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.

[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.

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.

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.

[Intracranial pressure monitoring in severe traumatic brain injury: A different perspective of the BestTrip trial]. / Monitorización de la presión intracraneal en el traumatismo craneoencefálico grave: otra visión del Best Trip trial.

The present study outlines a series of questions and reflections upon the recent publication of Chesnut et al., who compared 2 approaches to the treatment of intracranial hypertension (ICH) in severe head injuries: one with and the other without intracranial pressure monitoring (ICP). The authors concluded that no improved outcome was observed in the treatment group guided by ICP monitoring. The main concerns relate to the degree of training of the physicians involved in the monitoring and management of ICH in the ICP group, as well as to the possible inter-observer variability in interpreting the CT scans, the capacity of clinical signs to guide the treatment of ICH, and the suitability of randomization. The analysis of this trial should not be taken to suggest the futility of ICP monitoring but rather the need to correctly use the information afforded by ICP monitoring, with emphasis on the importance of the definition of alternative methods for non-invasive monitoring.

[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.

[Treatment alternatives in massive hemorrhage]. / Alternativas terapéuticas de la hemorragia masiva.

Massive hemorrhage is the main cause of mortality and morbidity in trauma patients, and is one of the most important causes in any patient following major surgery. Conventional treatment consists of volume replacement, including the transfusion of blood products, so that tissue perfusion and oxygenation may be maintained. Associated hypothermia, acidosis and coagulopathy is a lethal triad. This review focuses on the latest therapeutic management of massive hemorrhage. The authors advocate the use of crystalloids as per protocol (controlled volumes) in order to achieve a systolic blood pressure of 85mmHg. The administration of the three blood products (red cells, plasma, and platelets) should be on a 1:1:1 basis. Where possible, this in turn should be guided by thromboelastography performed at point of care near the patient. Coagulopathy can occur early and late. With the exception of tranexamic acid, the cost-benefit relationships of the hemostatic agents, such as fibrinogen, prothrombin complex, and recombinant F VII, are subject to discussion.

[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.

[Tranexamic acid therapy decreases mortality of traumatic hemorrhagic shock]. / El ácido tranexámico disminuye la mortalidad del shock hemorrágico traumático.

The CRASH 2, a randomized, double-blind, controlled trial, that enrolled 20,211 adult trauma patients, has shown that the administration of tranexamic acid significantly reduces all-cause mortality and that specifically associated with severe blood loss as well. We consider it a significant therapeutic advance, because, for the first time, a drug has been demonstrated to safely diminish mortality due to traumatic bleeding shock. On the basis of these results, and the high rate of death due to traumatic bleeding, we suggest that tranexamic acid should be considered for compassionate use in bleeding trauma patients prior to its definitive approval for this medical condition.

Ten physiological commandments for severe head injury. / Diez mandamientos fisiológicos a lograr durante el traumatismo craneoencefálico grave.

Advances in multiparametric brain monitoring have allowed us to deepen our knowledge of the physiopathology of head injury and how it can be treated using the therapies available today. It is essential to understand and interpret a series of basic physiological and physiopathological principles that, on the one hand, provide an adequate metabolic environment to prevent worsening of the primary brain injury and favour its recovery, and on the other hand, allow therapeutic resources to be individually adapted to the specific needs of the patient. Based on these notions, this article presents a decalogue of the physiological objectives to be achieved in brain injury, together with a series of diagnostic and therapeutic recommendations for achieving these goals. We emphasise the importance of considering and analysing the physiological variables involved in the transport of oxygen to the brain, such as cardiac output and arterial oxygen content, together with their conditioning factors and possible alterations. Special attention is paid to the basic elements of physiological neuroprotection, and we describe the multiple causes of cerebral hypoxia, how to approach them, and how to correct them. We also examine the increase in intracranial pressure as a physiopathological element, focussing on the significance of thoracic and abdominal pressure in the interpretation of intracranial pressure. Treatment of intracranial pressure should be based on a step-wise model, the first stage of which should be based on a physiopathological reflection combined with information on the tomographic lesions rather than on rigid numerical values.

Ten physiological commandments for severe head injury.

Advances in multiparametric brain monitoring have allowed us to deepen our knowledge of the physiopathology of head injury and how it can be treated using the therapies available today. It is essential to understand and interpret a series of basic physiological and physiopathological principles that, on the one hand, provide an adequate metabolic environment to prevent worsening of the primary brain injury and favour its recovery, and on the other hand, allow therapeutic resources to be individually adapted to the specific needs of the patient. Based on these notions, this article presents a decalogue of the physiological objectives to be achieved in brain injury, together with a series of diagnostic and therapeutic recommendations for achieving these goals. We emphasise the importance of considering and analysing the physiological variables involved in the transport of oxygen to the brain, such as cardiac output and arterial oxygen content, together with their conditioning factors and possible alterations. Special attention is paid to the basic elements of physiological neuroprotection, and we describe the multiple causes of cerebral hypoxia, how to approach them, and how to correct them. We also examine the increase in intracranial pressure as a physiopathological element, focussing on the significance of thoracic and abdominal pressure in the interpretation of intracranial pressure. Treatment of intracranial pressure should be based on a step-wise model, the first stage of which should be based on a physiopathological reflection combined with information on the tomographic lesions rather than on rigid numerical values.

Skull fracture, with or without clinical signs, in mTBI is an independent risk marker for neurosurgically relevant intracranial lesion: a cohort study.

PRIMARY OBJECTIVE: To explore the possibility of identifying skull fracture, with or without clinical signs, as a predictor of positive CT scans in mild traumatic brain injury (mTBI). RESEARCH DESIGN: Prospective cohort study, matched 1:1 for five potential confounding variables (age, sex, symptoms, mechanism of injury and extracranial trauma severity). METHODS AND PROCEDURES: The study was performed on patients with mTBI (Glasgow Coma Scale 15-14), with or without radiologically demonstrated skull fracture. The cohort with skull fracture included 155 patients selected from a sample of 5097 mTBI patients treated during 1998 at the Critical Care and Emergency Department of the Trauma Centre. The cohort without skull fracture was prospectively recruited from patients with mTBI treated in the same department from 2002-2005. MAIN OUTCOMES AND RESULTS: The percentage of patients with intracranial lesion (IL) was significantly higher in mTBI patients with skull fracture than in those without. The risk of requiring neurosurgery was 5-fold higher when skull fracture was present. Of mTBI patients with skull fracture and IL, 63.2% showed no clinical signs of bone injury. CONCLUSIONS: Skull fracture, with or without clinical signs, in mTBI patients is associated with an increased risk of neurosurgically-relevant intracranial lesion.

Paroxysmal sympathetic hyperactivity: An entity to keep in mind. / Hiperactividad simpática paroxística: una entidad que no debería pasar desapercibida.

Paroxysmal sympathetic hyperactivity (PSH) is a potentially life-threatening neurological emergency secondary to multiple acute acquired brain injuries. It is clinically characterized by the cyclic and simultaneous appearance of signs and symptoms secondary to exacerbated sympathetic discharge. The diagnosis is based on the clinical findings, and high alert rates are required. No widely available and validated homogeneous diagnostic criteria have been established to date. There have been recent consensus attempts to shed light on this obscure phenomenon. Its physiopathology is complex and has not been fully clarified. However, the excitation-inhibition model is the theory that best explains the different aspects of this condition, including the response to treatment with the available drugs. The key therapeutic references are the early recognition of the disorder, avoiding secondary injuries and the triggering of paroxysms. Once sympathetic crises occur, they must peremptorily aborted and prevented. of the later the syndrome is recognized, the poorer the patient outcome.