Ten good reasons to consider gastrointestinal function after acute brain injury.

The brain-gut axis represents a bidirectional communication linking brain function with the gastrointestinal (GI) system. This interaction comprises a top-down communication from the brain to the gut, and a bottom-up communication from the gut to the brain, including neural, endocrine, immune, and humoral signaling. Acute brain injury (ABI) can lead to systemic complications including GI dysfunction. Techniques for monitoring GI function are currently few, neglected, and many under investigation. The use of ultrasound could provide a measure of gastric emptying, bowel peristalsis, bowel diameter, bowel wall thickness and tissue perfusion. Despite novel biomarkers represent a limitation in clinical practice, intra-abdominal pressure (IAP) is easy-to-use and measurable at bedside. Increased IAP can be both cause and consequence of GI dysfunction, and it can influence cerebral perfusion pressure and intracranial pressure via physiological mechanisms. Here, we address ten good reasons to consider GI function in patients with ABI, highlighting the importance of its assessment in neurocritical care.

Associated Risk Factors and Impact in Clinical Outcomes of Multiorgan Failure in Patients with TBI.

BACKGROUND: Individual extracerebral organ dysfunction is common after severe traumatic brain injury (TBI) and impacts outcomes. However, multiorgan failure (MOF) has received less attention in patients with isolated TBI. Our objective was to analyze the risk factors associated with the development of MOF and its impact in clinical outcomes in patients with TBI. METHODS: This was an observational, prospective, multicenter study using data from a nationwide registry that currently includes 52 intensive care units (ICUs) in Spain (RETRAUCI). Isolated significant TBI was defined as Abbreviated Injury Scale (AIS) ≥ 3 in the head area with no AIS ≥ 3 in any other anatomical area. Multiorgan failure was defined using the Sequential-related Organ Failure Assessment as the alteration of two or more organs with a score of ≥ 3. We analyzed the contribution of MOF to crude and adjusted mortality (age and AIS head) by using logistic regression analysis. A multiple logistic regression analysis was performed to analyze the risk factors associated with the development of MOF in patients with isolated TBI. RESULTS: A total of 9790 patients with trauma were admitted to the participating ICUs. Of them, 2964 (30.2%) had AIS head ≥ 3 and no AIS ≥ 3 in any other anatomical area, and these patients constituted the study cohort. Mean age was 54.7 (19.5) years, 76% of patients were men, and ground-level falls were the main mechanism of injury (49.1%). In-hospital mortality was 22.2%. Up to 185 patients with TBI (6.2%) developed MOF during their ICU stay. Crude and adjusted (age and AIS head) mortality was higher in patients who developed MOF (odds ratio 6.28 [95% confidence interval 4.58-8.60] and odds ratio 5.20 [95% confidence interval 3.53-7.45]), respectively. The logistic regression analysis showed that age, hemodynamic instability, the need of packed red blood cells concentrates in the initial 24 h, the severity of brain injury, and the need for invasive neuromonitoring were significantly associated with MOF development. CONCLUSIONS: MOF occurred in 6.2% of patients with TBI admitted to the ICU and was associated with increased mortality. MOF was associated with age, hemodynamic instability, the need of packed red blood cells concentrates in the initial 24 h, the severity of brain injury, and the need for invasive neuromonitoring.

Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.05) but not at 24 h after TBI. Serum caspase 1 levels on admission were higher in patients with unfavorable outcomes (189.5 vs. 144.1 pg/mL; p = 0.009). Similarly, serum caspase 1 levels on admission were higher in patients who died vs. patients who survived (213.6 vs. 146.8 pg/mL; p = 0.03). A logistic regression model showed that the serum caspase 1 level on admission was an independent predictor of 6-month unfavorable outcomes (odds ratio 1.05; 95% confidence interval 1-1.11; p = 0.05). Caspase 1 levels were higher in patients with severe TBI compared with those with moderate TBI, those with mild TBI, and healthy controls (p < 0.001). We did not find any correlation between caspase 1 and the radiological variables studied. CONCLUSIONS: In this cohort of patients with TBI, we show that serum caspase 1 protein levels on admission are an independent prognostic factor after TBI. Serum caspase 1 levels on admission are higher in patients who will present unfavorable outcomes 6 months after TBI. Caspase 1 levels on admission are associated with the injury severity determined by the Glasgow Coma Scale.

Development of a new score for early mortality prediction in trauma ICU patients: RETRASCORE.

BACKGROUND: Severity scores are commonly used for outcome adjustment and benchmarking of trauma care provided. No specific models performed only with critically ill patients are available. Our objective was to develop a new score for early mortality prediction in trauma ICU patients. METHODS: This is a retrospective study using the Spanish Trauma ICU registry (RETRAUCI) 2015-2019. Patients were divided and analysed into the derivation (2015-2017) and validation sets (2018-2019). We used as candidate variables to be associated with mortality those available in RETRAUCI that could be collected in the first 24 h after ICU admission. Using logistic regression methodology, a simple score (RETRASCORE) was created with points assigned to each selected variable. The performance of the model was carried out according to global measures, discrimination and calibration. RESULTS: The analysis included 9465 patients: derivation set 5976 and validation set 3489. Thirty-day mortality was 12.2%. The predicted probability of 30-day mortality was determined by the following equation: 1/(1 + exp (- y)), where y = 0.598 (Age 50-65) + 1.239 (Age 66-75) + 2.198 (Age > 75) + 0.349 (PRECOAG) + 0.336 (Pre-hospital intubation) + 0.662 (High-risk mechanism) + 0.950 (unilateral mydriasis) + 3.217 (bilateral mydriasis) + 0.841 (Glasgow ≤ 8) + 0.495 (MAIS-Head) - 0.271 (MAIS-Thorax) + 1.148 (Haemodynamic failure) + 0.708 (Respiratory failure) + 0.567 (Coagulopathy) + 0.580 (Mechanical ventilation) + 0.452 (Massive haemorrhage) - 5.432. The AUROC was 0.913 (0.903-0.923) in the derivation set and 0.929 (0.918-0.940) in the validation set. CONCLUSIONS: The newly developed RETRASCORE is an early, easy-to-calculate and specific score to predict in-hospital mortality in trauma ICU patients. Although it has achieved adequate internal validation, it must be externally validated.

Machine learning techniques for mortality prediction in critical traumatic patients: anatomic and physiologic variables from the RETRAUCI study.

BACKGROUND: Interest in models for calculating the risk of death in traumatic patients admitted to ICUs remains high. These models use variables derived from the deviation of physiological parameters and/or the severity of anatomical lesions with respect to the affected body areas. Our objective is to create different predictive models of the mortality of critically traumatic patients using machine learning techniques. METHODS: We used 9625 records from the RETRAUCI database (National Trauma Registry of 52 Spanish ICUs in the period of 2015-2019). Hospital mortality was 12.6%. Data on demographic variables, affected anatomical areas and physiological repercussions were used. The Weka Platform was used, along with a ten-fold cross-validation for the construction of nine supervised algorithms: logistic regression binary (LR), neural network (NN), sequential minimal optimization (SMO), classification rules (JRip), classification trees (CT), Bayesian networks (BN), adaptive boosting (ADABOOST), bootstrap aggregating (BAGGING) and random forest (RFOREST). The performance of the models was evaluated by accuracy, specificity, precision, recall, F-measure, and AUC. RESULTS: In all algorithms, the most important factors are those associated with traumatic brain injury (TBI) and organic failures. The LR finds thorax and limb injuries as independent protective factors of mortality. The CT generates 24 decision rules and uses those related to TBI as the first variables (range 2.0-81.6%). The JRip detects the eight rules with the highest risk of mortality (65.0-94.1%). The NN model uses a hidden layer of ten nodes, which requires 200 weights for its interpretation. The BN find the relationships between the different factors that identify different patient profiles. Models with the ensemble methodology (ADABOOST, BAGGING and RandomForest) do not have greater performance. All models obtain high values ​​in accuracy, specificity, and AUC, but obtain lower values ​​in recall. The greatest precision is achieved by the SMO model, and the BN obtains the best recall, F-measure, and AUC. CONCLUSION: Machine learning techniques are useful for creating mortality classification models in critically traumatic patients. With clinical interpretation, the algorithms establish different patient profiles according to the relationship between the variables used, determine groups of patients with different evolutions, and alert clinicians to the presence of rules that indicate the greatest severity.

Twelve controversial questions in aneurysmal subarachnoid hemorrhage.

Critical care management of aneurysmal subarachnoid hemorrhage (aSAH) remains a major challenge. Despite the recent publication of guidelines from the American Heart Association/American Stroke Association and the Neurocritical Care Society, there are many controversial questions in the intensive care unit (ICU) management of this population. The authors provide an analysis of common issues in the ICU and provide guidance on the daily management of this specific population of neurocritical care patients.

Transcranial sonography in the critical patient.

Transcranial ultrasonography is a non-invasive, bedside technique that has become a widely implemented tool in the evaluation and management of neurocritically ill patients. It constitutes a technique in continuous growth whose fundamentals (and limitations) must be known by the intensivist. This review provides a practical approach for the intensivist, including the different sonographic windows and planes of insonation and its role in different conditions of the neurocritical patients and in critical care patients of other etiologies.

Effects of PEEP on intracranial pressure in patients with acute brain injury: An observational, prospective and multicenter study.

OBJECTIVE: To analyze the impact of positive end-expiratory pressure (PEEP) changes on intracranial pressure (ICP) dynamics in patients with acute brain injury (ABI). DESIGN: Observational, prospective and multicenter study (PEEP-PIC study). SETTING: Seventeen intensive care units in Spain. PATIENTS: Neurocritically ill patients who underwent invasive neuromonitorization from November 2017 to June 2018. INTERVENTIONS: Baseline ventilatory, hemodynamic and neuromonitoring variables were collected immediately before PEEP changes and during the following 30 min. MAIN VARIABLES OF INTEREST: PEEP and ICP changes. RESULTS: One-hundred and nine patients were included. Mean age was 52.68 (15.34) years, male 71 (65.13%). Traumatic brain injury was the cause of ABI in 54 (49.54%) patients. Length of mechanical ventilation was 16.52 (9.23) days. In-hospital mortality was 21.1%. PEEP increases (mean 6.24-9.10 cmH2O) resulted in ICP increase from 10.4 to 11.39 mmHg, P < .001, without changes in cerebral perfusion pressure (CPP) (P = .548). PEEP decreases (mean 8.96 to 6.53 cmH2O) resulted in ICP decrease from 10.5 to 9.62 mmHg (P = .052), without changes in CPP (P = .762). Significant correlations were established between the increase of ICP and the delta PEEP (R = 0.28, P < .001), delta driving pressure (R = 0.15, P = .038) and delta compliance (R = -0.14, P = .052). ICP increment was higher in patients with lower baseline ICP. CONCLUSIONS: PEEP changes were not associated with clinically relevant modifications in ICP values in ABI patients. The magnitude of the change in ICP after PEEP increase was correlated with the delta of PEEP, the delta driving pressure and the delta compliance.

External validation of the Glasgow Coma Scale-Pupils in patients with severe head injury. / Validación externa de la Escala de Coma de Glasgow con valoración pupilar en pacientes con traumatismo craneoencefálico grave.

OBJECTIVES: To compare the ability of the Glasgow Coma Scale (GCS) score, the GCS Pupils (GCS-P) score, and the Pupil Reactivity Score (PRS) to predict mortality in patients with severe head injury. MATERIAL AND METHODS: Retrospective analysis of all patients with severe head injury and initial GCS scores of 8 or lower on initial evaluation for whom records included pupil dilation information and clinical course after admission to intensive care units of participating hospitals. We assessed the ability of each of the 3 scores (GCS, GCS-P, and PRS) to predict mortality using discrimination analysis. Discrimination was estimated by calculating the areas under the receiver operating characteristic curves (AUC) and 95% CIs. RESULTS: A total of 1551 patients with severe head injury and pupil dilation records were studied. The mean age was 50 years, 1190 (76.7%) were males, and 592 (38.2%) died. No pupil dilation was observed in 905 patients (58.3%), 362 (23.3%) had unilateral mydriasis, and 284 (18.3%) had bilateral mydriasis. The GCS-P score was significantly better at predicting mortality, with an AUC of 0.77 (95% CI, 0.74-0.79), versus 0.69 (95% CI, 0.67-0.72) for the GCS, and 0.75 (95% CI, 0.72-0.77) for the PRS. As the GCS-P score decreased, mortality increased. CONCLUSION: The GCS-P was more useful than the GCS for predicting death after severe head injury.

OBJETIVO: Analizar la capacidad para predecir la mortalidad hospitalaria de la Escala de Coma de Glasgow con valoración pupilar (GCS-P) comparado con la Escala de Coma de Glasgow (GCS) y con la escala de reactividad pupilar (PRS) en pacientes con traumatismo craneoencefálico (TCE) grave. METODO: Análisis retrospectivo de cohortes de todos los pacientes con TCE, puntuación en la GCS # 8 en la atención inicial, datos de exploración pupilar inicial y del desenlace hospitalario ingresados en las unidades de cuidados intensivos participantes. Se determinó la capacidad predictiva de mortalidad de la GCS, PRS y la GCS-P mediante un análisis de discriminación. La discriminación se analizó empleando curvas operativas del receptor (COR), el área bajo la curva (ABC) y su intervalo de confianza del 95% (IC 95%). RESULTADOS: Se analizaron 1.551 pacientes con TCE grave y datos sobre exploración pupilar. La edad media fue de 50 años, 1.190 (76,7%) eran hombres, y hubo 592 (38,2%) defunciones. Hubo 905 (58,3%) pacientes sin alteraciones pupilares, 362 (23,3%) con midriasis unilateral y 284 (18,3%) pacientes con midriasis bilateral. El análisis del ABCCOR para predecir la mortalidad hospitalaria mostró de forma significativa una mejor capacidad predictiva del GCS-P con ABC = 0,77 (IC 95% 0,74-0,79) respecto al GCS con ABC = 0,69 (IC 95% 0,67-0,72). La reactividad pupilar mostró un ABC = 0,75 (IC 95% 0,72-0,77). Se observó un incremento de mortalidad con la disminución del GCS-P. CONCLUSIONES: La escala GCS-P presentó mejor rendimiento que la GCS para predecir mortalidad en el TCE grave.

Risk Factors Associated with Mortality in Severe Chest Trauma Patients Admitted to the ICU.

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.

Traumatic Brain Injury and Acute Kidney Injury-Outcomes and Associated Risk Factors.

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.

Inflammatory Biomarkers of Traumatic Brain Injury.

Traumatic brain injury (TBI) has a complex pathology in which the initial injury releases damage associated proteins that exacerbate the neuroinflammatory response during the chronic secondary injury period. One of the major pathological players in the inflammatory response after TBI is the inflammasome. Increased levels of inflammasome proteins during the acute phase after TBI are associated with worse functional outcomes. Previous studies reveal that the level of inflammasome proteins in biological fluids may be used as promising new biomarkers for the determination of TBI functional outcomes. In this study, we provide further evidence that inflammatory cytokines and inflammasome proteins in serum may be used to determine injury severity and predict pathological outcomes. In this study, we analyzed blood serum from TBI patients and respective controls utilizing Simple Plex inflammasome and V-PLEX inflammatory cytokine assays. We performed statistical analyses to determine which proteins were significantly elevated in TBI individuals. The receiver operating characteristics (ROC) were determined to obtain the area under the curve (AUC) to establish the potential fit as a biomarker. Potential biomarkers were then compared to documented patient Glasgow coma scale scores via a correlation matrix and a multivariate linear regression to determine how respective biomarkers are related to the injury severity and pathological outcome. Inflammasome proteins and inflammatory cytokines were elevated after TBI, and the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, tumor necrosis factor (TNF)-α, IL-4 and IL-6 were the most reliable biomarkers. Additionally, levels of these proteins were correlated with known clinical indicators of pathological outcome, such as the Glasgow coma scale (GCS). Our results show that inflammatory cytokines and inflammasome proteins are promising biomarkers for determining pathological outcomes after TBI. Additionally, levels of biomarkers could potentially be utilized to determine a patient's injury severity and subsequent pathological outcome. These findings show that inflammation-associated proteins in the blood are reliable biomarkers of injury severity that can also be used to assess the functional outcomes of TBI patients.

Lack of correlation among intracerebral cytokines, intracranial pressure, and brain tissue oxygenation in patients with traumatic brain injury and diffuse lesions.

OBJECTIVES: 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). DESIGN: Prospective and observational study. SETTING: Third-level university hospital. PATIENTS: 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. INTERVENTIONS: Microdialysis catheters with a high-cutoff membrane of 100 kDa were inserted. RESULTS: Sixteen patients were included in the analysis. There was a substantial interindividual variability between cytokine values. The highest concentrations for the interleukin-1ß, 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-1ß-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-1ß-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. CONCLUSIONS: 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.

Hypoxic hepatitis in critically ill patients: incidence, etiology and risk factors for mortality.

PURPOSE: Hypoxic hepatitis may be induced by hemodynamic instability or arterial hypoxemia in critically ill patients. We investigated the incidence, etiology, association with systemic ischemic injury and risk factors for mortality in this population. METHODS: Retrospective analysis of patients with hypoxic hepatitis admitted to a multidisciplinary intensive care unit (ICU) of a university hospital. Hypoxic hepatitis was defined as the existence of a compatible clinical setting (cardiocirculatory failure or arterial hypoxemia) and aminotransferase levels higher than 1000 IU/L. RESULTS: During the 8-year study period, 182 out of the 7674 patients admitted presented hypoxic hepatitis (2.4%). The most common cause was septic shock. The rate of in-hospital mortality in hypoxic hepatitis was 61.5% (112 patients), and was higher in patients with septic shock (83.3%) and cardiac arrest (77.7%). Ischemic pancreatitis (25.6%), rhabdomyolysis (41.2%) and renal failure (67.2%) were common in these patients. Risk factors of mortality were prolonged INR (p = 0.005), need for renal replacement therapy (p = 0.001) and septic shock (p = 0.005). CONCLUSIONS: Hypoxic hepatitis was not a rare condition, and was frequently accompanied by multiorgan injury, with high mortality. Risk factors for increased mortality were prolonged INR, need for renal replacement therapy, and septic shock.

Thyroid Disfunction in Critically Ill COVID-19 Patients. Relationship with In-Hospital Mortality.

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.

Factors associated with death due to trauma in patients with a Glasgow Coma Scale score of 3 and bilateral fixed dilated pupils. / Factores asociados con la mortalidad en pacientes traumáticos con puntuación de 3 en la escala de coma de Glasgow y midriasis bilateral arreactiva.

OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

OBJETIVO: 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. METODO: 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. RESULTADOS: 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. CONCLUSIONES: 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.

Use of diffusion tensor imaging to assess the vasogenic edema in traumatic pericontusional tissue.

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<0.05). 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.

Dexamethasone for the treatment of traumatic brain injured patients with brain contusions and pericontusional edema: Study protocol for a prospective, randomized and double blind trial.

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.

Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO2 response and acetazolamide treatment effects.

OBJECTIVE: In obesity-hypoventilation-syndrome patients mechanically ventilated for hypercapnic respiratory failure we investigated the relationship between CO2 response, body mass index, and plasma bicarbonate concentration, and the effect of acetazolamide on bicarbonate concentration and CO2 response. METHODS: CO2 response tests and arterial blood gas analysis were performed in 25 patients ready for a spontaneous breathing test, and repeated in a subgroup of 8 patients after acetazolamide treatment. CO2 response test was measured as (1) hypercapnic drive response (the ratio of the change in airway occlusion pressure 0.1 s after the start of inspiratory flow to the change in P(aCO2)), and (2) hypercapnic ventilatory response (the ratio of the change in minute volume to the change in P(aCO2)). RESULTS: We did not find a significant relationship between CO2 response and body mass index. Patients with higher bicarbonate concentration had a more blunted CO2 response. Grouping the patients according to the first, second, and third tertiles of the bicarbonate concentration, the hypercapnic drive response was 0.32 ± 0.17 cm H2O/mm Hg, 0.22 ± 0.15 cm H2O/mm Hg, and 0.10 ± 0.06 cm H2O/mm Hg, respectively (P = .01), and hypercapnic ventilatory response was 0.46 ± 0.23 L/min/mm Hg, 0.48 ± 0.36 L/min/mm Hg, and 0.22 ± 0.16 L/min/mm Hg, respectively (P = .04). After acetazolamide treatment, bicarbonate concentration was reduced by 8.4 ± 3.0 mmol/L (P = .01), and CO2 response was shifted to the left, with an increase in hypercapnic drive response, by 0.14 ± 0.16 cm H2O/mm Hg (P = .02), and hypercapnic ventilatory response, by 0.11 ± 0.22 L/min/mm Hg (P = .33). CONCLUSIONS: Patients with obesity-hypoventilation syndrome and higher bicarbonate concentrations had a more blunted CO2 response. Body mass index was not related to CO2 response. Acetazolamide decreased bicarbonate concentration and increased CO2 response.