Effectiveness of Pharmacological Therapies for Intracranial Hypertension in Children With Severe Traumatic Brain Injury--Results From an Automated Data Collection System Time-Synched to Drug Administration.

OBJECTIVES: To describe acute cerebral hemodynamic effects of medications commonly used to treat intracranial hypertension in children with traumatic brain injury. Currently, data supporting the efficacy of these medications are insufficient. DESIGN: In this prospective observational study, intracranial hypertension (intracranial pressure ≥ 20 mm Hg for > 5 min) was treated by clinical protocol. Administration times of medications for intracranial hypertension (fentanyl, 3% hypertonic saline, mannitol, and pentobarbital) were prospectively recorded and synchronized with an automated database that collected intracranial pressure and cerebral perfusion pressure every 5 seconds. Intracranial pressure crises confounded by external stimulation or mechanical ventilator adjustments were excluded. Mean intracranial pressure and cerebral perfusion pressure from epochs following drug administration were compared with baseline values using Kruskal-Wallis analysis of variance and Dunn test. Frailty modeling was used to analyze the time to intracranial pressure crisis resolution. Mixed-effect models compared intracranial pressure and cerebral perfusion pressure 5 minutes after the medication versus baseline and rates of treatment failure. SETTING: A tertiary care children's hospital. PATIENTS: Children with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 196 doses of fentanyl, hypertonic saline, mannitol, and pentobarbital administered to 16 children (median: 12 doses per patient). Overall, intracranial pressure significantly decreased following the administration of fentanyl, hypertonic saline, and pentobarbital. After controlling for administration of multiple medications, intracranial pressure was decreased following hypertonic saline and pentobarbital administration; cerebral perfusion pressure was decreased following fentanyl and was increased following hypertonic saline administration. After adjusting for significant covariates (including age, Glasgow Coma Scale score, and intracranial pressure), hypertonic saline was associated with a two-fold faster resolution of intracranial hypertension than either fentanyl or pentobarbital. Fentanyl was significantly associated with the most frequent treatment failure. CONCLUSIONS: Intracranial pressure decreased after multiple drug administrations, but hypertonic saline may warrant consideration as the first-line drug for treating intracranial hypertension, as it was associated with the most favorable cerebral hemodynamics and fastest resolution of intracranial hypertension.

Diazepam and pentobarbital protect against scorpion venom toxin-induced epilepsy

We have characterized earlier the long-term behavioural, electroencephalographic and histopatologicfeatures after a single TsTx microinjection, consisting of a neuropeptide isolated from the Tityus serrulatusscorpion venom, into the hippocampus of rats. TsTx was able to induce status epilepticus (SE)and developed later epilepsy. The present study was designed to investigate the outcomes of diazepamplus pentobarbital administered at 30 min, 1, 2 or 6 h after the beginning of TsTx-induced SE, on thedevelopment of spontaneous recurrent motor seizures (SRMSs), mossy fibre sprouting and hippocampalneurodegeneration in rats. The administration of diazepam (DZ) + pentobarbital (PB) 30 min after thebeginning of the TsTx-induced SE was able to markedly reduce the frequency of the SRMSs and preventthe development of mossy fibres sprouting and hippocampal lesion. In the other groups the augmentof the extent of hipocampal neurodegeneration, the frequency of SRMSs and degree of aberrant mossyfibre sproutingwas directly proportional to the time that the animalswere subjected to TsTx-induced SE.In conclusion, our results point out that the early blockade of the TsTx-induced SE with diazepam pluspentobarbital,was effective treatment against later epilepsy development. The effectiveness of this treatmentdepends on the time that the animals were subjected to the SE. Furthermore, the TsTx model couldbe a useful tool to study antiepileptogenic drugs in chronic epileptic animals, neuronal degeneration, aswell as for the mechanisms underlying epilepsy.

Effect of pentobarbital on pH and electrolyte levels after induced seizure in rats.

We studied the effects of high doses of pentobarbital (PB) and carbamazepine (CBZ) on electrolyte levels and pH in an epileptic animal model. Pentobarbital decreased Ca2+ and Na+ levels without pentylenetetrazole (PTZ). After this, Ca2+ and Na+ levels continued to decrease except when CBZ was used, which preserved the Ca2+ levels PTZ may have opposed effects on PB. Our results suggest that PB causes changes in electrolyte levels and pH, but these changes are diminished by CBZ.

Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L.

Citrus aurantium L. is commonly used as an alternative treatment for insomnia, anxiety and epilepsy. Essential oil from peel (EOP) and hydroethanolic (70% w/v) extract (HE) from leaves were obtained. Hexanic (HF), dichloromethanic (DF) and final aqueous (AF) fractions were obtained from HE by successive partitions. Swiss male mice (35-45 g) were treated orally with 0.5 or 1.0 g/kg of these preparations 30 min before the experiments for the evaluation of the sedative/hypnotic activity (sleeping time induced by sodium pentobarbital - SPB: 40 mg/kg, i.p.), anxiolytic activity (elevated plus maze--EPM) and anticonvulsant activity (induced by pentylenetetrazole--PTZ: 85 mg/kg, sc or by maximal electroshock--MES: 50 mA, 0.11 s, corneal). The results showed that EOP (0.5 g/kg) increased the latency period of tonic seizures in both convulsing experimental models. This effect was not dose-dependent. Treatment with 1.0 g/kg increased the sleeping time induced by barbiturates and the time spent in the open arms of the EPM. Specific tests indicated that the preparation, in both doses used, did not promote deficits in general activity or motor coordination. HF and DF fractions (1.0 g/kg) did not interfere in the epileptic seizures, but were able to enhance the sleeping time induced by barbiturates. The results obtained with EOP in the anxiety model, and with EOP, HF and DF in the sedation model, are in accord with the ethnopharmacological use of Citrus aurantium L., which could be useful in primary medical care, after toxicological investigation.

Respiratory mechanics and morphometric changes during anesthesia with ketamine in normal rats

Ketamine is believed to reduce airway and pulmonary tissue resistance. The aim of the present study was to determine the effects of ketamine on the resistive, elastic and viscoelastic/inhomogeneous mechanical properties of the respiratory system, lungs and chest wall, and to relate the mechanical data to findings from histological lung analysis in normal animals. Fifteen adult male Wistar rats were assigned randomly to two groups: control (N = 7) and ketamine (N = 8). All animals were sedated (diazepam, 5 mg, ip) and anesthetized with pentobarbital sodium (20 mg/kg, ip) or ketamine (30 mg/kg, ip). The rats were paralyzed and ventilated mechanically. Ketamine increased lung viscoelastic/inhomogeneous pressure (26 percent) compared to the control group. Dynamic and static elastances were similar in both groups, but the difference was greater in the ketamine than in the control group. Lung morphometry demonstrated dilation of alveolar ducts and increased areas of alveolar collapse in the ketamine group. In conclusion, ketamine did not act at the airway level but acted at the lung periphery increasing mechanical inhomogeneities possibly resulting from dilation of distal airways and alveolar collapse

Respiratory mechanics and morphometric changes during anesthesia with ketamine in normal rats.

Ketamine is believed to reduce airway and pulmonary tissue resistance. The aim of the present study was to determine the effects of ketamine on the resistive, elastic and viscoelastic/inhomogeneous mechanical properties of the respiratory system, lungs and chest wall, and to relate the mechanical data to findings from histological lung analysis in normal animals. Fifteen adult male Wistar rats were assigned randomly to two groups: control (N = 7) and ketamine (N = 8). All animals were sedated (diazepam, 5 mg, ip) and anesthetized with pentobarbital sodium (20 mg/kg, ip) or ketamine (30 mg/kg, ip). The rats were paralyzed and ventilated mechanically. Ketamine increased lung viscoelastic/inhomogeneous pressure (26%) compared to the control group. Dynamic and static elastances were similar in both groups, but the difference was greater in the ketamine than in the control group. Lung morphometry demonstrated dilation of alveolar ducts and increased areas of alveolar collapse in the ketamine group. In conclusion, ketamine did not act at the airway level but acted at the lung periphery increasing mechanical inhomogeneities possibly resulting from dilation of distal airways and alveolar collapse.

Manejo clínico del traumatismo encefalocraneano grave / Clinical management of the severe encephalocranial injuries

El TEC es la causa más frecuente de mortalidad e invalidez en niños y adultos jóvenes. Si bien el neurocirujano no puede prevenir los daños traumáticos primarios, la atención está dirigida a la prevención de los daños secundarios causados por hipotensión, hipoxemia y la prevención de complicaciones intracraneanas y sistémicas. Será fundamental el manejo de la presión intracraneana (PIC) con el fin de mantener una presión de perfusión cerebral (PPC) adecuada. Requiriendo todo paciente con un puntaje de 8 o menos en la escala de coma de glasgow (GCS) monitoreo de su PIC. Descartada la presencia de una lesión susceptible de manejo quirúrgico, las medidas indicadas son la hiperventilación moderada (pCO230-35 mm Hg) y el uso de sustancias hiperosmolares (manitol). En pacientes refractarios a estas medidas deberá discutirse como medida adicional el coma barbitúrico y la craneotomía decompresiva

Use of prenatal phenobarbital in the prevention of subependymal/intraventricular hemorrhage in premature infants

Background. Subependymal/intraventricular hemorrhage (SE/IVH) is a frequent cause of disability and mortality. Methods. This is a prospective, randomized, double-blind study which included 100 pergnant Mexican women who need to interrupt their pregnancy within 28-32 weeks of gestation. One group was given a single dose of intravenous (IV) phenobarbital 10 µg/kg (phenobarbital group, n=50), and the other was provided with diluted distilled water (control group). Measurements of phenobarbital serum concentrations were taken by both mother and newborn, and head sonograms were applied during the first 24 hours, at the 3rd and 7 th days of life. Results. The sample was made up of 42 newborns in the phenobarbital group, and 46 in the control group; the newborns had phenobarbital levels of 11.5 5.7 g/µl at birth, and of 9.5 ñ 5.9 g/µl 24 hours later. SE/IVH was found in 12 patients from the phenobarbital group and in 29 from the control group (p<0.005), the first group were 11 mild SE/IVH (2 grade I, and 9 grade II), and 26 in the control group (4 grade I, and 22 grade II), p <0.005. Severe hemorrhages were similar between groups. A larger frequency of SE/IVH was found in the newborns group which received mechanical ventilation (p=0.0008). Conclusions. Prenatal phenobarbital can reduce the SE/IVH frequency in premature infants younger than 32 weeks at birth. Its main effect could be shown in patients with mechanical ventilation

Utilizaçäo da máscara laríngea no cäo: aspectos hemodinâmicos, respiratórios e de microscopia óptica e eletrônica / Utilization of the laryngeal mask in dog: hemodynamic, respiratory and optical and electron microscopy aspects

Introduçäo e Objetivos: A utilizaçäo da cânula de intubaçäo endotraqueal em pacientes sob anestesia é eficaz na manutençäo da permeabilidade das vias áreas, mas näo é isenta de morbidade. Recentemente, foi introduzida, no homem, a máscara laríngea (ML), para manutençäo da permeabilidade das vias aéreas. Entretanto, surgiram vários relatos clínicos de morbidade com a ML, como disfagia, odinofagia, compressäo de nervos e vasos, que os autores têm relacionando à pressäo elevada em seu balonete. Entretanto, essa relaçäo ainda näo está perfeitamente estabelecida, porque na maioria dos relatos clínicos näo houve monitorizaçäo da pressäo no balonete da ML. Assim, os principais objetivos desta pesquisa foram os de estudar, no cäo, a efetividade da ML na manutençäo das vias aéreas, as repercussöes hemodinâmicas e respiratórias, os níveis de pressöes atingidos no balonete da ML e as eventuais lesöes do segmento faringolaríngeo à microscopia óptica e eletrônica de varredura. Material e Métodos: Dezesseis cäes foram submetidos à anestesia intravenosa com pentobarbital sódico, inserçäo da ML número 4 e ventilaçäo espontânea em sistema valvular com absorçäo de CO2, durante 2 horas. Grupos experimentais: G1 - inserçäo da ML com o balonete totalmente desinsuflado, seguida de insuflaçäo de 30 ml de ar, após sua inserçäo na hipofaringe; G2 - inserçäo da ML com o balonete semi-insuflado, seguida da insuflaçäo de 30 ml de ar, após sua inserçäo na hipofaringe. Atributos estudados: Frequência respiratória, volume corrente, pressäo expiatória final de CO2, saturaçäo de pulso O2, frequência de pulso, pressäo arterial média, pressäo venosa central, pressäo no balonete da máscara laríngea em ar ambiente (Par) e na faringe (Pfaringe), pressäo de mucosa faríngea (Pmucosa), (pfaringe - Par) estudo histopatológico e de microscopia eletrônica de varredura do segmento faringolaríngeo. Resultados: Em ambos os grupos houve aumento da frequência de pulso, em todos os momentos, e pequena diminuiçäo da pressäo arterial média nos momentos iniciais do estudo. A depressäo respiratória, devido à açäo do pentobarbital sódico, ocorreu em ambos os grupos, com diminuiçäo da frequência respiratória, responsável pelo aumento da pressäo expiatória final de CO2; entretanto, os valores do volume corrente e da saturaçäo de pulso de O2 mantiveram-se estáveis e dentro da normalidade. os valores médios da pressäo no balonete da ML no ar (Par) foram maiores em G2 (240 mmHg) do que em G1 (87 mmHg)...

Efeitos do alopurinol sobre as alteraçöes morfológicas produzidas pela isquemia testicular temporária em ratos / Reperfusion injury with allopurinol after short term testicular ischemia in rats

O objetivo do presente estudo foi avaliar, em ratos, se o alopurinol é capaz de proteger o testículo contra os efeitos da isquemia com duraçäo de uma hora, seguida de reperfusäo. Dezoito ratos adultos, Wistar-EPM1, com peso variando entre 300 e 340g, foram divididos em três grupos: controle (G1), isquemia (G2) e isquemia com alopurinol (G3) com seis animais cada. Após anestesia com pentobarbital sódico intraperitoneal (30mg/Kg), o testículo esquerdo era exteriorizado e mantido imerso em soluçäo salina (0,9 por cento) à temperatura ambiente durante uma hora. Nos grupos G2 e G3 o pedículo era clampeado durante o experimento (1h). No grupo G3 cada animal recebeu 50 mg/Kg de alopurinol V.O. nos dois dias anteriores e duas horas antes da isquemia. Após 60 dias os animais foram anestesiados, sacrificados e os testículos removidos, pesados e preparados para exame histopatológico (HE). As lâminas foram analisadas de acordo com a classificaçäo de Cosentino. Observou-se diminuiçäo significante do peso do testículo esquerdo nos grupos G2 e G3 (p<0,05) e o escore histopatológico mostrou grau importante de sofrimento testicular esquerdo nos grupos G2 e G3 (p<0,05). Concluiu-se que o alopurinol näo foi capaz de proteger o testículo do rato contra os efeitos do fenômeno de isquemia/reperfusäo

Utilización de pericardio bovino tratado con glutaraldehido liofilizado, en la reparación de defectos abdominales en ratas / Use of lyophilized glutaraldehyde treated bovine pericardium to repair abdominal defects in rats

Objetivo. Evaluar la utilidad del pericardio bovino tratado con glutaraldehido (PBYG) al 0.5 por ciento y liofilizado (PBTGL), en la reparación de defectos abdominales en ratas, comparándolo con PBTG preservado al 0.5 por ciento sin liofilizar y con pericardio bovino preservado con solución de Hank liofilizado (PBTHL). Diseño. Estudio experimental, prospectivo y con grupo control. Se empleo prueba de Chi cuadrada. Sede. Departamento de cirugía experimental del Instituto Nacional de Enfermedades Respiratorias, en México, D.F. Material y métodos. Utilizamos 30 ratas Wistar que fueron divididas en tres grupos de estudio, se les disecó y resecó un segmento de la pared abdominal ventral, lo que produjo un defecto de aproximadamente 2 x 1.5 cm que fue reparado con una bioprótesis de pericardio bovino. Grupo I. Reparación de la pared abdominal con pericardio bovino tratado con glutaraldehido al 0.5 por ciento (PBTG) (n=10). Grupo II. Reparación de la pared abdominal con PBTG liofilizado preservado al 0.5 por ciento (PBTGL) (n=10). Grupo III. Reparación del defecto con pericardio bovino preservado en solución de Hank liofilizado (PBTHL) (N=10). Los animales fueron evaluados clínicamente, diario la primera semana postcirugía, y cada tercer día el tiempo restante. Al finalizar el estudio los animales se sometieron a eutanasia con una sobredosis de pentobarbital sódico y se evaluó macroscópica y microscópicamente el estado de la bioprótesis. Resultados. Todos los animales sobrevivieron al procedimiento quirúrgico y al tiempo de estudio, que fue de 8 semanas. En los grupos I y II, macroscópicamente la bioprótesis se adaptó bien a la pared abdominal, no así en el grupo III en donde el material implantado fue rechazado. Microscópicamente, los animales de los grupos I y II, presentaron buena cicatrización con proliferación de fibroblastos y depósitos de colágena sobre y en la periferia de la prótesis, así como vasos sanguíneos de neoformación. En el grupo III se observó necrosis tanto en el borde quirúrgico como en la prótesis, con una reacción inflamatoria severa y numerosas células gigantes a cuerpo extraño. conclusión. El liofilizar el PBTG permite un mejor almacenamiento y transporte del mismo, además de que al rehidratarlo mantiene su resistencia, fácil manejo quirúrgico, no se rechaza y se integra bien al tejido muscular

Changes in pentobarbital induced sleeping-time in mice infected with Schistosoma mansoni and immunosuppressed

Para avaliar a intensidade da reacao granulomatosa hepatica induzida por ovos de S. mansoni tem relacao com o metabolismo de drogas, camundongos foram infectados 40 cercarias e testados quanto ao tempo de anestesia pelo pentobarbital sodico. Para diminuir a resposta inflamatoria usou-se irradiacao com 400 rad ou azatioprina na dose de 20mg/kg, 3 vezes por semana, por 4 semanas, respectivamente no ou a partir de 33º dia pos-infeccao...

Suppression of pilocarpine-induced status epilepticus and the late development of epilepsy in rats.

Status epilepticus (SE) has been related to subsequent development of epilepsy. The present work was aimed at elucidating the relationship between the duration of pilocarpine- (PILO)-induced SE and the subsequent development of epilepsy in rats. The latency for the appearance of the first spontaneous seizure, the frequency of spontaneous seizures, the cell density in the hippocampal formation and the density of supragranular neo-Timm staining were monitored. At 30 min, 1, 2 and 6 h after the beginning of SE, animals were treated with diazepam plus pentobarbital. In non-treated rats, SE remitted spontaneously. Animals exhibiting 30 min of PILO-induced SE did not develop spontaneous seizures. Hippocampal cell counts and the density of neo-Timm staining in these animals were similar to those observed in control rats. In the other groups longer SE durations were related to: shorter latency for the appearance of the first spontaneous seizure, increased number of the spontaneous recurrent seizures, severe cell loss in the hippocampal formation, or increased supragranular neo-Timm staining. These data suggest that more than 30 min of SE is required to produce hippocampal damage with subsequent synaptic reorganization of the mossy fibre pathway that could account for SRSs observed in the PILO model of epilepsy.

Pentobarbital oral para medicaçäo pré-anestésica em pacientes pediátricos ambulatoriais / Oral pentobarbital for premedication of pediatric outpatients

A eficácia do pentobarbital (2,5 mg.Kg-1) por via oral (VO) foi estudada na medicaçäo pré-anestésica (MPA) em crianças comparativamente à glicose a 5 por cento utilizada como placebo. As características comportamentais à separaçäo dos pais e à induçäo da anestesia bem como o tempo de permanênciana Sala de Recuperaçäo Pós-Anestésica (SRPA) foram os objetivos do estudo. Os resultados demonstram que o pentobarbital na dose de 2,5 mg.Kg-1 VO é eficaz como MPA, mas prolonga o tempo de permanência na SRPA sem afetar tempo para a alta hospitalar.

Status epiléptico en el embarazo: reporte de caso y revisión de la literatura / Status epilepticus in the pregnancy: report of case and review of the literature

Se informa del caso de una paciente de 27 años, III gestas, II para, quien fue ingresada en la Maternidad Concepción Palacios (MCP), de Caracas, en la semana 21 de su tercer embarazo, por presentar un status convulsivo que se había iniciado 14 horas antes. La paciente fue tratada con diazepán y difenilhidantoina, sin poder controlar las crisis, por lo cual se requirió administrar pentobarbital sódico. Dos meses después fue egresada, en buenas condiciones y con buena evolución del embarazo pero no pudimos conocer el desenlace final, pues no regresó a controles. Se revisa la literatura nacional y mundial sobre el tema