Assuntos
Oxigenoterapia Hiperbárica/efeitos adversos , Hipóxia/terapia , Meperidina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Pentobarbital/uso terapêutico , Ressuscitação , Animais , Animais Recém-Nascidos , Terapia Combinada , Hipóxia/mortalidade , Coelhos , Resultado do TratamentoRESUMO
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.
Assuntos
Anti-Hipertensivos/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Hipertensão Intracraniana/tratamento farmacológico , Pressão Intracraniana/efeitos dos fármacos , Adolescente , Anti-Hipertensivos/farmacologia , Lesões Encefálicas Traumáticas/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Fentanila/uso terapêutico , Escala de Coma de Glasgow , Humanos , Hipertensão Intracraniana/fisiopatologia , Masculino , Manitol/uso terapêutico , Pentobarbital/uso terapêutico , Estudos Prospectivos , Solução Salina Hipertônica/uso terapêutico , Falha de TratamentoRESUMO
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.
Assuntos
Masculino , Feminino , Humanos , Animais , Diazepam/uso terapêutico , Pentobarbital/uso terapêutico , Venenos de Escorpião/análise , Venenos de Escorpião/classificação , Venenos de Escorpião/uso terapêutico , Epilepsia/imunologia , Epilepsia/prevenção & controleRESUMO
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.
Assuntos
Eletrólitos/metabolismo , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Pentobarbital/farmacologia , Convulsões/metabolismo , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Cálcio/metabolismo , Carbamazepina/farmacologia , Carbamazepina/uso terapêutico , Modelos Animais de Doenças , Interações Medicamentosas , Hipnóticos e Sedativos/uso terapêutico , Masculino , Pentobarbital/uso terapêutico , Pentilenotetrazol , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Sódio/metabolismo , Estatísticas não ParamétricasRESUMO
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.
Assuntos
Ansiolíticos/uso terapêutico , Citrus , Hipnóticos e Sedativos/uso terapêutico , Óleos Voláteis/uso terapêutico , Animais , Ansiolíticos/isolamento & purificação , Ansiolíticos/farmacologia , Frutas , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Pentobarbital/farmacologia , Pentobarbital/uso terapêutico , Fitoterapia/métodos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Convulsões/tratamento farmacológico , Sono/efeitos dos fármacos , Sono/fisiologiaRESUMO
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
Assuntos
Animais , Masculino , Ratos , Anestesia , Anestésicos Dissociativos/uso terapêutico , Ketamina/uso terapêutico , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Adjuvantes Anestésicos/uso terapêutico , Elasticidade , Pulmão/patologia , Pulmão/fisiologia , Pulmão/fisiopatologia , Pentobarbital/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Sistema Respiratório/patologia , Sistema Respiratório/fisiopatologia , Tórax/patologia , Tórax/fisiologia , Tórax/fisiopatologiaRESUMO
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.
Assuntos
Anestesia , Anestésicos Dissociativos/farmacologia , Ketamina/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Adjuvantes Anestésicos/uso terapêutico , Animais , Elasticidade , Pulmão/patologia , Pulmão/fisiologia , Masculino , Pentobarbital/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Wistar , Mecânica Respiratória/fisiologia , Sistema Respiratório/patologia , Sistema Respiratório/fisiopatologia , Tórax/patologia , Tórax/fisiologiaRESUMO
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
Assuntos
Humanos , Traumatismos Craniocerebrais/terapia , Corticosteroides/efeitos adversos , Circulação Cerebrovascular , Craniotomia , Tratamento de Emergência , Necessidade Energética , Fentanila/uso terapêutico , Hipotensão/terapia , Hipóxia/terapia , Hipertensão Intracraniana , Pressão Intracraniana , Manitol/administração & dosagem , Manitol/efeitos adversos , Nimodipina/administração & dosagem , Nutrição Enteral/métodos , Nutrição Parenteral/métodos , Pentobarbital/uso terapêuticoRESUMO
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
Assuntos
Humanos , Feminino , Recém-Nascido , Adulto , Hemorragia Cerebral/prevenção & controle , Ventrículos Cerebrais , Método Duplo-Cego , Idade Gestacional , Recém-Nascido Prematuro , Pentobarbital/administração & dosagem , Pentobarbital/uso terapêutico , Gravidez , Cuidado Pré-Natal , Estudos Prospectivos , MéxicoRESUMO
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)...