Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

Brain injury biomarkers in the setting of cardiac surgery: Still a world to explore.

BACKGROUND: Brain injury is an important, potentially devastating, complication in cardiac surgery. A significant number of patients suffer perioperative complications involving the central nervous system. Clinical manifestations of brain injury are associated with significantly increased mortality, morbidity and health resource utilization. Serum biomarkers have been studied in cardiac surgery to measure the degree and incidence of brain injury and to improve patient management. METHODS: All relevant studies were identified by computerized searches of PubMed using the following Medical Subject Headings and keywords term: biomarker, cardiac surgery, brain injury and neurological complication. RESULTS: The biomarkers that appear to be better indicators of brain injury severity in cardiac surgery and its consequences are S100B protein, neuron-specific enolase, glial fibrillary acidic protein, tau protein, matrix metalloproteinase-9, ubiquitin C terminal hydroxylase-L1 and neurofilaments. CONCLUSIONS: These biomarkers, independently of clinical and radiological findings, show global cerebral situation at the cellular level and the degree of brain dysfunction. However, up to date, there is no biomarker entirely suitable for the detection of brain injury after cardiac surgery.

[Usefulness of biomarkers in the prognosis of severe head injuries]. / Utilidad de los biomarcadores en el pronóstico del traumatismo craneoencefálico grave.

Severe head injuries have a great socioeconomic and public health impact. Despite progress in diagnosis and treatment, no sufficiently reliable predictive models have been established for developing clinical trials and promoting effective therapeutic strategies capable of improving the prognosis. In the last decades, several brain damage biomarkers have been studied as potential diagnostic and prognostic tools in traumatic brain injury. However, all of them have limitations that preclude their universalized application. The properties of the known biomarkers -both those traditionally shown to correlate with severity and prognosis, and those recently announced as promising options- should be analyzed. New studies are needed to define their properties, both isolatedly and in combined use.

Mortality prediction using TRISS methodology in the Spanish ICU Trauma Registry (RETRAUCI).

OBJECTIVES: To validate Trauma and Injury Severity Score (TRISS) methodology as an auditing tool in the Spanish ICU Trauma Registry (RETRAUCI). DESIGN: A prospective, multicenter registry evaluation was carried out. SETTING: Thirteen Spanish Intensive Care Units (ICUs). PATIENTS: Individuals with traumatic disease and available data admitted to the participating ICUs. INTERVENTIONS: Predicted mortality using TRISS methodology was compared with that observed in the pilot phase of the RETRAUCI from November 2012 to January 2015. Discrimination was evaluated using receiver operating characteristic (ROC) curves and the corresponding areas under the curves (AUCs) (95% CI), with calibration using the Hosmer-Lemeshow (HL) goodness-of-fit test. A value of p<0.05 was considered significant. MAIN VARIABLES OF INTEREST: Predicted and observed mortality. RESULTS: A total of 1405 patients were analyzed. The observed mortality rate was 18% (253 patients), while the predicted mortality rate was 16.9%. The area under the ROC curve was 0.889 (95% CI: 0.867-0.911). Patients with blunt trauma (n=1305) had an area under the ROC curve of 0.887 (95% CI: 0.864-0.910), and those with penetrating trauma (n=100) presented an area under the curve of 0.919 (95% CI: 0.859-0.979). In the global sample, the HL test yielded a value of 25.38 (p=0.001): 27.35 (p<0.0001) in blunt trauma and 5.91 (p=0.658) in penetrating trauma. TRISS methodology underestimated mortality in patients with low predicted mortality and overestimated mortality in patients with high predicted mortality. CONCLUSIONS: TRISS methodology in the evaluation of severe trauma in Spanish ICUs showed good discrimination, with inadequate calibration - particularly in blunt trauma.

Acute predictors for mortality after severe TBI in Spain: Gender differences and clinical data.

OBJECTIVE: The main objective of this study is to determine whether gender affects global mortality and functional outcome after severe traumatic brain injury (TBI). METHODS: This retrospective cohort study included 629 patients with severe TBI (14.9% female) admitted to the ICU of a university hospital. Patients were split into gender groups to study potential differences in global mortality and functional outcome at ICU discharge and 6 months post-trauma using the GOS. The following variables were analysed: age, intracranial injury, injury mechanism, injury severity, factors contributing to secondary brain injury, monitoring level, treatment, complications, length of stay in the ICU and cause of death. RESULTS: No differences were found between gender groups in neuromonitoring level or surgical procedures. Women had higher APACHE II scores, a higher incidence of pre-hospital hypotension, anaemia and transfusion and higher mortality rates in the ICU (OR = 1.74; 95% CI = 1.09-2.77) and 6 months post-trauma (OR = 1.65; 95% CI = 1.02-2.67). There were no significant differences in functional outcome at ICU discharge or 6 months post-injury. The multivariate analysis did not show gender as an independent predictive factor in mortality after severe TBI. CONCLUSION: In this study, gender was not found to be an independent predictor for poorer outcome after severe TBI.

New oral anticoagulants in severe trauma patients: enemy at the gates?

The high incidence of trauma, especially in elderly people anticoagulated with new oral anticoagulants (NOAs), has become a major challenge, particularly in critical situations with life-threatening bleeding. Under these circumstances, urgent NOA reversion becomes mandatory. Prothrombin complex has become a frequent indication in critical situations in which rapid reversal of anticoagulation is needed and where the use of fresh frozen plasma is limited. This study offers our point of view regarding the usefulness of NOAs, not only in the prevention of cardioembolic events but also as regards their emergent reversion in cases of severe bleeding associated to trauma.

Predictors of mortality and poor functional outcome in severe spontaneous intracerebral hemorrhage: a prospective observational study.

OBJECTIVE: To analyze mortality and functional outcome in patients with severe spontaneous intracerebral hemorrhage (ICH), and identify the clinical characteristics, radiological findings and therapeutic procedures predictive of mortality in the Intensive Care Unit (ICU) and during hospitalization, as well as of poor functional results at 6 months. DESIGN: A prospective, observational study was carried out. SETTING: Neurocritical Care Unit of a university hospital. PATIENTS: Patients diagnosed with ICH were included over a period of 23 months. VARIABLES OF INTEREST: Demographic characteristics, cardiovascular risk factors, regular medication, laboratory test parameters, cranial CT findings, therapeutic procedures and outcome data. INTERVENTION: None. RESULTS: A total of 186 patients with ICH met the inclusion criteria. Surgery to evacuate ICH was performed in 25.8% of the patients. The mortality rate was 46.7%. The modified Rankin score at 6 months was 5 (RI: 4.6). Multivariate Cox regression analysis showed the presence of diabetes, prior anticoagulation, as well as APACHE II severity and the type of bleeding on the cranial CT scan to be predictors of mortality and poor functional outcomes. On the other hand, neurosurgical procedures and intracranial pressure (ICP) monitoring were associated with better outcomes. CONCLUSION: The presence of comorbidities such as diabetes, or previous anticoagulation, as well as the CT findings were associated to poorer outcomes. In contrast, ICP monitoring and early neurosurgery were predictive of longer survival and better functional outcomes.

Resuscitative goals and new strategies in severe trauma patient resuscitation.

Traumatic injuries represent a major health problem all over the world. In recent years we have witnessed profound changes in the paradigm of severe trauma patient resuscitation, new concepts regarding acute coagulopathy in trauma have been proposed, and there has been an expansion of specific commercial products related to hemostasis, among other aspects. New strategies in severe trauma management include the early identification of those injuries that are life threatening and require surgical hemostasis, tolerance of moderate hypotension, rational intravascular volume replacement, prevention of hypothermia, correction of acidosis, optimization of oxygen carriers, and identification of those factors required by the patient (fresh frozen plasma, platelets, tranexamic acid, fibrinogen, cryoprecipitates and prothrombin complex). However, despite such advances, further evidence is required to improve survival rates in severe trauma patients.

[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.

Ultrasound diagnosis of Terson syndrome as an indicator of extreme severity in neurocritical care patients.

INTRODUCTION: Terson syndrome (TS) is defined as any intraocular haemorrhage identified in patients with acute intracranial pathology. TS appears to be associated with clinical severity in patients with subarachnoid haemorrhage (SAH), but the association is yet to be defined in patients with traumatic brain injury (TBI) and intracerebral haemorrhage (ICH). This study aimed to evaluate the diagnostic performance of ocular ultrasound (OU) and its usefulness in clinical practice. MATERIAL AND METHODS: We performed an observational, prospective, single-centre study of neurocritical care patients. We analysed cases and controls, defined according to indirect ophthalmoscopy (IO) and OU findings. We determined the diagnostic characteristics of OU. A multivariate analysis was performed to identify clinically relevant associations. RESULTS: The sample included 91 patients diagnosed with ICH (41.76%), SAH (29.67%), and TBI (28.57%). TS was identified by OU in 8 patients (8.79%) and by IO in 24 (24.37%). The adjusted mortality rate in patients with TS showed an odds ratio (OR) of 4.15 (95% confidence interval [CI], 1.52-11.33). All patients with TS detected by OU presented Glasgow Coma Scale scores < 9, with an elevated risk of needing decompressive craniectomy (OR: 9.84; 95% CI, 1.64-59). OU presented an overall sensitivity of 30.43%, specificity of 98.53%, and diagnostic accuracy of 81.32%. For the detection of vitreous haemorrhage, sensitivity and specificity were 87.5% and 98.5%, respectively. CONCLUSIONS: OU diagnosis of TS identifies extremely critical patients, who may require the highest level of care; TS is an independent risk factor for in-hospital mortality.

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.

[Emergency transcranial doppler ultrasound: predictive value for the development of symptomatic vasospasm in spontaneous subarachnoid hemorrhage in patients in good neurological condition]. / Ultrasonografía doppler transcraneal urgente: utilidad predictiva del vasoespasmo sintomático en la hemorragia subaracnoidea espontánea en pacientes con buena situación neurológica.

PURPOSE: To examine the predictive value of an early transcranial Doppler ultrasound (TCD) study performed in the emergency department in patients with spontaneous subarachoniod hemorrhage (SAH) in good neurological condition, in order to know which patients are at high risk of developing delayed cerebral ischemia (DCI). DESIGN: A descriptive observational study was carried out involving a period of 3 years. SETTING: Critical Care and Emergency Department. PATIENTS: The study consecutively included patients with SAH of grade I-III on the Hunt and Hess scale. VARIABLES OF INTEREST: DCI (decrease of 2 points in GCS or focal deficit), Mean Velocity (MV) of middle cerebral arteries (MCA), Lindegaard Index (IL). Sonographic vasospasm pattern (SVP) was considered if MCA-MV>120cm/sc and IL>3. RESULTS: The mean age of the 122 patients was 54.1±13.7 years; 57.3% were women. SVP was detected in 24 patients (19.7%), although high velocities patterns (HVP) were present in 38 patients (31.1%). DCI developed in 21 patients (MV183+/-49cm/sc), all with previous SVP. In this group MV increased 22+/-5cm/sc/day during the first 3 days. The group without HVP (84 patients/MV of 67+/-16.6cm/sc), compared with DCI group, showed differences in highest MV (p<0.001), and also ΔMV/day (8.30+/-4,5cm/sc Vs 22+/-5cm/sc) during the first 3 days (p=0.009). In our series, ROC analysis selected the best cut-off value for ΔMV/day as 21cm/sc (p<0.001). CONCLUSION: During the first 3 days, an increase of 21cm/s/24h in MCA-MV was associated with the development of symptomatic vasospasm. TCD is a useful tool for the early detection of patients at risk of DCI after SAH.