Progesterona para el tratamiento del trauma craneoencefálico grave: una revisión sistemática y metaanálisis / Progesterone to treat severe traumatic brain injury: a systematic review and meta-analysis / Progesterona para o tratamento do traumatismo crânio-encefálico grave: revisão sistemática e meta-análise

Resumen: Objetivo: revisar sistemáticamente la evidencia sobre la administración de progesterona tras un trauma craneoencefálico grave en adultos y su relación con mortalidad y pronóstico neurológico. Criterios de inclusión: ensayos clínicos aleatorizados que incluyan a pacientes adultos mayores de 18 años, haber sufrido un traumatismo craneal grave (Glasgow <8), donde se compare la administración de progesterona vs grupo control (placebo o no administración). Método: se realizó la búsqueda en las siguientes bases de datos: MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injuries group y lista de referencia de los artículos. Resultados: no hubo reducción de la mortalidad comparado con el grupo control (RR 0,93, IC95% 0,79-1,10 p= 0,41), no hubo diferencias entre progesterona y el grupo control en desenlaces neurológicos positivos ni negativos (RR 1,07, IC95% 0,97-1,17 p= 0,20; RR 0,94, IC 95% 0,81-1,08 p= 0,27), respectivamente. Conclusiones: no se encontró evidencia respecto a que la administración de progesterona posterior a un traumatismo craneoencefálico reduzca la mortalidad o mejore desenlaces neurológicos, aunque se necesitan más estudios de buena calidad para extraer conclusiones definitivas.

Summary: Objective: to systematically review evidence on the administration of progesterone after a traumatic brain injury in adults and its relationship with mortality and neurological head prognosis. Inclusion criteria: randomized clinical trials that include: patients older than 12 years old, having had an injury (Glasgow <8), comparing the administration of Progesterone versus the control group (placebo or no administration). Methods: we searched the following databases: MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injury Group and reference list of articles. Results: there was no reduction in mortality in patients in the control group (RR 0.93, 95% CI 0.79-1.10 p = 0.41), there were no differences between progesterone and the control group in favorable or adverse neurological outcomes (RR 1.07, 95% CI: 0.97-1.17 p = 0.20, RR 0.94, 95% CI: 0.81 -1,08 p= 0.27), respectively. Conclusions: there is no evidence that the administration of progesterone after a traumatic brain injury reduces or improves neurological results, although further good quality studies are required to obtain conclusive results.

Resumo: Objetivo: realizar uma revisão sistemática da evidência sobre a administração de progesterona depois de traumatismo crânio-encefálico grave em adultos e sua relação com a mortalidade e o prognóstico neurológico. Critérios de inclusão: ensaios clínicos aleatorizados que incluam: pacientes adultos maiores de 18 anos, haver sofrido um traumatismo craniano grave (Glasgow <8) donde se compare a administração de progesterona versus grupo controle (placebo ou não administração). Métodos: foi feita uma pesquisa bibliográfica nas seguintes bases de dados: MEDLINE, Central Register of Controlled Trials (CENTRAL), PubMed, HINARI, EMBASE, Cochrane Injuries Group e nas referências bibliográficas dos artigos. Resultados: não foi observada uma redução da mortalidade comparada com o grupo controle (RR 0,93, IC del 95%: 0,79-1,10 p= 0,41), não foram observadas diferenças entre o grupo que recebeu progesterona e o grupo controle nos resultados neurológicos positivos ou negativos (RR 1,07, IC del 95%: 0,97-1,17 p= 0,20; RR 0,94, IC del 95%: 0,81-1,08 p= 0,27), respectivamente. Conclusões: não se encontrou evidência de que a administração de progesterona depois de um traumatismo crânio-encefálico reduza a mortalidade ou melhore os resultados neurológicos embora novos estudos de boa qualidade sejam necessários para chegar a conclusões definitivas.

Protective effects of Ganoderma lucidum on the changes made in the retinal damage induced by traumatic head injury / Efectos protectores de Ganoderma lucidum sobre los cambios producidos en el daño retinal inducido por lesión traumática en la cabeza

Head trauma affects the optic nerve visual function and visual acuity. As a result of head trauma occurring in the retina of the various biochemical, histological and immunohistochemical effects were investigated. The protective effect of Ganoderma lucidum was evaluated on the damage to the retina of the rats. Sprague-Dawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g-1 m weight-height impact. Thirty rats were divided into three groups as group 1 control, 2 group trauma, 3 group trauma+Gonoderma lucidum (20 mL/kg per day via gastric gavage) Ganoderma lucidum was administered for 7 days after trauma.All rats were decapitated 5 days after the induction of trauma, and the protective effects of Ganoderma lucidum in retina were evaluated by histological, immunohistochemical and biochemical analyses. The antioxidant effect of Ganoderma lucidum on the cellular degeneration extracellular matrix and retinal barrier in retina after head trauma was investigated.

El traumatismo craneal afecta al nervio óptico en relación a su función y la agudeza visual. Se estudiaron los diversos efectos bioquímicos, histológicos e inmunohistoquímicos en la retina producidos por una lesión y trauma a la cabeza. En esta investigación se evaluó el efecto protector de Gonaderin lucidum sobre el daño a la retina de ratas. Ratas Sprague-Dawley fueron sometidas a una lesión cerebral traumática con un dispositivo de caída de peso usando un impacto de 300 g-1 m de peso-altura. Treinta ratas se dividieron en tres grupos: grupo 1, de control; grupo 2, trauma; grupo 3, de trauma + Gonoderma lucidum (20 ml / kg día, a través de una sonda gástrica). Ganoderma lucidum se administró durante 7 días después del trauma. Todas las ratas fueron decapitadas 5 días después. La inducción del trauma y los efectos protectores de Ganoderma lucidum en la retina fueron evaluados mediante análisis histológicos, inmunohistoquímicos y bioquímicos. Se investigó el efecto antioxidante de Ganoderma lucidum sobre la degeneración celular en la matriz extracelular y la barrera retiniana en la retina después del traumatismo craneal.

Farmacoterapia no traumatismo craniano. Onde estamos? Para onde vamos? Porém, quando vamos? / Pharmacotherapy in Traumatic Brain Injury. Where we are? Where we are going? However, when?

O traumatismo cranioencefálico (TCE) apresenta aumento de sua prevalência e é um desafio para a sociedade atual. Lesões primárias são aquelas que ocorrem no momento do impacto. Lesões secundárias são as que ocorrem após a lesão inicial como uma resposta fisiológica/patológica. Isso causa uma cascata de eventos que pode durar um longo período. Enquanto as lesões primárias são irreverssíveis, as secundárias são potencialmente evitáveis se forem submetidas a triagem e estabilização adequadas, assim como ao correto manejo da oxigenação cerebral e controle da hipertensão intracraniana e pressão de perfusão cerebral. Devemos considerar o traumatismo craniano como um evento dinâmico com inúmeras janelas terapêuticas possíveis. Nesse contexto o desenvolvimento de agentes farmacológicos no tratamento do TCE é urgente. Na presente revisão os autores descrevem os principais fármacos que estão sendo estudados nos pacientes comtraumatismo craniano. Concluímos que, apesar de investimentos substanciais em estudos de fase I e II, ainda há muitas lacunas no conhecimento, portanto esforços são necessários para que haja uma translação maisrápida para estudos de fase III.

Traumatic brain injury (TBI) is an increasingly prevalent and complex challenge for society. Primary injuries are defined as those that occur at the moment of impact. Secondary injuries are those that occur after the initial injury as a consequence of physiologic / pathologic response to injury. This triggers a cascade of pathophysiological events that can extend over a long period of time. Whereas the primary injuries are considered irreversible, secondary injuries are potentially preventable with efficient triage and stabilization, management of parameters such as brain oxygenation, intracranial pressure, and cerebral perfusion pressure. Indeed, TBI should be thought of not as a static event, but rather a progressive injury with varying therapeutic windows. In this context the development of pharmacological treatmentwith traumatic brain injury is urgent. In this review the authors describe the main drugs that are being studied in TBI patients. We conclude, despite substantial and ongoing investments in both phase I and II studies, there remain significant gaps in knowledge and faster translation to phase III clinical studies is mandatory. of patients

Análise da ocorrência de hipertensão intracraniana refratária e da resposta ao tratamento de crianças com traumatismo crânio-encefálico grave / Analysis of the incidence of refractory intracranial hypertension and the response of children with severe head trauma to the treatment

Introdução: o traumatismo crânio-encefálico (TCE) grave é frequente em pediatria, mas as recomendações para seu tratamento têm baixo nível de evidência. Objetivo: analisar a ocorrência de hipertensão intracraniana (HIC) refratária e a resposta ao tratamento em crianças com TCE grave. Métodos: coorte incluindo pacientes com pontuação abaixo de nove na Escala de Coma de Glasgow (ECG) entre setembro de 2005 e agosto de 2008. Aprovado pelo Comitê de Ética em Pesquisa da Fhemig. Resultados: analisados 156 pacientes, 116 masculinos (74,4%), idades entre três meses e 18 anos, média nove, mediana 11. Mediana da pontuação na ECG: 6. Atropelamento: 54 pacientes (34,6%); lesões em ocupantes de veículos: 34 (21,8%); queda: 21 (13,5%); e lesões em ciclistas: 18 (11,5%). Tomografia alterada: 133 pacientes (85,3%); hemorragia intracraniana: 105 (67,3%); swelling: 66 (42,3%); lesão axonal difusa: (28,8%). A monitorização da pressão intracraniana foi realizada em 73 pacientes (46,8%). Foi encontrada HIC com necessidade de tratamento em 56 (76,7%) e refratária em 30 (41%) pacientes. Destes pacientes, 10 receberam barbitúrico e sete morreram. A craniectomia descompressiva foi realizada em nove pacientes, sendo que dois faleceram. O risco relativo de morte com barbitú- rico: 3,9 (IC 95%: 1,1 a 14,1; p=0,02), com significância estatística. O risco relativo de morte com craniectomia descompressiva: 0,3 (IC95%: 0,1 a 1,0, p=0,02). Ocorreram 33 óbitos (21,1%), 59% de redução em relação a estudo anterior da Instituição. Conclusões: HIC refratária foi muito frequente em crianças com TCE grave. O uso de coma barbitúrico para seu tratamento aumentou o risco de morte em quatro vezes.(AU)

Background: Severe head trauma is common in children, but there is a lack of evidence for the intracranial hypertension treatment in the literature. Objectives: To analyze the occurrence of refractory intracranial hypertension and the response of children and adolescents with severe head trauma to the treatment. Method: Cohort study between September 2005 and August 2008 involving pediatric patients with Glasgow coma scale (GCS) from 3 to 8 points. This study was approved by the ethical committee of FHEMIG. Results: From the 156 patients, 116 were male (74,4%). The range of age varied from tree months to 18 years, mean age 9, and median 11. Median of GCS score: 6. Running over crash: 54 patients (34,6%), car occupants injuries: 34 (21,8%), falls: 21 (13,5%) e cyclist´s injuries: 18 (11,5%). Abnormalities in computed tomography: 133 patients (85,3%), intracranial hemorrhage: 105 (67,3%), swelling: 66 (42,3%), diffuse axonal injury: (28,8%). Seventy three patients received intracranial pressure monitoring (46,3%); 56 had had intracranial hypertension that needed treatment (76,7%), and 30 had had refractory intracranial hypertension (41%). From the patients with refractory hypertension, 10 received barbiturates as treatment, seven died. Nine underwent decompressive craniectomy, two died. Relative risk of death with barbiturates: 3,9 (CI 95%: 1,1 a 14,1; p=0,02). Relative risk of death with decompressive craniectomy: 0,3 (IC95%: 0,1 a 1,0, p=0,02). Total mortality rate was 21,1% (33 patients). This showed a decrease of 59% in mortality comparing to previous study done in the same hospital. Conclusion: refractory intracranial hypertension were very common in pediatric patients with severe head injury. The use of barbiturates for its treatment increased the risk of death four times.(AU)

Enteral nutrition and phenytoin administration in head trauma patients

Seizure is common after head trauma and neurosurgery. Phenytoin is the most common anti-convulsant drug used in epileptic patients and for prevention of seizure in patients with head trauma and stroke. This drug has unique pharmacokinetic and pharmacodynamic characteristics. Phenytoin administration along with enteral nutrition in ICU patients may be accompanied by decreased phenytoin absorption and inadequate therapeutic concentration. The present study was performed to assess the effect of enteral nutrition on the pharmacokinetic therapeutic parameters of phenytoin given to our patients. In a clinical trial, the study group was divided into two groups of 15 patients each. After obtaining steady-state phenytion serum concentration, two blood samples were obtained from each patient on 2 consecutive days and then analyzed. The mean was assessed on the basis of serum albumin level of the patient. Clearance and maximum metabolic capacity were also calculated. Serum phenytoin level was below the therapeutic range [10- 20 mg/l] in 70% of patients in group 1 and was higher than the therapeutic range in 70% of patients in group 2 who received oral phenytoin [by dissolving in water] 2h after enteral nutrition. Mean phenytion concentration was 6.3 +/- 4mg/l and 24.7 +/- 9.4mg/l in group 1 and group 2, respectively. We found oral phenytoin administration with enteral nutrition [gavage solutions] to result in a significant decrease in absorption and blood concentration of phenytoin. We recommend administration of phenytoin with water only. In addition, monitoring of phenytoin serum concentration is necessary for assessment of therapeutic concentration and prevention of side effects

Evaluation of nimodipine in the treatment of severe diffuse head injury: a double-blind placebo-controlled trial.

AIMS: The aim of this study was to establish whether nimodipine given orally soon after severe diffuse head injury for a period of three weeks improved outcome. MATERIAL AND METHODS: The present report analyzes the results of a prospective randomized double-blind placebo-controlled trial of nimodipine in 97 severe head injury patients (GCS Score < or =8) treated at the Department of Neurosurgery, NIMHANS, between January 1995 and June 1996. The patients were randomly assigned to two groups which were matched for age, sex, mode of injury, time interval from injury to admission, neurological status and CT scan findings. One group was given nimodipine 30 mg Q6H and the other group was given a placebo. The outcome of these patients at 6 months was evaluated using the Glasgow Outcome Score by and a psychologist. RESULTS: Results showed no significant difference in the functional and psychological outcome between the two groups, even in patients with subarachnoid hemorrhage. No adverse drug events were recorded. CONCLUSION: Oral nimodipine given for three weeks does not improve outcome in patients with severe diffuse head injury.

Traumatismo encefalocraneano en la República Argentina, estudio piloto: modalidades en la atención, monitoreo, y tratamiento del paciente neurológico agudo / Traumatic brain injury in the Republica Argentina: a pilot study. Modalities in the attention, monitoring and treatment of the acute neurological patient

El GTN es un grupo interdisciplinario que está interesado en el tratamiento y secuelas del paciente neurocrítico. Este grupo está compuesto por neurocirujanos, anestesiólogos, neurólogos e intensivistas. Se realizó un estudio piloto para recabar datos en la admisión, tratamiento y secuelas de pacientes con trauma de cráneo en la Argentina. Estudio prospectivo, observacional y cooperativo que se llevó a cabo entre los meses de agosto a octubre de 1995 en 6 Servicios de Terapia Intensiva en dos ciudades. Se registraron todos los pacientes con TEC ingresados a esos Servicios. Los pacientes fueron clasificados a la admisión según la escala de coma de Glasgow. Fue utilizada la clasificación tomogáfica del TCDB (Traumatic Coma Data Bank). Se obtuvieron los siguientes resultados: el accidente fue la causa más importante de trauma de cráneo 97,6 por ciento, la media de Glasgow fue de 10,5 (incluyendo Glasgow 3); el monitoreo de la presión intracraneana se realizó en el 66,7 por ciento y la saturación yugular fue utilizada en el 29,3 por ciento de los pacientes. La mortalidad fue del 26,2 por ciento

Manejo farmacológico de algunos problemas asociados al trauma craneo-encefálico / Pharmacological management of several dysfunctions related to traumatic brain injury

El presente trabajo constituye una recopilación de los avances en el manejo farmacológico de varias disfunciones asociadas al traumatismo cerebral, en la fase sub-aguda de recuperación. Se ofrecen varias alternativas de tratamiento, debiendo considerarse una guía para el manejo terapéutico de pacientes con secuelas de trauma cráneo-encefálico en la etapa subaguda de rehabilitación

Manejo de la vía aérea y ventilación mecánica en el paciente con traumatismo craneoencefálico / Aurway management and mechanical ventilation in head injury

El cuidado del paciente con lesión aguda de cráneo incluye una rápida evaluación y corrección de la hipoxia con un manejo apropiado de la vía aérea y tratamiento de problemas asociados. El enfoque primario está en la corrección según la fisiopatología y en la prevención de la lesión cerebral secundaria. Los anestésicos y los relajantes musculares son utilizados para controlar la dinámica intracraneal manteniendo la perfusión cerebral y sistémica. El manejo de la vía aérea requiere una rápida intervención y control definitivo, mientras se protege la columna cervical. La preparación previa para la posibilidad de una intubación fallida es importante

Bronchomotor, haemodynamic and neuromuscular effects of atracurium and cis-atracurium [51/W89]: comparative experimental and clinical studies in critically ill mechanically ventilated patients

The effects of atracurium and cis-atracurium on histamine- induced submaximal contractions of isolated tracheal strips and on the airway resistance were tested in guinea pigs. Clinical studies included 24 chronic obstructive pulmonary disease [COPD] and 24 head injury patients, mechanically ventilated with the use of Puritan Bennett, 7200ae ventilator. Flow-volume loops were recorded and analyzed to determine the bronchomotor effects of atracurium 0.6 mg kg-1 or cis- atracurium 0.12 mg kg-1. Heart rate was monitored continuously and noninvasive blood pressure was recorded at specified time intervals. An acceleration piezo-electric transducer was used to monitor neuromuscular transmission. Atracurium produced potentiation of histamine-induced submaximal contractions of isolated tracheal strips and a dose-related increase in the airway resistance of intact anesthetized guinea pigs. The bronchoconstrictor effect of atracurium was abolished by mepyramine maleate. In clinical studies expiratory flow rates from a mean base-line value of 0.52 +/- SD 0.08 l sec-1 to reach 0.41 +/- 0.06 l sec-1, p <0.05. Further atracurium produced significant reductions in mean arterial pressure with a compensatory rise in heart rate in COPD and head injury patients. In contrast, cis-atracurium was not associated with any evidence of histamine-induced bronchospastic or hemodynamic effects. Cis- atracurium had significantly longer onset time than atracurium, with a mean difference ranging between 1.1-1.5 minutes. Time to 25% and 75% first twitch [T1] recovery, recovery index, and the time required for 70% recovery of train-of-4 ratio [T4/T1] were all shorter in head injury than COPD patients. Cis-atracurium appears to be the closest to the ideal neuromuscular blocking agent for use in critically ill patients

Traumatismo encefalocraneano grave: comparación de dos series pediátricas / Severe brain trauma: comparison between two pediatrics series

Objetivo: Comparar los resultados en la atención del traumatismo Encefalocraneano (TEC) en dos grupos de pacientes internados en la UTI durante el período 1992-1995. Materiales y métodos: Se investigaron restrospectivamente los pacientes internados en UTI con TEC severo (Glasgow menor a 9) durante el período comprendido entre el 1/1/92 hasta el 31/12/95, a los que se dividió en dos grupos: Grupo A (años 92-93) y Grupo B (años 94-95). En ambos se valoró el mecanismo del trauma, edad, sexo, Glasgow inicial, Indice del Trauma Pediátrico (ITP), monitoreo de Presión Intracraneana (PIC), Tomografía Axial Computada (TAC), complicaciones, terapéutica instalada, mortalidad. Se analizaron las variables mediante el programa Epi Info. Variables Dicotómicas y continuas; se tomó significativa una p < 0,05. Resultados: Ingresaron en el grupo A 20 pacientes y en B 18 pacientes. No hubo diferencias estadísticamente significativas en cuanto a edad, sexo, scores de gravedad: ITP (Grupo A media de 3, Grupo B media de 2,8), Glasgow inicial (Grupo A media de 6 mientras que el B 5,3). Con respecto a los mecanismos del trauma se observó en el grupo B un 61,1 por ciento de caídas en relación al 20 por ciento del Grupo A, dato estadísticamente significativo (P = 0,02). En cuanto a la terapéutica se monitoreó la PIC en el Grupo A al 25 por ciento (5/20) mientras que en el Grupo B al 66 por ciento (12/18). En el Grupo B se controló la presión de perfusión cerebral (PPC) manteniéndola en valores superiores a 60 mmHg. Se observó en el Grupo A que el 80 por ciento de los pacientes tuvieron complicaciones mientras que en el Grupo B un 39 por ciento (7/18). Diferencia estadísticamente significativa (p < 0,02). En el Grupo A se utilizó inotrópicos en 4/20 pacientes (siempre asociado al uso de tiopenthal) y en el Grupo B en 13/18 (sólo 2 recibieron tiopenthal) siendo la diferencia estadísticamente significativa (p = 0,003). La mortalidad global fue del 37 por ciento falleciendo en el Grupo A el 45 por ciento (9/20) y en el Grupo B el 27,8 por ciento (5/18); mostrando una tendencia favorable aunque no estadísticamente significativa