No description available.

Purpose: The purpose of this study was to create an experimental design to compare the regimen of ketamine-midazolam to chloral hydrate-meperidine-hydroxyzine for moderate oral conscious sedation. Methods: Patients between 36 and 83 months of age have been randomly assigned to receive 1 of the 2 regimens. Dosages, times, and vital signs will be recorded. Procedures will be recorded on video for assessment of sedation level and behavior. Patients will be contacted to evaluate postoperative sleeping, discomfort, and amnesia. Data will be analyzed using two-group t-tests (TOST) of equivalence in means to compare the two groups across the study period. Results: Patient enrollment of the study has begun. In order not to break the blind randomized code, future data analysis is pending final data collection. Conclusions: This study will assist clinicians by establishing if a regimen of ketamine-midazolam is a comparable alternative to a regimen of chloral hydrate-meperidine-hydroxyzine for sedations.

Alcohol use disorders (AUDs) are major health issues with few known genetic explanations. This project used the fruit fly (Drosophila melanogaster) model to identify genes and gene networks that influence alcohol intoxication, a phenotype related to alcohol abuse in humans. We used bioinformatic tools to build gene networks based on 24 published Drosophila ethanol-responsive genes with human orthologs. We then assessed the role of these networks in ethanol sedation by testing two of the networks seeded on IP3K2, a gene that regulates calcium signaling, and CG14630, a gene involved in carnitine biosynthesis. We knocked down several genes in each of the networks using RNAi and tested the knockdown flies in a behavioral assay for ethanol sedation. Nervous system RNAi expression against 7 of 20 genes in the IP3K2 network and 4 of 30 genes in the CG14630 network significantly affected the sensitivity of flies to ethanol. To determine whether the hit rates in these two networks were greater than would be expected by random chance alone, we also assessed the effects of nervous system RNAi targeting a random set of fly genes. Unexpectedly, the fraction of randomly selected genes that affected ethanol sensitivity in a primary screen was comparable to or even larger than that from bioinformatically-derived gene networks. Our data are consistent with two possibilities that are not mutually exclusive. One possibility is that there are a very large number of genes that impact ethanol sedation and our bioinformatic analyses did not substantially enrich for these genes. A second possibility is that expression of RNAi could influence ethanol sedation independent of target gene knock-down. These two possibilities will be examined in future experiments.

Purpose: The purpose of this study was to determine the relationship of CYP2B6 genotype to the clinical response to meperidine in pediatric dental patients. Methods: Twenty-five patients, ASA I/ II, 45–92 months old, received an oral sedative regimen containing meperidine for dental treatment. The North Carolina Behavior Rating Scale (NCBRS) and Overall Effectiveness of Sedation Scale (OESS) were used to assess their behavior and sedation outcome. Saliva DNA samples were genotyped by PCR-RFLP. Results: We found the following genotype distributions: homozygous wild-type 1*1 (n = 8, 32%), heterozygous 1*6 (n = 13, 52%), and homozygous variant 6*6 (n = 4, 16%). The genotypes were predictive of a significant decrease in the overall effectiveness of sedation. Conclusion: Variation in CYP2B6 appears to be predictive of less successful sedations; wild-type individuals experienced more successful sedations than the homozygous variant 6*6. Future research regarding the enzyme kinetics of meperidine is needed to determine the exact enzymatic function of CYP2B6 and its variants.

A significância clínica dos achados eletrocardiográficos para pacientes sem histórico de doença cardiovascular é pequeno ou inexistente, porém em pacientes com doenças cardiovasculares poderia justificar o uso de monitoração contínua, incluindo o uso de eletrocardiograma além de terapêutica comportamental ou medicamentosa para certos procedimentos odontológicos com níveis de estresse moderado a elevado. Este estudo teve como objetivo a avaliação das alterações eletrocardiográficas em cirurgias para a colocação de implantes dentários sob anestesia local com cloridrato de lidocaína 2% associado a epinefrina, com uso de pré-medicação ansiolítica com 15mg de midazolam. O estudo foi realizado em 15 pacientes ASA I, com necessidade de implantes dentários, bilaterais em mandíbula. O estudo foi comparativo com placebo administrado aleatoriamente, duplo cego 1 hora antes ao procedimento. O eletrocardiograma registrou 12 derivações estáticas a cada 2 minutos e o registro da derivação D2 de maneira contínua, avaliando o comportamento morfológico da onda eletrocardiográfica e a presença de arritmias durante o experimento. Não foram encontradas diferenças significantes entre os grupos estudados. Quando comparamos o comportamento dos parâmetros eletrocardiográficos durante as fases do procedimento, observamos diferenças estatística (p<0,01) para a freqüência cardíaca, amplitude da onda P e duração dos intervalos RR e QTc para o grupo com sedação. Foram observadas arritmias em 53,3% dos pacientes. As arritmias encontradas foram a taquicardia e a bradicardia sinusal, as extrasístoles supraventriculares, ventriculares e extrasístole atrial bloqueada, em ambos os grupos de maneira semelhante, com maior incidência nas fases inicio e perfuração. As arritmias encontradas foram consideradas de baixo risco para pacientes sem compromeitmento sistêmico. Concluiu-se que o uso de 15mg de midazolam não apresentou diferença quando comparado ao placebo. A fase incisão apresentou maiores valores de freqüência cardíaca e amplitude da onda P e menores para duração dos intervalos RR e QTc. As arritmias mais frequentes foram as extra-sístoles e a taquicardias sinusais. / The clinical significance of eletrocardiographic evalution in patients without cardiovascular disease is very small. However, continuous monitoring using electrocardiogram and anxiety control methods, such as behaviour manegement technique and premedication, may be justified in patients with cardiovascular disease undergoing dental procedures that cause stress. The aim of this study was to evaluate the electrocardiographic alterations that occur during oral implant surgeries under local anesthesia with a 2% lidocaine hydrochloride,1: 100,000 epinephrine and midazolam sedation. One hour prior to surgery, patients were given premedication (15 mg midazolam or placebo). The subjects of this study were 15 ASA I patients, who needed bilateral implant surgery on the lower jaw. A total of 30 implant surgeries were evaluated in a double blind study. Electrocardiographic tracing the 12 static leads every two minutes and Lead II was registered in a continuous manner during sugery. Automatic measurement of the following electrocardiographic parameters were also performed: heart rate (HR), duration and amplitude of P wave, ST segment depression, duration of PR segment, QRS complex, and duration of RR, QT and QTc intervals. No statistically significant differences were found between the groups, midazolam and placebo. Howerver, analysis of the data at different stages of implant surgery showed significant difference at 1% level in relation to heart rate and, amplitude of P wave, duration of RR and QTc intervals in the midazolam group. Cardiac arrhythmias were found in 53,3% of the patients. The following cardiac arrhythmias were detected: sinusal tachycardia and bradycardia, sinusal arrhythmia, supraventricular extrasystole, ventricular extrasystole, and blocked atrial extrasystole. Arrhythmias occurred, most frequently, at the begining of implant surgery and during drilling, in a similar pattern in both groups. The arrhythmias detected in these patients were considered low risk factors in patients with no systemic alterations. In conclusion, the use of 15 mg of midazolam seemed to be no different from placebo in this study. During incision, we observed the highest heart rate values and amplitude of P wave and the lowest RR and QTc intervals. Extrasystole and sinusal tachycardia were the most frequent arrhythmias detected in these patients.

O presente estudo objetivou avaliar a sedação e analgesia promovida pela morfina em teiús (Salvator merianae). Foram utilizados oito animais jovens, de ambos os sexos, pesando entre 300 e 1800gr, os quais foram submetidos a três tratamentos, a saber: G5 - 5mg/kg de morfina via intramuscular (IM); G10 - 10mg/kg de morfina IM e G0 - o qual recebeu 0,5mL de NaCl 0,9% IM. O presente estudo foi dividido em duas etapas. A primeira etapa avaliou a sedação promovida pela morfina através da avaliação da atividade locomotora e através dos parâmetros comportamentais. A segunda etapa consistiu na avaliação da analgesia promovida pela morfina frente a um desafio de estímulo térmico. Em ambas as etapas, os animais foram avaliados antes do tratamento (basal) e em 0,5, 1, 2, 3, 4, 6, 12 e 24 horas após o tratamento e os avaliadores desconheciam os tratamentos. As diferenças foram consideradas significantes quando P &lt; 0,05. A temperatura corpórea foi avaliada durante a realização das duas etapas, e em ambas, a temperatura se manteve constante em todos os grupos em relação ao basal, com exceção do momento 12 horas. Na comparação entre grupos, G5 e G10 diferiram de G0 nos momentos 4 e 6 horas durante a primeira etapa e não apresentaram diferenças em relação a G0 durante a segunda etapa. Na avaliação da atividade locomotora, G0 manteve-se constante em todos os momentos em relação ao basal, exceto no momento 12 horas, G5 se mostrou diferente do basal nos momentos 0,5, 4 e 12h e G10 entre os momentos 0,5 hora e 12 horas. Na comparação entre grupos, G5 foi menor que G0 e igual a G10 nos momentos 0,5, 3 e 4horas, porem foi maior que G10 e igual a G0 nos momentos 1,2 e 6h. A avaliação dos parâmetros comportamentais evidenciou diferença entre G5 e o basal nos momentos 2 e 4 horas e em G10 nos momentos 3 e 6 horas, na comparação entre grupos, G5 foi diferente de G0 nos momentos 2 e 4h, e G10 e G0 diferiram entre 1 e 6 horas. G5 e G10 foram iguais entre si em todos os momentos, com exceção do momento 6 horas. A avaliação da analgesia mostrou G0 igual ao basal em todos os momentos de avaliação, exceto em 12 horas após o tratamento, já G5 e G10 demonstraram maior tolerância ao estímulo térmico nos momentos 0,5, 1 e 12h e nos momentos 2, 3, 4, 6 e 12 horas, respectivamente. A comparação entre grupos demonstrou um maior tempo para a retirada do membro, G5 foi maior que G0 nos momentos 0,5, 1 e 4 horas e G10 a partir de 1 hora até 12 horas após o tratamento. A morfina promove redução da atividade locomotora, aumento na pontuação dos parâmetros comportamentais e aumento do tempo de retirada do membro de forma dose-dependente, sugerindo uma ação sedativa e analgésica em teiús. / This study aimed evaluate the sedation and analgesia provided by morphine in tegus (Salvator merianae). Eight young animals were used, of both sexes, weighing between 300 and 1800gr, which underwent three treatments: G5 - 5 mg / kg of morphine intramuscularly (IM); G10 - 10 mg / kg IM and G0 morphine - which received 0.5 ml of 0.9% NaCl (IM). The study was divided into two stages. The first step sedation assessed by morphine promoted by evaluating locomotor activity and through behavioral parameters. The second step was to assess the analgesia provided by morphine facing a challenge of thermal stimulus. In both phases, animals were assessed before treatment (baseline) and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours after treatment and blinded to the treatments. The body temperature was evaluated during the course of the two stages, and both the temperature remained constant in all groups compared to baseline, except the moment 12 hours. In the comparison between groups, G5 and G10 differed G0 in moments 4 and 6 hours during the first stage and showed no differences from G0 during the second stage. In the assessment of locomotor activity, G0 remained constant at all times over the baseline, except at 12 hours, G5 showed different from baseline at times 0.5, 4 and 12 hours and G10 times between 0.5 hours and 12 hours. In the comparison between groups, G5 was lower than G0 and the same of G10 at times 0.5, 3 and 4 hours, however was higher than G10 and the same as G0 in times 1.2 and 6 hours. The behavioral parameters showed difference between G5 and baseline at times 2 and 4 hours and G10 and baseline at times 3 and 6 hours, in comparison between groups G5 and G10 were different in at 2 and 4 hours, and G10 and G0 were different at 1 to 6 hours. G5 and G10 were the same at all times, except at 6 hours after treatment. The evaluation of analgesia showed G0 equal to baseline at all times except at 12 hours after treatment, as G5 and G10 showed increased tolerance to thermal stimulus at times 0.5, 1 and 12h and at times 2, 3, 4, 6 and 12 hours, respectively. Comparison between groups showed a longer time for the withdrawal hind limb, G5 is greater than G0 at times 0.5, 1 and 4 hours and G10 from 1 hour to 12 hours after treatment. Morphine causes a reduction of locomotor activity, increased score of behavioral parameters and increased time of withdrawal hind limb in a dose-dependent manner, suggesting a sedative and analgesic action in tegus.

Intensivvårdsmiljön innebär att patienter är i en utsatt situation där integritet och avskildhet kan bli åsidosatt. Därtill behandlas de med potenta sederande och analgetiska läkemedel som i sin tur ger ogynnsamma effekter. Det är därför av vikt att sträva efter att så låga doser som möjligt administreras. Syftet med studien var att undersöka om det fanns någon skillnad i förbrukning av analgetiska och sedativa läkemedel mellan patienter som vårdats på en specialdesignad intensivvårdssal och patienter som vårdats på en ordinär intensivvårdssal på ett medelstort sjukhus i Västsverige. I studien ingick 149 patienter som vårdadats på en specialdesignad intensivvårdssal eller en ordinär intensivvårdssal. Studien gjordes utifrån en randomiserad kontrollerad design med kvantitativ ansats. Genom retroperspektiv journalgranskning har det studerats hur åtgången av analgetiska och sedativa läkemedel varierat mellan dessa rum. Journalerna som granskades var från 2012 till 2014 och data analyserades utifrån fem faser med enskilda t-test samt multifaktoriell analys. I studien fann författarna vissa skillnader i förbrukningen av sedativa och analgetiska läkemedel men med bristande signifikans. Det krävs dock vidare forskning på området. / Program: Specialistsjuksköterskeutbildning med inriktning mot intensivvård

Pela sua alta incidência, morbidade, mortalidade e custos ao sistema de saúde, a sepse se destaca entre as diversas indicações de internação em unidade de terapia intensiva (UTI). A disfunção da microcirculação tem papel central na gênese e manutenção da síndrome séptica, sendo um marco fisiopatológico desta síndrome. Pacientes críticos invariavelmente estão ansiosos, agitados, confusos, desconfortáveis e/ou com dor. Neste contexto, drogas sedativas são amplamente utilizadas na medicina intensiva. A dexmedetomidina, um agonista potente e altamente seletivo dos receptores alfa-2 adrenérgicos, vem conquistando espaço como o sedativo de escolha nas UTIs por seus efeitos de sedação consciente, redução da duração e incidência de delirium e preservação da ventilação espontânea. Apesar destas possíveis vantagens, a indicação de uso da dexmedetomidina na síndrome séptica ainda carece de conhecimentos sobre seus efeitos na microcirculação e perfusão orgânica. Com o intuito de caracterizar os efeitos microcirculatórios da dexmedetomidina em um modelo murino de endotoxemia que permite estudos in vivo da inflamação e disfunção da perfusão microvascular, hamsters Sírios dourados submetidos à endotoxemia induzida por administração intravenosa de lipopolissacarídeo de Escherichia coli (LPS, 1,0 mg.kg-1) foram sedados com dexmedetomidina (5,0 &#956;g.kg.h-1). A microscopia intravital da preparação experimental (câmara dorsal) permitiu a realização de uma análise quantitativa das variáveis microvasculares e do rolamento e adesão de leucócitos à parede venular. Também foram analisados os parâmetros macro-hemodinâmicos e gasométricos (arterial e venoso portal), as concentrações de lactato arterial e venoso portal, a água pulmonar total e a sobrevivência do animal. Animais não-endotoxêmicos e/ou tratados com solução salina a 0,9% serviram como controles neste experimento. O LPS aumentou o rolamento e a adesão de leucócitos à parede venular, diminuiu a densidade capilar funcional e a velocidade das hemácias nos capilares e induziu acidose metabólica. O tratamento com dexmedetomidina atenuou significativamente estas respostas patológicas (p < 0,05). A frequência de pulso dos animais foi significativamente reduzida pela droga (p < 0,05). Outros resultados não foram tão expressivos (estatisticamente ou clinicamente). Estes resultados indicam que a utilização de dexmedetomidina produz um efeito protetor sobre a microcirculação da câmara dorsal de hamsters endotoxêmicos. Efeitos anti-inflamatórios da dexmedetomidina sobre os leucócitos e o endotélio poderiam melhorar a perfusão capilar e representar o mecanismo in vivo de ação da droga na microcirculação. / Due to its high incidence, morbidity, mortality and costs to the healthcare system, sepsis stands out among the many indications for intensive care unit (ICU) admission. The microcirculatory dysfunction plays a central role in the genesis and maintenance of the septic syndrome, being a pathophysiologic milestone in this syndrome. Critically ill patients are invariably anxious, agitated, confused, uncomfortable and/or with pain. In this context, sedative drugs are widely used in intensive care medicine. Dexmedetomidine, a potent and highly selective agonist of alpha-2 adrenergic receptors, is gaining ground as the sedative of choice in ICUs due to its effects of "conscious sedation", reducing the duration and incidence of delirium and preservation of spontaneous ventilation. Despite these potential advantages, the indication of dexmedetomidine in sepsis syndrome still lacks knowledge about its effects on microcirculation and perfusion. To characterize microcirculatory actions of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microvascular inflammation and perfusion dysfunction, endotoxemia-submitted Syrian golden hamsters, induced by intravenous Escherichia coli lipopolysaccharide (LPS, 1,0 mg.kg-1) administration, were sedated with dexmedetomidine (5,0 &#956;g.kg.h-1). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Macro-hemodynamic parameters, arterial and portal venous blood gases and lactate concentrations, pulmonary total water, and animal survival were also analyzed. Non-endotoxemic and/or normal saline treated animals served as controls in this experiment. LPS increased leukocyte rolling and adhesion, decreased functional capillary density and red blood cell velocity, and induced metabolic acidosis. Dexmedetomidine treatment significantly attenuated these pathologic responses (p < 0.05). The pulse rate was significantly reduced by the drug (p < 0.05). Other results were not as expressive (statistically or clinically). These results indicate that the use of dexmedetomidine yields a protective effect on the microcirculation of the dorsal skinfold in endotoxemic hamsters. Anti-inflammatory dexmedetomidine effects on leukocytes and the endothelium, subsequently improving capillary perfusion, could represent the in vivo mechanism of the microcirculatory action of the drug.

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / A depressÃo à uma doenÃa crÃnica, grave que afeta cerca de 350 milhÃes de pessoas no mundo. O objetivo deste trabalho foi estudar os efeitos antidepressivos do Ãcido lipÃico (ALA) associado a mirtazapina (MIRT) via mecanismos antioxidativos em modelo animal de depressÃo induzido por corticosterona. Camundongos machos adultos receberam 0,3% Tween 80, Corticosterona (CORT 20 mg/kg), MIRT (3 mg/kg), ALA (100 ou 200 mg/kg), sozinhos ou associados por 21 dias. No Ãltimo dia de tratamento os animais foram submetidos aos seguintes testes: campo aberto, labirinto em cruz elevado, suspensÃo de cauda, preferÃncia por sacarose, rota rod e tempo de sono. AlteraÃÃes oxidativas (glutationa reduzida-GSH e peroxidaÃÃo lipÃdica- MDA) e nitrito no cÃrtex prÃ-frontal (CPF), hipocampo (HC) e corpo estriado (CE); e fator neurotrÃfico derivado do cÃrebro (BDNF) no CPF e HC tambÃm foram abordadas. A administraÃÃo crÃnica de CORT desenvolveu alguns comportamentos tipo-depressivos que foram revertidos com MIRT e/ou ALA. A associaÃÃo de ALA e MIRT reverteu o efeito sedativo provocado pela administraÃÃo de MIRT sozinha, assim como a hipersonia causada pela administraÃÃo crÃnica de CORT. A administraÃÃo de CORT, ALA 200 e MIRT associados mostrou um aumento significativos nos nÃveis de GSH no cÃrtex prÃ-frontal (113%), hipocampo (90,27%) e corpo estriado (127%) quando comparado com o grupo tratado com CORT sozinha; efeitos semelhantes foram observados na peroxidaÃÃo lipÃdica e nos nÃveis de nitrito, com reduÃÃo dos nÃveis de MDA e nitrito no hipocampo e corpo estriado dos grupos tratados com a associaÃÃo de CORT, ALA 200 e MIRT quando comparados com o grupo tratado com CORT sozinha, respectivamente. No geral, ALA parece ser uma alternativa para o tratamento da depressÃo quando associado com MIRT, pois aumenta a neuroproteÃÃo e reduz o efeito colateral de sedaÃÃo. / Depression is a chronic, serious illness that affects about 350 million people worldwide. The objective of this work was to study the antidepressant effects of lipoic acid (ALA) associated with mirtazapine (MIRT) via antioxidative mechanisms in animal models of depression induced by corticosterone. Adult male mice received 0.3% Tween 80, corticosterone (Cort 20 mg / kg) MIRT (3 mg / kg), ALA (100 or 200 mg / kg), alone or associated for 21 days. On the last day of treatment the animals were subjected to the following tests: open field, elevated plus maze, tail suspension, preference for sucrose, route rod and sleep time. Oxidative changes (reduced glutathione and GSH-peroxidation lipÃdica- MDA) and nitrite in the prefrontal cortex (PFC), hippocampus (HC) and striatum (CE); and brain-derived neurotrophic factor (BDNF) in the CPF and HC were also addressed. Chronic administration of CORT developed some kind-depressive behaviors were reversed with MIRT and / or ALA. The association of ALA and MIRT reversed the sedative effect caused by the administration alone MIRT, as hypersomnia caused by the chronic administration of CORT. The administration CORT ALA 200 and associated MIRT showed significant increase in GSH levels in the prefrontal cortex (113%), hippocampus (90.27%) and striatum (127%) compared to the group treated with CORT alone; Similar effects were observed on lipid peroxidation and nitrite levels with reduction of MDA and nitrite levels in the hippocampus and striatum in the groups treated with the combination CORT ALA MIRT 200 and compared with the group treated with CORT alone respectively. Overall, ALA seems to be an alternative for treatment of depression associated with MIRT when, for neuroprotection increases and reduces the side effect of sedation.

Purpose: Compare the efficacy of two benzodiazepines (diazepam or midazolam) in combination with meperidine and hydroxyzine for pediatric dental sedation. Methods: A randomized, double blind observation study of behaviors and outcomes related to two sedation groups. Frankl and Houpt behavior scores were recorded at three time points: injection time, initiation of treatment and at the end of treatment. Postoperative phone call surveys were conducted within eight hours of discharge to assess sleep, activity, and behavior. Results: A total of 40 sedation subjects were included in the study, of which 20 were treated with diazepam triple Combination (Di+M+H) and 20 with midazolam triple regime (Mi+M+H). Treatment was successful for 45% of cases with midazolam and 70% with diazepam (P value=.20). Houpt sleep scores were significantly higher for diazepam than midazolam at injection (P-value=.0043) and during treatment (P-value=.0152). Although Frankl scores, Houpt move and Houpt cry scores tended to favor diazepam, none were statistically significantly different. More abnormal behavior was reported with midazolam, though not statistically significant (35% vs 6%, P-value=.0854). Postoperative sleep time was longer for midazolam, but not significantly different (median sleep time: 61 vs 45 minutes, P-value=.2071). Conclusion: The diazepam, meperidine, hydroxyzine triple combination sedation regimen shows promising results as a successful alternative to midazolam triple combination. Longer postoperative monitoring may be required with diazepam, but this study has shown postoperative sleep times to be less than previously reported. Larger sample size is needed to determine if the current trend will be maintained.