Dynamic Changes of Hemostasis in Patients with Traumatic Brain Injury Undergoing Craniotomy: Association with in-Hospital Mortality.

BACKGROUND: Traumatic brain injury (TBI) induces complex systemic hemostatic alterations associated with secondary brain damage and death. We specifically investigated perioperative changes of hemostasis in patients with isolated TBI undergoing major neurosurgery and searched for their influence on outcome. METHODS: Serial analysis (four time points, T0-T3) of conventional coagulation assay and rotational thromboelastometry data acquired during 72 h from admission of 68 patients who underwent craniotomy to remove hematoma and/or to decompress the brain was performed. The primary outcome was in-hospital mortality. Secondary outcomes were the prevalence of hypocoagulation and increased clotting activity, coagulation parameters between survivors and nonsurvivors, and cutoff values of coagulation parameters predictive of mortality. RESULTS: Overall mortality was 22%. The prevalence of hypocoagulation according to rotational thromboelastometry decreased from 35.8% (T0) to 15.9% (T3). Lower fibrinogen levels, hyperfibrinolysis and fibrinolysis shutdown in the early period (T0-T1) following TBI were associated with higher mortality. Optimal cutoff values were identified: fibrin polymerization thromboelastometry (FIBTEM) clot amplitude at 10 min after clotting time ≤ 13 mm at T0 and FIBTEM clot amplitude at 10 min after clotting time ≤ 16.5 mm at T1 increased the odds of death by 6.0 (95% confidence interval [CI] 1.54-23.13, p = 0.010) and 9.7 (95% CI 2.06-45.36, p = 0.004), respectively. FIBTEM maximum clot firmness ≤ 14.5 mm at T0 and FIBTEM maximum clot firmness ≤ 18.5 mm at T1 increased the odds of death by 6.3 (95% CI 1.56-25.69, p = 0.010) and 9.1 (95% CI 1.88-44.39, p = 0.006). Fibrinogen < 3 g/L on postoperative day 1 (T1) was associated with a 9.5-fold increase of in-hospital mortality (95% CI 1.72-52.98, p = 0.01). Increased clotting activity was not associated with mortality. CONCLUSIONS: Rotational thromboelastometry adds important information for identifying patients with TBI at increased risk of death. Early fibrinogen-related coagulation disorders are associated with mortality of patients with TBI undergoing major neurosurgical procedures. Maintenance of higher fibrinogen levels might be necessary for neurosurgical patients with acute TBI.

Implementing of Active Brain-Dead Donor Identification Strategy in a Single Donor Center: One Year Experience.

Background and objectives: Organ shortage is considered to be a major limitation for increasing transplantation rates. Brain-dead donors (DBDs) are an important source of organs, but up to 50% of potential DBDs might not be identified. An active brain-dead donor search could potentially increase a deceased donor pool. The aim of this study was to evaluate the effectiveness of an active potential DBD identification program and to evaluate one year impact on the potential organ donor pool in Lithuania's biggest medical institution. Materials and Methods: An organ donor coordinator service was established and active DBD search strategy was implemented in the hospital of LSMU Kauno Klinikos, and retrospective data analysis was performed between December 2016 and December 2017. Collected data was compared to the available data of the previous year in the same center and to the donation dynamics of the whole country. Results: A total of 6734 patients were treated in all intensive care units (ICU), and 234 (3.5%) of them were identified as possible donors. No increase in potential donor's number was observed in study year (n = 34) compared to remote year (n = 37). No significant difference in potential donor's demographic data, cause of death, family refusals and medical contraindication rates. Cerebral angiography (CA) repeated in 20% of potential donors in order to confirm brain death diagnosis. More potential donors for whom CA was repeated had decompressive craniectomy done (66.7% vs. 33.3%, p = 0.018). Decompressive craniectomy statistically significantly increases the rate of repeated CA (OR 12.7; 95% CI, 1.42-113.37; p = 0.023). Active search strategy increased length of hospital stay of potential donors comparing to previous year (3.97 ± 4.73 vs. 2.51 ± 2.63, p = 0.003). An optimal time of the first four days of hospitalization to identify a potential donor was observed during our study (OR 10.42; 95% CI, 4.29-25.34; p = 0.001). Conclusions: We were not able to demonstrate active donor identification strategy superiority over the passive strategy during a short one year period; nevertheless, valuable knowledge was gained in brain death diagnostics, new terminology was implemented, and the stability of actual donor numbers was observed in the experimental donor center in the light of decreasing national results. Long-term strategy is required to achieve sustainable results in organ donation.

Alterations of conjunctival glycocalyx and microcirculation in non-septic critically ill patients.

As of now the relationship between glycocalyx degradation and microcirculatory perfusion abnormalities in non-septic critical ill patients is unclear. In addition, conjunctival sidestream dark field-imaging for the purpose of glycocalyx thickness estimation has never been performed. We aimed to investigate whether changes in glycocalyx thickness in non-septic patients are associated with microcirculatory alterations in conjunctival and sublingual mucosa. In this single-centre prospective observational study, using techniques for direct in-vivo observation of the microcirculation, we performed a single measurement of microcirculatory perfusion parameters and visualized glycocalyx thickness in both ocular conjunctiva and sublingual mucosa in mixed cardio surgical (n = 18) and neurocritical patients (n = 27) and compared these data with age-matched healthy controls (n = 20). In addition we measured systemic syndecan-1 levels. In the sublingual and conjunctival region we observed a significant increase of the perfused boundary region (PBR) in both neuro-critical and cardiac surgical ICU patients, compared to controls. There was a significant increase of syndecan-1 in ICU patients comparing with controls and in cardiac patients comparing with neurological (120.0[71.0-189.6] vs. 18.0[7.2-40.7], p < 0.05). We detected a weak correlation between syndecan-1 and sublingual PBR but no correlations between global glycocalyx damage and conjuctival glycocalyx thickness. We found significantly lower perfused vessel density (PVD) of small vessels in sublingual mucosa in patients after cardiac surgery in comparison with healthy subjects. In neuro-critical, but not cardiac surgery patients conjunctival TVD and PVD of small vessels were found to be significantly lower in comparison with controls.

Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study.

BACKGROUND: The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain. METHODS: In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273. RESULTS: Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa. CONCLUSION: In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation.

Histology of human glioblastoma transplanted on chicken chorioallantoic membrane.

Glioblastoma is the most malignant tumor in the range of cerebral astrocytic gliomas. A lot of experimental models are used to evaluate various properties of glioblastoma. Chicken chorioallantoic membrane model is one of them. OBJECTIVE. To evaluate histology and survival of glioblastoma tumors taken immediately from operating theatre and transplanted on chicken chorioallantoic membrane. MATERIALS AND METHODS. Glioblastoma samples obtained from 10 patients were transplanted onto 200 eggs. Overall, we used 15 tumors; only 5 of them were not glioblastomas as it was revealed later. RESULTS. The transplanted tumors survive up to 6 days. Transplants do not survive longer because during embryo's development the nourishing membrane dries. Transplanted glioblastomas exhibited the same features as original glioblastomas - necrosis, endothelium proliferation, cellular polymorphism - while transplanted glioblastomas also showed glial fibrillary acidic protein (GFAP), vimentin, Ki67, S100 protein, neurofilament immunoreactivity, and infiltration of macrophages (CD68) and T cells (CD3(+), CD8(+)). Transplanted glioblastomas did not show any immunoreactivity of p53. Invasion of vessels from the chicken into transplanted tumor is not observed. Chicken erythrocytes did not appear within the transplants, and tumor cells invade chicken tissue at the minimum. CONCLUSION. Our data show that transplanted pieces of glioblastoma survive with all cytological features. The presence of macrophages (marker CD68) and T cells (markers CD3(+) and CD8(+)) can be registered in the transplant. The data revealed that transplanted glioblastoma remains as insulated unit, which survives from nourishment of the chorioallantoic membrane apparently only by diffusion. The features of original tumor-host reaction of the patient remained too.