[An experimental model of mass-type brain damage in the rat: expression of brain damage based on neurospecific enolase and protein S100B]. / Modelo experimental de lesión cerebral tipo masa en rata: expresión del daño cerebral mediante enolasa neuroespecífica y proteína S100B.

OBJECTIVE: To determine whether a model of transient mass-type brain damage (MTBD) in the rat produces early release of neurospecific enolase (NSE) and protein S100B in peripheral blood, as an expression of the induced brain injury. DESIGN: An experimental study with a control group. SETTING: Experimental operating room of the Institute of Biomedicine (IBiS) of Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: Fourteen adult Wistar rats. INTERVENTIONS: Blood was sampled at baseline, followed by: MTBD group, a trephine perforation was used to insert and inflate the balloon of a catheter at a rate of 500 µl/20 sec, followed by 4 blood extractions every 20 min. Control group, the same procedure as before was carried out, though without trephine perforation. PRIMARY STUDY VARIABLES: Weight, early mortality, serum NSE and S100B concentration. RESULTS: Differences in NSE and S100B concentration were observed over time within the MTBD group (P<.001), though not so in the control group. With the exception of the baseline determination, differences were observed between the two groups in terms of the mean NSE and S100B values. Following MTBD, NSE and S100B progressively increased at all measurement timepoints, with r=0.765; P=.001 and r=0.628; P=.001, respectively. In contrast, the control group showed no such correlation for either biomarker. CONCLUSIONS: Serum NSE and S100B concentrations offer an early indication of brain injury affecting the gray and white matter in an experimental model of mass-type MTBD in the rat.

Accuracy of the S100ß protein as a marker of brain damage in traumatic brain injury.

INTRODUCTION: This study tested the hypothesis that S100ß is a useful screening tool for detecting intracranial lesion (IL) in patients with a normal level of consciousness after traumatic brain injury (TBI). METHODS: One hundred and forty-three post-TBI patients without a decrease in consciousness (GCS = 15) and with at least one neurological symptom (e.g. transitory loss of consciousness, amnesia, headache, dizziness or vomiting) were prospectively included. A blood sample was drawn at 6-hours post-TBI. A routine CT scan was obtained within 24 hours post-injury. Diagnostic properties of S100ß for IL prediction in CT scan findings were tested using ROC-analysis. RESULTS: A total of 15 patients (10.5%) had IL. Serum levels were significantly higher in these patients. Significant differences were found between S100ß levels and CT scan findings (p = 0.007). ROC-analysis showed that S100ß is a useful tool for detecting the presence of IL in CT scans (p = 0.007). In this series, the best cut-off for S100ß is 0.130 µg L(-1), with 100% sensitivity and 32.81% specificity. CONCLUSION: Within the first 6 hours post-TBI, serum S100ß seems to be an effective biochemical indicator of IL in patients without a decrease in consciousness. These results indicate that higher S100ß cut-off values substantially improve the clinical relevance of this protein.

[Cerebral microdialysis in the current clinical setting]. / La microdiálisis cerebral en el ámbito clínico actual.

Cerebral microdialysis, introduced in experimental studies 40 years ago, has been used clinically since 1992 for the neurochemical monitoring of patients in intensive care. The principles underlying this technique are closely related to brain metabolism. The study of the metabolites detected at brain interstitial tissue level, through the semipermeable membrane of the device, allows us to assess different physiological pathways in the brain, analyzing the changes that occur when they become less efficient in terms of energy, and also detecting waste products secondary to tissue damage. Despite its current limitations, this technique provides relevant information for research and the clinical management of critical neurological patients.

Donation in Private Clinics as an Alternate Strategy to Increase the Pool of Donors.

In recent years, the donation process is being characterized by a decreased number of brain deaths and a logistical shift toward cardiac-death donation, both controlled and uncontrolled, in Spain. As we know, cardiac-death donors produce fewer usable organs than brain-death donors. Therefore, many of the Spanish transplant coordinators are working to find new strategies that bring efficiency to donor detection. Since 2012, at the Virgen del Rocío University Hospital, Seville, we have been trying to obtain more donors with the use of a huge logistical and administrative effort of all the elements that make up the donation and transplantation teams, because we have sought to get organ donors in all private clinics in the city. The result of this effort has succeeded in increasing the donation rate in Seville to 3 donors and >6 usable organs per year. This paper also analyzes the characteristics of these donors, comparing our results with our community and the country. The conclusion of all this, we believe, encourages persevering in those efforts and endorses a strategy that could be applied in other parts of the world with good results in terms of transplanted organs.

Non-Heart-Beating Donor Program: Results After 3 Years of Experience.

BACKGROUND: Non-heart-beating donation (NHBD) is a useful way to obtain organs and tissues. Therefore, since 2012 we have had an NHBD protocol in the metropolitan area of Seville. The aim of this work was to present the results obtained after 3 years of program. METHODS: Prospective observational study carried out from 2012 to 2014. We included all patients with an extrahospitalary sudden death who did not survive despite cardiopulmonary resuscitation, becoming a potential donors (PD). Variables included number of consultations, PD, allowed donor (AD), real donor (RD), and family or legal refusals; minutes of out-hospital care, in-hospital care, cannulation, and perfusion of the RD; and number of organs and tissues removed and viable proportion. Nonallowed donors were grouped according to the discarding cause. RESULTS: We received 97 consultations, of which 40 were performed as PD. Of these, 24 were AD (60%) and 22 RD (55%). There were only 2 family refusals. In 2012, 10 patients were donors, 5 in 2013, and 7 in 2014. The out-hospital median time was 71 (interquartile range [IQR] 60-76) minutes, in-hospital 29 (26-34) minutes, cannulation 28 (24-33) minutes, and perfusion 135 (105-177) minutes. Eighteen tissues and 43 organs were extracted, of which 32 were implanted (75%), with kidneys (96%) being more frequent. Nonallowed donors numbered 12 in 2012, 4 in 2013, and 1 in 2014, and out-hospital causes were the most frequent discard reason. CONCLUSIONS: NHBD is a useful program in our city with a low refusal rate (8%), an average of 1.45 organs per donor, and kidney the most frequent organ.

Serologic behavior of S100B protein in patients who are brain dead: preliminary results.

OBJECTIVE: The objective of this study is to assess the S100B protein serum concentrations from brain dead (BD) donors to understand whether its level could provide clinical information during BD diagnosis as a potential confirmatory test. METHODS: During 12 months, 26 patients declared BD were prospectively included in this study. Once the diagnosis of BD was achieved, serum S100B protein levels were measured using an electrochemiluminescence assay. For analytical purposes, we selected the maximum S100B serum value reached during the first 5 days of evolution from a historical cohort of 124 survived patients after a severe brain injury (SBI), as well as from 18 healthy donors (HD) and a subgroup of patients who had severe traumatic brain injuries (TBIs) without extracranial injuries. RESULTS: Mean age was 53.48 years (SD, 18.91 years). The BD group had significantly higher S100B serum levels (1.44 µg/L; interquartile ratio [IR], 0.63-3.68) than the SBI (0.34 µg/L; IR, 0.21-0.60) and HD groups (0.06 µg/L; IR, 0.03-0.07; P < .001). Analysis of S100B levels depending on the main cause responsible for BD development showed significant differences between subgroups (P = .012). S100B serum levels were higher in the isolated TBI BD group (P = .004). The S100B value showed an odds ratio for BD diagnosis of 8.38 (95% confidence interval [CI], 1.16-60.45; P = .035). Reciever operating characteristic analysis revealed an area under the curve of 0.92 (95% CI, 0.79-1.00; P = .007). We set a cut-off value of 2 µg/L in S100B serum concentrations. At this level, the diagnostic properties of S100B would reach 100% of specificity and positive predictive value (PPV), and sensitivity and negative predictive value (NPV) of 60% and 86.7%, respectively. CONCLUSION: This preliminary analysis shows for the very first time that BD is associated with higher S100B serum levels, compared with other neurocritical care patients. We also found that the cause of BD development must be considered. Specifically, S100B serum levels in severe isolated TBI patients-with clinical exploration compatible with BD-could be used in a future as confirmatory test.

A new percutaneous model of Subarachnoid Haemorrhage in rats.

OBJECTIVE: Describe the results obtained with a new percutaneous, intracisternal model of Subarachnoid Haemorrhage (SAH) in Wistar rats by a single injection of non-heparinised, autologous blood. METHODS: Once anaesthetized the rat was fixed prone in a stereotaxic frame. After identifying the projection of the occipital bone, the needle of the stereotaxic frame aspirated towards the foramen magnum until it punctured through the atlanto-occipital membrane and obtained cerebrospinal fluid. Autologous blood (100 µl) was withdrawn from the tail and injected intracisternally. This procedure was repeated in the sham group, injecting 100 µl of isotonic saline. On the fifth day post-intervention, the rats were anaesthetized and the brain was exposed. After a lethal injection of ketamine the brain was explanted and fixed in paraformaldehyde. Gross and microscopic inspection of the slices revealed the existence or non-existence of pathological findings. RESULTS: A total of 26 rats were operated on (13 in the SAH group/13 in the sham group). The average time between obtaining the blood and the start of the intracisternal injection was 10 (±1.2)s. The mortality rate was 16.12%. Intra- and extraparenchymal ischemic-haemorrhagic lesions were found in three animals (23.07%)--all from the SAH group--with ischemic neuronal cell injury detected in two of the three. CONCLUSIONS: The new murine model of SAH is easy to perform, with low mortality, minimally invasive, which makes it interesting for future studies on vasospasm-related delayed SAH complications.

Neurogenic stunned myocardium and cardiac transplantation: a case report.

We present the case of a 46-year-old woman referred to our center for urgent heart transplantation assessment, initially diagnosed as having cardiogenic shock of uncertain etiology. Some hours before she had suffered syncope without regaining consciousness. When she arrived at our hospital, the objective examination revealed bilateral unreactive mydriasis and absent brain-stem reflexes, and echocardiography showed global left ventricle wall hypokinesis sparing the apex. An urgent computed tomography (CT) imaging of the head was performed, which showed a massive subarachnoid hemorrhage and extensive cerebral edema. In the following hours, she fulfilled the criteria of brain-stem death and indeed became a multiorgan donor. The heart was rejected for transplantation because of the existence of left ventricle wall motion abnormalities associated with neurogenic stunned myocardium. Neurogenic stunned myocardium is a stress-related cardiomyopathy that occurs after an acute brain injury. It is especially frequent in subarachnoid hemorrhage, where it reaches an incidence of up to 40% of patients. It is characterized by acute electrocardiographic changes and regional hypokinesis of the left ventricle wall not consistent with the coronary artery distribution, and is thought to be a transient condition. For this reason it should not constitute an absolute contraindication to cardiac donation in young donors with no previous cardiac disease. In our hospital during the last year one third of the potential heart donors had regional left ventricle wall motion abnormalities compatible with neurogenic stunned myocardium. With the aim of improving the number of cardiac donors, several strategies have been described to try to demonstrate the reversibility of this entity, such as dobutamine stress echocardiography.