Elevated Red Cell Distribution Width is Associated with Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this retrospective single-center cohort of aSAH patients (October 2009-September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death. RESULTS: Of 179 patients, 27 % had a high Hunt-Hess grade (IV-V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07-6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30-7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt-Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04-629], p = 0.040). CONCLUSIONS: RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

Thromboelastography defines late hypercoagulability after TBI: a pilot study.

INTRODUCTION: Traumatic brain injury (TBI) is associated with a hypercoagulable state, the mechanism and duration of which remain unclear. We sought to determine whether thromboelastography (TEG) analysis could identify the hypercoagulable state after TBI, as defined by elevations in maximal amplitude (MA), thrombus generation (TG), G value (G), and alpha angle (αA). METHODS: Patients with moderate-severe TBI, defined primarily as a GCS <12, admitted between 1/2012 and 8/2013 were eligible for enrolment in this prospective cohort study. TEG profiles were obtained between 0-24 h (T1), 24-48 h (T2), 48-72 h (T3), 72-96 h (T4), and 96-120 h (T5) after admission. Early TEG was defined as 0-48 h, and late TEG was defined as >48 h. RESULTS: Twenty five patients (80 % men) and 7 age- and sex-matched control subjects were studied. Median age was 38 years (range 18-85). Early MA was [63.6 mm (60.5, 67.4)] versus late MA [69.9 mm (65.2,73.9); p = 0.02], early TG was [763.3 mm/min (712.8, 816.2)] versus late TG [835.9 mm/min (791.2,888.3); p = 0.02], and early G was [8.8 d/cm(2) (7.7,10.4)] versus late G [11.6 d/cm(2) (9.4,14.1); p = 0.02]. Study patients had higher MA (p = 0.02), TG (p = 0.03), and G (p = 0.02) values at T5 compared to controls. There was a linear increase per day of MA by 2.6 mm (p = 0.001), TG 31.9 mm/min (p ≤ 0.001), and G value by 1.3 d/cm(2) (p ≤ 0.001) when clustered by pairs in regression analysis. Lower MA values trended toward home discharge (p = 0.08). CONCLUSION: The data suggest a progressive and delayed hypercoagulable state observed days after initial TBI. The hypercoagulable state may reflect excess platelet activity.

Quantification of cerebral blood flow in adults by contrast-enhanced near-infrared spectroscopy: Validation against MRI.

The purpose of this study was to assess the accuracy of absolute cerebral blood flow (CBF) measurements obtained by dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) using indocyanine green as a perfusion contrast agent. For validation, CBF was measured independently using the MRI perfusion method arterial spin labeling (ASL). Data were acquired at two sites and under two flow conditions (normocapnia and hypercapnia). Depth sensitivity was enhanced using time-resolved detection, which was demonstrated in a separate set of experiments using a tourniquet to temporally impede scalp blood flow. A strong correlation between CBF measurements from ASL and DCE-NIRS was observed (slope = 0.99 ± 0.08, y-intercept = -1.7 ± 7.4 mL/100 g/min, and R2 = 0.88). Mean difference between the two techniques was 1.9 mL/100 g/min (95% confidence interval ranged from -15 to 19 mL/100g/min and the mean ASL CBF was 75.4 mL/100 g/min). Error analysis showed that structural information and baseline absorption coefficient were needed for optimal CBF reconstruction with DCE-NIRS. This study demonstrated that DCE-NIRS is sensitive to blood flow in the adult brain and can provide accurate CBF measurements with the appropriate modeling techniques.

The Safety of Multimodality Monitoring Using a Triple-Lumen Bolt in Severe Acute Brain Injury.

BACKGROUND: Multimodality monitoring is used frequently to guide care of patients with severe acute brain injury. The aim of this study was to examine the safety and reliability of multimodality monitoring. METHODS: From a prospective observational database at a Level I trauma center, 501 patients, including 300 men and 201 women (mean age 58 ± 39 years) were identified retrospectively. Each patient received a triple-lumen bolt and 3 monitors: intracranial pressure, brain temperature, and brain oxygen. Intensive care unit and hospital records were examined to identify complications, reasons for device replacement, malfunction and infection. Head computed tomography (CT) scans performed before and after the monitors were inserted were examined for evidence of monitor-related adverse effects. RESULTS: A total of 696 triple-lumen bolts were placed. Median duration of monitoring was 78.88 hours (interquartile range, 33.0-133.2 hours). Bilateral monitors were inserted in 22 (3.16%) patients. Ten (1.43%) monitors were replaced to allow magnetic resonance imaging, and 40 (5.74%) monitors were replaced to facilitate additional cranial surgery. Of 35 (5.02%) monitors that were replaced because they were thought to not be functioning properly, 19 (54.29%) were subsequently found to be functioning normally. Follow-up CT scans were compared with CT scans obtained before insertion of monitors; 9 (2.13%) small contusions and 10 (2.36%) extra-axial hematomas associated with the devices were identified. Based on the CT findings, the hematomas were thought to be associated with the insertion technique rather than the device; 4 hematomas required treatment. Twenty-two (3.16%) devices were incorrectly placed (e.g., the probe was in an infarct or an already existing contusion). Only 1 associated infection was identified. CONCLUSIONS: Placement of intracranial monitors for multimodality neuromonitoring using a triple-lumen bolt appears to be safe. The complication rate is similar to published complication rates for single-lumen bolts and single monitors.

Continuous non-invasive optical monitoring of cerebral blood flow and oxidative metabolism after acute brain injury.

Rapid detection of ischemic conditions at the bedside can improve treatment of acute brain injury. In this observational study of 11 critically ill brain-injured adults, we employed a monitoring approach that interleaves time-resolved near-infrared spectroscopy (TR-NIRS) measurements of cerebral oxygen saturation and oxygen extraction fraction (OEF) with diffuse correlation spectroscopy (DCS) measurement of cerebral blood flow (CBF). Using this approach, we demonstrate the clinical promise of non-invasive, continuous optical monitoring of changes in CBF and cerebral metabolic rate of oxygen (CMRO2). In addition, the optical CBF and CMRO2 measures were compared to invasive brain tissue oxygen tension (PbtO2), thermal diffusion flowmetry CBF, and cerebral microdialysis measures obtained concurrently. The optical CBF and CMRO2 information successfully distinguished between ischemic, hypermetabolic, and hyperemic conditions that arose spontaneously during patient care. Moreover, CBF monitoring during pressor-induced changes of mean arterial blood pressure enabled assessment of cerebral autoregulation. In total, the findings suggest that this hybrid non-invasive neurometabolic optical monitor (NNOM) can facilitate clinical detection of adverse physiological changes in brain injured patients that are otherwise difficult to measure with conventional bedside monitoring techniques.

Noninvasive continuous optical monitoring of absolute cerebral blood flow in critically ill adults.

We investigate a scheme for noninvasive continuous monitoring of absolute cerebral blood flow (CBF) in adult human patients based on a combination of time-resolved dynamic contrast-enhanced near-infrared spectroscopy (DCE-NIRS) and diffuse correlation spectroscopy (DCS) with semi-infinite head model of photon propogation. Continuous CBF is obtained via calibration of the DCS blood flow index (BFI) with absolute CBF obtained by intermittent intravenous injections of the optical contrast agent indocyanine green. A calibration coefficient ( γ ) for the CBF is thus determined, permitting conversion of DCS BFI to absolute blood flow units at all other times. A study of patients with acute brain injury ( N = 7 ) is carried out to ascertain the stability of γ . The patient-averaged DCS calibration coefficient across multiple monitoring days and multiple patients was determined, and good agreement between the two calibration coefficients measured at different times during single monitoring days was found. The patient-averaged calibration coefficient of 1.24 × 10 9 ( mL / 100 g / min ) / ( cm 2 / s ) was applied to previously measured DCS BFI from similar brain-injured patients; in this case, absolute CBF was underestimated compared with XeCT, an effect we show is primarily due to use of semi-infinite homogeneous models of the head.

Thromboelastography Parameter Predicts Outcome After Subarachnoid Hemorrhage: An Exploratory Analysis.

OBJECTIVE: Hypercoagulability after subarachnoid hemorrhage (SAH) is well described and may be platelet mediated. Thromboelastography (TEG) provides a global assessment of coagulation. We sought to determine whether the maximum amplitude (MA) parameter of TEG, a measure of platelet strength and function, is associated with outcome after SAH. METHODS: One hundred ten TEG analyses were performed for patients with moderate-to-severe SAH and compared with 6 healthy age- and sex-matched controls. TEG indices included MA, G value (G), alpha angle, and thrombus generation and were correlated to functional outcomes and laboratory tests including complete blood count, erythrocyte sedimentation rate, high sensitivity C-reactive protein, fibrinogen, and d-dimer, obtained on post-bleed days (PBDs) 1, 3, 5, 7, and 10. RESULTS: MA was significantly elevated compared with controls on PBD 3 (70.0 mm ± 4.5 mm vs. 64.1 mm ± 6.5 mm; P = 0.02), PBD 5 (72.6 mm ± 5.3 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), PBD 7 (73.0 mm ± 5.4 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), and PBD 10 (73.4 mm ± 6.0 mm vs. 64.1 mm ± 6.5 mm; P = 0.005). G was significantly elevated compared with controls on PBD 3 (P = 0.03), PBD 5 (P = 0.01), PBD 7 (P = 0.01), and PBD 10 (P = 0.02). The only biomarker associated with poor outcome was CRP. Multivariate logistic regression demonstrated an association between elevated MA and outcome (odds ratio 39.1, P = 0.006) independent of CRP, age, Hunt Hess grade, and transfusion. CONCLUSIONS: TEG indices are associated with poor outcome after SAH and may identify a platelet-mediated hypercoagulable state. The association between MA and outcome was stronger than that between traditional biomarkers and was independent of age and Hunt Hess grade.