A espécie leporina vem sendo utilizada de forma ampla como modelo experimental em diversas áreas da medicina e medicina veterinária. A escassez de estudos publicados nesta área torna questionável a utilização ética da espécie em experimentos cirúrgicos. O objetivo foi determinar a duração dos bloqueios motor e sensitivo da lidocaína e bupivacaína administradas pela via peridural sacrococcígea e lombossacra e seus efeitos cardiovasculares e respiratórios associados a anestesia geral inalatória em coelhos submetidos a orquiectomia. Foram utilizados 30 animais da espécie leporina, raça Nova Zelândia Branco, pesando entre 2,350 e 3,300 kg, distribuídos em cinco grupos experimentais. O grupo Lido LS recebeu 0,3 ml/kg de lidocaína a 2% pela via peridural lombossacra; o grupo Lido SC recebeu 0,3 ml/kg de lidocaína a 2% pela via peridural sacrococcígea; o grupo Bupi LS recebeu 0,3 ml/kg de bupivacaína a 0,5% pela via peridural lombossacra; o grupo Bupi SC recebeu 0,3 ml/kg de bupivacaína a 0,5% pela via peridural sacrococcígea e o grupo Controle recebeu 0,3 ml/kg de solução fisiológica pela via peridural lombossacra. A administração peridural foi realizada por meio de punção simples com agulha hipodérmica. Na primeira parte do experimento, os animais foram anestesiados com sevofluorano em oxigênio a 100% com auxílio de máscara, e após a administração do protocolo de cada grupo, os reflexos sensitivos foram testados por meio de pinçamento dos dermátomos cutâneos e dos dígitos dos membros pélvicos e cauda. Os reflexos motores foram avaliados por meio de escore de tônus muscular dos membros pélvicos e cauda. Esta fase teve como objetivo determinar a duração e padrão de dispersão do bloqueio sensitivo e motor. Duas semanas após a determinação da duração do bloqueio sensitivo e motor, os animais foram anestesiados com isofluorano em máscara, intubados, e a administração do mesmo protocolo de anestesia peridural foi realizada para a realização de orquiectomia. A frequência cardíaca, frequência respiratória, pressão arterial sistólica, média e diastólica, concentração de dióxido de carbono ao fim da expiração, concentração de isofluorano inspirado e expirado, saturação de oxihemoglobina e temperatura corpórea foram monitorados a cada 10 min durante 50 min. Logo após a administração peridural e ao fim do procedimento, uma amostra de sangue arterial foi colhida para avaliação hemogasométrica. A dispersão, avaliada pelo número de dermátomos bloqueados, nos grupos que receberam a administração lombossacra foi maior que nos grupos de administração sacrococcígea. O período médio de bloqueio sensitivo com a lidocaína foi de 70±13,78 min pela via lombossacra e 60,83±23,11 min pela via sacrococcígea. Com a administração de bupivacaína pela via lombossacra, a duração do bloqueio sensitivo foi de 199,16±15,30 min e pela via sacrococcígea foi de 168,33±44,57 min. O grupo controle teve maior consumo de anestésico geral e maior requerimento de analgésico trans-operatório e de fármacos vasoativos durante o procedimento, demonstrando analgesia insuficiente e depressão cardiovascular superior aos grupos em que houve a associação da anestesia peridural e geral. Houve ocorrência de bloqueio unilateral em 50 % dos animais que receberam a administração sacrococcígea. Conclui-se que a administração peridural lombossacra apresentou duração e dispersão maiores que a administração sacrococcígea em coelhos. A ocorrência de bloqueio unilateral foi maior com a utilização do sítio sacrococcígeo. Foi observada maior depressão cardiovascular nos animais que não receberam a administração de anestésico local no espaço epidural. A utilização de lidocaína e bupivacaína levou a anestesia peridural satisfatória na espécie leporina, sendo uma técnica eficiente e de fácil execução. / Rabbits have been widely used as an experimental model in different areas of medicine and veterinary medicine. The few published studies in this area make the ethical use of this species in surgical experiments questionable. The aim of this study was to determine the duration of sensory and motor block of lidocaine and bupivacaine epidurally administered in lumbosacral or sacrococcygeal sites and their cardiovascular and respiratory effects associated with inhalation anesthesia in rabbits undergoing orchiectomy. Thirty New Zealand White rabbits were used, weighing between 2,350 and 3.300 kg, divided into 5 experimental groups. The Lido LS group received 0.3 ml / kg of 2% lidocaine lumbosacral epidural; Lido SC group received 0.3 ml / kg of 2% lidocaine sacrococcygeal epidural; Bupi LS group received 0.3 ml / kg of 0.5% bupivacaine for lumbosacral epidural; Bupi SC group received 0.3 ml / kg of 0.5% bupivacaine for sacrococcygeal epidural; and the control group received 0.3 ml / kg of saline epidural lumbosacral. Epidural was performed by single puncture with hypodermic needle. In the first part of the experiment, the animals were anesthetized with sevoflurane in 100% oxygen mask, and after the administration of each protocol group, the sensitive reflexes were tested by pinching the skin dermatomes and the digits of the hind limbs and tail. The motor reflexes were evaluated by scoring muscle tone of the pelvic limbs and tail. Two weeks after the determination of the duration of sensory and motor block, the animals were anesthetized with isoflurane in mask, intubated, and the administration of the same protocol of epidural anesthesia was performed for the orchiectomy. Heart and respiratory rate, systolic, mean and diastolic arterial blood pressure, end-tidal CO2, concentration of isoflurane inhaled and exhaled, oxyhemoglobin saturation and body temperature were monitored every 10 minutes during a 50 minutes surgery. Soon after epidural administration and at the end of the procedure, a sample of arterial blood was collected for evaluation of arterial blood gases. The dispersion was measured by the number of dermatomes blocked and groups receiving lumbosacral administration had a higher number than groups that received sacrococcygeal administration. The mean duration of sensory block with lidocaine was 70±13.78 min via lumbosacral site and 60.83±23.11 min via sacrococcygeal site. In bupivacaine lumbosacral group, the duration of sensory block was 199.16±15.30 min and in sacrococcygeal group was 168.33±44.57 min. The control group had higher consumption of general anesthetic and trans-operative analgesic requirement and had higher vasoactive requirement during the surgical procedure, demonstrating greater cardiovascular depression than the groups that received an association of epidural and general anesthesia. There was 50% occurrence of unilateral block in animals that received the sacrococcygeal administration. It is concluded that epidural administration showed lumbosacral length and dispersion greater than sacrococcygeal administration in rabbits. The incidence of unilateral block was higher when used the sacrococcygeus site. Greater cardiovascular depression was observed in animals that did not receive the administration of local anesthetic into the epidural space. The use of lidocaine and bupivacaine led to satisfactory epidural anesthesia in rabbits, being an efficient and easy technique to perform.

Orientadores: Francisco Carlos Groppo, Maria Cristina Volpato / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-20T03:45:44Z (GMT). No. of bitstreams: 1 Nolasco_FabianaPinchetti_M.pdf: 1683899 bytes, checksum: b9140ed1fab0d06207e5a084fc6ea01e (MD5) Previous issue date: 2012 / Resumo: O presente estudo avaliou a eficácia anestésica das formulações: prilocaína 3% encapsulada em lipossomas unilamelares (Prilo-LUV, concentração lipídica 4mM), prilocaína 3% encapsulada em lipossomas multilamelares (Prilo-MLV, concentração lipídica 8mM) e prilocaína 3% com felipressina 0,03UI/mL (Prilo-Feli), em três modelos, bloqueio do nervo infraorbital (BNIO), bloqueio do nervo alveolar inferior (BNAI) e infiltração subcutânea em ferida cirúrgica (ISFC). Foram usadas como controle formulações lipossomais unilamelar e multilamelar sem anestésico e solução de NaCl 0,9%. No BNIO e BNAI as formulações anestésicas foram injetadas do lado direito e os controles no esquerdo. Para o BNIO, 30 ratos (10 animais/grupo) receberam 0,1 mL de uma das formulações próximo ao forame infraorbital. Foi avaliada a duração da anestesia por pinçamento do lábio superior, a cada 5 minutos. Para o BNAI 45 ratos (15 animais/grupo) receberam 0,2 mL das formulações próximo ao forame mandibular. Foram avaliados sucesso, latência e duração da anestesia pulpar com estímulo elétrico ("pulp tester"). Para a ISFC 36 ratos (6 animais/grupo) foram submetidos à incisão na pata traseira direita e 24 horas após, receberam 0,1 mL das formulações nas duas patas traseiras (com e sem incisão); a anestesia foi avaliada pelo analgesímetro de von Frey. Os resultados foram submetidos aos testes de Log-Rank, Kruskal-Wallis, Student-Newman-Keuls e Friedman (?= 5%). No BNIO, a Prilo-Feli proporcionou duração de anestesia maior que a Prilo-LUV (p<0,05); Prilo-MLV não diferiu das demais (p>0,05). A Prilo-Feli proporcionou maior sucesso de anestesia (p<0,05) que a Prilo-LUV e Prilo-MLV, sem diferença entre estas (p>0,05). Para o BNAI Prilo-Feli proporcionou maior sucesso e duração de anestesia que as formulações lipossomais (p<0,05); Prilo-MLV apresentou maior sucesso de anestesia que Prilo-LUV (p<0,05), mas não diferiu desta com relação à duração da anestesia (p>0,05). Não houve diferenças entre formulações com relação à latência (p>0,05). Para a ISFC, nas patas com hipernocicepção Prilo-Feli proporcionou maior duração de anestesia que Prilo-LUV e Prilo-MLV (p<0,05), sem diferença entre estas (p>0,05); nas patas sem hipernocicepção não houve diferenças entre as formulações (p>0,05). Com relação ao sucesso da anestesia, em ambas as condições, com e sem hipernocicepção, Prilo-Feli mostrou maior sucesso que Prilo-LUV e Prilo-MLV (p<0,05), sem diferença entre estas (p>0,05). Conclui-se que a encapsulação da prilocaína em lipossomas unilamelares e multilamelares resultou em menor eficácia anestésica em comparação á solução de prilocaína com felipressina nos modelos avaliados / Abstract: The present study assessed the anesthetic efficacy of the following formulations: 3% prilocaine with 0.03 UI/mL felypressin (Prilo-Fely), 3% prilocaine encapsulated in unillamellar liposomes (Prilo-LUV, 4 mM lipid concentration) and 3% prilocaine encapsulated in multillamelar liposomes (Prilo-MLV, 8 mM lipid concentration) in three models, in rats: infraorbital nerve block (IONB), inferior alveolar nerve block (IANB), and subcutaneous infiltration in surgical wound (SISW). The following were used as controls: unillamelar liposomal suspension, multillamelar liposomal suspension and 0.9% NaCl solution. For IONB and IANB the anesthetic formulations were injected in the right side and the respective controls in the left side. For IONB, 30 rats (10 animals per group) received 0.1mL of the anesthetic formulations near the infraorbital foramen. The duration of anesthesia was assessed by upper lip pinching every 5 minutes. For IANB, 45 rats (15 animals per group) received 0.2mL of the anesthetic formulations near the right mandibular foramen. The success, onset and duration of pulpal anesthesia were assessed by electric pulp tester. For SISW, 36 animals (6 animals per group) were submitted to incision in the right hind paw and 24h after they received 0.1mL of the formulations in both hind paws (with and without incision). Anesthesia was evaluated with von Frey anesthesiometer. Data were submitted to Log-Rank, Kruskal-Wallis, Student-Newman-Keuls and Friedman tests (?= 5%). For IONB Prilo-Fely presented longer anesthesia duration than Prilo-LUV (p<0.05); Prilo-MLV did not differ from the others (p>0.05). Prilo-Fely promoted higher anesthesia success (p<0.05) than Prilo-LUV and Prilo-MLV, with no difference between these two formulations (p>0.05). For IANB Prilo-Fely provided higher success and duration of anesthesia than the liposomal formulations (p<0.05); Prilo-MLV presented higher anesthesia success than Prilo-LUV (p<0.05), but did not differ from the latter concerning anesthesia duration (p>0.05). No differences among the formulations were observed for BNAI anesthesia onset (p>0.05). For SISW in the hypernociceptive paws, Prilo-Fely provided longer anesthesia duration than Prilo-LUV and Prilo-MLV (p<0.05), with no difference between these two formulations (p>0.05); in the non hypernociceptive paws no differences were observed among the formulations (p>0.05). In both conditions, with and without hypernociception, Prilo-Fely presented higher anesthesia success (p<0.05) than Prilo-LUV e Prilo-MLV, whith no difference between these two formulations (p>0.05). It can be concluded that the encapsulation of prilocaine in unillamelar and multillamelar liposomes provided lower anesthetic efficacy when compared to prilocaine with feypressin in the evaluated models / Mestrado / Farmacologia, Anestesiologia e Terapeutica / Mestre em Odontologia

Up to 80% of serious medical errors occur due to miscommunication from one provider to another (The Joint Commission, 2012). In order to ensure ongoing safe patient care, it is imperative that anesthesia providers communicate effectively and consistently when transferring patient responsibility to other providers, especially to post-anesthesia care unit (PACU) nurses. Multiple patient transfers occur each day and patients are commonly transferred between multiple providers during the same hospital stay. These opportunities are extremely vulnerable to communication errors. Structured patient handoff checklists or tools increase the consistency of information transferred from anesthesia providers to other providers. The Joint Commission recommended in 2012 that all anesthesia providers utilize a standardized patient handoff checklist to increase and improve the quality of data transferred from anesthesia provider to the PACU nurse. Certified Registered Nurse Anesthetists (CRNA) at a local surgical unit provide the bulk of patient handoffs in this postoperative unit, and currently, there is no mandated use of a standardized handoff checklist. As a result, the CRNAs provide a verbal patient handoff that is unscripted. Verbal patient handoffs differ among providers due to individual provider preference. Without using a standardized handoff checklist, there is a risk of increasing communication errors which increase medical errors and negative patient outcomes. Salzwedel (et al., 2013), in a study when utilizing a handoff checklist, concluded that critical patient data conveyed during patient handoffs increased by 32.4% to 48.7% (Salzwedel et al., 2013). Tscholl et al. (2015) and McElroy et al. (2015) through surveys, determined that data transferred between anesthesia providers was more structured. Handoff checklists increased PACU nurse satisfaction regarding the overall handoff experience (McElroy et al., 2015). No studies, to date, were found that understand the perceptions and thoughts of CRNAs regarding the utilization of patient handoff checklists or tools in clinical practice. This Doctor of Nursing Practice (DNP) project assesses the perceptions and thoughts of utilizing standardized handoff checklists among CRNAs. The hope of this study is to better understand CRNA perceptions in order to identify potential barriers or knowledge gaps regarding the benefit of utilizing a standardized patient handoff checklists. Data from this project may be used to structure future quality improvement projects aimed at decreasing communication errors and improve patient outcomes. The results of this project show the majority of CRNAs (89.5%) surveyed for this project were already familiar with handoff checklists. However, only 26.3% of those same participants agreed they currently use a standardized patient handoff checklist. Of the surveyed participants, only 36.8% were interested in utilizing a standardized patient handoff tool even though nearly 50% agreed that using a handoff checklist would increase the consistency of information transferred from anesthesia provider to nurses. This correlates with the 73.7% of participants who already believe they currently transfer pertinent patient information successfully without utilizing a standardized handoff checklist or tool. Despite studies reporting improved patient outcomes, decreased medical errors, and the Joint Commission’s recommendations to use standardized handoff checklists or tools, the majority of anesthesia providers at this facility do not choose to use handoff checklists. By surveying anesthesia providers' thoughts and perceptions, the researcher attempted to answer why anesthesia providers are not utilizing handoff checklists in their daily routines.

Ces 20 dernières années, la mortalité attribuable à l’anesthésie a été divisée par 10. Cette baisse de mortalité offre la possibilité de porter une attention plus importante à certains critères d’évaluation, reportés par les patients, tels que le vécu ou la satisfaction. Appliqué au contexte periopératoire, le vécu du patient peut constituer un indicateur de résultats de l’anesthésie, à classer aux côtés de la morbidité et de la mortalité. Une prémédication anxiolytique est largement pratiquée avant une intervention chirurgicale à travers le monde. Une autre stratégie répandue pour améliorer le vécu du patient consiste à réaliser une sédation prolongée au décours des interventions réalisées sous anesthésie locorégionale. Ces pratiques ne reposent que sur un faible niveau de preuve et leur efficacité n’est pas évaluée.Ce travail de thèse à permis de développer deux outils d’analyse de la période periopératoire, soit un questionnaire d’évaluation de l’anxiété préopératoire et une échelle d’évaluation du vécu periopératoire en anesthésie locorégionale. Ces outils ont été déployés au sein d’une démarche de recherche clinique afin d’évaluer formellement l’efficacité de la prémédication sédative et celle de la sédation peropératoire dans deux études prospectives randomisées distinctes. Les résultats mettent en évidence que si l’anxiété préopératoire est liée à un moins bon vécu global de la période periopératoire, la réalisation systématique d’une prémédication ou d’une sédation ne résulte pas en une meilleure expérience pour le patient et est à l’origine d’effets adverses significatifs. / The last 20 years, mortality due to anesthesia was divided by 10. This decline in mortality allows to bring more attention to certain evaluation criteria, reported by patients, such as experience or satisfaction. Applied to the perioperative context, the patient experience can be a major outcome of anesthesia, alongside morbidity and mortality. Different empirical approaches, are implemented for several years to improve the patient experience. Sedative premedication is widely practiced before surgery worldwide. Another common strategy to improve the patient experience is to perform continuous sedation in interventions performed under regional anesthesia. These practices rely on a low level of evidence and their effectiveness is not evaluated. Such an assessment would require the use of validated tools together with a clinical experimental approach placing the patient experience as the primary endpoint.This thesis allowed to develop two tools for analyzing the perioperative period, i.e. an evaluation of preoperative anxiety and the assessment of perioperative patient experience in regional anesthesia. These tools have been deployed in a clinical research process to formally evaluate the effectiveness of sedative premedication and intraoperative sedation in two separate randomized studies. The results show that if preoperative anxiety is related to poorer overall experience of the perioperative period, the systematic implementation of premedication or sedation does not result in a better experience for the patient and could lead to significant adverse effects.

Anesthetics have been used for nearly two centuries, and have proved to be one of the most important tools in surgical interventions, but their methods of action remain mysterious. Previous research has focused on high-level, low-resolution measurements (average activity of many neurons) or low-level, high-resolution measurements (single neurons). The nematode Caenorhabditis elegans provides an excellent model to bridge the gap between these two scales by measuring the activity of many neurons with single neuron resolution. C. elegans display analogous behaviors to humans under anesthesia. Employing confocal imaging of GCaMP, I measured neuronal activity at different isoflurane levels in C. elegans ganglia and in small behavior-controlling circuits. The activity in C. elegans ganglia is similar to that of human ganglia, as assessed using measures that are similar to EEG. Activity in the small behavior-controlling circuit is disrupted, but not suppressed, when dosed with moderate levels of isoflurane. Neural activity in the circuit is randomized resulting in a loss of coordination between neurons that define behavioral states of the system. As such, the onset of the behaviors of anesthesia appears to be the resultant of randomization rather than suppression of individual neuron activity. Employing light sheet microscopy and automated image analysis for neuronal tracking, I expanded the imaging techniques to measure activity of the majority of neurons in the animal’s head. Expansion of these measurements to the whole head region of the nematode confirms these findings, displaying significant decreases in neuron-to-neuron coordination, as well as randomization of individual neuron signals with the onset of anesthesia. These results reveal a new physiological mechanism of action for anesthetics, and provide an avenue forward for investigating the molecular mechanism including specific genetic mutations known to alter susceptibility to anesthetics. / 2021-05-26T00:00:00Z

Breathing is an essential homeostatic function and its disruption leads to disability, brain damage, and death. Serotonin (5-hydroxytryptamine; 5-HT) neurons in the brainstem play an important role in control of breathing. Medullary 5-HT neurons are stimulated by increased CO₂ and subsequently stimulate respiratory nuclei to increase ventilation and maintain normal blood gas levels. Anesthetic-induced breathing dysfunction is a serious concern in healthcare settings. In research settings, experiments are often performed under anesthesia, and therefore it is important to understand how these drugs affect animal physiology. Unfortunately, little is known about how anesthetics modulate 5-HT neurons, breathing, and CO₂ chemoreception in mice, as many of the previous studies have been performed in different species. Characterizing how anesthetics commonly used in both research and clinical settings affect 5-HT neurons, breathing and CO₂ chemoreception is valuable to the broader field of neuroscience since these drugs are so ubiquitously used in research. Breathing dysfunction and defects in the serotonergic system have been implicated in disorders, such as sudden unexpected death in epilepsy (SUDEP) and sudden infant death syndrome (SIDS), which means better characterizing the role of 5-HT neurons in breathing has translational impact as well. Here I examine whether halogenated inhalational anesthetics, which potentiate TWIK-related acid-sensitive K⁺ (TASK) currents and GABAA receptors, could mask an effect of CO₂ on 5-HT neurons. During in vivo plethysmography in mice, a therapeutic level of isoflurane (1%) markedly reduced the hypercapnic ventilatory response (HCVR) in all mouse strains tested. In dissociated cell cultures, isoflurane (1%) hyperpolarized 5-HT neurons and inhibited spontaneous firing. A subsequent decrease in pH from 7.4 to 7.2 depolarized 5-HT neurons, but that was insufficient to reach threshold for firing. Depolarizing current restored baseline firing and the firing frequency response to acidosis, indicating that isoflurane did not block the underlying mechanisms mediating chemosensitivity. These results demonstrate that isoflurane masks 5-HT neuron chemosensitivity in vitro, and markedly decreases the HCVR in vivo. Next, I demonstrate that ketamine-xylazine or urethane anesthesia also significantly reduced the HCVR in mice at both therapeutic and sub-therapeutic doses. However, mice treated with a sub-therapeutic dose of anesthesia decreased their O₂ consumption in parallel, and thus matched their ventilation to metabolic demands. Mice that were anesthetized with the therapeutic dose did not sufficiently match their breathing and metabolic demands, and thus anesthesia induced hypoventilation. Recordings from 5-HT neurons in culture indicated that neither ketamine nor urethane affected 5-HT neuron chemosensitivity. These data demonstrate that anesthetics with different molecular targets similarly reduce the HCVR in mice, but not all of their effects are mediated via 5-HT neurons. Moreover, both ketamine-xylazine and urethane anesthesia altered baseline breathing in different ways, suggesting they targeted different parts of the respiratory network. Finally I show that isoflurane anesthesia in neonatal mice caused depression of resting ventilation, which was different from isoflurane-anesthetized adults. This effect was more pronounced in wildtype mice compared to littermates with genetic deletion of 5-HT neurons. Isoflurane-induced breathing depression decreased and mice fully recovered following washout of isoflurane at P8. I observed that genetic deletion of 5-HT neurons in mice with a congenic C57Bl/6 background led to a more severe phenotype than previously described in mixed genetic background strains. These mice had decreased survival, severe growth retardation, and reduced baseline ventilation. These results indicate that 5-HT neurons have a different role during the neonatal period and that some mouse strains are more sensitive to genetic deletion of 5-HT neurons; thus, background genetics play an important role in phenotype presentation. In summary, different classes of anesthetics each strongly depress chemoreception. Isoflurane seems to affect breathing, in part, by hyperpolarizing 5-HT neurons and masking their chemosensitivity, whereas ketamine and urethane have less effect on 5-HT neurons. However, both ketamine-xylazine and urethane anesthesia alter baseline breathing. Isoflurane anesthesia decreases baseline ventilation in neonates, but this effect is absent in adults, which suggests that the effects of isoflurane on breathing changes as mice age. These data are important for the field of respiratory physiology because they highlight the sensitivity of breathing to the effects of anesthetics. These results are valuable to the broader field of neuroscience, because anesthetics are widely used during in vivo research. Additionally, some transgenic mouse strains are more sensitive to 5-HT neuron deletion depending on their genetic background. In the future it will be critical to characterize the molecular mechanisms that underlie these phenomena.

Seit Mitte der 1990er Jahre haben sich Fast-Track-Behandlungskonzepte in der Kardioanästhesie etabliert. Diese zielen darauf ab, unter Verwendung kurzwirksamer Anästhetika eine frühzeitige postoperative, tracheale Extubation der Patienten zu gewährleisten, und folgend die Dauer der postoperativen Behandlung auf der Intensivstation und im Krankenhaus sowie die Inzidenz an Komplikationen zu senken. Kernstück eines multimodalen, kardioanästhesiologischen Fast-Track-Konzeptes am Herzzentrum in Leipzig (HZL) ist eine postanästhesiologische Aufwacheinheit (PACU) mit 3 Patientenplätzen, in der Patienten postoperativ betreut werden, ohne dass eine Aufnahme auf die Intensivstation (ICU) erfolgen muss. Ziel dieser Arbeit ist, den Einfluss der PACU im Rahmen des Fast-Track-Konzeptes im Vergleich zur Behandlung auf der Intensivstation zu untersuchen. Hierzu führten wir eine prospektiv-randomisierte kontrollierte Studie mit insgesamt 200 elektiven, kardiochirurgischen Patienten durch. Resultat der Studie war eine signifikant kürzere Dauer bis zur Extubation in der PACU im Vergleich zur Kontrollgruppe, zudem war die Verweildauer in der PACU im Median signifikant kürzer als auf der ICU. Hinsichtlich der postoperativen Mortalität und Morbidität zeigten sich keine wesentlichen Unterschiede. Hieraus lässt sich schlussfolgern, dass eine postoperative Fast-Track-Behandlung in einer dedizierten PACU im Vergleich zur ICU zur früheren Extubation und Verlegung auf die weiterversorgenden Stationen führt, ohne dass die Sicherheit der Patienten beeinträchtigt wird.:Vorbemerkung Erklärung zum wissenschaftlichen Beitrag des Promovenden zur Publikation Bibliographische Beschreibung I. Einführung I. 1. Einführung und Grundlagen der Fast-Track-Rehabilitation I. 2. Entwicklung des Fast-Track in der Kardioanästhesie (FTCA) I. 3. Wesentliche Elemente der FTCA und deren Evidenz I. 4. Fast-Track-Behandlung am Herzzentrum Leipzig I. 5. Zielstellung der Arbeit II. Publikation III. Zusammenfassung III. 1. Hintergrund III. 2. Zielsetzung III. 3. Methode III. 4. Ergebnisse III. 5. Schlussfolgerung IV. Anlagen IV. 1. Literaturverzeichnis IV. 2. Verzeichnis der verwendeten Abkürzungen IV. 3. Eigenständigkeitserklärung

Sugammadex, a gamma cyclodextrin discovered in 2007, provides a safe and effective alternative to drugs currently used in surgery by anesthesiologists. A problem in the current practice of anesthesia is the use of Succinylcholine, a neuromuscular blocking agent used for the cessation of the patient's skeletal muscle movement. Succinylcholine is used due to its unique fast onset and short duration, ideal for short procedures, difficult intubation scenarios, and rapid sequence intubation. However, it is used cautiously due to several risks such as causing myalgia, hyperkalemia, fasciculations, and increasing intracranial, intragastric, and intraocular pressure. Sugammadex provides a safer alternative to Succinylcholine because it allows immediate reversal of a neuromuscular blockade through a different mechanism, which does not lead to harmful adverse effects. Sugammadex works by encapsulating its target muscle relaxant, Rocuronium. Rocuronium is a relatively safer drug than Succinylcholine with a similar time of onset, but a very long duration of action. Since Sugammadex is able to immediately reverse the effects of Rocuronium, this combination of Rocuronium and Sugammadex provides the same desired effect as Succinylcholine but without the harmful side effects. The current most widely used reversal agent for muscle relaxation is Neostigmine. The problems with Neostigmine are that it can lead to residual paralysis and recurarisation if under dosed. It also produces unwanted cholinergic side effects that lead to cardiovascular instability. Due to this, the medical community is in need for a better reversal agent that can both quickly and completely reverse muscle paralysis without the need to manage unwanted side effects. Sugammadex is able to address both the problems of Succinylcholine and Neostigmine. Studies have shown Sugammadex to provide a faster, safer, and more predictable reversal of Rocuronium - induced neuromuscular blockade than Neostigmine. Sugammadex has shown to also achieve faster recovery from Rocuronium - induced muscle paralysis than the fast spontaneous recovery of Succinylcholine. With no serious adverse effects observed in these studies, the data supports the use of Sugammadex and its potential to replace the current standards of practice with Succinylcholine and Neostigmine. Furthermore, high dosage of Sugammadex has shown to be capable of immediately reversing profound neuromuscular blockades, an ability that no reversal drug currently in the market possesses. This enables the anesthesiologist to provide optimal muscle relaxation for the surgeon throughout the operation without the concern of being unable to reverse the patient in a timely manner. Studies on multiple patient population groups do not show any serious adverse effects are linked to using Sugammadex. There have been incidences of drug induced QTc prolongation in cardiac patients, but its cause was not determined to be related solely with Sugammadex. Sugammadex has shown to be the safer reversal agent compared to Neostigmine in cardiac, pulmonary, and renal patients. One problem that prevents the routine use of Sugammadex is its cost. The cost is significantly higher than Neostigmine. This cost is justified, however, due to staff costs saved from a faster patient recovery and shorter stay in the hospital. Therefore, while Sugammadex is definitely warranted over Succinylcholine due to its safety profile, its use over Neostigmine is dependent on each healthcare facility. While Sugammadex is currently under review by the Food and Drug Administration, it will evolve the practice of anesthesia if allowed into the United States market.

Thesis (M.Sc.D.)--Boston University School of Graduate Dentistry, 1973. Pedodontics. / Bibliography included.

Anesthesia affects the central nervous system and can suppress cardiovascular activity. In this study, we compared two anesthetics, urethane and alpha-chloralose, to better understand their effect on sympathetic control of blood pressure, as well as how they would affect baroreceptor response and blood pressure in adult rats. To do this we performed baroreceptor tests in adult rats under isoflurane anesthesia and then either urethane (I.V. 1.25 g/kg, n=2) or alpha-chloralose (100 mg/kg, n=2). We found that baroreceptor responses were not significantly different between urethane or alpha-chloralose anesthesia. However, significant depression of baseline blood pressure occurred under alpha-chloralose anesthesia compared with urethane. Additionally, we observed significant elevation of baseline renal sympathetic nerve activity (RSNA) occurred under urethane anesthesia. Ultimately, our findings suggest that both urethane and alpha-chloralose provided sufficient induction of anesthesia without significantly modifying baroreceptor response. However, since urethane significantly raised baseline sympathetic nerve activity, it should be avoided in studies where raised sympathetic activity could confound with the test results. alpha-chloralose significantly lowered baseline blood pressure by nearly 30%, and its use should be avoided in studies where lowered blood pressure may confound the results.