RESUMEN
OBJECTIVE: To determine the effects of tight glycemic control on brain metabolism after traumatic brain injury using brain positron emission tomography and microdialysis. DESIGN: Single-center, randomized controlled within-subject crossover observational trial. SETTING: Academic intensive care unit. METHODS: We performed a prospective, unblinded randomized controlled within-subject crossover trial of tight (80-110 mg/dL) vs. loose (120-150 mg/dL) glycemic control in patients with severe traumatic brain injury to determine the effects of glycemic control on brain glucose metabolism, as measured by [18F] deoxy-D-glucose brain positron emission tomography. Brain microdialysis was done simultaneously. MEASUREMENTS AND MAIN RESULTS: Thirteen severely injured traumatic brain injury patients underwent the study between 3 and 8 days (mean 4.8 days) after traumatic brain injury. In ten of these subjects, global brain and gray matter tissues demonstrated higher glucose metabolic rates while glucose was under tight control as compared with loose control (3.2 ± 0.6 vs. 2.4 + 0.4, p = .02 [whole brain] and 3.8 ± 1.4 vs. 2.9 ± 0.8, p = .05 [gray matter]). However, the responses were heterogeneous with pericontusional tissue demonstrating the least state-dependent change. Cerebral microdialysis demonstrated more frequent critical reductions in glucose (p = .02) and elevations of lactate/pyruvate ratio (p = .03) during tight glycemic control. CONCLUSION: Tight glycemic control results in increased global glucose uptake and an increased cerebral metabolic crisis after traumatic brain injury. The mechanisms leading to the enhancement of metabolic crisis are unclear, but delivery of more glucose through mild hyperglycemia may be necessary after traumatic brain injury.
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Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Glucosa/metabolismo , Estrés Fisiológico/fisiología , Adolescente , Adulto , Anciano , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/fisiopatología , Estudios Cruzados , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Masculino , Microdiálisis , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Radiofármacos/farmacocinética , Índices de Gravedad del Trauma , Adulto JovenRESUMEN
BACKGROUND: Optimal resuscitation after traumatic brain injury (TBI) remains uncertain. We hypothesize that cerebral metabolic crisis is frequent despite adequate resuscitation of the TBI patient and that metabolic crisis negatively influences outcome. METHODS: We assessed the effectiveness of a standardized trauma resuscitation protocol in 89 patients with moderate to severe TBI, and determined the frequency of adequate resuscitation. Prospective hourly values of heart rate, blood pressure, pulse oximetry, intracranial pressure (ICP), respiratory rate, jugular venous oximetry, and brain extracellular values of glucose, lactate, pyruvate, glycerol, and glutamate were obtained. The incidence during the initial 72 h after injury of low brain glucose <0.8 mmol/L, elevated lactate/pyruvate ratio (LPR) >25, and metabolic crisis, defined as the simultaneous occurrence of both low glucose and high LPR, were determined for the group. RESULTS: 5 patients were inadequately resuscitated and eight patients had intractable ICP. In patients with successful resuscitation and controlled ICP (n = 76), within 72 h of trauma, 76% had low glucose, 93% had elevated LPR, and 74% were in metabolic crisis. The duration of metabolic crisis was longer in those patients with unfavorable (GOSe ≤ 6) versus favorable (GOSe ≥ 7) outcome at 6 months (P = 0.011). In four multivariate models the burden of metabolic crisis was a powerful independent predictor of poor outcome. CONCLUSIONS: Metabolic crisis occurs frequently after TBI despite adequate resuscitation and controlled ICP, and is a strong independent predictor of poor outcome at 6 months.
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Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/metabolismo , Lesiones Encefálicas/epidemiología , Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Reanimación Cardiopulmonar/estadística & datos numéricos , Adulto , Presión Sanguínea/fisiología , Encefalopatías Metabólicas/fisiopatología , Lesiones Encefálicas/fisiopatología , Reanimación Cardiopulmonar/normas , Enfermedad Crítica/epidemiología , Femenino , Glucosa/metabolismo , Ácido Glutámico/metabolismo , Glicerol/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Incidencia , Ácido Láctico/metabolismo , Masculino , Microdiálisis/métodos , Persona de Mediana Edad , Oximetría , Valor Predictivo de las Pruebas , Ácido Pirúvico/metabolismoRESUMEN
Exposure of one tissue to ischemia-reperfusion confers a systemic protective effect, referred to as remote ischemic preconditioning (RIPC). Confirmation that the desired effect of ischemia is occurring in tissues used to induce RIPC requires an objective demonstration before this technique can be used consistently in the clinical practice. Enrolled patients underwent three to four RIPC sessions on non-consecutive days. Sessions consisted of 4 cycles of 5 min of leg cuff inflation to 30 mmHg above the systolic blood pressure followed by reperfusion. Absence of leg pulse was confirmed by Doppler evaluation. To evaluate limb transient ischemia, patients were monitored with muscle microdialysis. Glucose, lactate, lactate/pyruvate ratio, and glycerol levels were measured. Fourteen microdialysis sessions were performed in seven patients undergoing RIPC (42.8 % male; mean age, 51.8; Fisher grade 4 in all seven patients, Hunt and Hess grade 5 in five patients, four in one patient and one in one patient). An average follow-up of 29 days demonstrated no complications associated with the procedure. Muscle microdialysis during RIPC sessions showed a significant increase in lactate/pyruvate ratio (21.2 to 26.8, p = 0.001) and lactate (3.0 to 3.9 mmol/L, p = 0.002), indicating muscle ischemia. There was no significant variation in glycerol (234 to 204 µg/L, p = 0.43), indicating no permanent cell damage. The RIPC protocol used in this study is safe, well tolerated, and induces transient metabolic changes consistent with sublethal ischemia. Muscle microdialysis can be used safely as a confirmatory tool in the induction of RIPC.
RESUMEN
Chronic brain atrophy after traumatic brain injury (TBI) is a well-known phenomenon, the causes of which are unknown. Early nonischemic reduction in oxidative metabolism is regionally associated with chronic brain atrophy after TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent positron emission tomography (PET) and volumetric magnetic resonance imaging (MRI) within the first week and at 6 months after injury. Regional lobar assessments comprised oxidative metabolism and glucose metabolism. Acute MRI showed a preponderance of hemorrhagic lesions with few irreversible ischemic lesions. Global and regional chronic brain atrophy occurred in all patients by 6 months, with the temporal and frontal lobes exhibiting the most atrophy compared with the occipital lobe. Global and regional reduction in cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose were observed. The extent of metabolic dysfunction was correlated with the total hemorrhage burden on initial MRI (r=0.62, P=0.01). The extent of regional brain atrophy correlated best with CMRO(2) and CBF. Lobar values of OEF were not in the ischemic range and did not correlate with chronic brain atrophy. Chronic brain atrophy is regionally specific and associated with regional reductions in oxidative brain metabolism in the absence of irreversible ischemia.
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Atrofia , Lesiones Encefálicas , Encéfalo , Oxígeno/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atrofia/metabolismo , Atrofia/patología , Atrofia/fisiopatología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Circulación Cerebrovascular/fisiología , Metabolismo Energético , Femenino , Glucosa/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/fisiología , Tomografía de Emisión de Positrones , Flujo Sanguíneo Regional/fisiología , Adulto JovenRESUMEN
PURPOSE: To study the contrast agent dose sensitivity of hemodynamic parameters derived from brain dynamic susceptibility contrast MRI (DSC-MRI). MATERIALS AND METHODS: Sequential DSC-MRI (1.5T gradient-echo echo-planar imaging using an echo time of 61-64 msec) was performed using contrast agent doses of 0.1 and 0.2 mmol/kg delivered at a fixed rate of 5.0 mL/second in 12 normal subjects and 12 stroke patients. RESULTS: 1) Arterial signal showed the expected doubling in relaxation response (DeltaR2*) to dose doubling. 2) The brain signal showed a less than doubled DeltaR2* response to dose doubling. 3) The 0.2 mmol/kg dose studies subtly underestimated cerebral blood volume (CBV) and cerebral blood flow (CBF) relative to the 0.1 mmol/kg studies. 4) In the range of low CBV and CBF, the 0.2 mmol/kg studies overestimated the CBV and CBF compared with the 0.1 mmol/kg studies. 5) The 0.1 mmol/kg studies reported larger ischemic volumes in stroke. CONCLUSION: Subtle but statistically significant dose sensitivities were found. Therefore, it is advisable to carefully control the contrast agent dose when DSC-MRI is used in clinical trials. The study also suggests that a 0.1 mmol/kg dose is adequate for hemodynamic measurements.
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Velocidad del Flujo Sanguíneo , Isquemia Encefálica/fisiopatología , Encéfalo/fisiopatología , Imagen Eco-Planar/métodos , Gadolinio DTPA/administración & dosificación , Encéfalo/irrigación sanguínea , Encéfalo/patología , Isquemia Encefálica/patología , Medios de Contraste/administración & dosificación , Relación Dosis-Respuesta a Droga , Humanos , Aumento de la Imagen/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To determine whether nonconvulsive electrographic post-traumatic seizures result in increases in intracranial pressure and microdialysis lactate/pyruvate ratio. DESIGN: Prospective monitoring with retrospective data analysis. SETTING: Single center academic neurologic intensive care unit. PATIENTS: Twenty moderate to severe traumatic brain injury patients (Glasgow Coma Score 3-13). MEASUREMENTS AND MAIN RESULTS: Continuous electroencephalography and cerebral microdialysis were performed for 7 days after injury. Ten patients had seizures and were compared with a matched cohort of traumatic brain injury patients without seizures. The seizures were repetitive and constituted status epilepticus in seven of ten patients. Using a within-subject design, post-traumatic seizures resulted in episodic increases in intracranial pressure (22.4 +/- 7 vs. 12.8 +/- 4.3 mm Hg; p < .001) and an episodic increase in lactate/pyruvate ratio (49.4 +/- 16 vs. 23.8 +/- 7.6; p < .001) in the seizure group. Using a between-subjects comparison, the seizure group demonstrated a higher mean intracranial pressure (17.6 +/- 6.5 vs. 12.2 +/- 4.2 mm Hg; p < .001), a higher mean lactate/pyruvate ratio (38.6 +/- 18 vs. 27 +/- 9; p < .001) compared with nonseizure patients. The intracranial pressure and lactate/pyruvate ratio remained elevated beyond postinjury hour 100 in the seizure group but not the nonseizure group (p < .02). CONCLUSION: Post-traumatic seizures result in episodic as well as long-lasting increases in intracranial pressure and microdialysis lactate/pyruvate ratio. These data suggest that post-traumatic seizures represent a therapeutic target for patients with traumatic brain injury.
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Epilepsia Postraumática/complicaciones , Epilepsia Postraumática/metabolismo , Hipertensión Intracraneal/etiología , Ácido Láctico/metabolismo , Ácido Pirúvico/metabolismo , Estudios de Casos y Controles , Electroencefalografía , Epilepsias Parciales/complicaciones , Epilepsias Parciales/metabolismo , Epilepsias Parciales/fisiopatología , Epilepsia Generalizada/complicaciones , Epilepsia Generalizada/metabolismo , Epilepsia Generalizada/fisiopatología , Epilepsia Postraumática/fisiopatología , Humanos , Hipertensión Intracraneal/fisiopatología , Microdiálisis , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Estado Epiléptico/complicaciones , Estado Epiléptico/metabolismo , Estado Epiléptico/fisiopatologíaRESUMEN
Continuous electroencephalography (cEEG) is potentially useful in determining prognosis in patients with traumatic brain injuries (TBI). The objective of this prospective, observational cohort study was to determine if the percent alpha variability (PAV) on cEEG was predictive of outcome following TBI. Injury characteristics were indexed to assess whether lesions in specific cerebral loci were correlated with PAV and patient recovery. Fifty-three TBI patients were studied using cEEG recording and serial neuroimaging. Clinical recovery was assessed at regular intervals in hospital and following discharge. The principal outcome measures included the mean 3-day PAV score, the 7-day PAV pattern, delineation of the anatomical sites of brain injury, and the 6-month clinical outcome, as measured by the Glasgow Outcome Scale (GOS). Significant univariate (p = 0.030) and multivariate (p = 0.008) relations were identified between PAV and GOS scores. PAV offered good discrimination between favorable and unfavorable 6-month outcomes (AUC 0.76) and, with a cutpoint of 0.20, had a sensitivity of 87% and negative predictive value of 82%. Multivariate modeling revealed that injuries of the thalamus (p = 0.009) and basal ganglia (p = 0.016), and the presence of diffuse edema (p = 0.009), were the key anatomical predictors of PAV. Brainstem injuries (p = 0.020) and indicators of diffuse cerebral trauma, such as deep white matter shearing (p = 0.036) and multiple subcortical lesions (p = 0.033), were the principal determinants of 6-month recovery. Inclusion of PAV enhanced the accuracy of prediction models that encompassed a selective combination of clinical and anatomical variables (adjusted R(2) = 0.458, p < 0.001). The two main results of this study are (1) PAV is a sensitive predictor of 6-month clinical outcomes following TBI, and (2) injury to the thalamus is related to impaired PAV. PAV appears best utilized as a functional adjunct to traditional clinical and anatomical predictors.
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Ritmo alfa , Lesiones Encefálicas/diagnóstico , Electroencefalografía , Tálamo/lesiones , Adolescente , Adulto , Anciano , Lesiones Encefálicas/fisiopatología , Lesiones Encefálicas/cirugía , Descompresión Quirúrgica , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Valor Predictivo de las Pruebas , Pronóstico , Tálamo/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating form of stroke commonly resulting in severe morbidity and high mortality. Secondary brain injury often occurs in the days following the initial hemorrhage and is associated with significant neurological deterioration. The neurochemistry associated with secondary injury is poorly understood. The purpose of this study is to characterize the neurochemical changes in perihematomal tissue during frameless minimally invasive evacuation of spontaneous hematomas. METHODS: This is a nonrandomized prospective microdialysis study of 12 consecutive patients undergoing Frameless Stereotactic Aspiration and Thrombolysis (FAST) of deep ICHs. Hourly glucose, lactate, pyruvate, and glutamate were measured in the perihematomal tissue of patients undergoing minimally invasive hematoma evacuation. Analyte concentrations were compared to evaluate the natural history of perihematomal neurochemistry and to identify changes potentially related to secondary injury. RESULTS: Brain hematoma volumes were reduced 87% during FAST and National Institute of Health Stroke Scale (NIHSS) scores were improved from an average of 19 at admission to 12.6 at time of discharge from the intensive care unit. Glutamate average values decreased from the first 24 hours of measurement (12 mmol/L +/- 6) to the final 24-hour epoch (5 mmol/L +/- 6). Glutamate reduction showed a significant linear (p = 0.0007) and quadratic (p <0.05) trend during hematoma drainage. Lactate pyruvate ratios (LPR), a common marker of ischemia, were unchanged. CONCLUSIONS: This study reports that elevated levels of glutamate are found in the perihematomal region after ICH and are decreased during hematoma drainage. Conversely, ischemic LPRs are not found in perihematomal regions and were unchanged during hematoma drainage. These data suggest that excitotoxicity related to glutamate may have an important impact on secondary injury. The data failed to support the role of ischemia in secondary perihematomal damage.
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Hemorragia Cerebral/tratamiento farmacológico , Ácido Glutámico/sangre , Ácido Láctico/sangre , Ácido Pirúvico/sangre , Terapia Trombolítica , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Angiografía Cerebral , Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Ventrículos Cerebrales/patología , Femenino , Humanos , Masculino , Microdiálisis/métodos , Estudios Prospectivos , Técnicas Estereotáxicas , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To determine that intensive glycemic control does not reduce microdialysis glucose concentration brain metabolism of glucose. DESIGN: Prospective monitoring followed by retrospective data analysis of cerebral microdialysis and global brain metabolism. SETTING: Single center, academic neurointensive care unit. PATIENTS: Forty-seven moderate to severe traumatic brain injury patients. INTERVENTIONS: A nonrandomized, consecutive design was used for glycemic control with loose insulin (n=33) for the initial 2 yrs or intensive insulin therapy (n=14) for the last year. MEASUREMENTS AND MAIN RESULTS: In 14 patients treated with intensive insulin therapy, there was a reduction in microdialysis glucose by 70% of baseline concentration compared with a 15% reduction in 33 patients treated with a loose insulin protocol. Despite this reduction in microdialysis glucose, the global metabolic rate of glucose did not change. However, intensive insulin therapy was associated with increased incidence of microdialysis markers of cellular distress, namely elevated glutamate (38+/-37% vs. 10+/-17%, p<.01), elevated lactate/pyruvate ratio (38+/-37% vs. 19+/-26%, p<.03) and low glucose (26+/-17% vs. 11+/-15%, p<.05, and increased global oxygen extraction fraction. Mortality was similar in the intensive and loose insulin treatment groups (14% vs. 15%, p=.9), as was 6-month clinical outcome (p=.3). CONCLUSIONS: Intensive insulin therapy results in a net reduction in microdialysis glucose and an increase in microdialysis glutamate and lactate/pyruvate without conveying a functional outcome advantage.
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Lesiones Encefálicas/complicaciones , Encéfalo/metabolismo , Glucosa/metabolismo , Hiperglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adulto , Ensayos Clínicos Controlados como Asunto , Femenino , Humanos , Hiperglucemia/etiología , Hipoglucemia/inducido químicamente , Hipoglucemia/fisiopatología , Hipoglucemiantes/efectos adversos , Infusiones Intravenosas , Insulina/efectos adversos , Masculino , Microdiálisis , Persona de Mediana Edad , Análisis Multivariante , Análisis de Regresión , Estudios RetrospectivosRESUMEN
Disturbed glucose brain metabolism after brain trauma is reflected by changes in extracellular glucose levels. The authors hypothesized that posttraumatic reductions in extracellular glucose levels are not due to ischemia and are associated with poor outcome. Intracerebral microdialysis, electroencephalography, and measurements of brain tissue oxygen levels and jugular venous oxygen saturation were performed in 30 patients with traumatic brain injury. Levels of glucose, lactate, pyruvate, glutamate, and urea were analyzed hourly. The 6-month Glasgow Outcome Scale extended (GOSe6) score was assessed for each patient. In regions of increased glucose utilization defined by positron emission tomography, the extracellular glucose concentration was less than 0.2 mmol/l. Extracellular glucose values were less than 0.2 mmol during postinjury days 0 to 7 in 19% to 30% of hourly samples on each day. Transient decreases in glucose levels occurred with electrographic seizures and nonischemic reductions in cerebral perfusion pressure and jugular venous oxygen saturation. Glutamate levels were elevated in the majority of low-glucose samples, but the lactate/pyruvate ratio did not indicate focal ischemia. Terminal herniation resulted in reductions in glucose with increases in the lactate/pyruvate ratio but not in lactate concentration alone. GOSe6 scores correlated with persistently low glucose levels, combined early low glucose levels and low lactate/glucose ratio, and with the overall lactate/glucose ratio. These results suggest that the level of extracellular glucose is typically reduced after traumatic brain injury and associated with poor outcome, but is not associated with ischemia.
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Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Espacio Extracelular/química , Glucosa/metabolismo , Ácido Láctico/metabolismo , Microdiálisis , Adulto , Encéfalo/patología , Lesiones Encefálicas/patología , Lesiones Encefálicas/terapia , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Estadística como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Pulse oximetry is a frequently used, noninvasive monitoring tool for assessing arterial blood oxygenation. Physicians, registered nurses, and respiratory therapists are responsible for the accurate interpretation of pulse oximetry data as part of the evaluation and management of acutely and critically ill patients. OBJECTIVES: (1) To evaluate the extent of current knowledge about pulse oximetry and (2) to increase clinicians' knowledge of research-based practices related to the appropriate use of pulse oximetry and interpretation of its results. METHODS: A test/survey of 17 true-false questions based on the research-based practice protocol of the American Association of Critical-Care Nurses was developed to evaluate current knowledge of pulse oximetry. A convenience sample of medical, nursing, and respiratory therapy staff was invited to complete the test/survey before and several months after an educational program to improve staff members' knowledge of pulse oximetry. The program included educational forums, policy changes, competency checklists, and verification of inclusion of research-based principles in orientation programs. RESULTS: A total of 442 staff members completed the test/survey given before the educational program: 331 nurses, 82 physicians, and 29 respiratory therapists. The overall mean percentage of correct answers was 66%. Differences between disciplines were significant: respiratory therapists scored slightly higher (76%) than did nurses (64%) and physicians (66%) (P = .01). The scores on the test/survey given after the educational program increased significantly, from 66% to 82% (P < .01). CONCLUSIONS: This educational project improved staff members' knowledge of pulse oximetry monitoring.