Prover analgesia efetiva nas dores nociceptiva ou neuropática permanece um desafio, devido à limitada eficácia dos agentes disponíveis, ou então haver risco de efeitos adversos associados ao uso de determinadas substâncias. Novos conhecimentos fisiológicos e farmacológicos conferem à anestesia e analgesia subaracnóide um lugar de destaque na prática anestésica moderna. Este estudo objetivou investigar os efeitos farmacológicos da administração subaracnóide de opióides hiperbáricos e bupivacaína hipobárica na espécie ovina. Foram utilizados 12 ovinos adultos saudáveis, divididos em três grupos: GM (grupo morfina) a qual foi administrado 0,01 mg.kg -1 de morfina hiperbárica, GF (grupo fentanil) que recebeu 0,5 μg.kg -1 de fentanil hiperbárico e GB (grupo bupivacaína) recebendo bupivacaína a 0,1% hipobárica, todas pela via subaracnóide por punção única no espaço lombo-sacro. Para conferir uma característica hiperbárica à soluções, foi utilizada dextrose a 10%, e para característica hipobárica, agua destilada estérea, sendo tais densidades observadas através de um refratômetro óptico, o mesmo realizado com o líquido céfalo raquidiano. Avaliaram-se efeitos cardiorrespiratórios, comportamentais e o limiar doloroso através de um estímulo térmico através de uma lâmpada de 650 W, sobre os dermátomos das regiões glútea e torácica. Os resultados mostraram que o GM apresentou uma analgesia mais prolongada e intensa em relação aos outros dois grupos com o tempo médio de 315 + 30 minutos, contra 60 + 0 para o GF e 90 + 54,7 para o GB. Tal analgesia foi segmentar na região glútea, não sendo observado na região torácica em nenhum dos três grupos, no entanto, sedação foi observada no grupo GF e bloqueio motor no GB. No GM não houve alterações tanto dos parâmetros cardiorrespiratórios, como sinais de excitação ou sedação do sistema nervoso central, indicando concomitante a analgesia segmentar a não migração cranial da morfina hiperbárica no espaço subaracnóide. A característica hiperbárica da morfina com a dextrose a 10% é eficaz para a analgesia segmentar na espécie ovina. / Providing effective analgesia in nociceptive or neuropathic pain remains a challenge due to limited efficacy of available agents, or no risk of adverse effects associated with the use of certain substances. Through new physiological and pharmacological knowledge, give the subarachnoid anesthesia and analgesia, a place in modern anesthetic practice. This present study aimed to investigate the pharmacological effects of subarachnoid administration of hyperbaric and hypobaric opioids in sheep. A total of 12 healthy adult sheep were divided into three groups: MG (morphine group) which was given 0.01 mg.kg -1 morphine hyperbaric FG (fentanyl group) received 0.5 fentanyl μg.kg -1 hyperbaric and BG (bupivacaine group) received 0.1% hypobaric bupivacaine, all through a single puncture in subarachnoid space lumbosacral. To give a characteristic of hyperbaric solutions was used 10% dextrose, and characteristic hypobaric steric distilled water, these densities being observed through an optical refractometer, carried out in the same cerebrospinal fluid. We evaluated cardiorespiratory effects, and behavioral pain threshold through a thermal stimulus using a 650 W lamp, thoracic and gluteal regions. The results showed that MG showed an intense and more prolonged analgesia for the other two groups with the timely average of 315 ± 30 minutes from 60 ± 0 to FG and 90 ± 54.7 to BG. This analgesia is in the buttocks segment, was not observed in the thoracic region, any of the groups, however, sedation was observed in group FG and motor blockade in BG. MG no changes in both the cardiorespiratory parameters, as signs of arousal or sedation of the central nervous system, indicating concomitant segmental analgesia not cranial migration of morphine in hyperbaric subarachnoid space. The characteristic hyperbaric morphine with 10% dextrose is effective for analgesia segment in sheep.

Prover analgesia efetiva nas dores nociceptiva ou neuropática permanece um desafio, devido à limitada eficácia dos agentes disponíveis, ou então haver risco de efeitos adversos associados ao uso de determinadas substâncias. Novos conhecimentos fisiológicos e farmacológicos conferem à anestesia e analgesia subaracnóide um lugar de destaque na prática anestésica moderna. Este estudo objetivou investigar os efeitos farmacológicos da administração subaracnóide de opióides hiperbáricos e bupivacaína hipobárica na espécie ovina. Foram utilizados 12 ovinos adultos saudáveis, divididos em três grupos: GM (grupo morfina) a qual foi administrado 0,01 mg.kg -1 de morfina hiperbárica, GF (grupo fentanil) que recebeu 0,5 μg.kg -1 de fentanil hiperbárico e GB (grupo bupivacaína) recebendo bupivacaína a 0,1% hipobárica, todas pela via subaracnóide por punção única no espaço lombo-sacro. Para conferir uma característica hiperbárica à soluções, foi utilizada dextrose a 10%, e para característica hipobárica, agua destilada estérea, sendo tais densidades observadas através de um refratômetro óptico, o mesmo realizado com o líquido céfalo raquidiano. Avaliaram-se efeitos cardiorrespiratórios, comportamentais e o limiar doloroso através de um estímulo térmico através de uma lâmpada de 650 W, sobre os dermátomos das regiões glútea e torácica. Os resultados mostraram que o GM apresentou uma analgesia mais prolongada e intensa em relação aos outros dois grupos com o tempo médio de 315 + 30 minutos, contra 60 + 0 para o GF e 90 + 54,7 para o GB. Tal analgesia foi segmentar na região glútea, não sendo observado na região torácica em nenhum dos três grupos, no entanto, sedação foi observada no grupo GF e bloqueio motor no GB. No GM não houve alterações tanto dos parâmetros cardiorrespiratórios, como sinais de excitação ou sedação do sistema nervoso central, indicando concomitante a analgesia segmentar a não migração cranial da morfina hiperbárica no espaço subaracnóide. A característica hiperbárica da morfina com a dextrose a 10% é eficaz para a analgesia segmentar na espécie ovina. / Providing effective analgesia in nociceptive or neuropathic pain remains a challenge due to limited efficacy of available agents, or no risk of adverse effects associated with the use of certain substances. Through new physiological and pharmacological knowledge, give the subarachnoid anesthesia and analgesia, a place in modern anesthetic practice. This present study aimed to investigate the pharmacological effects of subarachnoid administration of hyperbaric and hypobaric opioids in sheep. A total of 12 healthy adult sheep were divided into three groups: MG (morphine group) which was given 0.01 mg.kg -1 morphine hyperbaric FG (fentanyl group) received 0.5 fentanyl μg.kg -1 hyperbaric and BG (bupivacaine group) received 0.1% hypobaric bupivacaine, all through a single puncture in subarachnoid space lumbosacral. To give a characteristic of hyperbaric solutions was used 10% dextrose, and characteristic hypobaric steric distilled water, these densities being observed through an optical refractometer, carried out in the same cerebrospinal fluid. We evaluated cardiorespiratory effects, and behavioral pain threshold through a thermal stimulus using a 650 W lamp, thoracic and gluteal regions. The results showed that MG showed an intense and more prolonged analgesia for the other two groups with the timely average of 315 ± 30 minutes from 60 ± 0 to FG and 90 ± 54.7 to BG. This analgesia is in the buttocks segment, was not observed in the thoracic region, any of the groups, however, sedation was observed in group FG and motor blockade in BG. MG no changes in both the cardiorespiratory parameters, as signs of arousal or sedation of the central nervous system, indicating concomitant segmental analgesia not cranial migration of morphine in hyperbaric subarachnoid space. The characteristic hyperbaric morphine with 10% dextrose is effective for analgesia segment in sheep.

Prover analgesia efetiva nas dores nociceptiva ou neuropática permanece um desafio, devido à limitada eficácia dos agentes disponíveis, ou então haver risco de efeitos adversos associados ao uso de determinadas substâncias. Novos conhecimentos fisiológicos e farmacológicos conferem à anestesia e analgesia subaracnóide um lugar de destaque na prática anestésica moderna. Este estudo objetivou investigar os efeitos farmacológicos da administração subaracnóide de opióides hiperbáricos e bupivacaína hipobárica na espécie ovina. Foram utilizados 12 ovinos adultos saudáveis, divididos em três grupos: GM (grupo morfina) a qual foi administrado 0,01 mg.kg -1 de morfina hiperbárica, GF (grupo fentanil) que recebeu 0,5 μg.kg -1 de fentanil hiperbárico e GB (grupo bupivacaína) recebendo bupivacaína a 0,1% hipobárica, todas pela via subaracnóide por punção única no espaço lombo-sacro. Para conferir uma característica hiperbárica à soluções, foi utilizada dextrose a 10%, e para característica hipobárica, agua destilada estérea, sendo tais densidades observadas através de um refratômetro óptico, o mesmo realizado com o líquido céfalo raquidiano. Avaliaram-se efeitos cardiorrespiratórios, comportamentais e o limiar doloroso através de um estímulo térmico através de uma lâmpada de 650 W, sobre os dermátomos das regiões glútea e torácica. Os resultados mostraram que o GM apresentou uma analgesia mais prolongada e intensa em relação aos outros dois grupos com o tempo médio de 315 + 30 minutos, contra 60 + 0 para o GF e 90 + 54,7 para o GB. Tal analgesia foi segmentar na região glútea, não sendo observado na região torácica em nenhum dos três grupos, no entanto, sedação foi observada no grupo GF e bloqueio motor no GB. No GM não houve alterações tanto dos parâmetros cardiorrespiratórios, como sinais de excitação ou sedação do sistema nervoso central, indicando concomitante a analgesia segmentar a não migração cranial da morfina hiperbárica no espaço subaracnóide. A característica hiperbárica da morfina com a dextrose a 10% é eficaz para a analgesia segmentar na espécie ovina. / Providing effective analgesia in nociceptive or neuropathic pain remains a challenge due to limited efficacy of available agents, or no risk of adverse effects associated with the use of certain substances. Through new physiological and pharmacological knowledge, give the subarachnoid anesthesia and analgesia, a place in modern anesthetic practice. This present study aimed to investigate the pharmacological effects of subarachnoid administration of hyperbaric and hypobaric opioids in sheep. A total of 12 healthy adult sheep were divided into three groups: MG (morphine group) which was given 0.01 mg.kg -1 morphine hyperbaric FG (fentanyl group) received 0.5 fentanyl μg.kg -1 hyperbaric and BG (bupivacaine group) received 0.1% hypobaric bupivacaine, all through a single puncture in subarachnoid space lumbosacral. To give a characteristic of hyperbaric solutions was used 10% dextrose, and characteristic hypobaric steric distilled water, these densities being observed through an optical refractometer, carried out in the same cerebrospinal fluid. We evaluated cardiorespiratory effects, and behavioral pain threshold through a thermal stimulus using a 650 W lamp, thoracic and gluteal regions. The results showed that MG showed an intense and more prolonged analgesia for the other two groups with the timely average of 315 ± 30 minutes from 60 ± 0 to FG and 90 ± 54.7 to BG. This analgesia is in the buttocks segment, was not observed in the thoracic region, any of the groups, however, sedation was observed in group FG and motor blockade in BG. MG no changes in both the cardiorespiratory parameters, as signs of arousal or sedation of the central nervous system, indicating concomitant segmental analgesia not cranial migration of morphine in hyperbaric subarachnoid space. The characteristic hyperbaric morphine with 10% dextrose is effective for analgesia segment in sheep.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-09-15T18:22:21Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO.pdf: 6914963 bytes, checksum: b59dc4afc22cc256f6af81abdcd285cc (MD5) / Made available in DSpace on 2016-09-15T18:22:21Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO.pdf: 6914963 bytes, checksum: b59dc4afc22cc256f6af81abdcd285cc (MD5) Previous issue date: 2016-02-24 / Introdução: Os aneurismas intracranianos trazem consequências importantes para o paciente acometido. A hemorragia subaracnóidea (HSA) possui uma forte correlação com aneurismas saculares e devido a sua gravidade e alta ocorrência de sequelas, o seu estudo merece importância. Uma alteração sensorial que pode esta relacionada à HSA é o déficit olfatório. Dentre os métodos de avaliação do olfato descritos, os quantitativos são ferramentas que podem ser utilizados a fim de garantir resultados mais fidedignos considerando o quadro clínico desses pacientes. Objetivos: Caracterizar o olfato de pacientes pré e pós tratamento cirúrgico para hemorragia subaracnóidea aneurismática. Método: Esta dissertação está composta por dois artigos. O primeiro constou de um artigo de revisão com título Métodos de avaliação do olfato em pacientes vítimas de hemorragia subaracnóidea: revisão sistemática. O segundo é um artigo original intitulado Avaliação do olfato na hemorragia subaracnóidea aneurismática antes e após o tratamento cirúrgico, neste foram estudados 15 adultos com hemorragia subaracnóidea aneurismática, atendidos no Hospital da restauração de Pernambuco, avaliados em três momentos distintos: Após a hemorragia, com uma semana de pós-operatório e com três meses de pós-operatório. A pesquisa foi iniciada após aprovação pelo Comitê de Ética em Pesquisa do hospital. Após a aplicação do Termo de Consentimento Livre e Esclarecido foi realizada a revisão do prontuário, entrevista com o participante e avaliação do olfato por meio de um teste de soluções aquosas, adaptado de outros estudos, construído pela farmácia escola da UFPE. Resultados: O primeiro artigo mostrou heterogeneidade nos métodos utilizados para avaliação do olfato na hemorragia subaracnóidea, como também no momento selecionado para aplicação das avaliações, com evidencias de déficit olfatório nesta população. Nos resultados provenientes do estudo original desta dissertação foi observado maior número de classificações olfatórias normais, além disso, não foi encontrada correlação significativa entre a pontuação olfatória com as seguintes variáveis (Idade, Intervalo em dias entre a hemorragia subaracnóidea e a avaliação olfatória, escolaridade e topografia do aneurisma). Não houve mudança significativa na pontuação olfatória após a cirurgia. Houve diferença estatística significativa na comparação entre a pontuação olfatória com uma semana de pós-operatório e com três meses de pós-operatório. Considerações finais: Os resultados deste estudo mostram a ocorrência de alteração olfatória após a hemorragia subaracnóidea aneurismática, assim como piora na classificação do olfato após a cirurgia. Foi observada melhora no olfato após três meses de pós-operatório, com significância estatística. Sugere-se a continuação de estudos com o tema, como também que façam investigação da percepção subjetiva do olfato visando o esclarecimento dos prejuízos que a alteração olfatória causa na vida dessa população. / Introduction: Intracranial aneurysms bring important consequences for the affected patient. The subarachnoid hemorrhage (HSA) has a strong correlation with saccular aneurysms and due to its gravity and high occurrence of sequels, its study deserves importance. A sensory change can this ASH-related is the olfactory deficit. Among the methods of valuation of smell described, are quantitative tools that can be used to ensure more reliable results considering the clinical picture of these patients.Objectives: Characterize the smell of patients before and after surgical treatment for aneurysmal subarachnoid hemorrhage. Method: This dissertation is composed of two articles. The first consisted of a review article with title Methods of evaluation of smell in victims of subarachnoid hemorrhage patients: a systematic review. The second is an original article entitled Olfactory evaluation in aneurysmal subarachnoid hemorrhage before and after surgery, this 15 were studied adults with aneurysmal subarachnoid hemorrhage, met at the Hospital da Restauração de Pernambuco, evaluated in three different moments: After the bleeding, a week after surgery and three months postoperatively. The search was started after approval by the Research Ethics Committee of the Hospital. After the application of informed consent was held to review the medical records, interview with the participant and evaluation of smell through a test of aqueous solutions, adapted from other studies, built by the Pharmacy School, Federal University of Pernambuco. Results: The first article showed heterogeneity of the methods used to evaluate the smell in aneurysmal subarachnoid hemorrhage and in the methods selected for application of evaluations, with evidence of olfactory deficits in this population. The results from the original study of this dissertation it was observed as many olfactory normal ratings, moreover, was not found significant correlation between olfactory score with the following variables (age, interval in days between the subarachnoid hemorrhage and the olfactory evaluation, education and topography of the aneurysm). There was no significant change in scoring olfactory after surgery. There was a statistically significant difference in the comparison between the olfactory score with a week after surgery and three months postoperatively. Final considerations: The results of this study show the occurrence of olfactory disfunction after aneurysmal subarachnoid hemorrhage, as well as worsens the classification of smell after surgery. Improvement was observed in the nose after three months postoperatively, with statistical significance. It is suggested a continuation of studies with the theme, but also to make the subjective perception of smell to identify the problems that the disfunction olfactory cause in this population´s life.

Introdução: O acesso pterional é uma das craniotomias mais utilizadas. Entretanto, apresenta algumas desvantagens, como a dissecação ampla do músculo temporal, que pode causar atrofia e deformidade do contorno facial. A craniotomia minipterional descrita em 2007 propiciou exposição anatômica semelhante a da craniotomia pterional clássica. Objetivos: Comparar os resultados clínicos, funcionais e estéticos dos dois acessos cirúrgicos destinados ao tratamento de aneurismas da circulação anterior. Métodos: Cinquenta e oito doentes, com aneurismas rotos (40) e não rotos (18) foram admitidos no estudo. No grupo A, 28 indivíduos foram submetidos à craniotomia minipterional. No grupo B, 30 doentes foram operados com a craniotomia pterional clássica. Doentes com hematomas intracranianos, aneurismas do segmento oftálmico e aneurismas gigantes foram excluídos. Os resultados estéticos foram analisados por meio de dois métodos. No primeiro, uma autoavaliação utilizava uma régua escalonada de 0 a 100, na qual o zero representou o melhor resultado e 100 o pior resultado na percepção do próprio doente. Fotografias dos doentes foram mostradas a dois observadores independentes. Os resultados foram classificados como ótimo, bom, regular e mau (de acordo com uma escala pré-determinada). A gradação da atrofia foi mensurada por meio de três métodos, utilizando a tomografia computadorizada de crânio. No primeiro, observou-se a percentagem de redução do complexo músculo temporal, tecido subcutâneo e pele. No segundo método, a percentagem de redução da espessura do músculo temporal foi analisada isoladamente. O terceiro método foi a mensuração da volumetria do músculo temporal, tecido subcutâneo e pele calculados a partir da margem superior do arco zigomático até a linha temporal superior utilizando-se o software OsiriX (Pixmeo Sarl Geneva/ Suíça OsiriX). Para os resultados clínicos e funcionais, foi utilizada a Escala de Rankin modificada. Outras variáveis, como paralisia do ramo frontal do nervo facial, hemorragia pós-operatória, fistula liquórica, hidrocefalia e mortalidade, também foram analisadas. Resultados: Em ambos os grupos, os dados demográficos e as características pré-operatórias foram similares. A satisfação com o resultado estético foi observada em 79% (19) no grupo A e 52% (13) no grupo B (p=0,07). O valor médio da régua foi 27 no grupo A e 45,8 no grupo B (p=0,03). Quando somente doentes classificados como Rankin modificado 0 ou 1 foram analisados, o valor médio da régua foi de 25,2 no grupo A e 39,4 no grupo B (p=0,11). Dois avaliadores independentes analisaram as fotografias dos doentes e o coeficiente de correlação kappa para os resultados estéticos foi de 0,73. De acordo com os mesmos ótimo e bom, foram observados em 87% (21) no grupo minipterional e 48% (12) no grupo pterional. A percentagem de redução do músculo temporal, subcutâneo e pele (método 1) foi de 14,9% no grupo A e 24,3% no grupo B (p=0,01). Quando somente o músculo temporal foi analisado (método 2), a percentagem de redução foi de 12,7% no grupo A e 22% no grupo B (p=0,005). A redução volumétrica das estruturas (método 3) foi de 14,8% no grupo A e 24,5% no grupo B (p=0,012). Na avaliação clínica no 6? mês, os valores da Escala de Rankin modificada foram similares (p=0,99). O óbito ocorreu em 4 doentes no grupo A e 5 doentes no grupo B (p=1,0). Conclusão: Os resultados clínicos demonstraram que a craniotomia minipterional é um procedimento seguro, com prognóstico similar ao da técnica convencional. Os resultados cosméticos foram melhores com menor deformidade no contorno facial, uma vez que a percentagem de redução da espessura, do volume do músculo temporal, do tecido subcutâneo e da pele foi menor com a técnica proposta. A craniotomia minipterional foi a melhor alternativa em relação à craniotomia pterional clássica para tratar aneurismas rotos e não rotos da circulação anterior / Introduction: The pterional approach is one of the most commonly used craniotomy. However it has disadvantages, such as complete dissection of the temporalis muscle. This may lead to muscular atrophy and facial deformity. The minipterional craniotomy was described in 2007 and the anatomic exposure provided by the pterional and minipterional approaches were similar in the total area of exposure and angular view. Objectives: This prospective randomized study was designed to compare the clinical, functional and aesthetic results of two surgical techniques for microsurgical clipping of anterior circulation aneurysms. Methods: Overall, 58 eligible patients admitted with ruptured and unruptured anterior circulation aneurysms were enrolled in the study. In group A, 28 patients were operated with the minipterional technique. In Group B 30 patients were operated according to the classical pterional craniotomy. Patients with intracranial haematomas, ophthalmic aneurysms and giant aneurysms were excluded. The aesthetic results were analyzed with 2 methods. In the first, the patients were showed to a rule, with a scale from 0 to 100, in which 0 mean the best result and 100 the worst result. Photos were taken and showed to two independent observers, the results were classified as excellent, good, regular or poor, according to a pre-determined scale. The degree of atrophy was measured with three methods. In the first one, the authors observed the percentage of thick reduction in the temporal muscle, subcutaneous tissue and skin. In the second method the percentage of thick reduction of the isolated temporal muscle was observed and the third the volumetric analysis of the temporal muscle, subcutaneous tissue and skin was calculated from the superior edge of zygomatic arch to superior temporal line using the OsiriX software (OsiriX - Pixmeo Sarl Geneva/Suíça). The functional results were compared using the Modified Rankin Score. Others variables such frontal facial palsy, post-operative hemorrhage, cerebrospinal fistulas, hydrocephalus and mortality were also analyzed. Results: In both groups the demographic and pre-operative characteristics were similar. The satisfaction with aesthetic results were observed in 79% (19) in group A and 52% (13) in group B (p=0,07). The mean value observed in the rule was 27 in group A and 45,8 in group B (p=0,03). When patients classified as Rankin Modified Score of 0 or 1 only were included the mean value observed in the rule was 25,2 in group A and 39,4 in group B (p=0,11). Two independent observers analyzed the patients photos and the kappa coefficient correlation for the aesthetic results was 0,73. According to them excellent and good results were observed in 87% (21) in minipterional group and 48% (12) in the pterional group. The degree of atrophy of temporal muscle, subcutaneous tissue and skin (method 1) was14,9% in group A and 24,3% in group B (p=0,01). The measurement of temporal muscle (method 2) revealed that the degree of atrophy was 12,7% in group A and 22% in group B (p=0,005). The volumetric reduction of the structures (method 3) was 14,8% in group A and 24,5% in group B (p=0,012). Rankin Modified Score was similar in both groups in the 6-month evaluation (p=0,99). Mortality occurred in 4 patients in group A and 5 patients in group B (p=1,0). Conclusion: These clinical results indicate that the minipterional is a safe procedure. We can estimate the better cosmetic results with less facial contour deformity since the percentage of thick and volumetric reduction in temporal muscle, subcutaneous tissue and skin were demonstrated. It can be an excellent and better alternative to the classical pterional approach

Orientador: Donizeti Cesar Honorato / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T22:21:39Z (GMT). No. of bitstreams: 1 Kaleff_PauloRoland_D.pdf: 1126011 bytes, checksum: 23cb0c05a54790e4896ebd16d8754941 (MD5) Previous issue date: 2012 / Resumo: A angiotomografia cerebral 3D (ATC) passou a ser uma alternativa à angiografia por subtração digital (ASD) para a detecção dos aneurismas intracranianos. As recomendações atuais para a hemorragia subaracnóidea aguda (HSA) secundária à ruptura de aneurismas intracranianos incluem o tratamento definitivo precoce. O objetivo primário deste estudo foi o de avaliar a contribuição da ATC para a diminuição do tempo entre o diagnóstico da HSA e o diagnóstico do aneurisma, bem como para a diminuição do tempo entre a admissão do paciente e a exclusão do aneurisma, quando comparada com a ASD. Como objetivo secundário buscou-se comparar a sensibilidade de ambos os métodos diagnósticos, comparar os resultados clínicos de dois grupos de pacientes diagnosticados pala ATC e/ou pela ASD e avaliar a contribuição da ATC na abordagem cirúrgica aos hematomas secundários à ruptura de aneurismas intracranianos. Uma análise retrospectiva foi conduzida cobrindo 100 pacientes admitidos com HSA e diagnosticados para aneurisma via ATC (n=60) ou via ASD (n=40). Os dados coletados foram divididos de acordo com o método diagnóstico utilizado inicialmente para a detecção do aneurisma. Os tempos transcorridos entre o diagnostico da HSA e o diagnóstico do aneurisma foi consistentemente inferior para os pacientes submetidos à ATC (p<0.000005). Em relação ao tempo transcorrido entre a admissão e o tratamento definitivo, 70% das ocorrências para pacientes submetidos à ATC ficaram abaixo de 72 horas enquanto 60% das ocorrências para pacientes submetidos à ASD excederam 72 horas (p<0.003). A sensibilidade da ATC para aneurismas rotos foi de 0, 967 e para todos os aneurismas de 0, 931. A maioria dos casos submetidos à ATC antes da drenagem do hematoma teve o aneurisma tratado no mesmo procedimento cirúrgico. A ATC contribuiu para a redução do tempo entre o diagnóstico da HSA e o diagnóstico do aneurisma, bem como para a redução do tempo entre a admissão e o tratamento definitivo do aneurisma. A sensibilidade dos métodos foi equivalente, especialmente para os aneurismas rotos, em exames tecnicamente satisfatórios. Nos casos de hematomas secundários à ruptura de aneurismas intracranianos, a realização da ATC previamente à abordagem cirúrgica contribuiu para o tratamento definitivo do aneurisma no mesmo procedimento cirúrgico da drenagem do hematoma / Abstract: Due to its technical advancements, 3D cerebral computed tomography angiography (CTA) is increasingly being considered as an alternative to digital subtraction angiography (DSA) in the detection of intracranial aneurysms. Actual guidelines for acute subarachnoid hemorrhage (aSAH) recommend early definitive treatment. The primary goal of this study was to evaluate the contribution of CTA in shortening of time span between the diagnosis of the aSAH and the diagnosis of the aneurysm, as well as the shortening of time span between admission and definitive aneurysm treatment, when compared to DSA. As secondary goals we aimed at comparing the sensitivity of both methods, at comparing the clinical results between two studied patient groups diagnosed by CTA and/or by DSA and at evaluating the contribution of CTA to the surgical approach to intracranial hematomas secondary to aneurysm rupture. A retrospective analysis was performed covering 100 patients admitted with aSAH and diagnosed with intracranial aneurysms either by CTA (n=60) or by DSA (n=40). The data collected for both groups were separated according to the method used for the initial diagnosis of the aneurysm. The time spans between the diagnosis of the aSAH and the diagnosis of the aneurism were consistently smaller for CTA patients than for DSA patients (p<0.000005). Regarding the time spans between the admission and the final treatment, 70% of the outcomes for CTA patients remained below 72 hours and 60% of the outcomes for the DSA group exceeded 72 hours (p<0.003). The sensitivity for ruptured aneurysms was 0,967 and for all aneurysms 0,931. In the majority of cases where a CTA was performed previously to the hematoma evacuation the aneurysm could be treated in the same surgical procedure. CTA contributed to the shortening of the time elapsed between the diagnosis of the aSAH and the diagnosis of the aneurysm, as well as to the shortening of the time elapsed between admission and definitive treatment. The sensitivity of the methods was equivalent, especially for ruptured aneurysms, in technically satisfactory CTA. The use of CTA did not have a negative impact in the clinical outcome or the treatment. CTA performed previously to hematoma evacuation contributed to the definitive treatment of the aneurism in the same surgical approach / Doutorado / Neurologia / Doutor em Ciências Médicas

The rupture of an aneurysm in subarachnoid hemorrhage (SAH) is a dramatic event causing a severe impact on the brain and a transient or permanent ischemic condition. Several types of responses to meet the challenges of SAH have been found in the acute phase, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, elevated levels of brain natriuretic peptide (BNP), and disturbances in cerebral and systemic metabolism. Cerebral metabolism and the endocrine stress response in the ultra-early phase was investigated in a novel porcine model of SAH in which autologous blood was injected to the anterior skull base. Early activation of the HPA axis was found with rapid elevation of adrenocorticotrophic hormone, cortisol and aldosterone. The peak values of these hormones were early and may be impossible to catch in patients. There were indications of a sympathetic nervous response with excretion of catecholamines in urine as well as plasma chromogranin-A elevation. Cerebral microdialysis suggested immediate substrate failure followed by hypermetabolism of glucose. The animal model seems suited for further studies of aneurysmal SAH. NT-proBNP was investigated in 156 patients with SAH, there was a dynamic course with increasing levels during the first 4 days of the disease. Factors predicting high NT-proBNP load included female sex, high age, high Troponin-I at admission, angiographic finding of an aneurysm and worse clinical condition at admission. High levels of NT-proBNP were correlated to factors indicating a more severe disease, suggesting the initial injury in aneurysmal SAH is an important factor in predicting high NT-proBNP during the acute stage of the disease. Measurements with indirect calorimetry were performed daily during the first week after SAH on 32 patients with SAH. There was a dynamic course with increasing energy expenditure (EE) the first week after SAH. Comparisons with three predictive equations indicated that measured EE generally is higher than predicted, but considerable variation exists within and between patients, indicating that prediction of EE in SAH is difficult. Altogether, the studies demonstrate a complicated response in acute SAH that needs to be further studied to increase possibility of good outcome in SAH patients.

Background: Subarachnoid haemorrhage (SAH) is a severe stroke that in 85% of all cases is caused by the rupture of a cerebral aneurysm. The median age at onset is 50-55 years and the overall mortality is approximately 45%.Sufficient cortisol levels are important for survival. After SAH hypothalamic/pituitary blood flow may be hampered this could result in inadequate secretion of cortisol. SAH is also associated with a substantial inflammatory response. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and increased ADMA levels may be involved in inflammation and endothelial dysfunction. Continuous electroencephalogram (EEG) monitoring can be used to detect non-convulsive seizures, leading to ischemic insults in sedated SAH patients. Elevated ADMA levels are risk factors for vascular diseases. Vascular disease has been linked to stress, inflammation and endothelial dysfunction. SAH possesses all those clinical features and theoretically SAH could thus induce vascular disease. Aims: 1. Assess cortisol levels after SAH, and evaluate associations between cortisol and clinical parameters. 2. Assess ADMA levels and arginine/ADMA ratios after SAH and evaluate associations between ADMA levels and arginine/ADMA ratios with severity of disease, co-morbidities, sex, age and clinical parameters. 3. Investigate occurrence of subclinical seizures in sedated SAH patients. 4. Evaluate if patients that survive a SAH ≥ one year have an increased risk of vascular causes of death compared to a normal population. Results: Continuous infusion of sedative drugs was the strongest predictor for a low (&lt;200 nmol/L) serum cortisol. The odds ratio for a sedated patient to have a serum cortisol &lt; 200 nmol/L was 18.0 times higher compared to an un-sedated patient (p &lt; 0.001). Compared to admission values, 0-48 hours after SAH, CRP increased significantly already in the time-interval 49-72 hours (p&lt;0.05), peaked in the time-interval 97-120 hours after SAH and thereafter decreased. ADMA started to increase in the time-interval 97-120 hours (p&lt;0.05). ADMA and CRP levels were significantly higher, and arginine/ADMA ratios were significantly lower in patients with a more severe condition (p&lt;0.05). Epileptic seizure activity, in sedated SAH patients, was recorded in 2/28 (7.1%) patients during 5/5468 (0.09%) hours of continuous EEG monitoring. Cerebrovascular disease was significantly more common as a cause of death in patients that had survived a SAH ≥ one year, compared to the population from the same area (p&lt;0.0001). Conclusions: Continuous infusion of sedative drugs was associated with low (&lt;200 nmol/L) cortisol levels. ADMA increased significantly after SAH, after CRP had peaked, indicating that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation. Patients with a more severe condition had significantly higher ADMA and CRP levels, and significantly lower arginine/ADMA ratio. Continuous sedation in sedated SAH patients seems to be beneficial in protecting from subclinical seizures. Cerebrovascular causes of death are more common in SAH survivors. / <p>Funding: The Swedish Society of Medicine, the Faculty of Medicine at Umeå University, The Kempe Foundations and The Stroke Foundation of Northern Sweden supported this study financially.</p>

Objective: This study aims to derive a clinically-applicable decision rule to predict the risk of symptomatic vasospasm, a neurological deficit primarily due to abnormal narrowing of cerebral arteries supplying an attributable territory, in aneurysmal subarachnoid hemorrhage (SAH). Methods: SAH patients presenting from 2002 to 2011 were analyzed using logistic regression and recursive partitioning to identify clinical, radiological, and laboratory features that predict the occurrence of symptomatic vasospasm. Results: The incidence of symptomatic vasospasm was 21.0%. On multivariate logistic regression analysis, significant predictors of symptomatic vasospasm included age 40-59 years, high Modified Fisher Grade (Grades 3 and 4), and anterior circulation aneurysms. Conclusion: Development of symptomatic vasospasm can be reliably predicted using a clinical decision rule created by logistic regression. It exhibits increased accuracy over the Modified Fisher Grade alone and may serve as a useful clinical tool to individualize vasospasm risk once prospectively validated in other neurosurgical centres.

Background Aneurysmal subarachnoid hemorrhage can lead to multi-organ disturbances as a result of central and autonomic nervous system injuries. Alterations in the brain-body interface associated with this cerebrovascular disorder have significant impact on patient morbidity and mortality. Knowledge of the most pertinent brain-body associations, as well as demographic, systemic and neurological prognostic factors on hospital admission, along with their progression during hospitalization can assist the clinician and patient family in the process of treatment decision making. Objectives The goals of this dissertation are to: (1) synthesize and critically appraise the methodologic quality of existing studies that derive clinical predictor tools and clinical predictors used to determine outcome prognosis in patients with aneurysmal subarachnoid hemorrhage (SAH), (2) synthesize and critically appraise the methodologic quality of existing studies that derive pathophysiologic mechanisms of brain-body associations in aneurysmal SAH, (3) provide new insights into the significance of brain-body associations that are essential in influencing outcome in aneurysmal SAH, and (4) create a decision making algorithm for aneurysmal SAH patients that is useful in bedside prognostication and clinical treatment decision making. Methods Existing prospective and retrospective cohort studies and randomized controlled trials were included in the systematic review investigating prognostic factors and clinical prediction tools associated with determining the neurologic outcome in adults patients with aneurysmal SAH. Existing prospective and retrospective cohorts were included in the systematic review investigating the pathophysiologic mechanisms of brain-body associations in patients with ruptured brain aneurysms. The multicenter Tirilazad database (3551 patients) was used to create the aneurysmal SAH prognostic model, in order to elucidate significant brain-body associations. Traditional binary logistic regression models were used. The classification and regression tree analysis technique is applied to the multicenter Tirilazad database in order to create a decision making algorithm. Results Systematic review of the literature confirmed the most frequently retained clinical outcome predictors, namely, age, neurological grade, aneurysm size and blood clot thickness. Systematic review of the literature clarified currently known pathophysiologic mechanisms of brain-body associations in aneurysmal SAH, specifically, sympathetic activation of the cardiopulmonary system with subsequent delayed activation of neuro-cardio-endocrinological responses as part of the secondary injury cascade in response to the primary ictus of aneurysmal SAH. Logistic regression models found the significance of hepatic disease and hypertension in development of brain edema, and the negative consequences of seizures in those with history of myocardial infarction and post admission fever worsening neurological outcome. A clinically useful classification and regression tree revealed prognostic subgroups with important explanatory nodes including neurological grade, age, post admission fever and post-admission stroke. Discussion This dissertation clarified existing information on clinical predictors and pathophysiologic mechanisms of brain-body associations in aneurysmal SAH. It also provides novel information on brain-body associations that are essential in influencing outcome in aneurysmal SAH patients despite scarce existing literature on such important relationships. A clinically useful classification and regression tree was generated to guide both bedside prognostication and clinical treatment decision making in aneurysmal SAH patients. / Thesis / Doctor of Philosophy (PhD)