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.

Loss of cortisol circadian rhythm in patients with traumatic brain injury: a microdialysis evaluation.

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

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial.

INTRODUCTION: Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. METHODS: This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation < or = 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. RESULTS: A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis--undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital--thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. CONCLUSIONS: Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups. TRIAL REGISTRATION: (Trial registration: US Clinical Trials registry NCT00622570.).

A SIMPLIFIED EQUATION FOR TOTAL ENERGY EXPENDITURE IN MECHANICALLY VENTILATED CRITICALLY ILL PATIENTS.

INTRODUCTION: "tight calorie control" concept arose to avoid over- and under-feeding of patients. OBJECTIVE: to describe and validate a simplified predictive equation of total energy expenditure (TEE) in mechanically ventilated critically ill patients. METHODS: this was a secondary analysis of measurements of TEE by indirect calorimetry in critically ill patients. Patients were allocated in a 2:1 form by a computer package to develop the new predictive equation TEE (prediction cohort) and the validation cohort. Indirect calorimetry was performed with three different calorimeters: the Douglas-bag, a metabolic computer and the CalorimetR. We developed a new TEE predictive equation using measured TEE (in kcal/kg/d) as dependent variable and as independent variables different factors known to influence energy expenditure: age, gender, body mass index (BMI) and type of injury. RESULTS: prediction cohort: 179 patients. Validation cohort: 91 patients. The equation was: TEEPE (kcal/Kg/d) = 33 - (3 x A) - (3 x BMI) - (1 x G). Where: A (age in years): ≤ 50 = 0; > 50 = 1. BMI (Kg/m2): 18.5 - 24.9 = 0; 25 - 29.9 = 1; 30 - 34.9 = 2; 35 - 39.9 = 3. G (gender): male = 0; female = 1. The bias (95% CI) was -0.1 (-1.0 - 0.7) kcal/kg/d and the limits of agreement (} 2SD) were -8.0 to 7.8 kcal/kg/d. Predicted TEE was accurate (within 85% to 115%) in 73.6% of patients. CONCLUSION: the new predictive equation was acceptable to predict TEE in clinical practice for most mechanically ventilated critically ill patients.

Introducción: el concepto de "control calorico estricto" surgio para evitar la excesiva y la deficiente nutricion de los pacientes. Objetivo: describir y validar una ecuacion simplificada para el calculo del gasto energetico total (GET) en pacientes criticos con ventilacion mecanica. Métodos: analisis secundario de las mediciones de GET por calorimetria indirecta en pacientes criticos. Los pacientes fueron asignados de forma 2:1 por un paquete estadistico; el primer grupo se empleo para desarrollar la nueva ecuacion predictiva del GET (grupo predictivo) y el segundo para validarla (grupo validacion). La calorimetria indirecta se realizo con tres calorimetros diferentes: la bolsa de Douglas, un computador metabolico y el equipo CalorimetR. Hemos desarrollado la nueva ecuacion predictiva del GET utilizando el GET medido (en kcal/kg/d), como variable dependiente, y como variables independientes los diferentes factores que influyen en el gasto energetico: edad, genero, indice de masa corporal (IMC) y tipo de lesion. Resultados: el grupo de prediccion incluyo 179 pacientes y el de validacion 91 pacientes. La ecuacion predictiva fue: GETEP = 33 - (3 x E) - (3 x IMC) - (1 x G). Donde: E (edad en anos): ≤ 50 = 0; > 50 = 1. IMC (kg / m2): 18,5- 24,9 = 0; 25-29,9 = 1; 30-34,9 = 2; 35-39,9 = 3. G (genero): hombre = 0; mujer = 1. El sesgo (IC del 95%) entre el GET medido y el predicho fue de -0,1 (-1,0 a 0,7) kcal/ kg/dia y los limites de acuerdo (} 2SD) fueron -8,0 a 7,8 kcal/kg/d. El GET por la ecuacion predictiva fue preciso (entre el 85% y el 115%) en el 73,6% de los pacientes. Conclusiones: La nueva ecuacion predictiva fue aceptable para predecir el GET de la mayoria de pacientes criticos con ventilacion mecanica en la practica clinica.

A simplified equation for total energy expenditure in mechanically ventilated critically ill patients / Ecuación simplificada para el cálculo del gasto energético total en pacientes críticos con ventilación mecánica

Introduction: 'tight calorie control' concept arose to avoid over- and under-feeding of patients. Objective: to describe and validate a simplified predictive equation of total energy expenditure (TEE) in mechanically ventilated critically ill patients. Methods: this was a secondary analysis of measurements of TEE by indirect calorimetry in critically ill patients. Patients were allocated in a 2:1 form by a computer package to develop the new predictive equation TEE (prediction cohort) and the validation cohort. Indirect calorimetry was performed with three different calorimeters: the Douglas-bag, a metabolic computer and the Calorimet®. We developed a new TEE predictive equation using measured TEE (in kcal/kg/d) as dependent variable and as independent variables different factors known to influence energy expenditure: age, gender, body mass index (BMI) and type of injury. Results: prediction cohort: 179 patients. Validation cohort: 91 patients. The equation was: TEEPE (kcal/Kg/d) = 33 - (3 x A) - (3 x BMI) - (1 x G). Where: A (age in years): ≤ 50 = 0; > 50 = 1. BMI (Kg/m2 ): 18.5 - 24.9 = 0; 25 - 29.9 = 1; 30 - 34.9 = 2;35 - 39.9 = 3. G (gender): male = 0; female = 1. The bias (95% CI) was -0.1 (-1.0 - 0.7) kcal/kg/d and the limits of agreement (± 2SD) were -8.0 to 7.8 kcal/kg/d. Predicted TEE was accurate (within 85% to 115%) in 73.6% of patients. Conclusion: the new predictive equation was acceptable to predict TEE in clinical practice for most mechanically ventilated critically ill patients (AU)

Introducción: el concepto de 'control calórico estricto' surgió para evitar la excesiva y la deficiente nutrición de los pacientes. Objetivo: describir y validar una ecuación simplificada para el cálculo del gasto energético total (GET) en pacientes críticos con ventilación mecánica. Métodos: análisis secundario de las mediciones de GET por calorimetría indirecta en pacientes críticos. Los pacientes fueron asignados de forma 2:1 por un paquete estadístico; el primer grupo se empleó para desarrollar la nueva ecuación predictiva del GET (grupo predictivo) y el segundo para validarla (grupo validación). La calorimetría indirecta se realizó con tres calorímetros diferentes: la bolsa de Douglas, un computador metabólico y el equipo Calorimet®. Hemos desarrollado la nueva ecuación predictiva del GET utilizando el GET medido (en kcal/kg/d), como variable dependiente, y como variables independientes los diferentes factores que influyen en el gasto energético: edad, género, índice de masa corporal (IMC) y tipo de lesión. Resultados: el grupo de predicción incluyó 179 pacientes y el de validación 91 pacientes. La ecuación predictiva fue: GETEP = 33 - (3 x E) - (3 x IMC) - (1 x G). Donde: E (edad en años): ≤ 50 = 0; > 50 = 1. IMC (kg / m2): 18,5- 24,9 = 0; 25-29,9 = 1; 30-34,9 = 2; 35-39,9 = 3. G (género): hombre = 0; mujer = 1. El sesgo (IC del 95%) entre el GET medido y el predicho fue de -0,1 (-1,0 a 0,7) kcal/ kg/día y los límites de acuerdo (± 2SD) fueron -8,0 a 7,8 kcal/kg/d. El GET por la ecuación predictiva fue preciso (entre el 85% y el 115%) en el 73,6% de los pacientes. Conclusiones: La nueva ecuación predictiva fue aceptable para predecir el GET de la mayoría de pacientes críticos con ventilación mecánica en la práctica clínica (AU)

Intravascular cooling for rapid induction of moderate hypothermia in severely head-injured patients: results of a multicenter study (IntraCool).

OBJECTIVES: To evaluate the feasibility, safety and effectiveness of a new method of intravascular temperature management for inducing moderate hypothermia (MHT). DESIGN AND SETTINGS: Prospective, international-multicenter clinical trial conducted in four university hospitals. PATIENTS: In a 2-year period 24 patients with severe head injury and refractory high ICP were treated with MHT (32.5 degrees C) by intravascular methods. RESULTS: Seventeen were males and seven females, with a median age of 25 years (range 15-60). The median Glasgow Coma Scale upon admission was 7 (range 3-13) and the median Injury Severity Score was 22 (range 13-43). A total of 75% of patients presented a diffuse lesion in the pre-enrollment computed tomography. Median time from injury until reaching refractory high ICP was 71.5 h after injury (minimum 14 h, maximum 251 h). Twelve patients (50%) reached this situation within the first 72 h after injury. MHT was attained in a median time of 3 h. Pre-enrollment median ICP was 23.8 mmHg and was reduced to 16.8 mmHg upon reaching target temperature. At 6 months after injury, nine patients had died (37.5%), six were severely disabled (25%), two moderately disabled (8.3%) and seven had a good recovery (29.2%). Of the nine patients who died, in four the cause was rebound ICP during rewarming, one death was attributed to accidental potassium overload, two to septic shock, one to cardiac arrest of unknown origin and the ninth to a pulmonary embolism. CONCLUSION: Intravascular methods to induce MHT combined with precooling with cold saline at 4 degrees C appear to be feasible and effective in reducing ICP in patients with high ICP refractory to first-line therapeutic measures.

Ultrasonographic cerebral perfusion in assessment of brain death: a preliminary study.

OBJECTIVE: The purpose of this series was to describe the ultrasonographic perfusion pattern in patients with brain death. METHODS: Thirteen patients with different neurologic disorders in whom brain death developed were studied. Transcranial perfusion was analyzed after injection of 2.5 mL of a sulfur hexafluoride ultrasonographic contrast agent. Time-intensity curves were analyzed in predetermined regions of interest. RESULTS: In all patients, analysis of regions of interest showed no bolus-like curve progression. This finding implies a complete absence of cerebral perfusion. CONCLUSIONS: Patients with brain death studied by ultrasonographic perfusion techniques have a characteristic pattern.