Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2 mg estradiol (E2) continuously during 28- day cycles. Synthetic progestins or natural progesterone were added sequentially during the last 14 days, and compared to a placebo addition. Before treatment, as well as during the last week of each treatment cycle the pharmacodynamic response to pregnanolone was assessed using saccadic eye movement measurements. Throughout the studies daily symptom ratings were made. In the study regarding synthetic progestins, platelet serotonin transporter and 5-HT2A receptor binding were assayed before entering the study, as well as during the last week of each treatment cycle. In the study on reproductive women, blood samples were collected for analysis of platelet serotonin transporter and 5-HT2A receptor binding at six different points in time during the menstrual cycle. Results and conclusion: The addition of synthetic progestins to estrogen treatment increased negative mood symptoms and physical symptoms, whereas positive symptoms decreased. The addition of progestins also increased the sensitivity to pregnanolone. The addition of natural progesterone to estrogen treatment increased the sensitivity to pregnanolone. However, in this study the pregnanolone sensitivity was enhanced also during estrogen treatment. Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity. Thus, it is evident that mood deterioration during HRT is associated with altered neurosteroid sensitivity. Platelet serotonin transporter and 5-HT2A receptor binding did not change during the different treatment conditions in HRT. Thus, we were unable to explain the negative mood changes of HRT by use of these peripheral serotonergic parameters. In the study on reproductive women however, it was clear that the serotonergic variables did change during the menstrual cycle. Binding to the serotonin transporter was higher in the late follicular phase than in the ovulatory, early luteal or mid-luteal phases. Binding to the 5-HT2A receptor was higher in the early follicular phase and the early luteal phase than in the mid-luteal phase. These findings may provide a link between the ovarian steroids, and the GABAergic and serotonergic neurotransmitter systems, which in turn, could explain part of the specific vulnerability that women have for the development of adverse mood effects during HRT, mood and anxiety disorders and for the deterioration of mood so frequently seen during the luteal phase.

Les effets cardiovasculaires des alpha-2 agonistes, particulièrement importants chez les chiens, limitent leur utilisation en pratique vétérinaire. La perfusion à débit constant (PDC) de ces drogues, comme la médétomidine (MED) permettrait un contrôle plus précis de ces effets. Les effets hémodynamiques de plusieurs doses de MED en PDC ont été évalués chez le chien. Lors de cette étude prospective, réalisée en double aveugle, 24 chiens en santé, ont reçu de façon aléatoire une des 6 doses de MED PDC (4 chiens par groupe). Les chiens ont été ventilés mécaniquement pendant une anesthésie minimale standardisée avec de l’isoflurane dans de l’oxygène. Une dose de charge (DC) de médétomidine a été administrée aux doses de 0.2, 0.5, 1.0, 1.7, 4.0 ou 12.0 µg/kg pendant 10 minutes, après laquelle la MED PDC a été injectée à une dose identique à celle de la DC pendant 60 minutes. L’isoflurane a été administré seul pendant une heure après l’administration d’une combinaison d’ISO et de MED PDC pendant 70 minutes. La fréquence cardiaque (FC), la pression artérielle moyenne (PAM) et l’index du débit cardiaque (IC) ont été mesurés. Des prélèvements sanguins ont permis d’évaluer le profil pharmacocinétique. D’après ces études, les effets hémodynamiques de la MED PDC pendant une anesthésie à l’isoflurane ont été doses-dépendants. L’IC a diminué progressivement alors que la dose de MED augmentait avec: 14.9 (12.7), 21.7 (17.9), 27.1 (13.2), 44.2 (9.7), 47.9 (8.1), and 61.2 (14.1) % respectivement. Les quatre doses les plus basses n’ont provoqué que des changements minimes et transitoires de la FC, de la PAM et de l’IC. La pharmacocinétique apparaît clairement dose-dépendante. De nouvelles expériences seront nécessaires afin d’étudier l’utilisation clinique de la MED PDC. / The cardiovascular effects of alpha-2 agonists, particularly pronounced in dogs, limit their use in veterinary practice. The use of these drugs, namely medetomidine (MED), by constant rate infusion (CRI), could allow more precise control of the cardiovascular effects. The haemodynamic responses of MED CRI at several dosages in dogs were investigated. In a prospective, blinded study, 24 healthy beagles randomly received one of 6 MED CRI regimens (4 dogs per regimen). Dogs were mechanically ventilated to maintain stable low-level isoflurane (ISO) anaesthesia in oxygen. A loading MED infusion was administered at 0.2, 0.5, 1.0, 1.7, 4.0 or 12.0 µg•kg-1 for 10 min, followed by maintenance CRI for 60 min providing identical dose amounts for all dogs (total duration for MED and ISO: 70 min). Isoflurane was then administered alone for an additional hour. Heart rate (HR), mean arterial blood pressure (MAP), and cardiac index (CI) were recorded. Blood sampling was performed to establish pharmacokinetic profiles. Based on this study, the hemodynamic effects of MED CRI during ISO anaesthesia were found to be dose-dependent. Baseline CI decreased dose-dependently as MED dose increased by: 14.9 (12.7), 21.7 (17.9), 27.1 (13.2), 44.2 (9.7), 47.9 (8.1), and 61.2 (14.1) % respectively. The four lowest dosages created limited and transient changes in HR, MAP, and CI. Pharmacokinetics were dose-dependent. Further investigations for perioperative use are warranted.

No description available.

Made available in DSpace on 2014-06-11T19:33:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-03-30Bitstream added on 2014-06-13T21:05:39Z : No. of bitstreams: 1 menezes_tec_dr_araca.pdf: 231708 bytes, checksum: 9b342af7faf18025f1ee1db5e5205661 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste estudo foi observar resultados de procedimentos odontológicos realizados em pessoas com deficiência, sob sedação consciente com Midazolam, via endovenosa, realizados no Centro de Assistência Odontológica à Pessoa com Deficiência, da Faculdade de Odontologia de Araçatuba – UNESP. Acompanhou-se 460 procedimentos, independente do gênero, idade ou deficiência dos pacientes, que não permitiram a realização de tratamento odontológico previamente. Os resultados foram classificados como sucesso (quando realizados sem problemas, ainda que necessária contenção auxiliar suave, ou houve algum problema contornável, mas os procedimentos planejados puderam ser realizados) e insucesso (quando não foi possível a realização do tratamento planejado). Registrou-se, ainda, o uso de medicamentos pelos pacientes e as prováveis causas de insucesso. A pressão arterial, freqüência cardíaca, saturação de oxigênio e temperatura corporal foram monitorados antes, durante e após o procedimento. As dosagens de Midazolam administradas foram entre 05 a 60mg, de acordo com o peso corporal do paciente. Na maioria dos casos, foi possível a realização do tratamento planejado, sem danos aos pacientes nem à equipe odontológica e os sinais vitais se mantiveram dentro de valores normais. A sedação consciente com Midazolam, via endovenosa, pode ser considerada uma alternativa eficaz para o tratamento odontológico em pessoas com deficiência não colaboradores / The objective of this study was to observe the results of dental procedures performed in disable persons under conscious sedation with Midazolam, intravenously, assisted at the Dental Care Center for Patients with Special Needs, School of Dentistry of Araçatuba - UNESP. 460 procedures were observed, regardless of gender, age or disability of the patients, which did not allow their dental treatment realization. The results were classified as success (when carried out without problems, even it was necessary restraint gentle help, or there was some manageable problem, but the planned procedures could be performed) and failure (when it was not possible to perform the planned treatment). It was also recorded, the use of medicines by patients and the probable causes of failure results. Blood pressure, heart rate, oxygen saturation and body temperature were monitored before, during and after the procedure. The doses of Midazolam were administered between 05 to 60mg, according to the patient's body weight. In most cases it was possible to perform the planned treatment without problems to the patients or to the dental staff and their vital signs remained within normal values. The conscious sedation with Midazolam, intravenously, can be considered an effective alternative for dental treatment to disable persons not employees

O mecanismo do efeito sedativo da clonidina (CLO), um agonista α2-adrenérgico não é claro. Como a ativação dos receptores α2-adrenérgicos induz a liberação de Óxido Nítrico (NO) das células endoteliais, testamos a hipótese de que o efeito sedativo e antinociceptivo da CLO sistêmica dependeria de mecanismos relacionados a via NOGMPc. O 7-NI reduziu significativamente o tempo de sono induzido pela clonidina. O tempo de sono induzido pelo tiopental (TST) foi aumentado pela CLO, α-metildopa, rilmenidina (RIL) and midazolam. O L-NAME reduziu o prolongamento do TST da CLO, α-metildopa, RIL, sem alterar o efeito do midazolam. O efeito inibitório do L-NAME no prolongamento do TST com a CLO foi revertido pela L-arginine. Os resultados sugerem mecanismos NO-dependentes no efeito sedativo da clonidina. Esses efeitos parecem ser específicos para a ação sedativa dos agonistas α2-adrenérgicos. Avaliamos também a possível ligação envolvendo opóides e a via do NO-GMPc no efeito antinociceptivo da CLO. O efeito antinociceptivo induzido pela administração sistêmica de CLO e RIL foi avaliado utilizando o teste das contorções abdominais em camundongos e o teste tailflick. A CLO (3120 g/kg) and RIL induziram efeito antinociceptivo dose-dependente no teste das contorções abdominais e TFL. O efeito antinociceptivo da CLO foi significativamente reduzido pela inibição da NO-syntase and guanylyl ciclase. O efeito da RIL também foi reduzido pelo 7-NI. O efeito antinociceptivo da morfina foi inibido pela naloxona, que não inibiu o efeito da CLO. Nossos resultados sugerem que o efeito da CLO sistêmica não envolve receptor opióide e é modulado por uma via NO-GMPc. / The mechanism of sedative effect of clonidine (CLO), an α2-adrenoceptor agonist remain unclear. As the activation of α2-adrenoceptors induces release of nitric oxide (NO) from endothelial cells, which has led us to test the hypothesis that sedative and antinociceptive effect from systemic CLO depends on the NO-cGMP pathway mechanisms. The sleeping time in rats induced by CLO was significantly decreased by 7-NI. Thiopental sleeping time (TST) was increased by CLO, α-methyldopa, rilmenidine (RIL) and midazolam. L-NAME reduced the prolongation effect of clonidine, α-methyldopa, RIL, but did not alter the effect of midazolam on the TST. The inhibitory effect of L-NAME on CLO -dependent prolongation of TST was reversed by L-arginine. These results suggest that NO-dependent mechanisms are involved in the sedative effect of CLO. In addition, this effect seems to be specific for the sedative action of α2-adrenoceptors agonists. The possible involvement of an opioid and NO-GMPc pathway link in the antinociceptive effect of CLO was also evaluated. The antinociceptive effect induced by systemic administration of CLO and rilmenidine (RIL) was evaluated using the mice writhing tests and TFL. CLO (3120 g/kg) and RIL induces a dose-dependent antinociceptive effect in the writhing tests and TFL. The antinociceptive effect of CLO was significantly reduced by NO-synthase and guanylyl cyclase inhibition. RIL effect was also reduced by 7-NI.The antinociceptive effect of morphine, but not CLO, was inhibited by naloxone. Our current results suggest that the antinociceptive effect of systemic clonidine does not involve the opioid receptor and is modulated by the NO-cGMP pathway.

Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-05-10T20:18:04Z No. of bitstreams: 2 Tese - Heloisa de Sousa Gomes Rodrigues - 2016.pdf: 24514601 bytes, checksum: 5d8491e9be339376d5b3114ac0b8fd41 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-05-11T12:08:41Z (GMT) No. of bitstreams: 2 Tese - Heloisa de Sousa Gomes Rodrigues - 2016.pdf: 24514601 bytes, checksum: 5d8491e9be339376d5b3114ac0b8fd41 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-05-11T12:08:41Z (GMT). No. of bitstreams: 2 Tese - Heloisa de Sousa Gomes Rodrigues - 2016.pdf: 24514601 bytes, checksum: 5d8491e9be339376d5b3114ac0b8fd41 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-12-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Paediatric dental treatment may stress children and their parents influencing the child behaviour and the maternal dental anxiety. It is important to understand those behavioural and physiological alterations to aid using of adequate sedatives techniques during paediatric dental procedure. The aim of this study was to evaluate the stress of children and their mothers during the paediatric dental treatment using different sedation protocols. Also, the maternal dental anxiety, the child’s behaviour and age and its associations were evaluated. This observational study is a secondary analysis of two randomised controlled clinical trials. Children aged 2-6 years old received one tooth restoration under moderate sedation according to the groups: [A] 18 children received oral midazolam (1.0 mg/kg) and [B] 18 children received placebo in a crossover design [Clinical Trials database (NCT01795222)]; [C] 14 children received oral midazolam (0.5 mg/kg) and oral ketamine (3.0 mg/kg) plus sevoflurane inhalation (0.3% - 0.4%) and [D] 13 children had oral midazolam (0.5 mg/kg) and oral ketamine (3.0 mg/kg) plus oxygen inhalation in a parallel design (NCT02284204). The sessions were video recorded for evaluation of child behaviour using OSUBRS scale (Ohio State University Behavioural Rating Scale) and mothers answered the Brazilian version of Dental Anxiety Scale (DAS). The saliva samples were collected on children and on their mothers at 4 moments: waking up (T0), upon arrival at Dental School (T1), 25 minutes after the local anaesthesia injection on child (T2) and 25 minutes after the end of procedure (T3). Salivary cortisol was measured using an immunoassay kit (ELISA). As the data presented non normal distribution (Shapiro Wilk, p>0,05), Kruskal-Wallis and Mann-Whitney tests were used for non paired comparisons and Mann-Whitney for associations among the variables. For paired comparisons, Friedman and Wilcoxon tests were used (p<0,05). The increase of cortisol levels from T1 to T2 (reactivity to stressful stimulus – local anaesthesia) was higher in children of group [B] [median (interquartile)] – [0.53 (0.60)] following by groups [D] – [0.21 (0.35)], [C] – [0.11 (0.49)] and [A] – [0.02 (0.59)] (p=0.02). The decrease of cortisol levels from T2 to T3 (regulation to stress) was higher in children of group [B] – [0.08 (0.29)] following by groups [A] [-0.02 (0.40)], [C] – [-0.18 (0.41)] and [D] – [-0.19 (0.8)] (p=0.02). Majority of mothers were not stressed during their child’s local anaesthesia injection (67.9%) and presented low/moderate anxiety (69.6%), while 25.0% of them presented high/severe anxiety (DAS scale). Mothers who reacted to stress (increasing of cortisol at least 10% from T1 to T2) had higher cortisol levels at the moments T2 [0.15 (0.48)] and T3 [0.16 (0.50)] compared to T1 [0.09 (0.17)] (p<0.01 and p<0.006, respectively). On the other hand, mothers who did not react to stress had higher cortisol levels at the moments: T1 [0.36 (0.18)] compared to T2 [0.16 (0.18)] (p<0.01) and T3 [0.10 (0.12)] (p<0.01) and T2 compared to T3 (p=0.01). There was no statistically significant association between maternal stress (salivary cortisol levels) with child behaviour (p=0.56), child’s age (p=0.48) and maternal dental anxiety (DAS) (p=0.69). The findings of this study allow to conclude that sedation protocol using oral ketamine caused higher liberation of salivary cortisol at the moments of local anaesthesia and at the end of procedure (higher reactivity and lower regulation) indicating a prolonged response to physiological stress in children, which was not observed during the use of oral midazolam. Although, there was any maternal dental anxiety most of mothers were not stressed during the dental treatment under sedation of their children. Also, maternal dental anxiety, child’s age and child behaviour did not influence the maternal stress. / O tratamento odontopediátrico pode causar estresse em crianças e em seus acompanhantes prejudicando o comportamento infantil e a ansiedade odontológica materna. A compreensão dessas alterações fisiológicas e comportamentais é de suma importância a fim de auxiliar no uso de técnicas sedativas adequadas durante o atendimento odontológico infantil. O objetivo deste estudo foi avaliar o estresse de crianças e de suas respectivas mães durante o tratamento odontopediátrico sob diferentes protocolos de sedação. Além disso, objetivou-se avaliar a ansiedade odontológica materna e o comportamento infantil, bem como a associação destas características. Este estudo observacional é uma análise de dados de dois ensaios clínicos randomizados e controlados. Crianças de 2 a 6 anos de idade receberam tratamento odontológico restaurador padronizado sob sedação moderada de acordo com os grupos: [A] 18 crianças receberam midazolam oral 1,0 mg/kg e [B] 18 crianças receberam placebo, em um desenho cruzado [Clinical Trials database (NCT01795222)]; [C] 14 crianças receberam midazolam oral 0,5 mg/kg e cetamina oral 3,0 mg/kg mais inalação de sevoflurano (0,3% - 0,4%) e [D] 13 crianças tiveram midazolam oral 0,5 mg/kg e cetamina oral 3,0 mg/kg mais inalação de oxigênio, em um desenho paralelo (NCT02284204). As sessões foram filmadas para posterior avaliação do comportamento infantil usando a escala OSUBRS (Ohio State University Behavioural Rating Scale) e as mães responderam a versão Brasileira da Dental Anxiety Scale (DAS). As coletas de saliva foram realizadas concomitantemente nas crianças e mães em 4 momentos: ao acordar (T0), na chegada na clínica (T1), 25 minutos após a aplicação da anestesia local na criança (T2) e 25 minutos após o término do procedimento (T3). O cortisol salivar foi mensurado por meio de ensaio imunoenzimático (ELISA). Como os dados apresentaram distribuição não normal (Shapiro Wilk, p>0,05), o teste de KruskalWallis seguido de Mann-Whitney foram utilizados para comparações não pareadas e MannWhitney para associação entre as variáveis. Para análises pareadas, o teste de Friedman seguido de Wilcoxon foi utilizado adotando-se como nível de significância um valor de 5% (p<0,05). O aumento do cortisol de T1 para T2 (reatividade ao estímulo estressor – anestesia) foi maior em crianças do grupo [B] [mediana (interquartil)] – [0,53 (0,60)] seguido dos grupos [D] – [0,21 (0,35)], [C] – [0,11 (0,49)] e [A] – [0,02 (0,59)] (p=0,02). Já a redução do cortisol de T2 para T3 (regulação ao estresse) foi maior em crianças do grupo [B] – [0,08 (0,29)] seguido dos grupos [A] [-0,02 (0,40)], [C] – [-0,18 (0,41)] e [D] – [-0,19 (0,8)] (p=0,02). A maioria das mães não ficaram estressadas durante a aplicação da anestesia local em seus filhos (67,9%) e apresentaram ansiedade baixa/moderada (69,6%), enquanto 25,0% delas apresentaram alta/severa ansiedade (escala DAS). As mães que reagiram ao estresse (aumento de pelo menos 10% do nível de cortisol salivar do momento T1 ao T2) tiveram maiores níveis de cortisol nos momentos T2 [0,15 (0,48)] e T3 [0,16 (0,50)] comparado com T1 [0,09 (0,17)] (p<0,01 e p=0,006, respectivamente). Por outro lado, mães que não reagiram tiveram maior nível de cortisol nos momentos: T1 [0,36 (0,18)] comparado a T2 [0,16 (0,18)] (p<0,01) e T3 [0,10 (0,12)] (p<0,01); T2 comparado a T3 (p=0,01). Não houve associação estatisticamente significante entre o nível de cortisol salivar das mães com o comportamento infantil (p=0,56); idade das crianças (p=0,48) e ansiedade odontológica materna (DAS) (p=0,69). Os achados obtidos no presente estudo permitem concluir que o uso do protocolo de sedação com cetamina oral provocou aumento da liberação de cortisol salivar tanto no momento da anestesia quanto ao final do tratamento (maior reatividade e menor regulação) indicando uma resposta prolongada ao estresse fisiológico das crianças, o que não foi observado com o uso de midazolam oral. Embora algum grau de ansiedade odontológica materna tenha sido evidenciada, a maioria das mães não ficaram estressadas durante o tratamento odontológico sob sedação de seus filhos. Adicionalmente, a ansiedade odontológica das mães, bem como a idade e o comportamento infantil não influenciaram o estresse materno.

Durante muitos anos a sedação consciente com a mistura de oxigênio e óxido nitroso foi utilizada por cirurgiões-dentistas em vários países do mundo. Já no Brasil, essa utilização só foi regulamentada com a edição da resolução do Conselho Federal de Odontologia CFO 51/04 (CFO, 2004b). Como todo instrumento de regulamentação, este também deve ser analisado para que possa ser melhor entendido. Assim, o presente estudo teceu comentários acerca dos aspectos integrantes de tal resolução, procurando destacar a importância e a relevância de cada um deles. Tal avaliação reveste-se de grande importância, pois a organização dos cursos que habilitarão os cirurgiões-dentistas a aplicar a sedação consciente com a mistura de oxigênio e óxido nitroso terá que cumprir os requerimentos presentes na citada resolução. Ressalte-se que não se pretendeu esgotar o assunto, até mesmo porque isso seria impossível, mas suscitar o interesse dos pesquisadores no desenvolvimento de investigações mais aprofundadas sobre a matéria. / For many years the conscious sedation with nitrous oxide and oxygen has been used in various countries in the world. This usage in Brazil has only been regulated with the present Resolução do Conselho Federal de Odontologia CFO 51/04. As any other regulating instrument, this also needs analysis for its complete understanding. In this study every aspect of the Conselho´s Resolution were analyzed, trying to underline their importance and relevance of each one of them. This evaluation becomes of great importance because it is based on its requirements that the courses for the habilitation of dentists who intend to use the technique of conscious sedation with nitrous oxide and oxygen will be developed and ruled. This study intends to be one of the tools that will be used to fully understand this resolution.

O uso do propofol em sedação para colonoscopia e outros procedimentos endoscópicos é cada vez mais frequente, devido ao seu rápido início de efeito e curto período de recuperação, com poucos efeitos residuais, o que o torna um anestésico ideal para o uso em condutas médicas realizadas em regime ambulatorial. Seu perfil farmacológico o posiciona como um anestésico adequado a métodos de administração endovenosa contínuos ou titulados, possibilitando maior controle na sua concentração plasmática. Devido à sua alta lipossolubilidade, o propofol difunde-se rapidamente ao sistema nervoso e outros tecidos aonde exercerá seu efeito clínico, intimamente ligado à propofolemia, com diminuição da atividade do sistema nervoso central, que determinará tanto a sedação nos seus diversos níveis, quanto os indesejados efeitos depressores do sistema cardiovascular e respiratório, podendo levar a uma diminuição importante do débito cardíaco e pressão arterial e também a uma depressão central do sistema regulatório da respiração, que pode gerar apneia ou hipoventilação significativas. O presente estudo teve como objetivo avaliar clinicamente, e com dosagem sérica, o propofol em três esquemas diferentes de infusão endovenosa. Foram avaliados aleatoriamente 50 pacientes submetidos à colonoscopia nos Serviços de Endoscopia do Hospital Ana Costa (Santos - SP) e no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (São Paulo-SP). Os pacientes foram divididos em três grupos, conforme o esquema de sedação que foi utilizado. O Grupo 1 recebeu fentanil no início, uma dose inicial de propofol de um miligrama por quilo em um minuto na indução, posteriormente recebeu propofol em infusão intermitente de doses fracionadas de 30 mg (bolus) conforme necessidade clínica durante o exame. O Grupo 2 recebeu fentanil no início, uma dose inicial de propofol de 1 mg/kg em um minuto na indução, após essa, recebeu propofol contínuo em uma solução diluída a 0,2% em solução glicosada a 5%, em uma dose inicial de 1 gota/kg de peso do paciente, o que equivale a aproximadamente 100 ug/kg/min, controlada manualmente e alterada conforme a necessidade clínica do exame. O Grupo 3 recebeu fentanil no início do exame, e propofol com dose calculada e administrada por bomba eletrônica computadorizada (Diprifusor®) em esquema de infusão contínua alvo controlada, numa dose inicial de indução de 4 ug/mL administrada em um minuto, baixada a 2 ug/mL após a dose inicial completada, e alteradas para mais ou para menos conforme a necessidade clínica do exame. Os pacientes foram monitorizados com eletrocardiografia contínua, pressão arterial não invasiva medida de dois em dois minutos, oximetria de pulso, capnografia de aspiração lateral e índice bispectral (BIS). As dosagens séricas de propofol foram feitas em três amostras de sangue colhidas por paciente. A primeira amostra, cinco minutos após a indução, a segunda ao endoscopista alcançar o ceco durante o exame e a terceira a cinco minutos após a última dose de propofol administrada ou ao término da infusão contínua, no final do exame. Não houve diferença estatística significativa entre os Grupos em relação às características físicas pessoais dos pacientes como: sexo (p = 0,976), estado físico de acordo com a American Society of Anestesiology (ASA) (p = 0,945), idade (p = 0,896), peso (p = 0,340), altura (p = 0,947), índice de massa corpórea (IMC) (p = 0406), nos parâmetros clínicos observados como menor valor de índice BIS (p = 0,871) e o tempo para alcançá-lo (p = 0,052), tempo médio do exame (p = 0,123) e efeitos adversos observados como a queda da saturação de oxigênio abaixo de 90% (p = 0,054). Houve diferença estatisticamente significativa nas pressões arteriais iniciais dos Grupos 2 e 3, que foram ligeiramente elevadas em relação ao Grupo 1 a sistólica (p = 0,008), diastólica (p = 0,018) e média (p = 0,008), porém após a indução, a média das pressões arteriais sistólica (p = 0,440), diastólica (p = 0,960) e média (p = 0,815), e as menores pressões alcançadas não foram estatisticamente diferentes: sistólica (p = 0,656), diastólica (p = 0,783) e média (p = 0,993). Não houve diferença estatística em relação à frequência cardíaca inicial (p = 0,453), média após indução (p = 0,702), e menor frequência cardíaca alcançada (p = 0,788). Houve diferença entre o número de agitações médias entre os Grupos (p = 0,001), sendo maior no Grupo 1, porém este número foi relacionado ao esquema de administração do propofol no Grupo 1, que foi administrado após a indução quando o paciente apresentou algum grau de agitação que necessitou aprofundamento anestésico. Houve queda de saturação de oxigênio em seis pacientes (12%) da amostra avaliada, revertidas em tempo menor que cinco minutos com manobras de elevação da mandíbula do paciente ou utilização de cânula de Guedel para desobstrução das vias aéreas. Antes das quedas na saturação de oxigênio, foram percebidas alterações típicas de obstrução de vias aéreas, hipopneia ou apneia nas ondas de capnografia em 16 pacientes (32%), sendo que, em alguns pacientes por mais de uma vez, demonstrando esse ser um bom parâmetro de monitorização para prevenir hipóxia, não houve diferença entre os Grupos no parâmetro de obstrução de vias aéreas/apneia (p = 0,543). Em relação à propofolemia, o comportamento médio dos pacientes dos três Grupos foi estatisticamente igual ao longo dos momentos de avaliação (p = 0,830), não havendo diferença média estatisticamente significativa entre os Grupos (p = 0,964). Não houve diferença entre o consumo do propofol médio por minuto de exame (p = 0,748). Em relação à análise de custos com a administração do propofol, o Grupo 1 apresentou o menor valor médio para as colonoscopias avaliadas com gasto médio de R$ 7,00, o Grupo 2 gastou em média R$ 17,50 e o Grupo 3 gastou em média R$ 112,70 com diferença estatisticamente significativa entre eles (p < 0,001). A conclusão é que os esquemas de administração do propofol testados foram seguros, e houve semelhança entre os Grupos nos parâmetros avaliados incluindo a propofolemia, porém com custos diferenciados entre eles. Em relação ao Grupo 1, devido ao maior número de agitações por minuto este pode ser um bom método para procedimentos mais curtos, para procedimentos mais longos os Grupos 2 e 3 se mostraram mais confortáveis para o responsável pela sedação / The use of propofol sedation for colonoscopies and other endoscopic procedures is increasing due to the rapid onset of effect and short recovery time with few residual effects, which makes it an ideal anesthetic for usingin outpatient medical procedures. Its pharmacological profile places it as a suitable anesthetic to continuous or titred intravenous administration, providing increased control in its plasma levels. Due to its high liposolubility, propofol diffuses rapidly to the central nervous system and other tissues where it shall perform its clinical effects, closely related to plasma concentration, and providing sedation at different levels, as much as the unwanted depressant effects of the cardiovascular and respiratory system, it may lead to a significant reduction in cardiac output and blood pressure and also a central regulatory breathing system depression, that can result in significant apnea or hypoventilation. This study aimed to evaluate clinically and serum, propofol in three different regimens of intravenous infusion. 50 patients submitted to colonoscopy in the endoscopy centers at Hospital Ana Costa (Santos - SP), and Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (São Paulo-SP), have been randomly assessed. Such patients were divided into three groups, according to the sedation scheme that was used for them. Group 1 received fentanyl at first, then a one milligram per kilogram propofol dose, at induction, in a minute, later they received intermittent infusion of propofol in fractionated doses of 30 mg (Bolus) according to clinical needs during the test. Group 2 received fentanyl in the beginning, a starting dose of propofol 1 mg/kg at induction in one minute, after that received propofol in a 0.2% solution diluted in 5% glucose solution at an initial 1 drop/kg of patient weight dose, equivalent to about one 100 u100/min, manually controlled and changed according to clinical need of the examination. Group 3 received in the beginning of the examination fentanyl and propofol calculated by target controlled continuous infusion electronic device (Diprifusor®), an initial loading dose of 4 ug/mL was administered in one minute, reduced at 2 ug/mL after the initial dose, changed up or down according to clinical needs of examination. Patients were monitorized with continuous electrocardiography, non-invasive blood pressure measured every two minutes, pulse oximetry, side suction capnography and bispectral index (BIS). Serum levels of propofol were performed on three samples of blood taken by each patient. The first sample, five minutes after the induction, the second when the endoscopist reached the cecum during the examination and the third sample five minutes after the last administered dose or the end of continuous infusion of propofol, at the end of the test. No statistically significant difference between groups with respect to personal physical characteristics of patients as: sex (p = 0.976), physical state according to the American Society of Anesthesiology (ASA) (p = 0.945), age (p = 0.896), weight (p = 0.340), height (p = 0.947), body mass index body (BMI) (p = 0.406) in clinical parameters observed as a minor reached bispectral index value (BIS) (p = 0.871) and time to reach it (p = 0.052), mean procedure time (p = 0.123) and adverse effects observed as a drop in oxygen saturation below 90% (p = 0.054). There was a difference between the number of averages agitations between groups (p = 0.001), being higher in Group 1, but that number was related to propofol administration scheme in Group 1, as this was administered after induction when the patient had some agitation that required deeper anesthesia. There was a statistically significant difference in initial blood pressures of groups 2 and 3, which were slightly higher compared to Group 1: systolic (p = 0.008), diastolic (p = 0.018) and mean (p=0.008), but after induction, the average systolic (p = 0.440), diastolic (p = 0.960) and average (p = 0.815), and lower pressures achieved: systolic (p = 0.656) and diastolic (p = 0.783) and average (p = 0.993), were not statistically different. There was no statistical difference from the initial heart rate (p = 0.453), average heart rate after induction (p=0.702), and lower heart rate achieved (p = 0.788). There was oxygen dessaturation below 90% in six patients (12%) of the study sample, reversed in less than five minutes with patient jaw thrust maneuver or use of Guedel cannula, for airway clearance. Before the declines in oxygen saturation, typical tract obstruction, hypopnea or apnea wave changes were noted in capnography in sixteen patients (32%), and in some patients for more than once, showing this to be a good monitoring parameter to prevent hypoxia in patients, there was no difference between Groups in the airway obstruction/apnea parameter (p = 0.543). Regarding serum propofol, the average behavior of patients in the three Groups were statistically similar over the time (p = 0.830), with no statistically significant mean difference between groups (p = 0.964). There was no difference between the average propofol consumption per minute examination (p = 0.748). Regarding cost analysis with the administration of propofol, Group 1 had the lowest average value for colonoscopies evaluated with an average expense of R$ 7.00, Group 2 spent on average R$ 17.50 and the Group spent 3 on average R$ 112.70 with a statistically significant difference (p < 0.001). The conclusion is that propofol administration schemes tested were safe and there was similarity between the Groups in the evaluated parameters including propofolemia, but with different costs among them. With respect to Group 1 due to the larger number of agitations per minute, this is a good method for shorter procedures, for longer procedures groups 2 and 3 were more comfortable for the person responsible for sedation

Bakgrund: Smärta hos intensivvårdspatienter är vanligt förekommande och kan medföra förlängd vårdtid och leda till flera negativa konsekvenser för patienten samt bidra till ökad mortalitet. Smärtskattning med ett validerat smärtskattningsinstrument som Critical-Care Pain Observation Tool (CPOT) kan underlätta smärtskattningen och förbättra smärtbehandlingen samt minska översedering. Syfte: Syftet med denna studie är att beskriva om införandet av smärtskattningsverktyget CPOT, anpassat för patienter i ventilatorbehandling, påverkar dygnsdoserna av smärtlindrande- och sederande läkemedel samt om sederingsbehandlingen förändras. Syftet är även att undersöka hur ofta sjuksköterskorna smärtskattar patienterna med CPOT och om antalet smärtskattningar överensstämmer med gällande rekommendationer. Metod: Kvantitativ journalgranskningsstudie med retrospektiv design. Vuxna patienter som ventilatorbehandlades under minst ett dygn på en intensivvårdsavdelning i Sverige inkluderades (n=55). Resultat: Totalt 55 patienter inkluderades i två grupper, före och efter införandet av CPOT. Doserna av smärtlindrande läkemedel ökade i gruppen som undersöktes efter att CPOT infördes. Patienterna erhöll i genomsnitt 1,4 mg morfin/kg/dygn jämfört med 1,1 mg morfin/kg/dygn innan införandet. Dosen av det sederande läkemedlet Propofol® minskade efter införandet av CPOT från 48,3 mg/kg/dygn till 47,5 mg/kg/dygn. Alla patienter i studiegruppen förutom två (92 %) smärtskattades vid minst ett tillfälle under mätdygnet efter införandet av CPOT. Slutsats: Doserna av smärtlindrande läkemedel var högre och doserna av det sederande läkemedlet Propofol® var lägre efter införandet av CPOT. Skillnaderna var dock inte statistiskt signifikanta. Patienterna i studiegruppen hade en något ytligare sederingsnivå enligt RASS-skalan. Patienterna smärtskattades med CPOT i genomsnitt 1,6 gånger under mätdygnet. Studien kan bidra till en ökad medvetenhet om vikten av att skatta smärta med ett validerat bedömningsinstrument hos intensivvårdspatienter. / Background: Critically ill intensive care patients frequently experience pain and pain may lead to consequences such as prolonged length of hospital stay and increased mortality. The Critical-care Pain Observation Tool (CPOT) is a validated tool for pain assessment in mechanical ventilated patients and is used to enable pain assessment, improve pain management and reduce over-sedation.  Aim: The aim is to examine if the implementation of CPOT affects the doses of analgetics, sedatives administered to the Intensive Care Unit (ICU) patients and/or the sedation levels using RASS-scores. The aim was also to study how often pain-assessments were performed by nurses. Method: A quantitative study with retrospective design, data was collected from patients’ medical records. Included were adult patients treated under mechanical ventilation &gt;24h at an intensive care unit in Sweden (n=55). Results: For this study 55 patients were included and divided into two groups, before and after the introduction of CPOT at the intensive care unit. The amount of analgetics increased among the patients after CPOT was implemented, they were given 1,4 mg of morphine/kg/24h compared to 1,1 mg of morphine/kg/24h before the implementation. The amount of sedatives, Propofol®, given to the patients decreased from 48,3 mg/kg/24h to 47,5 mg/kg/24h after CPOT was implemented. CPOT was used to assess pain levels in all patients except for two (98%) after the implementation of CPOT. Conclusion: The doses of analgetics were higher and the doses of sedatives (Propofol®) were lower after the implementation of CPOT. However, the differences between groups were not statistically significant. Patients were less sedated, according to RASS-scores, after the implementation of CPOT. Nurses used CPOT on an average 1, 6 times/ 24 h. This study can be used to increase the awareness for the need of using a validated tool for assessing pain in ICU-patients.

Magister Scientiae Dentium - MSc(Dent) / AIM:The aim of this study was to review the data available from the Department of Health(DOH), on pre-school paediatric patients treated under Dental General Anaesthesia(DGA), at public health facilities in the Western Cape (WC) in order to ascertain the type and nature of treatment provided.METHODOLOGY:This retrospective descriptive study reviewed the records on the Department of Health(DoH) Database of 16 732 pre-school patients treated under dental general anaesthesia in the period 1 January 2005 until 31 December 2007. A questionnaire was also completed telephonically with 22 dentists from the district dental health clinics.Summary descriptive statistics were calculated from data collected and comparisons were drawn between services available at the health districts and academic hospitals.RESULTS:Of the 58 255 procedures recorded for pre-school patients in the district health clinics in the Western Cape, 99.94% were for extractions provided and 0.5% for restorations.The average number of teeth extracted was 10.4 (SD ±3.9).The average rate of DGA per 1000 of the population was 1.06. Only 9% (2) of dentists at district clinics reported that pre-DGA prevention was provided and 5% (1) reported including post-DGA prevention. The Academic Hospital at Tygerberg Oral Health Centre was the only facility in the Western Cape that provided comprehensive dental treatment for pre-school patients which included restorations, extractions, pre and post DGA prevention. Red Cross Children’s Hospital provided treatment for pre-school patients under DGA that included extractions, pre- and post DGA, but no restorative treatment. CONCLUSION:The demand for DGA in pre-school patients in the WC was high. The lack of prevention associated with DGA in the public health service is the most likely reason the retreatment rate under DGA was reported by dentists as being 77%. There was an absence of protocol regarding DGA for pre-school patients in the public health service.RECOMMENDATIONS:Guidelines formulated were recommended for use in the public service for pre-school patients being treated under DGA and includes the provision of preventive interventions such as regular topical fluoride applications, oral hygiene instruction and dietary advice.