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.

Optimized detection of lung IL-6 via enzymatic liquefaction of low respiratory tract samples: application for managing ventilated patients.

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.

Exosome-mediated inflammasome signaling after central nervous system injury.

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-1ß 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-1ß 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-1ß and IL-18 = pro-inflammatory cytokines.

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.

Neural-Cardiac Inflammasome Axis after Traumatic Brain Injury.

Traumatic brain injury (TBI) affects not only the brain but also peripheral organs like the heart and the lungs, which influences long-term outcomes. A heightened systemic inflammatory response is often induced after TBI, but the underlying pathomechanisms that contribute to co-morbidities remain poorly understood. Here, we investigated whether extracellular vehicles (EVs) containing inflammasome proteins are released after severe controlled cortical impact (CCI) in C57BL/6 mice and cause activation of inflammasomes in the heart that result in tissue damage. The atrium of injured mice at 3 days after TBI showed a significant increase in the levels of the inflammasome proteins AIM2, ASC, caspases-1, -8 and -11, whereas IL-1ß was increased in the ventricles. Additionally, the injured cortex showed a significant increase in IL-1ß, ASC, caspases-1, -8 and -11 and pyrin at 3 days after injury when compared to the sham. Serum-derived extracellular vesicles (EVs) from injured patients were characterized with nanoparticle tracking analysis and Ella Simple Plex and showed elevated levels of the inflammasome proteins caspase-1, ASC and IL-18. Mass spectrometry of serum-derived EVs from mice after TBI revealed a variety of complement- and cardiovascular-related signaling proteins. Moreover, adoptive transfer of serum-derived EVs from TBI patients resulted in inflammasome activation in cardiac cells in culture. Thus, TBI elicits inflammasome activation, primarily in the atrium, that is mediated, in part, by EVs that contain inflammasome- and complement-related signaling proteins that are released into serum and contribute to peripheral organ systemic inflammation, which increases inflammasome activation in the heart.

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.

Potential effects of corticosteroids on physiological dead-space fraction in acute respiratory distress syndrome.

BACKGROUND: Increased dead-space fraction is common in patients with persistent acute respiratory distress syndrome (ARDS). We evaluated the changes in the oxygenation and dead-space fraction in patients with persistent ARDS after corticosteroid therapy. METHODS: This was a non-randomized non-placebo, controlled observational study including 19 patients with persistent ARDS treated with corticosteroids. We measured P(aO(2))/F(IO(2)) and dead-space fraction at days 0, 4, and 7 after corticosteroids treatment (methylprednisolone) initiation. Patients were classified in intermediate group when corticosteroids were initiated between days 8-14 after ARDS onset, and in late group when initiated after 14 days. RESULTS: Mean time from the diagnosis of the ARDS to methylprednisolone treatment was 11 ± 2 days in the intermediate group (10 patients) and 21 ± 8 days in the late group (9 patients). When comparing days 0, 4, and 7 after methylprednisolone treatment, we found an increase in the P(aO(2))/F(IO(2)) (145 ± 64 mm Hg, 190 ± 68 mm Hg, and 226 ± 84 mm Hg, respectively, P < .001) and a decrease in the physiological dead-space fraction (0.66 ± 0.10, 0.58 ± 0.12, and 0.53 ± 0.11, respectively, P < .001). No differences were found between the intermediate and late groups. CONCLUSIONS: In patients with persistent ARDS, the increase in oxygenation was accompanied by a decrease in the dead-space fraction after a few days of corticosteroid treatment. To confirm potential benefit of corticosteroids on physiological parameters and mortality will require a powered randomized placebo controlled trial.

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.

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.

Correlation between Thyroid Responses and Inflammatory Cytokines in Critically Ill COVID-19 Patients.

Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death.

Direct observation of human microcirculation during decompressive craniectomy after stroke.

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.

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.

Diminished Consciousness in a Woman Following an Unsuspected Scopolamine Overdose.

Scopolamine is used clinically, but it is also used as a recreational drug and as an incapacitating drug, in sexual crimes and robberies. In this paper, the authors report the case of a woman with a diminished consciousness following an unsuspected overdose with scopolamine and review published articles on scopolamine poisoning that included concentrations in biological samples. Scopolamine was identified in the patient's serum and urine samples collected 1 h post-admission to intensive care unit at concentrations of 8.4 ng/mL and 62,560 ng/mL (169,539 ng/mg creatinine), respectively. In non-fatal cases, the median [interquartile range] of serum scopolamine levels was 1.9 [2.1] ng/mL. The serum concentration found in our case would explain the abrupt clinical presentation suffered by the patient. Scopolamine in urine could be detected up to 48 h after admission. This report illustrates that broad toxicology screening, including scopolamine, should be considered when patients with diminished consciousness are attended after ruling out infection or cerebrovascular disease. This can play an important role in identifying this potentially life-threatening etiology.

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.