Submitted by DANIEL CARVALHO DE MENEZES null (menezesdcc@hotmail.com) on 2016-04-11T00:33:09Z No. of bitstreams: 1 Dissertação - Mestrado - Daniel Carvalho de Menezes.pdf: 1004576 bytes, checksum: ed91db99176a44b0b049ca9ff16a1a70 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-04-12T17:59:09Z (GMT) No. of bitstreams: 1 menezes_dc_me_bot.pdf: 1004576 bytes, checksum: ed91db99176a44b0b049ca9ff16a1a70 (MD5) / Made available in DSpace on 2016-04-12T17:59:09Z (GMT). No. of bitstreams: 1 menezes_dc_me_bot.pdf: 1004576 bytes, checksum: ed91db99176a44b0b049ca9ff16a1a70 (MD5) Previous issue date: 2016-03-03 / Introdução: a presença de dor pós-operatória é uma grande preocupação quando o remifentanil é usado em Anestesia Venosa Total (AVT) devido à meia-vida muito curta desse fármaco e possíveis mecanismos de hiperalgesia e tolerância. Opioides com duração de ação mais prolongada - como sufentanil – têm sido usados durante a indução da AVT com infusão contínua de remifentanil no intuito de suplantar essa limitação. Contudo, a efetividade desta estratégia carece de evidência decorrente de ensaios clínicos. Objetivo: avaliar a eficácia e a segurança da estratégia de administrar sufentanil durante a indução de AVT com remifentanil na analgesia pós-operatória por meio de ensaio clínico randomizado. Método: quarenta pacientes em programação de cirurgia abdominal aberta eletiva foram randomizados para receber infusão contínua de remifentanil em anestesia venosa total, com ou sem a administração de uma dose única de sufentanil, durante a indução da anestesia. Foram avaliados a intensidade da dor pós-operatória, o consumo de morfina e a ocorrência de complicações como náuseas, vômitos, prurido, agitação, sonolência e depressão respiratória, até 48 horas após a cirurgia. O desfecho primário foi o consumo de morfina durante as primeiras 24 horas após a cirurgia. Resultados: a média do consumo de morfina durante as primeiras 24 horas após a cirurgia foi 21,55 mg e 26,68 mg para o grupo que recebeu a dose única de sufentanil e para o grupo controle, respectivamente (p = 0,31). Os pacientes que receberam sufentanil necessitaram de menor quantidade de morfina durante o tempo na Sala de Recuperação Pós-anestésica (SRPA) (média do consumo de morfina total de 7,77 mg versus 15,63 mg, p= 0,02). As diferenças nos escores de dor durante todo o período de estudo e no consumo de morfina após a alta da SRPA não alcançaram significância estatística. A frequência de efeitos adversos não foi estatisticamente diferente entre os grupos. Conclusão: a administração de sufentanil durante a indução anestésica de anestesia venosa total com remifentanil em infusão contínua apresentou superioridade analgésica pós-operatória no período até a alta da SRPA, sem a ocorrência de uma maior proporção de efeitos adversos em relação ao grupo que não recebeu sufentanil. / Background: the presence of postoperative pain is a major concern when remifentanil is used for Total Intravenous Anesthesia (TIVA) because of the very short half-life of this medication and possible mechanisms of hyperalgesia and tolerance. Longer acting opioids – such as sufentanil – have been used during induction of remifentanil-based TIVA as a means to overcome this shortcoming. However, the effectiveness of the strategy still lacks evidence from randomized clinical trials. Objective: we conducted a randomized clinical trial to assess the postoperative analgesic efficacy and safety of a single dose of sufentanil administered during the induction of remifentanil-based TIVA. Methods: forty patients scheduled for elective open abdominal surgery were randomized to receive remifentanil-based TIVA with or without the administration of a single dose of sufentanil during anesthesia induction. We assessed postoperative pain intensity, morphine consumption and the occurrence of complications such as nausea, vomiting, pruritus, agitation, somnolence and respiratory depression up to 48 hours after surgery. The primary outcome was morphine consumption during the first 24 hours after surgery. Results: the mean morphine consumption during the first 24 hours after surgery was 21,55 mg and 26,68 mg for the group that received sufentanil and the control group, respectively (P=0,31). Patients in the sufentanil group required less morphine during their time in the Post-Anesthetic Care Unit (PACU) (mean total morphine consumption of 7,77 mg versus 15,63 mg, P=0,02). Differences in pain scores during the whole study period and morphine consumption after discharge from PACU were not statistically significant. The frequency of adverse effects did not statistically vary between the groups. Conclusion: the administration of sufentanil during anesthetic induction of remifentanil-based TIVA continuous infusion showed superior postoperative analgesic efficacy in the period until discharge from PACU and did not increase the incidence of adverse effects.

Orientador: Francisco José Teixeira Neto / Banca: Antônio José de Araújo Aguiar / Banca: Denise Tabacchi Fantoni / Banca: Silvia Renata Gaido Cortopassi / Banca: Carlos Augusto Araújo Valadão / Resumo: O efeito do remifentanil sobre a concentração alveolar mínima do isoflurano (CAMISO) foi estudado em seis cães com peso médio de 27,7±4,3 kg. Os animais foram anestesiados com isoflurano sob ventilação mecânica, mantendo-se normocapnia (PaCO2 média: 38,5 mm Hg) e normotermia (temperatura corpórea média: 38,1oC). A CAMISO, determinada por meio da estimulação nociceptiva (50V/50Hz/10ms) do membro torácico, foi mensurada antes (basal), durante a infusão contínua de diferentes doses de remifentanil (0,15; 0,30; 0,60 e 0,90 μg/kg/min) e aproximadamente 80 minutos após o término da infusão do opióide. Após um intervalo de 7 dias, a CAMISO foi determinada às 2, 4 e 6 horas após o início da infusão de 0,15 μg/kg/min de remifentanil. As variáveis foram analisadas por meio de ANOVA seguida pelo teste de Tukey ou Dunnett (P<0,05). A CAMISO redeterminada ao término da infusão (1,22±0,20%) não diferiu da CAMISO basal (1,38±0,20%). Os valores da CAMISO foram significativamente mais baixos nas três maiores taxas de infusão em relação à menor (0,15 μg/kg/min). Observou-se redução significativa da CAMISO com todas as taxas de infusão de remifentanil (reduções percentuais em relação ao valor basal de 43±10%, 59±10%, 66±9% e 71±9% para as taxas de 0,15; 0,30; 0,60 e 0,90 μg/kg/min, respectivamente). Embora o valor da CAMISO não tenha diferido entre as taxas de infusão de 0,30; 0,60 e 0,90 μg/kg/min, a percentagem de redução na CAMISO foi maior com a dose de 0,90 em relação à dose de 0,30 μg/kg/min. A CAMISO não se modificou ao longo do tempo com a taxa de 0,15 μg/kg/min. Em uma segunda etapa de experimentos, os efeitos hemodinâmicos da anestesia com remifentanil e isoflurano foram estudados nos mesmos cães. Adicionalmente, amostras de sangue foram colhidas para mensurar a concentração plasmática de arginina vasopressina... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The isoflurane-sparing effect of remifentanil on the minimum alveolar concentration (MACISO) was evaluated in six dogs weighing 27.7±4.3 kg. The dogs were anesthetized with isoflurane and mechanically ventilated to maintain eucapnia (mean PaCO2: 38.5 mm Hg). Mean core temperature was kept at 38.1oC. Noxious stimulation (50V/50Hz/10ms) was applied to the thoracic limb for determination of MACISO before (baseline), during different infusion rates of remifentanil (0.15, 0.30, 0.60 and 0.90 μg/kg/min) and approximately 80 minutes after stopping remifentanil infusion. After a 7-day washout period, MACISO was determined within 2, 4 and 6 hours of a constant rate infusion of remifentanil (0.15 μg/kg/min). Data were analyzed by ANOVA followed by a Tukey or Dunnett test whenever appropriate (P<0.05). After stopping remifentanil infusion, MACISO (1.22±0.20%) did not differ from baseline MACISO (1.38%±0.20). Mean values of MACISO were significantly lower during the infusion rates of 0.30, 0.60 and 0.90 μg/kg/min compared to the lowest infusion rate (0.15 μg/kg/min). All infusion rates of remifentanil decreased MACISO significantly (percentage reductions compared to baseline MACISO were 43±10%, 59±10%, 66±9% and 71±9% for the infusion rates of 0.15, 0.30, 0.60 and 0.90 μg/kg/min, respectively). Although MACISO did not differ among the three highest infusion rates of remifentanil, the percentage reduction in MACISO was significantly greater during 0.90 μg/kg/min compared to 0.30 μg/kg/min. The effect of remifentanil on MACISO was stable during a prolonged constant rate infusion (0.15 μg/kg/min). In a second set of experiments, the hemodynamic changes during remifentanil-isoflurane anesthesia were evaluated in the same six dogs. Additionally, blood samples were collected to determine plasma concentrations of arginine vasopressin. In a randomized cross-over design, the dogs received... (Complete abstract click electronic access below) / Doutor

Orientador: Fernanda Bono Fukushima / Resumo: Introdução: a presença de dor pós-operatória é uma grande preocupação quando o remifentanil é usado em Anestesia Venosa Total (AVT) devido à meia-vida muito curta desse fármaco e possíveis mecanismos de hiperalgesia e tolerância. Opioides com duração de ação mais prolongada - como sufentanil – têm sido usados durante a indução da AVT com infusão contínua de remifentanil no intuito de suplantar essa limitação. Contudo, a efetividade desta estratégia carece de evidência decorrente de ensaios clínicos. Objetivo: avaliar a eficácia e a segurança da estratégia de administrar sufentanil durante a indução de AVT com remifentanil na analgesia pós-operatória por meio de ensaio clínico randomizado. Método: quarenta pacientes em programação de cirurgia abdominal aberta eletiva foram randomizados para receber infusão contínua de remifentanil em anestesia venosa total, com ou sem a administração de uma dose única de sufentanil, durante a indução da anestesia. Foram avaliados a intensidade da dor pós-operatória, o consumo de morfina e a ocorrência de complicações como náuseas, vômitos, prurido, agitação, sonolência e depressão respiratória, até 48 horas após a cirurgia. O desfecho primário foi o consumo de morfina durante as primeiras 24 horas após a cirurgia. Resultados: a média do consumo de morfina durante as primeiras 24 horas após a cirurgia foi 21,55 mg e 26,68 mg para o grupo que recebeu a dose única de sufentanil e para o grupo controle, respectivamente (p = 0,31). Os pacient... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: the presence of postoperative pain is a major concern when remifentanil is used for Total Intravenous Anesthesia (TIVA) because of the very short half-life of this medication and possible mechanisms of hyperalgesia and tolerance. Longer acting opioids – such as sufentanil – have been used during induction of remifentanil-based TIVA as a means to overcome this shortcoming. However, the effectiveness of the strategy still lacks evidence from randomized clinical trials. Objective: we conducted a randomized clinical trial to assess the postoperative analgesic efficacy and safety of a single dose of sufentanil administered during the induction of remifentanil-based TIVA. Methods: forty patients scheduled for elective open abdominal surgery were randomized to receive remifentanil-based TIVA with or without the administration of a single dose of sufentanil during anesthesia induction. We assessed postoperative pain intensity, morphine consumption and the occurrence of complications such as nausea, vomiting, pruritus, agitation, somnolence and respiratory depression up to 48 hours after surgery. The primary outcome was morphine consumption during the first 24 hours after surgery. Results: the mean morphine consumption during the first 24 hours after surgery was 21,55 mg and 26,68 mg for the group that received sufentanil and the control group, respectively (P=0,31). Patients in the sufentanil group required less morphine during their time in the Post-Anesthetic Care... (Complete abstract click electronic access below) / Mestre

Introdução: Os opioides são os analgésicos mais efetivos para tratamento da dor moderada a intensa. No entanto, evidências crescentes têm demonstrado que seu uso pode levar a mudanças na sensibilidade dolorosa. Nesse contexto, a hiperalgesia induzida pelo remifentanil (r-IH) envolve um desequilíbrio nos sistemas inibitórios e excitatórios. Postula-se que um dos mecanismos centrais seja a disfunção do sistema modulador descendente da dor. Então, neste estudo, testamos a hipótese de que a estimulação transcraniana de corrente contínua (ETCC), devido aos seus efeitos analgésicos, poderia prevenir a r-IH. Os desfechos primários incluíram a escala numérica de dor (END 0-10) durante o teste repetitivo ao frio (rCOLDT), e a alteração na END (0-10) durante o teste de modulação condicionada de dor (CPM-TASK). Os desfechos secundários foram os limiares de dor ao calor (HPT) e o tempo de reação durante o teste de dor à água gelada [zero graus oC, (IPT)]. Métodos: Ensaio clínico randomizado, fatorial, duplo cego, que incluiu 48 homens saudáveis, com idades entre 19 e 40 anos. Os sujeitos foram randomizados em quatro grupos (n=12): ativo (a) - ETCC / solução salina, Sham (s) - ETCC / solução salina, a-ETCC / remifentanil e s-ETCC / remifentanil. Foi aplicado o ETCC sobre o córtex motor primário, com uma sessão única de 20 min e 2 mA. Resultados: Durante o rCOLDT, houve um efeito significativo entre os grupos nos escores cumulativos da END (P = 0,01). O grupo s-ETCC / remifentanil apresentou maiores escores de dor durante rCOLDT, [media (SD) 5,49 (1,04)] e a-ETCC / remifentanil apresentaram escores relativamente menores [4,15 (1,62)]. Este achado mostra que o efeito da ETCC bloqueou a HI-R. Os grupos a-ETCC / solução salina e s-ETCC / salina apresentaram menor índice de dor durante rCOLDT, [3.11 (1.2)] e [3.15 (1.62)], respectivamente. A incidência de hiperalgesia definida como um aumento de 15% na END durante o rCOLDT foi de: 31% no grupo s-ETCC/remifentanil; 22% no grupo a-ETCC/remifentanil; 11% no grupo a-ETCC/salina; e 8.3% no grupo s-ETCC/salina. Os grupos com remifentanil apresentaram escore positivo na END (0-10) durante a tarefa CPM, ou seja, produziu um desengate do sistema modulador descendente de dor (DPMS). Além disso, s-ETCC / Remifentanil em comparação com a-ETCC/remifentanil apresentou menor HPT e maior tempo de reação durante o IPT. Conclusão: Esses achados sugerem que os efeitos da a-ETCC previne a disfunção da capacidade inibitória do sistema modulador descendente da dor induzido pelo remifentanil durante o rCOLDT. / Background: Opioids are the most effective analgesics to treat moderate to severe pain. However, growing evidence shows that opioids can elicit unexpected changes in pain sensitivity. In this sense, remifentanil-induced hyperalgesia (r-IH) involves an imbalance in the inhibitory and excitatory systems. It postulates that one of the central mechanisms is the dysfunction of the descending pain modulating system. We tested the hypothesis that transcranial Direct Current Stimulation (t-DCS), given its analgesics effects, could prevent r-IH. The primary outcomes included the Numerical Pain Score NPS (0-10) during the repetitive cold test (rCOLDT) and the change on the NPS (0-10) during the conditioned pain modulation (CPM)-task. The secondary outcomes were the heat pain threshold (HPT) and the reaction-time during the Ice-Water Pain Test (IPT). Methods: This double blinded, explanatory factorial randomized trial included 48 healthy males, ages ranging 19 to 40 years. They were randomized into four equal groups: active (a)-tDCS/saline, sham (s)-tDCS/saline, a-tDCS/remifentanil and s-tDCS/remifentanil. We applied tDCS over the primary motor-cortex, with a single session of 20 minutes and 2mA. Results: During the rCOLDT, there was a significant group effect on the cumulative NPS scores (P=0.01). The s-tDCS/remifentanil group presented larger pain scores during rCOLDT, [mean (SD) 5.49 (1.04)] and a-tDCS/remifentanil group had relative lower pain scores [4.15 (1.62)]; showing its blocking effect on r-IH. a-tDCS/saline and s-tDCS/saline groups showed lowest pain scores during rCOLDT, [3.11(1.2)] and [3.15(1.62)], respectively. The incidence of hyperalgesia defined as a 15% increase in NPS during rCOLDT was: 30.3% in the s-tDCS / remifentanil group; 22% in the a-tDCS / remifentanil group; 11% in the a- tDCS / saline group; 8.3% in the s-tDCS / saline group. Remifentanil groups showed positive scores in the NPS (0-10) during the CPM-task, that is, it produced a disengagement of the descending pain modulatory system (DPMS). Also, s- tDCS/Remifentanil compared to a-tDCS/Remifentanil showed lower HPT and larger reaction-time during the IPT. Conclusion: These findings suggest that the effects of a-tDCS prevents the dysfunction of the inhibitory capacity of the descending modulatory pain system induced by remifentanil during rCOLDT.

Submitted by (edna.saturno@ufrpe.br) on 2016-10-13T11:48:46Z No. of bitstreams: 1 Jairo de Macedo.pdf: 599046 bytes, checksum: 6a11dd425d912b6f9c15d757a5cee99d (MD5) / Made available in DSpace on 2016-10-13T11:48:46Z (GMT). No. of bitstreams: 1 Jairo de Macedo.pdf: 599046 bytes, checksum: 6a11dd425d912b6f9c15d757a5cee99d (MD5) Previous issue date: 2008-02-29 / Several anesthesic protocols aiming to reduce undisirable haemodinamics effects, allowing safetier return with minimal side effects to patient. Thus, the objective of this study was to evaluate the possible changes in vital parameters related to ECG, heart rate and body temperature in bitches pre-treated with atropine, anesthetized with ketamine and xylazine, associated or not to different doses on a continuous infusion of remifentanil. It was used 15 clinical healthy bitches, distributed acoording to experimental groups: G1= ketamine+ xylazine; G2= ketamine + xylazine + continuous remifentanil infusio(0,125 g/Kg/min); G3 = ketamine + xylazine + continuous remifentanil infusion (0,25 g/Kg/min). The variable measurement was accomplished before pre-anesthesia (M0), simultaneously to skin incision (M1), during the closing of right ovarian pedicle (M2), during the occlusion of the uterine stump (M3) and half for finish of the skin synthesis (M4). Data showed a sudden increasing on average and standard deviation of cardiac frequency in all groups at M1 (178.6 20.6), having decreasing, although with tachycardia tendency until M4 (157.3 18.3). Such M1 elevation is correspondent to surgical cut moment, suggesting the biggest nociceptive moment, following by right pedicle closing M2, (176.0 15.2). It was not observed apnea on animals, just an considerable repiratory decreasing on six animals (6/15) being one of them (1/5) on G1, thre animals (3/5) on G2 and two animals (2/5) on G3. The corporal temperature values measured by rectum did not showed biological significant among groups, keeping these averages compatibles qith physiological parameters for specie. According to the resultspresented one can suggest that the increase in T wave may be related to electrolyte imbalance, and disrritmia heart, being observed framework of hypoxemia. Further studies with a larger number of animals may confirm the efficiency of the anesthetic protocol using atropine, xylazine, ketamine associated with continuous infusion for remifentanil under the effective control of pain. / Os diversos protocolos anestésicos visam abreviar os efeitos hemodinâmicos indesejáveis, proporcionando um retorno mais seguro, com os mínimos efeitos colaterais para o paciente. Dessa forma, objetivou-se com este trabalho avaliar as possíveis alterações de parâmetros vitais relacionadas à eletrocardiografia, freqüência respiratória e temperatura corporal em cadelas pré-tratadas com atropina, anestesiadas com quetamina e xilazina, associadas ou não a diferentes doses de remifentanil sob infusão contínua. Para tanto, foram utilizadas 15 cadelas clinicamente sadias, distribuídas de acordo com os grupos experimentais: G1 = quetamina + xilazina ; G2 = quetamina + xilazina + infusão contínua com remifentanil (0,125μg/Kg/min); G3 = quetamina+ xilazina + infusão contínua com remifentanil (0,25μg/Kg/min). As mensurações das variáveis foram realizadas antes da pré-anestesia (M0), simultaneamente à incisão da pele (M1), durante a ligadura do pedículo ovariano direito (M2), durante a ligadura do coto uterino (M3) e na metade do término da síntese cutânea (M4). Os resultados apresentaram aumento nas médias e desvio padrão na freqüência cardíaca em todos os grupos no M1 (178,6±20,6), sendo posteriormente decrescente, porém, com tendência à taquicardia até M4 (157,3±18,3). Tal elevação em M1, corresponde ao momento de incisão cirúrgica, sugerindo o momento de maior estímulo nociceptivo, seguido da ligadura do pedículo direito (M2, 176,0±15,2). Não se observou apnéia em nenhum dos animais, apenas queda considerável da freqüência respiratória em seis animais (6/15), sendo um animal (1/5) no G1, três animais (3/5) no G2 e dois animais (2/5) no G3. Os valores da temperatura corporal,mensuradas via retal, não apresentaram diferenças biologicamente significativa entre os grupos, mantendo suas médias dentro dos parâmetros fisiológicos para espécie. De acordo com os resultados apresentados pode-se sugerir que o aumento da onda T pode estar relacionado a desequilíbrio eletrolítico, além de disrritmia cardíaca, sendo observado quadro de hipoxemia. Estudos posteriores com um maior número de animais poderão confirmar a eficiência do protocolo anestésico utilizando atropina, xilazina, quetamina associadas ao remifentanil sob infusão contínua para o efetivo controle da dor.

The main drives of development of fast track cardiac anaesthesia are the increase burden of health care cost and the shortage of intensive care beds. Fast track (FT) is multidisciplinary process that leads to rapid patient recovery and discharge without affecting morbidity and mortality. Fast track cardiac anaesthesia (FTCA) was proved to be safe, efficient and economically effective. Leipzig FT protocol was first introduced in November 2005 for elective cardiac surgery patients in the heart center of Leipzig University. It is characterized by using intraoperative remifentanil as main opioid with treating the patients postoperatively in post-anaesthesia care unit (PACU) completely bypassing ICU admission. Remifentanil was unavailable in Germany from February to July 2017, therefore the protocol had to be modified and sufentanil was used instead. The aim of this retrospective study was to compare the effects of remifentanil and sufentanil on the well-established FT concept. The primary end points were ventilation time, LOS in PACU (LOS PACU), the visual analogue score (VAS) and the piritramide consumption on the day of operation. The secondary end points were LOS in intermediate care (LOS IMC), hospital LOS, FT failure (FTF), in-hospital mortality and postoperative complications such as postoperative nausea and vomiting (PONV), delirium and the incidence of reintubation. All cardiac surgery patients consecutively admitted to PACU during the period from February to July 2017 (n=622), received sufentanil (FT-S), were compared to patients (n=679) from the same time period of the previous year treated with continuous remifentanil infusion (FT-R) according to the standard FT protocol. To minimise selection bias and to obtain comparable groups, we used a 1:1 nearest neighbour propensity score matching approach resulted in total 1218 patients divided in 2 equal groups. In FT-R, an uninterrupted continuous infusion of remifentanil (0.2-0.3 µg/kg/min) was used for maintenance of anaesthesia throughout the whole operation. In FT-S, a continuous infusion of sufentanil was used during maintenance of anaesthesia as follows: 1 µg/kg/h until sternotomy, 0.5 µg/kg/h until cardiopulmonary bypass and 0.25 µg/kg/h until chest closure, then the infusion was stopped. Otherwise, the Leipzig FT protocol was used as previously published. Remifentanil was more effective in reducing time to extubation (by 40 minutes) and length of stay in the post anaesthetic care unit during fast track cardiac anaesthesia than sufentanil. There was an increased need of piritramide when remifentanil was used. The hospital length of stay was longer in remifentanil group. There were no differences between both groups regarding postoperative complications. Clinically, a detailed and time-directed weaning protocol is more important than the use of a specific opioid during fast track treatment in cardiac surgery patients.:TABLE OF CONTENTS 1. List of Abbreviations 3 2. Bibliographic description 5 3. Abstract 5 4. Introduction 6 4.1 Fast-track cardiac anaesthesia 6 4.1.1 Definitions 6 4.1.2 Current evidence of FTCA 7 4.1.2.1 The safety of FTCA 7 4.1.2.2 The efficiency of FTCA 7 4.1.2.3 Economic Implications of FTCA 8 4.1.3 Different FTCA pathways 8 4.1.4 Patient selection and optimization 9 4.1.5 Anaesthesia aspects of FT 11 4.1.6 Cardiopulmonary bypass aspects of FT 12 4.2 Leipzig FT Protocol 12 4.3 Opioids 16 4.3.1 Remifentanil 16 4.3.2 Sufentanil 17 5. Objective of the work 19 6. Materials and Methods 19 7. Results 21 8. Discussion 26 9. Publication manuscript: „ A comparison of sufentanil versus remifentanil in fast-track cardiac surgery patients “Anaesthesia 2019, 74, 602–608“. 30 10. Summary 37 11. Bibliography 39 12. Appendix (Anlagen): 43 12.1 Declaration of Independence (Selbstständigkeitserklärung) 43 12.2 Declaration of co-authors’ contribution 44 12.3 Publications 45 12.4 Acknowledgment 46

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Hintergrund: In dieser Arbeit wurde untersucht, ob durch die Nutzung von Remifentanil eine Verbesserung der Narkoseführung und Beschleunigung der postoperativen Erholung bei kurzen, schmerzarmen, diagnostischen Eingriffen zu erzielen ist. In der vorliegenden Studie wird ein Narkosekonzept unter Verwendung von Remifentanil/Propofol/Isofluran einer häufig für kurze gynäkologische Operationen genutzten Kombination Ketamin/Propofol/Lachgas gegenübergestellt. Methode: Die Untersuchung fand im Zeitraum April 1997 bis März 1998 im Krankenhaus im Friedrichshain (Berlin) statt. Einer statistischen Zufallsliste entsprechend wurden 108 Patientinnen, die vorher festgelegte Einschlusskriterien erfüllten, einer der beiden Narkosemethoden im einfach-blind Modus zugeordnet. Zur Bearbeitung der Fragestellung wurden kurze gynäkologische Eingriffe (Kürettagen, Interruptiones) ausgewählt. Die Dokumentation der Erholung erfolgte unmittelbar postnarkotisch unter Anwendung psychomotorischer und kognitiver Leistungstests (Memo- Test, Zahlen nachsprechen, Zahlenverbindungstest, Test d2, Maddox wing, Finger-Tapping). Die Aussage dieser Untersuchungen wurde durch Analogskalen (Schmerz-Score, Befindlichkeitsskala) und standardisierte Fragen (intraoperatives Träumen, Zufriedenheit) ergänzt. Die Teilnehmerinnen wurden dreimal hintereinander der selben standardisierten Untersuchungs-, Test- und Befragungsfolge unterzogen. Ergebnisse: Die beiden Untersuchungsgruppen waren hinsichtlich der allgemeinen Ausgangsdaten Alter, Gewicht, Größe, Body-Maß-Index und Nebenerkrankungen vergleichbar. Hinsichtlich der am Vortag (t0) erhobenen Ausgangsdaten und der Verteilung von Persönlichkeitscharakteristika gab es zwischen den Gruppen keine Unterschiede. Die in den Untersuchungen erhobenen Daten zeigten deutliche Vorteile in der psychomotorischen Erholung für die Remifentanil-Gruppe. Schnellere postoperative Erholung konnte durch die psychomotorischen Leistungstests sowie in den Analogskalen belegt werden. Vorteil der Verwendung von Remifentanil ist das Erwachen am Ende der Operation mit sofortigem Wiedererlangen der Koordination. Die narkosebedingten Nachwirkungen Übelkeit und Erbrechen sind selten und die Patienten fühlen sich wohl. Ein entscheidender Nachteil der Kombination Propofol/Remifentanil ist jedoch der intraoperative Abfall von Blutdruck und Herzfrequenz. In der Ketamin-Gruppe ist die Häufigkeit intraoperativer Träume erstaunlich hoch. Schlussfolgerung: Der Einsatz von Remifentanil bei Eingriffen, die postoperativ mit geringen bis mäßigen Schmerzen verbunden sind, sichert eine komplikationsarme und im Vergleich zu Ketamin schnellere postoperative Erholung. Der Überwachungsaufwand und die Überwachungsdauer können somit erheblich reduziert werden. Der indikationsgerechte Einsatz von Remifentanil bei diesen Eingriffen kann dazu beitragen, die Patientensicherheit zu erhöhen und gleichzeitig Aufwand und Kosten für die postoperative Patientenbetreuung zu senken. / Background: Aim of this study was to figure out, if the use of remifentanyl can improve management of anaesthesia and cause faster recovery after minor gynaecological operative procedures. For that reason we compared the common anaesthetic procedure using ketamine/ propofol/ nitrous oxide with the combination remifentanil/ propofol/ isoflurane. Method: The investigation was performed during April 1997 until March 1998 in the hospital Krankenhaus im Friedrichshain (Berlin). 108 female patients, who met fixed inclusion criteria before, were assigned to a statistic coincidence list according to one of the two methods of anaesthesia in single-blind mode. Short gynaecological interventions as curettages or termination of pregnancy were selected for the study. The recovery documentation took place immediately post narcotic, using psychomotor and cognitive performance tests (word recall, number recall, Maddox wing, finger tapping, number-connection test, test d2). The results of these investigations were supplemented by the results of line analogue rating scales (pain score, feeling scale) and standardized questions (intraoperative dreaming, satisfaction). According to a standardized schedule, the participants underwent three times the same standardized investigations-, tests- and questioning sequences. Results: The two groups of investigations were comparable regarding the general data age, weight, size, and Body measure index and side diseases. Regarding the original data, obtained at the previous day (t0), and the distribution of personality characteristics, there were no differences between the groups. The data raised in the investigations showed clear advantages in the psychomotor recovery for the group of remifentanil. Faster post narcotic recovery can be proved by the psychomotor performance tests as well as in the rating scales. Most important advantage of the use of remifentanil is awaking at the end of the operation with the immediate regaining of the coordination. The anaesthesia related side effects as nausea and vomiting are rare and the patients feel well. A remarkable disadvantage of the combination propofol/remifentanil is, however, the intraoperative drop of blood pressure and heart frequency, especially in elderly patients. Frequency of intraoperative dreaming can be observed much more in the ketamine group. Conclusion: By the use of remifentanil in operative procedures, causing less, up to moderate postoperative pain, we secured rare complications and post surgical faster recovery compared with the ketamine group. The postoperative monitoring expenditure as well as the duration of monitoring can be substantially reduced. The indication-fair use of remifentanil in these surgical procedures surgery can contribute to increase patient security and to lower expenditure and costs of the post surgical patient care at the same time.

Aspiration of gastric content and delayed or failed intubation are the leading causes of anesthesia-related mortality and morbidity. In the recovery period, airway obstruction with subsequent hypoxia is a relatively common cause of morbidity, and is highly associated to the amount of opioids administered, especially in obese patients. The overall aim of this thesis was to study these risk factors for airway complications and postoperative hypoxia in obese patients, and to evaluate possible strategies for their prevention. In Study I, intubation times and incidence of failed intubation in obese patients were compared between direct laryngoscopy and videolaryngoscopy with the Stortz® C-MAC™. In Studies II and III, the effect of esmolol vs. remifentanil on the esophageal junction, and the possible analgesic properties of low-dose esmolol vs. placebo were evaluated using high-resolution manometry and the cold pressor test, respectively. Finally, in Study IV, the possible opioid-sparing effect of esmolol after laparoscopic gastric bypass surgery was evaluated. The use of videlaryngoscopy did not shorten intubation times, however appeared to reduce the incidence of failed intubation. Our results also show that esmolol has a favorable profile, compared to remifentanil, with regard to the protection against passive regurgitation and aspiration of gastric content. No analgesic effect of low-dose esmolol was however demonstrated. The intraoperative administration of esmolol instead of remifentanil also did not reduce the requirement of morphine for treatment of post-operative pain. The use of Stortz® C-MAC™ may be recommended for intubation of obese patients. Further studies are however required to clarify the possible role of esmolol in anesthesia.

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