences (p<0.05) are identified by asterisk. In cases for which CSF samples were available at both 7 and 10 days post-rupture, the higher marker level was considered.</p

Relationship between peak CSF neurodegeneration biomarker levels and hemorrhage severity.

<p>The mean (+/- S.E.M.) peak level of each biomarker from 3–10 days post-rupture is depicted in relation to the initial severity of the aneurysm dichotomized according to the Hunt-Hess grade.</p

Relationship between peak CSF neurodegeneration biomarker levels and long-term outcome.

<p>The mean (+/- S.E.M.) peak level of each biomarker from 3–10 days post-rupture is depicted in relation to long-term outcome dichotomized according to the Glasgow Outcome Scale - Extended.</p

CSF changes in 3 neurodegeneration biomarkers after aneurysm rupture.

<p>(A) Western blot analyses of 14-3-3β, a calpain-cleaved α-spectrin COOH-terminal fragment (CCSctf), and UCH-L1 in 3 aSAH cases at the indicated times post-rupture (in days). Case 25 is representative of the subset of aSAH patients exhibiting large elevations in every neurodegeneration biomarker. Case 9, in contrast, shows a delayed increased in neurodegeneration biomarkers starting on day 5 after aneurysm rupture. Case 19 is representative of the subset of aSAH cases exhibiting consistently low or undetectable biomarker levels over the entire 10 day post-rupture period. (B) Western blot analysis of CCSctf levels 5 days post-rupture for 13 aSAH cases. Quantitative analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028938#s2" target="_blank">Methods</a>) showed that CSF levels of this biomarker vary by 100-fold across patients.</p