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The rapid antidepressant effect of ketamine changed the direction of the research of potential antidepressants and its effect was also evaluated in this thesis. However, the main focus of this thesis is a new methodological approach to the research of depressive disorder. The main interest lies with the evaluation of automated monitoring of behaviour in this research. The first aim of this thesis was to evaluate the antidepressant effect of ketamine in the forced swimming test using software enabling automated monitoring of behaviour. The second aim was to meassure the change in phosphorylated Mammalian target of rapamycin (mTOR), using Enzyme-Linked ImmunoSorbent Assay (ELISA). The last, but the most important aim of this thesis was to implement the utilization of Phenotyper boxes in the automated behavioural evaluation of the olfactory bulbectomy model of depressive disorder and also evaluate the effect of ketamine in this model. Ketamine did not show an antidepressant effect in forced swimming test, however this observation could be influenced by chosen dose and mouse strain. Sensitivity of the test to chosen experimental protocol shows insufficient validity of this test. Observed change in level of phosphorylated mTOR corresponded with the behavioural results. Data collected from Phenotyper...

Under anaesthesia or in deep sleep, different parts of the brain have a distinctive slow oscillatory activity, characterised by states of high membrane potential and intensive spiking activity, the Up-states; followed by hyperpolarisation and quiescence, the Down-states. This activity has been previously described in vitro and in vivo in the cortex and the striatum, across several species. Here, we look into it, during anaesthesia, in the mouse brain. Using whole-cell patch-clamp recordings of cortical cells, it was possible to compare different signal processing methods used to extract the Up-and- Down states in extracellular recordings of the cortex. Our results show that the method based on the Multi-Unit Activity (&gt; 200Hz) have better ac- curacy than High-Gamma Range (20 100Hz) or wavelet decomposition (&lt; 2Hz band). After establishing the most robust method, this was used to compare the intracellular recordings of striatal cells to different parts of the cortex. The results obtained here support a functional connection between the dorsolateral striatal neurons and the ipsilateral barrel field. They also support a functional connection between dorsomedial striatal cells and the primary visual cortex. The analysis of delay between recordings allowed to establish temporal relationships between the contralateral barrel field, the ipsilateral barrel field, and the dorsolateral striatum; and between the ipsilateral barrel field, the ipsilateral primary visual field and the dorsomedial striatum. / <p>External Advisor: Dr. Ramon Reig, from Karolinska Institutet</p>

Der Einsatz von Ketamin erfolgt in der Humananästhesie, vor allem aufgrund seiner vielfältigen Nebenwirkungen, nur noch nach strenger Indikation. In der Veterinärmedizin ist Ketamin tierartenübergreifend für die Injektionsnarkose weit verbreitet. Um den bekannten Nebenwirkungen vorzubeugen, wird Ketamin mit verschiedenen anderen Anästhetika kombiniert und stellt so ein sicheres Narkoseverfahren bei Tieren dar. Eine besondere Herausforderung ist die Anästhesie bei ophthalmologischen Patienten unter Berücksich-tigung der Kontrolle des Intraokularen Drucks (IOP). In diesem Zusammenhang gibt es in der Literatur widersprüchliche Angaben zur Auswirkung von Ketamin auf den IOP beim Menschen und verschiedenen Tierarten. Auch für die Auswirkungen von Propofol und der endotrachealen Intubation auf den IOP existieren widersprüchliche Aussagen. In der vorliegenden Arbeit wurde untersucht, ob gängige Ketamin-Kombinationsnarkosen bei der augengesunden Katze einen Einfluss auf den IOP haben. Angeregt durch Berichte in der Literatur wurde zudem untersucht, ob die Applikation von Propofol sowie die endotracheale Intubation den IOP bei der Katze beeinflussen. Methodik: Untersucht wurden 48 adulte, augengesunde Katzen, die dem chirurgischen Patientengut der Klinik für Kleintiere der Universität Leipzig entstammten. Es handelt sich um eine prospektive, randomisierte Blindstudie. Die Patienten wurden vier Untersuchungsgruppen zugeordnet. Zur intramuskulären Narkoseeinleitung erhielten Tiere der KX-Gruppe Ketamin (10 mg/kg) und Xylazin (1 mg/kg), der KXAtr-Gruppe Ketamin (10 mg/kg), Xylazin (1 mg/kg) und Atropin (0,025 mg/kg), der KA-Gruppe Ketamin (20 mg/kg) und Acepromazin (0,5 mg/kg) und der KM-Gruppe Ketamin (10 mg/kg) und Medetomidin (50 g/kg). Bei allen Patienten wurde mittels Tono-Pen® XL zu verschiedenen Zeitpunkten der IOP bestimmt: vor Narkoseeinleitung (Ausgangswert), nach Narkoseeinleitung nach 5, Zusammenfassung 86 10, 15 und 20 Minuten und direkt nach der Intubation sowie final nach Beendigung der Narkose während der Aufwachphase. Einige Tiere erhielten zur Vertiefung der Narkose vor der Intubation Propofol. Im Anschluss erfolgte eine ophthalmologische Untersuchung der Patienten, um eine Augenerkrankung auszuschließen. Ergebnisse: Der mittlere Ausgangs-IOP aller Tiere beträgt 15,8 mmHg. Mit p = 0,756 besteht kein signifikanter Unterschied zwischen den Gruppen. Getrennt nach linken (OS) und rechten (OD) Augen ist der mittlere IOP 15,7 und 15,8 mmHg. Dieser Unterschied ist nicht signifikant (p = 0,442). Daher wird für die Auswertung der Mittelwert aller 6 Datenpunkte pro Tier und Messzeitpunkt zugrunde gelegt. Im Vergleich zum Ausgangswert zeigt die KX-Gruppe keine signifikanten IOP-Änderungen. Die KXAtr-Gruppe und die KM-Gruppe weisen zur Final-Messung einen signifikanten IOP-Abfall um 16 % (p = 0,012) bzw. 17 % (p = 0,021) im Vergleich zum Ausgangswert auf. Die KA-Gruppe zeigt zur 15-Minuten-Messung den stärksten IOP-Abfall mit 21 % Prozent (p = 0,001) gegenüber dem Ausgangswert. Ab der 10-Minuten-Messung bis zur post-Intubations-Messung ist der IOP-Abfall der KA-Gruppe signifikant. Für die Gesamtstichprobe hat die Intubation keinen signifikanten Einfluss auf den IOP (p = 0,063). Die Gabe von Propofol zur Vertiefung der Narkose bei einzelnen Tieren hat ebenfalls keinen signifikanten Einfluss auf den IOP (p = 0,42). Schlussfolgerung: Die verwendeten Ketamin-basierten Narkoseprotokolle bewirken bei der augengesunden Katze keinen signifikanten IOP-Anstieg. Die Gruppen KX, KXAtr und KM gewährleisten für den Zeitraum von 20 Minuten nach Narkoseeinleitung einen relativ stabilen IOP. Trotz des signifikanten IOP-Abfalls in der KA-Gruppe sind sämtliche IOP-Schwankungen aller Gruppen klinisch nicht relevant. Die gemessenen IOP-Werte bewegen sich alle im physiologischen Bereich. Zudem geben die Ergebnisse keinen Hinweis auf eine IOP-Steigerung infolge Propofolgabe und Intubation bei der Katze. / Ketamine is used in human medicine based on strict indications, mainly due to its numerous side effects. In veterinary medicine however Ketamine is commonly used to induce anesthesia intramuscularly throughout all species. To minimize the well known side effects Ketamine is used in combination with several other anesthetics and thus represents a safe anesthetic procedure in animals. Ophthalmological patients are a particular challenge for anesthetists with regard to maintaining the intraocular pressure (IOP). Conflicting data can be found in the literature about the effects of Ketamine on IOP in humans and various animal species. The literature also contains various statements about the effects of Propofol and endotracheal intubation on IOP. In this clinical trial we investigated the effects of commonly used Ketamine-based anesthetic protocols on IOP in cats. Motivated by conflicting statements in the literature the analysis of the effects of Propofol and endotracheal intubation on IOP was included in the study. Methods: This is a prospective, randomized, blinded study. 48 adult cats without ophthalmological abnormalities, recruited from the pool of admitted surgical patients of the Department of Small Animal Medicine of the University of Leipzig were included in the study. The patients were assigned to one of the following four groups and anesthesia was induced intramuscularly. Cats in the KX-group were induced with Ketamine (10 mg/kg) and Xylazine (1 mg/kg). Cats in the KXAtr-group were induced with Ketamine (10 mg/kg), Xylazine (1 mg/kg) and Atropine (0,025 mg/kg). Cats in the KA-group were induced with Ketamine (20 mg/kg) and Acepromazine (0,5 mg/kg). Cats in the KM-group were induced with Ketamine (10 mg/kg) and Medetomidine (50 g/kg). In all patients the IOP was measured three times per eye using the Tono-Pen® XL at particular times: baseline IOP before induction of anesthesia, at 5, 10, 15 and 20 minutes after induction of anesthesia, after intubation and final IOP after completion of surgery. Some cats received a single bolus of Propofol to be able to tolerate endotracheal intubation. After the final IOP-measurement all Zusammenfassung 88 cats were subjected to an ophthalmological examination, including slitlamp biomicroscopy and gonioscopy, in order to exclude patients with ophthalmological pathologies. Results: The mean baseline IOP for all animals is 15,8 mmHg (SD 4,0). There is no significant difference between the four groups (p = 0,756). The mean IOP for the right (OD) and left eyes (OS) of all patients was 15,8 mmHg and 15,7 mmHg, respectively. There is no significant difference between right (OD) and left eyes (OS) (p = 0,442). Therefore all further analyses are based on the mean of all six data points per animal and measuring time. The KX-group shows no significant IOP-change relative to baseline-IOP. The KXAtr and KM-group show a significant decrease in IOP of 16 % and 17 %, respectively, at the final measurement compared with baseline-IOP. The KA-group shows a significant decrease in IOP starting at 10 minutes after induction of anesthesia until the post-intubation measurement. The maximum decrease in IOP in this group is 21 % relative to baseline-IOP 15 minutes after induction of anesthesia. For the total data no significant influence of endotracheal intubation on IOP could be detected (p = 0,063). The application of Propofol in a total of 14 cats has no significant effect on IOP (p = 0,42). Conclusion: The Ketamine-based anesthetic protocols used in this study do not cause a significant increase in IOP in cats without ophthalmological abnormalities. The KX, KXAtr and KM-group ensure a relatively stable IOP for the time period of 20 minutes after induction of anesthesia. Despite the significant IOP-decrease in the KA-group none of the IOP-changes in all groups examined are of clinical relevance. All of the collected IOP-values are within the physiological range for cats. There is no evidence for an increase in IOP caused by endotracheal intubation or the application of Propofol.

Le cortex cérébral est impliqué dans plusieurs fonctions entre autres le traitement des informations sensorielles. Il inclut des zones recevant directement une entrée sensorielle telle que le cortex visuel primaire (V1) qui traite les informations visuelles. Au niveau du V1 des mammifères, chaque neurone présente une combinaison préférentielle de stimuli pour lesquels sa réponse est optimale. Cela dit, chaque attribut de stimulus tel que les fréquences temporelle et spatiale, l’orientation et la direction du mouvement induit une réponse maximale du neurone. Le neurone du V1 est donc sélectif. Cependant, cette sélectivité n’est pas le résultat de l’activité du neurone en question seul, mais plutôt du réseau neuronal dans lequel il est impliqué. L’ensemble des préférences d’un neurone ainsi que le réseau neuronal auquel il appartient demeurent sensiblement inchangés, tant que les facteurs contextuels ne varient que peu ou pas. Toutefois, si les composantes de l’environnement changent de manière imposante, la sélectivité neuronale et l’organisation du réseau original seront modifiées pour induire un nouvel état d’équilibre. C’est la plasticité neuronale. Le but ultime de cette thèse est de comprendre et d’approfondir les connaissances relatives aux mécanismes régissant la sélectivité à l’orientation ainsi que la plasticité dans V1, et ce, par différentes études qui sont organisées, dans cette thèse en trois sections. Les sections (3) et (4) se basent sur une étude pharmacologique qui vise à examiner l’effet de la kétamine sur la sélectivité à l’orientation (section 3) et sur l’adaptation visuelle tout en traitant la connectivité neuronale (section 4). La section (5) vise à examiner l’effet de l’adaptation sur l’affinité des courbes d’accord des neurones. Ce travail a permis d’étudier l’effet de la kétamine et de l’adaptation visuelle sur les propriétés sélectives à l’orientation des neurones ainsi que sur la dynamique des relations fonctionnelles au sein du microcircuit. / The cerebral cortex plays a key role in several functions including the processing of sensory information. It contains areas that receive direct sensory input such as the primary visual cortex (V1) which processes visual information. V1 neurons of mammals are selective for several attributes, such as spatial and temporal frequencies, orientation, and direction of motion. Thus, V1 neurons exhibit selectivities. This neuronal selectivity rests in the convergence of clusters of synapses involved in the network. Neural selectivity and networks are formed during the sensitive period of brain development and is present throughout the animal’s life. However, in V1 during postnatal life, the neuronal selectivity and the neural circuitry are further shaped by experience, thus, rendering it plastic. The main objective of the current thesis is to understand the mechanisms involved in the orientation selectivity as well as the neuroplasticity in V1. To this aim, different investigations, organized in this thesis, in three sections, were carried out. The sections (3) and (4) are based on a pharmacological study that aim to examine the effect of ketamine on orientation selectivity (section 3) and on visual adaptation in relation with neural connectivity (section 4). The study presented in the third section (section 5) investigated the effect of adaptation on the cell’s tuning. Here, we disclose the effects of ketamine and visual adaptation on the cell’s tuning properties as well as on the dynamics of functional relationships between neurons in the microcircuit.

La kétamine est un antagoniste des récepteurs NMDA fréquemment utilisée pour des procédures anesthésiques et moins fréquemment pour traiter la douleur chronique. Des travaux de notre laboratoire ont montré que l’utilisation de la kétamine en combinaison avec la xylazine chez des rats âgés d’environ deux ans pouvait prolonger la durée d’anesthésie. Considérant que les patients gériatriques présentent des caractéristiques physiologiques demandant des adaptations au niveau de la pharmacothérapie, que cette classe de patient requiert fréquemment des anesthésies afin de réaliser des interventions chirurgicales et qu’elle représente la sous-population qui consomme le plus de médicaments pour traiter des problèmes de douleur aiguë et chronique, il convient alors d’investiguer l’impact que l’âge peut avoir sur le métabolisme des médicaments. Le but de ce projet est donc d’évaluer l’impact de l’âge sur le métabolisme de la kétamine à l’aide de fractions cellulaires (in vitro) et d’une technique de chromatographie en phase liquide couplée à la spectrométrie de masse. En premier lieu, nous avons dû confirmer la voie métabolique principale de formation de la norkétamine en utilisant le substrat et l’inhibiteur de référence de la voie métabolique du CYP3A qui sont respectivement le midazolam et le kétoconazole. De plus, nous avons caractérisé l’interaction métabolique de la kétamine fréquemment combinée au midazolam. Ensuite, nous avons comparé les profils de dégradation de la kétamine par des fractions S9 hépatiques de rats âgés de 3, 6, 12 et 18 mois. Les valeurs (±ÉT) de Vmax obtenues étaient respectivement de 2.39 (±0.23), 2.61 (±0.18), 2.07 (±0.07) pour les plus jeunes comparé à 0.68 (±0.02) pour le groupe de 18 mois (p < 0.001). Ces résultats suggèrent donc que le CYP3A est rapidement saturé par la présence de kétamine. De plus, la valeur de Km a diminué de 6 à 7 fois pour le groupe de 18 mois comparé aux autres groupes (p < 0.05). Ainsi, on peut émettre l’hypothèse que l’enzyme subit une modification de sa conformation tridimentionnelle, ce qui résulte en une diminution de formation de norkétamine. Finalement, nous avons tenté d’évaluer la contribution du métabolisme cérébral au métabolisme de la kétamine. Toutefois, nous n’avons pas trouvé de différence significative dans les concentrations de kétamine ou de midazolam entre le début de la réaction et 60 minutes plus tard. Le même constat a été observé pour d’autres substrats du CYP3A et CYP2D (dextromethorphan et codéine). D’autres expériences sont nécessaires afin d’arriver à des conclusions définitives. Les différences observées entre les différents groupes d’âge suggèrent que la voie métabolique hépatique du CYP3A est détériorée de façon importante. Les protocoles anesthésiques pour patients âgés devraient donc tenir compte de cette importante diminution d’activité métabolique étant donné que l’exposition aux concentrations systémiques risque d’être significativement augmentée. / Ketamine is a NMDAR antagonist widely used for anesthetic procedures and less often to treat chronic pain. Work in our laboratory showed that the use of ketamine combined to xylazine is a poor anesthetic choice for aged rats of approximately 2 years. Considering that geriatric patients present physiological characteristics demanding adaptations of the pharmacotherapy, that this class of patients frequently needs anesthesia to perform surgeries and that they represent the subpopulation that uses many drugs to treat acute and chronic pain, it is relevant to investigate the impact of aging on drug metabolism. The goal of this project was to assess the impact of aging on ketamine metabolism using cellular fractions (in vitro) and liquid chromatography tandem mass spectrometry. First, we needed to confirm the main metabolic pathway of norketamine formation using well-established reference substrate and inhibitor of CYP3A metabolic pathway which are respectively midazolam and ketoconazole. Furthermore, we also characterized the metabolic interaction of ketamine frequently combined with midazolam. Second, we compared the degradation profiles of ketamine in liver S9 fractions of rats aged of 3, 6, 12 and 18 months. Vmax values (±SD) were respectively of 2.39 (±0.23), 2.61 (±0.18), 2.07 (±0.07) for the younger groups compared to 0.68 (±0.02) for the 18 month older group (p < 0.001). Those results suggest that CYP3A is quickly saturated by the presence of ketamine. Moreover, Km value showed a 6 to 7 fold decrease for the oldest group compared to the younger one (p < 0.05). Therefore, we hypothesized that the enzyme undergoes conformational changes, which results in a decrease of norketamine formation. Finally, we intend to assess the contribution of brain metabolism to the overall ketamine metabolism. Unfortunately, we did not find any significative difference in ketamine or midazolam concentrations between the beginning of the reaction and 60 minutes later. The same ascertainment has been observed with other susbstrates of CYP3A and CYP2D (dextromethorphan and codeine). Other experiences are needed to definetely conlude that brain metabolism is negligible. The differences observed between age groups suggest that the hepatic metabolic pathway of CYP3A is severely impaired. Anesthetic protocols for aging patients should take into consideration the diminished metabolic activity since it may lead to a significant increase of exposition to systemic drug concentrations.

INTRODUÇÃO: A clonidina é um agonista seletivo do receptor adrenérgico alfa2 com propriedades sedativas, analgésicas e possibilita a redução do consumo de outros anestésicos. Suas ações podem mitigar o impacto hemodinâmico e psíquico da S+ Cetamina. Os grandes queimados são de difícil manejo e ainda não existe uma técnica anestésica padrão para estes pacientes, sendo a cetamina amplamente utilizada nestes pacientes em regimes muito variados, apresentando várias vantagens. Os objetivos do estudo foram avaliar os efeitos hemodinâmicos e psíquicos da interação da clonidina e da S+ cetamina e propor uma técnica anestésica para grandes queimados. MÉTODOS: O estudo foi prospectivo, duplo encoberto, aleatório e placebo controlado, planejado para 48 pacientes adultos grandes queimados, estado físico ASA II ou III, que foram agendados para trocas de curativos ou debridamentos cirúrgicos. Para a anestesia foi usado midazolam 0,07mg/kg e duas doses de 1 mg/kg de S+ cetamina. No Grupo Clonidina foi usada a dose de 2 mcg/kg e soro fisiológico no Grupo Placebo. Foram avaliadas as alterações hemodinâmicas durante o intra-operatório. Durante as duas primeiras horas foram avaliadas detalhadamente as alterações psíquicas utilizando 13 variáveis, o retorno da consciência, a analgesia e a ocorrência de complicações. Após 24 horas foram avaliadas a analgesia, a ocorrência de sonhos e delírios. RESULTADOS: O Grupo Clonidina apresentou redução estatisticamente significativa nas pressões arteriais durante o procedimento. Dentre as 13 variáveis psíquicas analisadas, 5 foram menores com significância estatística no Grupo Clonidina durante a avaliação de 30 minutos, incluindo Corpo, Arredores, Pensamento, Sonolento e Ansioso. Na avaliação de duas horas, apenas a variável Ansioso teve redução estatisticamente significativa no Grupo Clonidina. A frequência cardíaca, a ocorrência de delírio e sonhos e a analgesia pós-operatória foram similares nos dois grupos. Não houve diferença entre os grupos na ocorrência de complicações. CONCLUSÃO: O uso de Clonidina em anestesia para pacientes grandes queimados, com S+ cetamina e midazolam reduz as pressões arteriais durante o procedimento e os efeitos psíquicos, sem aumentar a ocorrência de complicações / Abstract: Clonidine is a selective alpha2-adrenoceptor agonist with sedative, analgesic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may reduce the hemodynamic and psychic effects of S+ ketamine and improve analgesia. The ketamine is commonly used in burned patients worldwide. The objectives of this study were to evaluate the interactions between clonidine and ketamine in hemodynamic and psychic effects and also to propose an anesthetic technique for major burned patients. Method: A prospective, double-blind, placebo controlled study designed for 48 patients with major burns, aged 18-60 years, physical status ASA II or III, that were scheduled for dressing changes and wound debridements. For the anesthesia was used midazolam 0,07mg/kg, two doses of S+ ketamine 1 mg/kg, placebo or clonidine 2mcg/kg. Intraoperative hemodynamic alterations over time were assessed. During the first two hours after the procedures were evaluated, psychic effects in detail using 13 variables, the return of conscience, analgesia, dreaming and delirium and after 24 hours, analgesia, dreaming and delirium. Results: The Clonidine Group had low arterial pressure during the procedure. At the 30 minute evaluation of the psychic variables 5 out of 13 were lower in the Clonidine Group with statistically significance, these being Body, Surroundings, Thoughts, Drowsy and Anxious. At the 2 hour evaluation only the Anxious variable was lower in the Clonidine Group with statistically significance. Cardiac frequency, postoperative analgesia, occurrence of delirium and dreaming weren\'t different between both groups. There wasn\'t any difference in complication rates between both groups. Conclusion: We concluded that the use of Clonidine in S+ ketamine plus midazolam anesthesia in patients with major burns reduces the arterial pressures and the postoperative psychic effects, without increasing the complications

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.

No description available.

Thesis (Ph. D.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).