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Our objective was to analyze the contribution of acute kidney injury (AKI) to the mortality of isolated TBI patients and its associated risk factors. Observational, prospective and multicenter registry (RETRAUCI) methods were used, from March 2015 to December 2019. Isolated TBI was defined as abbreviated injury scale (AIS) ≥ 3 head with no additional score ≥ 3. A comparison of groups was conducted using the Wilcoxon test, chi-square test or Fisher’s exact test, as appropriate. A multiple logistic regression analysis was conducted to analyze associated risk factors in the development of AKI. For the result, overall, 2964 (30.2%) had AIS head ≥ 3 with no other area with AIS ≥ 3. The mean age was 54.7 (SD 19.5) years, 76% were men, and the ground-level falls was 49.1%. The mean ISS was 18.4 (SD 8). The in-hospital mortality was 22.2%. Up to 310 patients (10.6%) developed AKI, which was associated with increased mortality (39% vs. 17%, adjusted OR 2.2). Associated risk factors (odds ratio (OR) (95% confidence interval)) were age (OR 1.02 (1.01–1.02)), hemodynamic instability (OR 2.87 to OR 5.83 (1.79–13.1)), rhabdomyolysis (OR 2.94 (1.69–5.11)), trauma-associated coagulopathy (OR 1.67 (1.05–2.66)) and transfusion of packed red-blood-cell concentrates (OR 1.76 (1.12–2.76)). In conclusion, AKI occurred in 10.6% of isolated TBI patients and was associated with increased mortality.

Background and objective Cerebral edema is a frequent and serious complication of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique to assess white matter integrity after TBI. The objective of this prospective, observational study was to assess the characteristics of the vasogenic edema in the traumatic pericontusional tissue and compare it to the vasogenic edema found in brain tumors. We also included a control group. Methods Using DTI, the Apparent diffusion coefficient (ADC) and Fractional anisotropy (FA) were measured in the area of vasogenic edema in both TBI and tumor patients. The measurements in the control group were done in the gray and white matter. We included 15 TBI patients, 18 tumor patients and 15 controls. Results ADC and FA showed no differences between TBI and tumor patients (p = 0.27 for AF; p = 0.79 for ADC). Compared to healthy controls, TBI and tumor patients presented higher ADC values and lower FA values. The differences between TBI and controls were statistically significant (p Conclusions In this prospective observational study using DTI-MRI in a selected group of mild and moderate TBI patients with vasogenic pericontusional edema we have shown that there were no significant differences of the ADC and FA values compared to brain tumor patients. Furthermore, healthy controls showed significant lower ADC values and higher FA values compared to TBI and tumor patients. Future studies, using DTI-MRI, should address whether any therapy has a favorable impact on the vasogenic edema of TBI patients with brain contusions.

Lung IL-6 is a promising biomarker for predicting respiratory failure during pulmonary infections. This biomarker is found in respiratory samples which need to be liquefied prior to analysis. Traditional liquefying methods use reducing agents such as dithiothreitol (DTT). However, DTT impairs immunodetection and does not liquefy highly viscous samples. We propose an enzymatic method that liquefies samples by means of generating O2 bubbles with endogenous catalase. Low respiratory tract specimens from 48 mechanically ventilated patients (38 with SARS-CoV-2 infection) were treated with DTT or with the enzymatic method. We used turbidimetry to compare the liquefaction degree and IL-6 was quantified with ELISA. Finally, we used AUC-ROC, time-to-event and principal component analysis to evaluate the association between respiratory compromise or local inflammation and IL-6 determined with both methods. Enzymatically treated samples were better liquefied than those reduced by DTT, which resulted in higher ELISA signals. Lung IL-6 levels obtained with the enzymatic procedure were negatively correlated with the oxygenation index (PaO2/FiO2) and the time of mechanical ventilation. The proposed enzymatic liquefaction method improves the sensitivity for lung IL-6 detection in respiratory samples, which increases its predictive power as a biomarker for evaluating respiratory compliance.

Our objective was to determine outcomes of severe chest trauma admitted to the ICU and the risk factors associated with mortality. An observational, prospective, and multicenter registry of trauma patients admitted to the participating ICUs (March 2015–December 2019) was utilized to collect the patient data that were analyzed. Severe chest trauma was defined as an Abbreviated Injury Scale (AIS) value of ≥3 in the thoracic area. Logistic regression analysis was used to evaluate the contribution of severe chest trauma to crude and adjusted ORs for mortality and to analyze the risk factors associated with mortality. Overall, 3821 patients (39%) presented severe chest trauma. The sample’s characteristics were as follows: a mean age of 49.88 (19.21) years, male (77.6%), blunt trauma (93.9%), a mean ISS of 19.9 (11.6). Crude and adjusted (for age and ISS) ORs for mortality in severe chest trauma were 0.78 (0.68–0.89) and 0.43 (0.37–0.50) (p < 0.001), respectively. In-hospital mortality in the severe chest trauma patients without significant traumatic brain injury (TBI) was 5.63% and was 25.71% with associated significant TBI (p < 0.001). Age, the severity of injury (NISS and AIS-head), hemodynamic instability, prehospital intubation, acute kidney injury, and multiorgan failure were risk factors associated with mortality. The contribution of severe chest injury to the mortality of trauma patients admitted to the ICU was very low. Risk factors associated with mortality were identified.

The incidence of thyroid disfunction has not been analyzed in critically ill COVID-19 patients. Our objective was to analyze the relationship of the thyroid profile and in-hospital mortality in critically ill COVID-19 patients. This was a prospective single-center study involving critically ill COVID-19 patients admitted to the ICU of a tertiary University Hospital. Thyroid hormones were measured through drawing blood samples from a central venous catheter at ICU admission and on the fifth day. A multiple logistic regression analysis was performed to analyze the variables associated with mortality. The ability of the different thyroid hormones to predict in-hospital mortality was evaluated by calculating the receiver operating characteristics (ROCs) and the area under the curve (AUC). A total of 78 patients were included in the study at ICU admission, 72 had their thyroid profile measured at day 5. In-hospital mortality reached 29.5%. Multiple logistic regression analysis showed that variables associated with mortality were age and prior beta-blocker therapy at ICU admission and age fT4 at day 5. The AUC for in-hospital mortality predictions of fT4 at day 5 was 0.69. Thyroid responses are commonly observed in critically ill COVID-19 patients. fT4 at day 5 after ICU admission was associated with mortality.

Lung IL-6 is a promising biomarker for predicting respiratory failure during pulmonary infections. This biomarker is found in respiratory samples which need to be liquefied prior to analysis. Traditional liquefying methods use reducing agents such as dithiothreitol (DTT). However, DTT impairs immunodetection and does not liquefy highly viscous samples. We propose an enzymatic method that liquefies samples by means of generating O

The objectives of this study were to assess the association between serum caspase 1 levels and known clinical and radiological prognostic factors and determine whether caspase 1was a more powerful predictor of outcome after traumatic brain injury (TBI) than clinical indices alone, to determine the association between the serum levels of caspase 1 and the 6-month outcome, and to evaluate if there is any association between caspase 1 with clinical and radiological variables. This prospective and observational study was conducted in a university hospital and included patients with TBI who required hospital admission. Serum samples were collected at hospital admission and 24 h after TBI. Caspase 1 levels were determined by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were obtained to test the potential of caspase 1 to predict mortality (Glasgow Outcome Scale Extended score of 1) and unfavorable outcome (Glasgow Outcome Scale Extended scores of 1–4). Multivariate logistic regression was used to assess the effect of serum caspase 1 levels, adjusted by known clinical and radiological prognostic indices, on the outcome. One hundred thirty-two patients and 33 healthy controls were included. We obtained 6-month outcome in 118 patients. On admission, the mean serum levels of caspase 1 were higher in patients with TBI compared with controls (157.9 vs. 108.5 pg/mL; p

To compare patients with a Glasgow Coma Scale (GCS) score of 3 stratified according to pupillary reaction and to explore factors associated with in-hospital death in those with bilateral fixed dilated pupils.Prospective, observational, multicenter study. We included all patients with trauma and GCS scores of 3 admitted to the intensive care unit from March 2015 to December 2019. Factors associated with in-hospital mortality in the patients with bilateral dilated pupils were explored using multiple regression analysis.Of the 933 patients included, 454 (48.7%) had responsive pupils, 201 (21.5%) had a single fixed dilated pupil, and 278 (29.8%) had bilateral dilation. Hospital mortality was high in all 3 groups: 32.5% in those with normal responsive pupils, 54.6% in those with a single unreactive pupil, and 91.0% in those with bilateral dilation. Factors significantly associated with in-hospital death were age, a score of 3 or more on the Abbreviated Injury Scale for the head, and shock or refractory shock. Types I or II diffuse lesions and evacuated mass lesions were protective in patients with GCS scores of 3 and bilateral dilated pupils. Twelve of the 26 patients (46.1%) with bilateral dilated pupils and GCS scores of 3 had GCS scores of 14 or 15 on discharge from the hospital.The in-hospital mortality was 91% in this study of trauma patients with GCS scores of 3 and bilateral dilated pupils. Factors significantly associated with in-hospital death were age, a score of 3 or more on the Abbreviated Injury Scale for the head, and shock or refractory shock. Types I or II diffuse lesions and evacuated mass lesions were protective in patients with GCS scores of 3 and bilateral dilated pupils.Comparar los pacientes traumáticos con una puntuación de 3 en la escala de coma de Glasgow (Glasgow Coma Scale, GCS) en función de la reactividad pupilar e investigar los factores asociados a la mortalidad hospitalaria en los pacientes con GCS 3 y midriasis bilateral arreactiva.Estudio observacional, prospectivo y multicéntrico. Se incluyeron todos los pacientes traumáticos recogidos con GCS 3 ingresados en las unidades de cuidados intensivos (UCI) participantes desde marzo 2015 hasta diciembre 2019. Se realizó un análisis de regresión logística para el estudio de los factores asociados a la mortalidad hospitalaria en pacientes con GCS 3 puntos y midriasis bilateral arreactiva.De los 933 pacientes con GCS 3 puntos, 454 (48,7%) presentaron pupilas simétricas y reactivas, 201 (21,5%) anisocoria arreactiva y 278 (29,8%) midriasis bilateral arreactiva. La mortalidad hospitalaria fue elevada en los 3 grupos: 32,5% con pupilas normales, 54,6% con anisocoria arreactiva y 91,0% con midriasis bilateral arreactiva. La edad, la puntación de 3 o más en el Abbreviated Injury Scale (cabeza) y el shock o shock refractario se asociaron de forma significativa con la mortalidad hospitalaria, siendo la lesión difusa tipo I y II y la lesión masa evacuada factores protectores en los pacientes con 3 puntos en la GCS y midriasis bilateral arreactiva. De los 26 pacientes que sobrevivieron con GCS 3 y midriasis bilateral arreactiva, 12 (46,1%) tuvieron un GCS de 14-15 al alta hospitalaria.La mortalidad hospitalaria de los pacientes traumáticos con 3 puntos en la GCS y midriasis bilateral arreactiva fue del 91%. La edad, la puntación de 3 o más en el Abbreviated Injury Scale (cabeza) y el shock o shock refractario se asociaron de forma significativa con la mortalidad hospitalaria, siendo la lesión difusa tipo I y II, y la lesión masa evacuada factores protectores en este grupo de pacientes.

Supplemental Digital Content is available in the text, Background: Traumatic brain injury (TBI) constitutes a leading cause of death and disability. Patients with TBI and cerebral contusions developing pericontusional edema are occasionally given dexamethasone on the belief that this edema is similar to that of tumors, in which the beneficial effect of dexamethasone has been demonstrated. Methods: The DEXCON TBI trial is a multicenter, pragmatic, randomized, triple-blind, placebo controlled trial to quantify the effects of dexamethasone on the prognosis of TBI patients with brain contusions and pericontusional edema. Adult patients who fulfill the elegibility criteria will be randomized to dexamethasone/placebo in a short and descending course: 4 mg/6 h (2 days); 4 mg/8 hours (2 days); 2 mg/6 hours (2 days); 2 mg/8 hours (2 days); 1 mg/8 hours (2 days); 1 mg/12 hours (2 days). The primary outcome is the Glasgow Scale Outcome Extended (GOSE) performed 1 month and 6 months after TBI. Secondary outcomes are: number of episodes of neurological deterioration; symptoms associated with TBI; adverse events; volume of pericontusional edema before and after 12 days of treatment; results of the neuropsychological tests one month and 6 months after TBI. The main analysis will be on an “intention-to-treat” basis. Logistic regression will estimate the effect of dexamethasone/placebo on GOSE at one month and at 6 months, dichotomized in unfavorable outcome (GOSE 1–6) and favorable outcome (GOSE 7–8). Efficacy will also be analyzed using the 'sliding dichotomy’. An interim and safety analysis will be performed including patients recruited during the first year to calculate the conditional power. A study with 600 patients would have 80% power (2 sided alpha = 5%) to detect a 12% absolute increase (from 50% to 62%) in good recovery. Discussion: This is a confirmative trial to elucidate the therapeutic efficacy of dexamethasone in a very specific group of TBI patients: patients with brain contusions and pericontusional edema. This trial could become an important milestone for TBI patients as nowadays there is no effective treatment in this type of patients. Trial Registration: eudraCT: 2019–004038–41; Clinical Trials.gov: NCT04303065.

Cerebral edema is a frequent and serious complication in traumatic brain injury (TBI) patients. The objective is to study the effect of dexamethasone in patients with brain contusions, and to assess its effect on the vasogenic component of the pericontusional edema. Prospective-observational study to quantify, using magnetic resonance imaging, the volume of the edema before and after 10 days of dexamethasone in patients with brain contusions. Using diffusion tensor imaging, we have examined the effect of dexamethasone on fractional anisotropy (FA) and apparent diffusion coefficient (ADC). To assess changes, the pre- and post-treatment values for each patient were compared using a paired-samples Student t test. We included 30 TBI patients, 15 in each group. The volume of the vasogenic edema in the group of patients treated with dexamethasone decreased from 22 to 19 mL and this decrease was statistically significant (P < .05). Nevertheless, in the non-steroids group the volume of the vasogenic edema increased from 11 to 15 mL. There was a significant decrease in the ADC value (from 1.78-1.59; P < .05); and a significant increase in the FA value (0.09-0.11; P < .05) in the patients treated with dexamethasone. Using diffusion tensor imaging we have shown in a selected group of TBI patients with vasogenic pericontusional edema, a reduction of edema volume, a decrease in the ADC and an increase in the FA after treatment with dexamethasone. However, we have no data if such results are beneficial in terms of improving functional outcome.

Background To compare the main outcomes of trauma patients with and without traumatic brain injury (TBI), hemorrhagic shock, and the combination of both using data from the Spanish trauma intensive care unit (ICU) registry (RETRAUCI). Methods Patients admitted to the participating ICUs from March 2015 to May 2019 were included in the study. The main outcomes were analyzed according to the presence of TBI, hemorrhagic shock, and/or both. Comparison of groups with quantitative variables was performed using the Kruskal-Wallis test, and differences between groups with categorical variables were compared using the Chi-square test or Fisher’s exact test as appropriate. A P value Results Overall, 310 patients (3.98%) were presented with TBI and hemorrhagic shock. Patients with TBI and hemorrhagic shock received more red blood cell (RBC) concentrates, fresh frozen plasma (FFP), a higher ratio FFP/RBC, and had a higher incidence of trauma-induced coagulopathy (60%) ( P < .001). These patients had higher mortality ( P < .001). Intracranial hypertension was the leading cause of death (50.4%). Conclusions Concomitant TBI and hemorrhagic shock occur in nearly 4% of trauma ICU patients. These patients required a higher amount of RBC concentrates and FFP and had an increased mortality.

To analyze factors associated with the development of early and late multiorgan failure (MOF) in trauma patients admitted to the intensive care unit (ICU).Spanish Trauma ICU Registry (RETRAUCI). Data collected from 52 trauma ICU between March 2015 and December 2019. We analyzed the incidence, outcomes, and the risk factors associated with early (72 h) or late (beyond 72 h) MOF in trauma ICU patients. Multiple logistic regression analysis was performed to analyze associated factors.After excluding patients with incomplete data, 9,598 trauma ICU patients constituted the study population. Up to 965 patients (10.1%) presented with MOF, distributed by early MOF in 780 patients (8.1%) and late MOF in 185 patients (1.9%). The multivariate analysis showed that early MOF was associated with: ISS ≥ 16 (OR 2.80), hemodynamic instability (OR from 2.03 to 43.05), trauma-associated coagulopathy (OR 2.32), and acute kidney injury (OR 4.10). Late MOF was associated with: age65 years (OR 1.52), hemodynamic instability (OR from 1.92 to 9.94), acute kidney injury (OR 4.22), and nosocomial infection (OR 17.23). MOF was closely related to mortality (crude OR (95% CI) 4.77 (4.22-5.40)).Multiorgan failure was recorded in 10% of trauma ICU patients, with early MOF being the predominant form. Early and late MOF forms were associated with different risk factors, suggesting different pathophysiological pathways. Early MOF was associated with higher severity of injury and severe bleeding-related complications and late MOF with advanced age and nosocomial infection.

Cerebral edema is a frequent and serious complication of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique to assess white matter integrity after TBI. The objective of this prospective, observational study was to assess the characteristics of the vasogenic edema in the traumatic pericontusional tissue and compare it to the vasogenic edema found in brain tumors. We also included a control group.Using DTI, the Apparent diffusion coefficient (ADC) and Fractional anisotropy (FA) were measured in the area of vasogenic edema in both TBI and tumor patients. The measurements in the control group were done in the gray and white matter. We included 15 TBI patients, 18 tumor patients and 15 controls.ADC and FA showed no differences between TBI and tumor patients (p=0.27 for AF; p=0.79 for ADC). Compared to healthy controls, TBI and tumor patients presented higher ADC values and lower FA values. The differences between TBI and controls were statistically significant (p0.05).In this prospective observational study using DTI-MRI in a selected group of mild and moderate TBI patients with vasogenic pericontusional edema we have shown that there were no significant differences of the ADC and FA values compared to brain tumor patients. Furthermore, healthy controls showed significant lower ADC values and higher FA values compared to TBI and tumor patients. Future studies, using DTI-MRI, should address whether any therapy has a favorable impact on the vasogenic edema of TBI patients with brain contusions.

OBJECTIVE The objectives of this study were to evaluate levels of inflammasome-signaling proteins in serum and CSF of patients with traumatic brain injury (TBI), and to correlate these protein levels with intracranial pressure (ICP) and clinical outcomes at 6 months after injury. METHODS This is a prospective and observational study in patients with moderate and severe TBI who required an external ventricular drain as part of their treatment. Serum and CSF samples were collected 3 times a day for the first 5 days after TBI. The authors have determined the protein concentration of caspase-1 in the CSF and serum of patients with TBI by using commercially available enzyme-linked immunosorbent assays. The ICP value was recorded hourly. The 6-month outcome was assessed using the Glasgow Outcome Scale–Extended. RESULTS A total of 21 patients were included in this study, and a total of 234 paired serum-CSF samples were analyzed. The area under the curve (AUC) value of caspase-1 in CSF during the 5-day period was 2452.9 pg/mL·hr in the group of patients with high ICP vs 617.6 pg/mL·hr in the patients with low ICP. The differences were mainly on day 2 (19.7 pg/mL vs 1.8 pg/mL; p = 0.06) and day 3 (13.9 pg/mL vs 1 pg/mL; p = 0.05). The AUC value of caspase in CSF during the 5-day period was 1918.9 pg/mL·hr in the group of patients with poor outcome versus 924.5 pg/mL·hr in the patients with good outcome. The protein levels of caspase-1 in CSF were higher in patients with unfavorable outcomes during the first 96 hours after TBI. CONCLUSIONS In this cohort of patients with TBI who were admitted to the neurosurgical ICU, the inflammasome protein caspase-1 is increased in the CSF of patients with high ICP, especially on days 2 and 3 after TBI. Also the protein levels of caspase-1 in CSF were higher in patients with poor outcome during the first 96 hours after TBI. Moreover, not only the absolute value of caspase-1 in CSF but also its trend is associated with poor outcomes.

Resumen Introduccion Comparamos el Geriatric Trauma Outcome score (GTOS) con la probabilidad de supervivencia empleando la metodologia TRISS (PS-TRISS) en pacientes traumaticos ancianos ingresados en las Unidades de Cuidados Intensivos (UCI) participantes en el registro de traumatismo en UCI (RETRAUCI). Metodos Analisis retrospectivo del RETRAUCI. Los datos cuantitativos se expresan como mediana (rango intercuartil), los datos categoricos como numero (porcentaje). Analizamos la validez del GTOS y la PS-TRISS para la prediccion de supervivencia. La discriminacion se evaluo mediante curvas receiver operating characteristics. La calibracion de los modelos se analizo mediante el test de bondad de ajuste de Hosmer-Lemeshow. Un valor de p Resultados La cohorte incluyo a 1.417 pacientes ≥ 65 anos. Mediana edad 75,5 (70,5-80,5) anos, varones 1.003 (68,2%), mediana Injury Severity Score 18 (13-25). Ventilacion mecanica, 61%. Las caidas fueron el mecanismo de lesion en 659 pacientes (44,8%). Mortalidad hospitalaria: 18,2%. El area bajo la curva para PS-TRISS fue 0,69 (IC del 95% 0,66-0,73) y para GTOS 0,66 (IC del 95% 0,62-0,70); p Conclusiones En nuestra muestra de pacientes traumaticos ancianos la precision de GTOS fue inferior a la de la metodologia TRISS en la prediccion de la supervivencia hospitalaria. Ambos scores tuvieron una mala calibracion en la poblacion anciana.

Our purpose was to assess the amino acids’ (AAs) profile in trauma patients and to assess the effect of the route of nutrition and the exogenous ALA-GLN dipeptide supplementation on plasma AAs’ concentration. This is a secondary analysis of a previous randomized controlled trial. On day 1 and day 6 after trauma, plasma concentration of 25 AAs was measured using reverse phase high-performance liquid chromatography. Results were analyzed in relation to the route of nutrition and supplementation of ALA-GLN dipeptide. Differences between plasma AAs’ concentrations at day 1 and day 6 were evaluated using the Student’s t test or Mann–Whitney–Wilcoxon test. One-way ANOVA and the Kruskal–Wallis test were used to compare groups. A two-sided p value less than 0.05 was considered statistically significant. Ninety-eight patients were analyzed. Mean plasma concentrations at day 1 were close to the lower normal level for most AAs. At day 6 we found an increase in the eight essential AAs’ concentrations and in 9 out of 17 measured non-essential AAs. At day 6 we found no differences in plasma concentrations for the sum of all AAs (p = .72), glutamine (p = .31) and arginine (p = .23) distributed by the route of nutrition. Administration of ALA-GLN dipeptide increased the plasma concentration of alanine (p = .004), glutamine (p

Introduction Acute kidney injury (AKI) constitutes a common complication after severe trauma. Our objective was to analyse the associated risk factors and outcomes of AKI in a large, multicentre sample of trauma ICU patients. Materials and methods Observational, prospective and multicentre nationwide registry (RETRAUCI). We included all patients admitted to the participating ICUs from November 2013 to May 2017. We analysed the impact of AKI evaluated by the Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) definition. Comparison of groups was performed using Wilcoxon test, Chi-Square Test or Fisher's exact test as appropriate. A multiple logistic regression analysis was performed to analyse associated factors to the development of AKI. Logistic regression was used to calculate AKI-related mortality. A P value Results During the study period, 5882 trauma patients were admitted. Complete data were available for 5740 patients. Among them, 871 had AKI (15.17%), distributed by RIFLE R 458 (7.98%), RIFLE I 234 (4.08%) and RIFLE F 179 (3.12%). Associated risk factors were: age (OR 3.05), haemodynamic instability (OR 2.90 to OR 8.34 depending on the severity of hypotension), coagulopathy (OR 1.82), rhabdomyolysis (OR 4.67) and AIS abdomen (OR 1.54). AKI was associated with mortality (crude OR 1.93 (1.59-2.36)), even after adjusting by potential confounders (adjusted OR 1.40 (1.13-1.73)). Conclusion In our large sample of trauma ICU patients we found an incidence of AKI of 15%, which was associated with an increased mortality.

Objective To analyze outcomes and factors related to mortality among very elderly trauma patients admitted to intensive care units (ICUs) participating in the Spanish trauma ICU registry. Design A multicenter nationwide registry. Retrospective analysis. November 2012–May 2017. Setting Participating ICUs. Patients Trauma patients aged ≥80 years. Interventions None. Main variables of interest The outcomes and influence of limitation of life sustaining therapy (LLST) were analyzed. Comparisons were established using the Wilcoxon test, Chi-squared test or Fisher's exact test as appropriate. Multiple logistic regression analysis was performed to analyze variables related to mortality. A p-value Results The mean patient age was 83.4 ± 3.3 years; 281 males (60.4%). Low-energy falls were the mechanisms of injury in 256 patients (55.1%). The mean ISS was 20.5 ± 11.1, with a mean ICU stay of 7.45 ± 9.9 days. The probability of survival based on the TRISS methodology was 69.8 ± 29.7%. The ICU mortality rate was 15.5%, with an in-hospital mortality rate of 19.2%. The main cause of mortality was intracranial hypertension (42.7%). The ISS, the need for first- and second-tier measures to control intracranial pressure, and being admitted to the ICU for organ donation were independent mortality predictors. LLST was applied in 128 patients (27.9%). Patients who received LLST were older, with more severe trauma, and with more severe brain injury. Conclusions Very elderly trauma ICU patients presented mortality rates lower than predicted on the basis of the severity of injury.

Object The aim of this study is to identify pre-operative clinical and/or radiological predictors of clinical failure of decompressive hemicraniectomy (DH) in the setting of malignant hemispheric infarction. These predictors could guide the decision for adjunctive internal brain decompression (e.g. strokectomy) at the time of the initial DH. Methods Retrospective chart review of all patients with malignant hemispheric infarction who underwent DH at our institution, from November 2008 to January 2013. Demographics, pre- and post-operative clinical characteristics and neuroimaging data were reviewed. The surgical outcome after DH was evaluated and clinical failure was defined as follows: lack of post-operative resolution of basal cistern effacement, and/or failure to achieve a post-operative decrease in midline shift by at least 50%, and/or post-operative neurological deterioration felt to be due to persistent mass effect, with or without a second, salvage operation (strokectomy). Results Out of 26 patients included in the study, 7 were considered to have clinical failure of their DH. Preoperative clinical and imaging variables were similar in the two groups, except that the presence of a nonreactive pupil immediately before surgery was associated clinical failure of the DH (p = 0.0015). Patients in the clinical failure group had a lower postoperative GCS motor score and a strong but not statistically significant trend towards less favorable functional outcome (GOS 1–3). Conclusions The presence of a nonreactive pupil before surgery is associated with clinical failure of DH, and should be taken into account when deciding whether to perform strokectomy at the time of DH.

Objective To describe the alterations of the cortical microcirculation of the brain (blood flow and vessel density) in TBI patients who and compare them with a control group. Methods Prospective and observational study in a third-level university hospital. Cortical microcirculation in the brain was directly observed using sidestream dark-field (SDF) imaging in 14 patients who underwent surgery: 5 subdural hematomas (SDH) and 9 parenchymal lesions (contusions/hematomas). In this last set of patients, images were recorded in the “pericontusional” areas and in the “surrounding” brain (areas that were as far from the lesion as the craniotomy allowed). These patients were compared to five patients who underwent craniotomy for a disease that did not affect the cortex. Results There were fewer “pericontusional” images that could be analyzed due to the presence of subarachnoid hemorrhage. The proportion or perfused vessels was similar in all groups: control 99.5% ± 1.3%; SDH 98.6% ± 2.4%; “pericontusional” area 98.2% ± 2.4%; “surrounding” area 98.4% ± 2.5% (p = 0.145). The perfused vessel density index was smaller in the “pericontusional” area: control 6.5 ± 1.6 l/mm; SDH 6.5 ± 2.5 l/mm; “pericontusional” area 5.4 ± 2.6 l/mm; “surrounding” 6.6 ± 2.1 l/mm (p = 0.07). Conclusions Although the analysis of pericontusional zone was difficult, there were fewer vessels than in the controls and there was no change in the flow. In the surrounding zone and in patients with SDH, we did not document alterations in the microcirculation. Direct imaging of cerebral microcirculation in TBI patients showed that despite serious brain injury the cerebral microcirculation was remarkably well preserved.

Geriatric trauma constitutes an increasingly recognized problem. Aging results in a progressive decline in cellular function which leads to a loose of their capacity to respond to injury. Some medications commonly used in this population can mask or blunt the response to injury. Falls constitute the most common cause of trauma and the leading cause of trauma-related deaths in this population. Falls are complicated by the widespread use of antiplatelets and anticoagulants, especially in patients with brain injury. Under-triage is common in this population. Evaluation of frailty could be helpful to solve this issue. Appropriate triaging and early aggressive management with correction of coagulopathy can improve outcome. Limitation of care and palliative measures must be considered in cases with a clear likelihood of poor prognosis.

Purpose To evaluate the effect of the intravenous (i.v.) l-alanyl-l-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit (ICU).

Background The inflammasome plays an important role in the inflammatory innate immune response after central nervous system (CNS) injury. Inhibition of the inflammasome after traumatic brain injury (TBI) results in improved outcomes by lowering the levels of caspase-1 and interleukin (IL)-1b. We have previously shown that inflammasome proteins are elevated in the cerebrospinal fluid (CSF) of patients with TBI and that higher levels of these proteins were consistent with poorer outcomes after TBI when compared to patients that presented these inflammasome proteins at lower levels. Methods and findings Here we extend our work by analyzing serum from 21 TBI patients and CSF from 18 TBI patients compared to 120 serum samples and 30 CSF samples from no-TBI donor controls for the expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin(IL)-1b and IL-18. Analysis was carried out using the Ella Simple Plex system (Protein Simple) to determine the sensitivity and specificity of inflammasome proteins as biomarkers of TBI. Receiver operator characteristic (ROC) curves, confidence intervals and likelihood ratios for each biomarker was determined. ROC curves, confidence intervals, sensitivity and specificity for each biomarker examined revealed that caspase-1 (0.93 area under the curve (AUC)) and ASC (0.90 AUC) in serum and ASC (1.0 AUC) and IL-18 (0.84 AUC) in CSF are promising biomarkers of TBI pathology. Importantly, higher protein levels (above 547.6 pg/ml) of ASC (0.91 AUC) were consistent with poorer outcomes after TBI as determined by the Glasgow Outcome Scale-Extended (GOSE). Conclusion These findings indicate that inflammasome proteins are excellent diagnostic and predictive biomarkers of TBI., This work was supported by a STTR grant (4R42NS086274-012) from the NINDS/NIH to RWK: https://www.nih.gov/; and by a public grant from Fondo de Investigacion Sanitaria (FIS PI16/00737) to JPB: https://portalfis.isciii.es/es/Paginas/inicio.aspx.No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This work was supported by a STTR grant (4R42NS086274-012) from the NINDS/NIH to RWK and WDD and by a public grant from Fondo de Investigacion Sanitaria (FIS PI16/00737) to JPB.

The diagnosis of brain death remains a clinical challenge for intensive care unit physicians. Worldwide regulations in its diagnosis may differ, and the need of ancillary tests after a clinical examination is not uniform. Transcranial sonography is a noninvasive, bedside, and widely available technique that can be used in the diagnosis of the cerebral circulatory arrest that preceeds brain death. In this paper we review the general concepts, the technical requisites, the patterns of Doppler signal confirming cerebral circulatory arrest, the vessels to insonate, and the options in cases with poor acoustic window. Future research perspectives in the field of transcranial sonography are discussed as well.

To determine the evolution of cytokine patterns using microdialysis in patients with traumatic brain injury with diffuse lesions and to study the relationship between cytokines and intracranial pressure, brain tissue oxygenation and lesion type on the computed cranial tomography scan (patients with and without brain swelling).Prospective and observational study.Third-level university hospital.Patients between 15 and 65 yrs with severe traumatic brain injury and a diffuse lesion requiring intracranial pressure and brain tissue oxygenation monitoring were eligible.Microdialysis catheters with a high-cutoff membrane of 100 kDa were inserted.Sixteen patients were included in the analysis. There was a substantial interindividual variability between cytokine values. The highest concentrations for the interleukin-1β, interleukin-6, and interleukin-8 were measured during the first 24 hrs followed by a gradual decline. The average concentration for interleukin-10 did not vary over time. This pattern is the most frequent in patients with traumatic brain injury with diffuse lesions. The intracranial pressure-cytokines correlation coefficients for the 16 patients varied substantially: interleukin-1β-intracranial pressure (-0.76 to 0.63); interleukin-6-intracranial pressure (-0.83 to 0.78); interleukin-8-intracranial pressure (-0.86 to 0.84); and interleukin-10-intracranial pressure (-0.36 to 0.65). The brain tissue oxygenation-cytokine correlation coefficients, like with intracranial pressure, also varied between patients: interleukin-1β-brain tissue oxygenation (-0.49 to 0.68), interleukin-6-brain tissue oxygenation (-0.99 to 0.84); interleukin-8-brain tissue oxygenation (-0.65 to 0.74); and interleukin-10-brain tissue oxygenation (-0.34 to 0.52). Similarly, we found no difference in the cytokine values inpatient microdialysis with and without swelling in the computed tomographic scan.No clear relationship was found between the temporal pattern of cytokines and the behavior of the intracranial pressure, brain tissue oxygenation, and the presence or absence of swelling in the computed tomography scan. This study demonstrates the feasibility of microdialysis in recovering cytokines for a prolonged time, although there may be some nonresolved methodologic problems with this technique when we try to study the inflammation during traumatic brain injury that could affect the results and make interpretation of microdialysis data prone to difficulties.

Objectives: Most knowledge related to the pathophysiology of microcirculation in ischemic stroke comes from experimental research. Unfortunately, data on microcirculation in the human brain are limited, partially as a result of the lack of appropriate investigational techniques. The objective of our study was to test the hypothesis that cortical microcirculatory alterations in the brain, in terms of blood flow and vessel density, occur in patients with stroke who require surgical decompression compared with a control group. Design: Prospective and observational study. Setting: Third-level university hospital. Patients: Six patients who had undergone decompressive surgery as a result of a space-occupying hemispheric infarction. These patients were compared with five patients who had undergone craniotomy for a disease not affecting the cortex. Interventions: Cortical microcirculation in the brain was directly observed using sidestream dark-field imaging. All images were analyzed offline. Measurements and Main Results: In patients with stroke with a space-occupying hemispheric infarction, 18 good-quality movie images were compared with 25 control group images. In the control group, cortical vessels showed a continuous flow in small, medium, and large vessels compared with patients with stroke who presented intermittent or no flow in all vessels. The proportion of perfused vessels was near 100% in control subjects and 63.44% in patients with stroke. The perfused vessel density index was also higher in control subjects (6.16 1/mm; interquartile range, 5.65-7.56) than in patients with stroke (2.77 1/mm; interquartile range, 1.75-3.86). Conclusion: Sidestream dark-field imaging allowed direct visualization of cerebral microcirculatory alterations in the operating room. This technique allowed the documentation of a significant blood flow reduction in the cortical microvascular and a decreased vascular density in patients with stroke compared with control subjects. (Crit Care Med 2011; 39:1126-1129)

Traumatic brain injury (TBI) is commonly associated with disturbances of the hypothalamic–pituitary–adrenal axis secretion. Cerebral microdialysis techniques have been recently applied to measure brain interstitial cortisol levels. We evaluated for the first time the circadian rhythm of cortisol secretion at 08:00, 16:00, and 24:00 h in the acute phase of TBI by determination of total serum and brain interstitial cortisol levels (microdialysis samples) in 10 patients with TBI. Non-parametric Friedman’s two way analysis of variance test was used. Mean age was 29.8 ± 13.6 years. Median Glasgow Coma Scale score after resuscitation was 5 (range 3–10). No differences were found in total serum (P = 0.26) and brain interstitial cortisol (P = 0.77) in the whole sample. Intraindividual analysis showed that circadian variability was lost in all patients, both in serum and brain interstitial cortisol samples in the acute phase after TBI. In our series, circadian variability of cortisol evaluated by serum and cerebral microdialysis samples seems to be lost in TBI patients.

Background: There are reports with conflicting results on the expression of toll-like receptors (TLRs) in trauma patients. In addition, these studies analyzed TLR expression only at patients' hospital admission but not later when complications usually arise. Objectives: To analyze the surface expression of TLR2 and TLR4 on circulating monocytes from trauma patients during the hospitalization period and to correlate this with cytokine production after stimulation with TLR2 and TLR4 agonists. The phagocytic capacity of monocytes was analyzed at the same time points of TLR expression analysis; to correlate these molecular findings with the presence or absence of infections. Methods: Prospective and observational study from June 2005 to June 2007. In all analysis, a control group composed of healthy subjects was included. Results: We studied 70 trauma patients admitted to the intensive care unit (ICU) of a tertiary hospital, and 30 healthy volunteers. Blood samples were collected at hospital admission, on day 7 and 14. Forty-four patients (63%) developed at least one episode of infection. Monocytes from trauma patients expressed higher levels of TLR2 and TLR4 than monocytes from control subjects at all time points. Expression of TLR2 and TLR4 in monocytes from those patients who developed any infection was significantly lower than in those patients without infection but still significantly higher than in control subjects. Cellular responses to TLR4 agonist were impaired. Monocytes from traumatic patients phagocytosized less efficiently than monocytes from control subjects. Conclusions: These results indicate that trauma patients present a dysregulation of the innate immune system that persists during the first 14 days after hospital admission.

Entre las distintas causas de la hipoxia tisular en el traumatismo craneoencefálico grave (TCEG) se encuentran las alteraciones de la microcirculación, que se pueden estudiar in vivo mediante el sistema SDF (Side Stream Dark Field). Dicho sistema se basa en un pequeño microscopio de mano que emite una luz polarizada ortogonal. La imagen obtenida del lecho capilar luego puede analizarse mediante un software específico que permite cuantificar la longitud y la densidad de los capilares sanguíneos. Presentamos el caso de un paciente con TCEG, intervenido para evacuación de una contusión cerebral. Durante la intervención se grabó, mediante el microscopio SDF, la microcirculación cerebral en la zona lesionada. Los resultados obtenidos se compararon con el patrón de un paciente intervenido de forma electiva por un aneurisma incidental. Tanto la imagen como el análisis cuantitativo muestran diferencias en el estado de la microcirculación cerebral, y se aprecia una reducción en la longitud y la densidad de los vasos de pequeño calibre en el paciente con traumatismo. El sistema SDF permite el estudio in vivo y de forma no invasiva de la microcirculación cerebral, y puede contribuir a profundizar en la fisiopatología de la hipoxia tisular postraumática.

Endocrine disturbances are common after traumatic brain injury (TBI). Hypothalamic-pituitary-adrenal (HPA) axis response in TBI patients may be related with hemodynamic status. However, its relationship with outcome is unclear. Our objective was to evaluate HPA axis response in the acute phase after TBI in patients with or without extracerebral trauma (ECT), and to investigate the impact of systemic injury and the mechanisms underlying HPA response.We prospectively studied 165 patients with moderate to severe TBI. Between 24 and 48 h after TBI, blood samples were taken for plasma adrenocorticotrophin hormone (ACTH) and baseline cortisol measurements. Afterwards, a short corticotrophin hormone test (250 mug Synacthen) was performed and samples were obtained at 30 and 60 min. We compared HPA response in TBI patients presenting with and without ECT and investigate potential mechanisms underlying this response.One hundred and eight patients presented with isolated TBI, whereas 57 patients presented associated ECT. Both groups were comparable. Overall, 23.6% of patients fulfilled adrenal insufficiency (AI) criteria. Patients with plasma ACTH9 pg/ml and patients presenting with hemorrhagic shock were more likely to present adrenal impairment. Variables associated with mortality were Injury Severity Score, Glasgow Coma Scale, Traumatic Coma Data Bank classification different than type II, need of second level measures to control intracranial pressure and plasma ACTH9 pg/ml.Patients with TBI presenting with or without associated ECT present similar acute HPA response. AI is present in 23.6% of patients. Risk is increased in patients with low plasma ACTH levels and in patients with hemorrhagic shock. Both primary and secondary mechanisms of HPA failure were found. However, AI did not affect outcome.

Objective We evaluated the expression of Toll-like receptors 2 and 4 (TLR-2 and TLR-4) in circulating monocytes from peripheral blood of critical care patients treated with and without glutamine. Because no research has been published to date on the effect of glutamine on TLR receptors in critical patients, it was determined in an initial sample of 30 patients. Methods This was a prospective, randomized, single-blind study with 15 patients assigned to receive parenteral nutrition with a daily glutamine supplement of 0.35 g/kg. The control group received isocaloric-isonitrogenous parenteral nutrition. Blood samples were extracted before beginning the treatment and at 5 and 14 d. Expressions of CD14, TLR-2, and TLR-4 were determined by flow cytometry. Levels of TLRs were expressed as mean fluorescence intensity (mfi). Results Basal characteristics were similar in both groups. The expressions of TLR-2 in the treatment group with glutamine were 4.67 ± 3.82 mfi before treatment, 3.91 ± 2.04 mfi at 5 d, and 4.28 ± 2.47 mfi at 14 d. The expressions of TLR-2 in the control group were 5.49 ± 3.20 mfi before treatment, 4.48 ± 2.15 mfi at 5 d, and 4.36 ± 2.36 mfi at 14 d. The expressions of TLR-4 in the treatment group were 1.65 ± 1.89 mfi before treatment, 1.23 ± 1.10 mfi at 5 d, and 1.77 ± 1.97 at 14 d. The expressions of TLR-4 in the control group were 1.51 ± 1.76 mfi before treatment, 1.36 ± 0.99 mfi at 5 d, and 1.26 ± 0.59 mfi at 14 d. Infections were detected in 11 patients who received glutamine and 13 control patients (P = 0.51). Conclusion In critical care patients, parenteral nutrition supplemented with glutamine does not increase the expression of TLR-2 or TLR-4 in peripheral blood monocytes.

La fístula carótido-cavernosa postraumática (FCCt) es una complicación poco frecuente tras un traumatismo craneoencefálico (TCE). Se diagnostica mediante la arteriografía cerebral habitualmente cuando ya ha aparecido la sintomatología clínica. El dúplex transcraneal codificado en color (DTCC) es una técnica no invasiva que en la cabecera del paciente permite la visualización del polígono de Willis (PW) y del segmento intracavernoso de la arteria carótida interna (ACIi). Los patrones sonográficos iniciales que sugieren la presencia de una FCCt mediante DTCC son una imagen en mosaico en el modo color, la presencia de flujos arteriales y venosos mezclados con elevadas velocidades y bajas resistencias. Exponemos nuestra experiencia en el diagnóstico precoz y no invasivo de la FCCt en una Unidad de Cuidados Intensivos.

Background Refractory intracranial hypertension (ICH) to second level measures after severe traumatic brain injury (TBI) is associated with mortality up to 84% to 100%. The use of external lumbar drainage (ELD) has been described in these patients. We report our experience with the use of ELD in 17 cases of refractory ICH after severe TBI. Methods In our Level 3 Intensive Care Unit (ICU) at a university hospital, ICH is treated according to a progressive approach following the Brain Trauma Foundation guidelines. When second level measures fail to control ICH, we use an ELD as a rescue therapy if basal cisterns are discernible. Outcome at ICU discharge and 6 months after injury were analyzed using Glasgow Outcome Scale (GOS). Results Mean age was 32.5 +/- 13.3 years. ICH was reduced in all patients. ICP before ELD was 30.9 +/- 7.9 mm Hg and after ELD 14.1 +/- 5.9 mm Hg. Four patients (24%) had an ICH rebound after 5 days of ELD placement and died in the ICU. At 6 months after TBI, 13 patients (76%) presented a good outcome (GOS score of 4 and 5). No patient presented pupillary changes or cerebrospinal fluid infection during ELD use. Conclusion External lumbar drainage is an effective and safe procedure to treat refractory ICH when basal cisterns are discernible. Control of refractory ICH with ELD is associated with an important reduction of mortality and a good functional recovery at 6 months.

Neuroinflammation is a response against harmful effects of diverse stimuli and participates in the pathogenesis of brain and spinal cord injury (SCI). The innate immune response plays a role in neuroinflammation following CNS injury via activation of multiprotein complexes termed inflammasomes that regulate the activation of caspase 1 and the processing of the pro-inflammatory cytokines IL-1β and IL-18. We report here that the expression of components of the nucleotide-binding and oligomerization domain (NOD)-like receptor protein-1 (NLRP-1) inflammasome, apoptosis speck-like protein containing a caspase recruitment domain (ASC), and caspase 1 are significantly elevated in spinal cord motor neurons and cortical neurons after CNS trauma. Moreover, NLRP1 inflammasome proteins are present in exosomes derived from CSF of SCI and traumatic brain-injured patients following trauma. To investigate whether exosomes could be used to therapeutically block inflammasome activation in the CNS, exosomes were isolated from embryonic cortical neuronal cultures and loaded with short-interfering RNA (siRNA) against ASC and administered to spinal cord-injured animals. Neuronal-derived exosomes crossed the injured blood-spinal cord barrier, and delivered their cargo in vivo, resulting in knockdown of ASC protein levels by approximately 76% when compared to SCI rats treated with scrambled siRNA. Surprisingly, siRNA silencing of ASC also led to a significant decrease in caspase 1 activation and processing of IL-1β after SCI. These findings indicate that exosome-mediated siRNA delivery may be a strong candidate to block inflammasome activation following CNS injury. We propose the following signaling cascade for inflammasome activation in peripheral tissues after CNS injury: CNS trauma induces inflammasome activation in the nervous system and secretion of exosomes containing inflammasome protein cargo into cerebral spinal fluid. The inflammasome containing exosomes then fuse with target cells to activate the innate immune response in peripheral tissues. We suggest that these findings may be used to develop new therapeutics to treat the devastating inflammation and cell destruction evoked by CNS injuries. IL-1β and IL-18 = pro-inflammatory cytokines.

In recent years, intracranial aneurysms that cause subarachnoid hemorrhage have been treated by an endovascular approach. The use of endovascular Guglielmi detachable coils (GDCs) has improved the radiologic and neurologic outcome of these patients, reaching results similar to those of craniotomy. 1 This technique implies certain risks that are decreasing because of the development of new delivery systems and softer GDCs and the increasing experience of neuroradiologists. 2 Displacement of coils is not an uncommon complication after endovascular embolization of cerebral aneurysms.3 Transcranial color-coded sonography (TCCS) is a noninvasive reliable bedside technique that allows an anatomic and hemodynamic follow up after embolization of aneurysms. 4 , 5 We report the case of a patient in which a displacement of the coil occurred after GDC treatment of a cerebral aneurysm. A segment of the coil invaded the cerebral vessel, causing a partial blockage of blood flow. This complication was correctly diagnosed by TCCS, permitting a posterior endovascular solution.