Sedan början av 2000-talet har ambulanssjukvården haft en snabb utveckling inom flera områden. Möjligheten att administrera smärtlindring har utvecklats och dagens ambulanser är nu mer välutrustade med ett flertal smärtlindrande preparat att välja mellan. Detta ställer stora krav på den specialistsjuksköterska som vårdar patienten. År 2015 infördes nya läkemedel och även ett, för ambulanssjukvården nytt administreringssätt: intranasalt. En stor andel av patienterna i ambulanssjukvården lider av akut smärta och är således i behov av smärtlindring. Sufentanil är en stark opioid med egenskaper lämpade för intranasal administrering. Det finns dock få prehospitala studier om intranasal smärtlindring generellt och än färre gällande sufentanil. Dessutom har ingen tidigare forskning har jämfört effekten av intranasalt administrerat sufentanil mellan barn, vuxna och äldre.   Syftet med denna studie var att beskriva användningen av intranasalt administrerat sufentanil i en prehospital kontext. Vidare studerades frågeställningar gällande grad av smärtlindring, förekomst av biverkningar, etablering av perifer infart, i vilken miljö patienten befann sig samt personalens upplevelser.   Författarna analyserade ett antal utvärderingsprotokoll som fyllts i av sjuksköterskor som administrerat intranasalt sufentanil. Studiens data delades upp i tre grupper utifrån deltagarnas ålder. De tre grupperna var barn, vuxna och äldre. Kvantitativ ansats användes och datan analyserades med hjälp av ANOVA och chi2test beroende på datanivå. Jämförande analyser gällande skillnad i medelvärde samt förekomst genomfördes mellan grupperna. Till exempel jämfördes grad av smärtlindring, mängd givet läkemedel samt förekomst av biverkningar mellan grupperna.   Resultatet visade att samtliga grupper erhåller en adekvat smärtlindring, vilket definierades som tre poäng eller lägre mätt med visuell analog skala [VAS] vid avlämning på akutmottagningen. Barn erhöll signifikant högre doser jämfört med både vuxna och äldre samt hade en lägre VAS vid avlämning på akutmottagning. Andningsdepression förekom i två fall och då i gruppen äldre. Illamående och kräkningar var den vanligaste biverkan hos vuxna och äldre medan det hos barn var slöhet. I barngruppen så etablerades signifikant färre antal perifera venkatetrar [PVK] jämfört med övriga grupper. Sjuksköterskorna uppskattade att behandlingen hade bäst i effekt på barn och därefter äldre samt vuxna.   Slutsatsen var att prehospital administrering av sufentanil tycks ge en bra smärtlindring som ligger inom behandlingsmålet, andelen biverkningar är inte större än i tidigare studier. Däremot visade vårt resultat att barn i viss utsträckning blir slöa vid behandling med intranasalt sufentanil. / Since the beginning of the 2000s, Emergency Medical Services has had rapid development in several areas. The possibility to administer pain relief has been developed and today's ambulances are well-equipped with a variety of pain relief preparations to choose from. This places great demands on the specialist nurse who cares for the patient. In 2015, new medicines were introduced alongside with a, for the ambulance service, new route of administration: Intranasal. A large proportion of the patients in the ambulance service are suffering from acute pain and are therefore in need of adequate pain relief. Sufentanil is a strong opioid that has properties to be the optimal intranasal drug for pain management. However, there are few studies on intranasal pain management in a pre-hospital context. In addition, no previous studies have compared the effect of intranasally administered sufentanil between children, adults and the elderly.   The aim of the study was to describe the use of intranasally administered sufentanil in the pre hospital environment. More specifically we studied: the degree of pain relief, the occurrence of side effects, the establishment of peripheral lines, the environment in which the patient was and also the experience of the staff.   The authors analyzed evaluation protocol witch had been filled in by nurses, who had administered intranasal sufentanil. The protocols were divided into three groups based on age. The groups where children, adults and elderly. Quantitative approach where used and data were analyzed according to ANOVA and chi2test depending on the data grade. Both nominal and ordinal data were included in the analysis. Data presented in visual analogue scale (VAS) before pain management and at arrival at emergency department (ED), dose and incidence of adverse effects were analyzed and compared between the groups.   The results showed that all groups receive adequate pain relief, which was defined as three points or lower measured by visual analogue scale [VAS] on handoff at the emergency department [ED]. Children received significantly higher doses compared to adults and elderly and they also scored a lower VAS at arrival to the ED. Respiratory depression occurred in two cases in the elderly group. The most common adverse effects were nausea and vomiting except in children where sedation was the dominant adverse effect. In children significantly lower number of peripheral lines were established compared to adults and elderly. Nurses appreciated the effect of the intervention as good but with greater contented in the children.   The conclusion was that pre-hospital administration of sufentanil appears to provide a good pain relief within the treatment target, the proportion of adverse reactions is not greater than in previous studies. On the other hand, our results showed that children to a certain extent become drowsy in treatment with intranasal sufentanil.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

No description available.

Att ge smärtstillande prehospitalt kan i vissa fall vara ett problem. Sjuksköterskan i ambulansen måste först göra en bedömning av patientens status, utvärdera och behandla. Det vanligaste alternativet för smärtbehandling idag är att patienten får morfin intravenöst. I flera regioner finns idag sufentanil tillgängligt att administrera intranasalt prehospitalt. Detta är ett enklare sätt att tillför analgetika. Dock visar det sig att i det ambulansområde författaren undersöker administreras mycket lite sufentanil i förhållande till morfin.Syftet med studien var att beskriva sjuksköterskors erfarenhet av att administrera sufentanil intranasalt vid prehospital sjukvård.Författaren har använt sig av en enkätstudie, ansatsen var kvantitativ och data samlades in med en enkät i likertskala vilken skickades ut till all personal inom en ambulansentreprenörs område i en region i mellansverige. Data analyserades sedan med deskriptiv statistik, data var ordinal.I resultatet analyserades frågorna utifrån erfarenhet av sufentanil ur begreppen användande, effekt och erfarenhet i yrket hos sjuksköterskorna. Även effekt på barn analyserades ur separat.Resultatet blev att sjuksköterskorna till stor del har erfarenhet av att de inte använder sig av sufentanil som förstahandspreparat utan endast när de inte lyckas eller inte har möjlighet att etablera intravenös kanyl. Denna inställning minskade ju mindre erfarenhet i yrket sjuksköterskan hade och barn behandlades oftare med sufentanil än vuxna. Effekten av preparatet ur sjuksköterskornas erfarenhets perspektiv bedömdes som tveksam, återigen med ett högre positivt resultat från de mer oerfarna sjuksköterskorna. Erfarenheten av effekt på barn har även bedömts som bättre än för vuxna.Slutsatsen blev att sufentanil intranasalt ej övervägdes att användas i den utsträckning som kan förväntas i förhållande till att det är ett lättare läkemedel att administrera och är mer skonsamt att använda på barn. Orsaken till detta kan vara att sjuksköterskorna hade dåliga erfarenheter av effekten på läkemedlet prehospitalt. Detta i sin tur kan bero på en låg initial dos enligt behandlingsanvisningarna. Dessutom visade studien att erfarenheten i yrket förstärker dessa argument samt att barn övervägs behandling oftare än vuxna.Det behövs fler studier i ämnet för att klargöra vilka brister och fördelar det finns med sufentanil intranasalt prehospitalt. / Administration of analgetics in the prehospital setting may occassionally be a problem. The ambulance nurse first has to make an assessment of the patient’s status, evaluate and treat the condition. The most commonly used analgetics are morphine administrated intravenously. Several regions in Sweden also have access to sufentanil to administrate intranasally, which is a more easy way to medicate the patient. Though it is obvoius in the studied area that the amount of administrations of sufentanil in comparison to morphine is very low, the author asks himself, why?The purpose of the study was to describe nurses´ experiences of administering sufentanil intranasally in the prehospital setting.The method used by the author was a post-positivistic study with a quantitative approach. Data was collected from results of a survey sent to the ambulance staff in a specific area. The data was then analyzed and presented by descriptive statistiscs. The concepts of experience from the use of and effects of, were used as main categories. The data was further analyzed in the two minor categories, experience in profession and experience of the effect on children.The outcome was that the ambulance nurses in large parts do not experience that they use sufentanil as the first choice when treating pain; they rather install an intravenous catheter to be able to administrate morphine. This attitude declines the less experienced in the profession the ambulance nurses were and the ambulance nurses also experienced that children were offered sufentanil at a higher rate than adult patients. Also, the most experienced nurses in the profession claimed to have experienced that sufentanil was insufficient for pain relief, although they still admitted they experienced it had better effects on children.The conclusion was that the ambulance nurses experience did not use sufentanil intranasally as can be expected considering that is is easier to administrate than other substances and is more gentle when treating children. The reson for this could be that nurses had bad experiences of the effect of the substance in the prehospital setting. This, in turn could be the effect of using a low initial dose as prescripted in the guidelines. Furthermore the study demonstrated that the length of experience in the profession enhances these arguments and that sufentanil to children is more often considered than to adults.There is a need for further studies to clarify what negative and positive aspects there are of using sufentanil intranasally in the prehospital setting.

Zusammenfassung: Fentanyl und Sufentanil sind zwei synthetisch hergestellte Opioide, die in der Anästhesiologie für die intraoperative Analgesie eingesetzt werden. Sie weisen ein unterschiedliches pharmakodynamisches Profil auf. Im Jahr 2014 wurde das Opioidregime für minimal-invasive Standardeingriffe im Klinikum Fulda von Fentanyl auf Sufentanil umgestellt. In der geplanten retrospektiven Datenerhebung sollten Daten von Patienten, die vor 2014 mit Fentanyl analgesiert wurden, verglichen werden mit Daten von Patienten, bei denen nach 2014 Sufentanil in die Narkoseführung implementiert war. Untersucht werden sollte, ob der Wechsel auf ein Opioid mit einem vermeintlich geeigneteren Profil für die Narkoseführung tatsächlich die kalkulierten Vorteile erbracht hat. Die retrospektive Datenerhebung sollte aufzeigen, ob Patienten während und nach MIC-CHE oder MIC-TEP von einer Sufentanil-Gabe gegenüber der Fentanyl-Gabe profitieren: Verkürzt sich die Ausleitungsphase, haben die Patienten bei Ankunft im Aufwachraum (AWR) eine bessere Oxygenierung und/oder eine stabilere Kreislaufsituation? Leiden die Patienten nach Sufentanil unter weniger postoperativer Übelkeit und Erbrechen (PONV), benötigen sie weniger Schmerzmittel? Die Untersuchung sollte zudem klären, ob biometrische Faktoren wie Geschlecht, Alter, Gewicht und BMI in Zusammenhang mit dem eingesetzten Opioid eine relevante Rolle für das postoperative Befinden der Patienten spielten, und ob sich aus der Umstellung von Fentanyl auf Sufentanil ökonomische Vorteile ergaben. Ergebnis: Kombination Desfluran mit Sufentanil für alle untersuchten Gruppen von klinischem Vorteil. Bevorzugter Einsatz bei MIC-Eingriffen in der Allgemein- und Viszeralchirurgie empfehlenswert. - Geringerer postoperativer Schmerzmittelbedarf - Bessere postoperative Oxygenierung - Kürzere postoperative Aufwachzeit - Niedrigerer intraoperativer Opioidbedarf - Wirtschaftlich/ökonomische Gleichwert Begründete Aussage, dass Sufentanil bei MIC-Eingriffen in der Allgemein- und Viszeralchirurgie im Vergleich zu Fentanyl das überlegene Medikament ist. (überwiegend statistisch signifikant) Steigerung dieses Effekts über die Kombination mit Desfluran möglich. / Summary: Fentanyl and sufentanil are two synthetically produced opioids that are used in anesthesiology for intraoperative analgesia. They have a different pharmacodynamic profile. In 2014, the opioid regime for minimally invasive standard interventions at the clinic in Fulda was changed from fentanyl to sufentanil. In the planned retrospective data collection, data from patients who were analgesized with fentanyl before 2014 should be compared with data from patients in whom sufentanil was implemented in anesthesia after 2014. It should be investigated whether the change to an opioid with a supposedly more suitable profile for anesthesia has actually produced the calculated benefits. The retrospective data collection should show whether patients benefit from administration of sufentanil compared to administration of fentanyl during and after MIC-CHE or MIC-TEP: Shorter elimination phase? Better oxygenation-situation on arrival in the recovery room or a more stable circulatory situation? Do the patients suffer less postoperative nausea and vomiting (PONV) after sufentanil, do they need less pain-medication? The investigation should also clarify whether biometric factors such as gender, age, weight and BMI in connection with the opioid used to play an important role in the postoperative condition of the examined patients and whether there were any economic benefits in switching from fentanyl to sufentanil. Result: The combination of desflurane with sufentanil was of clinical advantage for all examined groups. Recommended for use in MIC- operations in visceral surgery. - Less need for post-operative pain medication - Better post-operative oxygenation - Shorter post-operative wake-up time - Lower intraoperative opioid requirement - Economic / economic equivalence Well-founded statement that sufentanil is the superior drug compared to fentanyl in MIC-procedures in visceral surgery. (mostly statistically significant) This effect can be increased by combining it with desflurane.

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: 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

Orientadores: Eneida de Paula, Cíntia Maria Saia Cereda / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-20T18:07:47Z (GMT). No. of bitstreams: 1 Queiroz_VivianeAparecida_M.pdf: 5281811 bytes, checksum: 4084a85b3806be04ca8c3375db357399 (MD5) Previous issue date: 2012 / Resumo: Dentre os fármacos usados para prevenir e aliviar a dor encontram-se os anestésicos locais (AL). A bupivacaína (BVC) é um dos AL do tipo amino-amida mais utilizado na terapia da dor aguda e crônica. Sua combinação com opióides lipofílicos tornou-se uma prática comum para analgesia em procedimentos cirúrgicos, com o objetivo de reduzir a dose necessária de AL sem comprometer a qualidade de analgesia. Contudo, a BVC é conhecida por apresentar uma acentuada toxicidade para o sistema nervoso central e sistema cardiovascular. Uma alternativa para diminuir os efeitos tóxicos, bem como aumentar o efeito terapêutico é a utilização de sistemas de liberação modificada de fármacos, que empregam carreadores como as ciclodextrinas. Neste trabalho avaliamos a eficácia anestésica e o perfil farmacocinético da BVC (na forma do complexo BVC hidroxipropil-beta-ciclodextrina - BVC:HP--CD, na razão molar de 1:1) em associação com o opióide sufentanil (SUF), em modelos animais. Foram realizados também ensaios de citotoxicidade in vitro, em cultura de células de fibroblastos 3T3 e de neurogliomas NG97, sendo a viabilidade celular determinada através do teste de redução do MTT. Para avaliação da atividade analgésica, realizou-se o teste pressão na pata em ratos da linhagem Unib: Wistar; os animais foram tratados com injeção intratecal de: BVC e BVC:HP-?-CD nas concentrações de 4, 8 e 16 mM (0,125; 0,25 e 0,5%, respectivamente), associadas ou não com 38,8 ?M de SUF; o bloqueio motor induzido por essas formulações foi também avaliado. Para determinação da concentração plasmática e do perfil farmacocinético das formulações descritas, foram utilizados coelhos albinos da raça Nova Zelândia, que receberam tratamento por via intratecal, com BVC livre ou complexada (16 mM), associada ou não com SUF (38,8 ?M); as amostras foram analisadas por espectrometria de massas. Nos testes de avaliação de toxicidade in vitro, células 3T3 e NG97 foram tratadas com as formulações acima, mas em concentrações que variaram de 0,2 a 4 mM, para a BVC livre ou complexada, em associação ou não com SUF em concentração proporcionalmente correspondentes à dos testes in vivo (9,5 ?M). Nos resultados de atividade analgésica, o tratamento com BVC:HP-?-CD+SUF prolongou o efeito analgésico, em comparação com BVC+SUF, em 1,9 e 1,8 vezes nas concentrações de BVC de 4 e 8 mM, respectivamente. Além disso, não foram verificadas diferenças estatísticas entre os grupos quanto à função motora dos animais. Em relação ao perfil farmacocinético da BVC, o grupo BVC:HP-?-CD apresentou características de lenta liberação, com baixos níveis plasmáticos, que não foram alteradas após a associação ao coadjuvante SUF. Esses resultados evidenciam uma potencial aplicação clínica da associação medicamentosa BVC:HP-?-CD e SUF, para reduzir a frequência de administração e também a concentração necessária de BVC para promover analgesia em procedimentos cirúrgicos / Abstract: Local anesthetics (LA) are among the most important medicines used to prevent and alleviate pain. Bupivacaine (BVC) is the drug of choice in the treatment of acute and cronic pain, worldwide. It has been used in association with lipophilic opioids in surgical procedures, reducing the required amount of anesthetic without loss of the analgesic level achieved. Bupivacaine is also known to be toxic for the Central Nervous and Cardiovascular systems. The development of drug delivery systems, with carriers such as cyclodextrins, is an interesting approach to reduce toxic side effects and to enhance the therapeutic index of biological active compounds. Here we evaluated the anesthetic activity as well as the pharmacokinetic profile of BVC (free and complexed with hydroxypropyl-beta-cyclodextrins - BVC:HP--CD in a1:1 molar ratio) in association with the opioid sufentanil (SUF) in animal models. The cytotoxicity of such formulations against 3T3 fibroblasts and NG97 neuroglioma cells in culture were also investigated by the use of MTT reduction tests. Sensorial (paw pressure test) and motor blockage was evaluated after intrathecal administration of BVC and BVC:HP-?-CD at concentrations = 4, 8 and 16mM (0.125; 0.25 and 0,5%, respectively), associated or not with 38.8 ?M SUF, to Unib WH rats. BVC plasma levels and pharmacokinetic profile were evaluated through mass spectroscopy in New Zealand rabbits, intrathecally administrated with 16 mM BVC (free or complexed with HP--CD), associated of not with 38.8 ?M SUF. For the in vitro tests 3T3 and NG97 cells were treated with the formulations at concentrations that ranged from 0.2 to 4 mM BVC (free or complexed) plus 9.5 ?M SUF, i.e. proportionally equivalent to the concentration used at the in vivo tests. Treatment with BVC:HP-?-CD+SUF was able to improve the antinonciceptive effect of bupivacaine 1.8-1.9 times (4 and 8 mM, respectively), in comparison to BVC+SUF. No statistical differences were observed for the motor blockade among the groups. Regarding the pharmacokinetic profile of BVC, the BVC:HP-?-CD group showed slow release characteristics with low plasma levels, with no changes after the association to the SUF supporting. Altogether these results point toward a potential application for the pharmaceutical association of BVC:HP-?-CD with SUF, reducing the concentrations and the administration frequency required for analgesia effect in surgical procedure / Mestrado / Bioquimica / Mestre em Biologia Funcional e Molecular

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

Univerzita Karlova 1. lékařská fakulta Studijní program: Biomedicína Studijní obor: Preventivní medicína MUDr. Karolína Hronová Polymorfismus genů účastnících se v metabolismu léčiv jako potenciální cíl prevence závažných komplikací léčby u novorozenců a dětí Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants Disertační práce- ABSTRAKT V ANGLICKÉM JAZYCE Školitel: prof. MUDr. Ondřej Slanař, Ph.D. Konzultant: MUDr. Pavla Pokorná, PhD. Praha, 2018 Abstract Background and aims: The safety of analgosedative drugs includes drug interactions, adverse effects, withdrawal syndrome and drug dependence are factors that significantly affect morbidity and mortality. Its prevention is critical for quality improvement of care in paediatric patients. The aim of the thesis was to evaluate the prediction of efficacy and safety of analgosedative drugs sufentanil, midazolam, tramadol and valproic acid in neonates and children based on the occurrence of selected pharmacogenetic biomarkers. The incidence of drug interactions of phenobarbital with other analgosedative drugs has also been evaluated. Methodology: The thesis is based on two studies conducted on Intensive and Resuscitation Care Unit of the Clinic of Paediatric and Adolescent...