Made available in DSpace on 2016-12-08T16:24:17Z (GMT). No. of bitstreams: 1 PGCA14MA134.pdf: 1248046 bytes, checksum: af3ac6b025f01fe9a2d5a20f8a4685e3 (MD5) Previous issue date: 2014-02-28 / The aim of this study was to compare the efficacy and safety of premedication with detomidine and morphine in sheep kept under inhalation anesthesia with isoflurane or total intravenous anesthesia with propofol, both associated with lumbosacral spinal anesthesia. Fourteen adult, female, sheep, mean weight 27,2±2,4 Kg were used. All animals were pre medicated with 0,3 mg.Kg-1 of morphine IM, and 5 minutes later received 20 mcg.Kg-1 of detomidine IV. Subsequently were assigned into two groups: GISO (n=7), which were induced with 0,5mg.Kg-1 of diazepam associated with 5 mg.Kg-1 of ketamine IV, and maintenance of anesthesia was through isoflurane diluted in 100 % oxygen; the GPRO (n=7), animals were induced with 4 mg.Kg-1 propofol and maintained with continuous infusion of propofol in the initial rate of 0,3 mg.Kg-1.min-1 and subsequently adjusted to maintain adequate depth of anesthesia. Mechanical ventilation was iniciated to maintain normocapnia during the anesthesia. All animals underwent bilateral tibial osteotomy, therefore, received 0,5mg.Kg-1 0,75% ropivacaine associated with 0,1 mg.Kg-1 morphine by the intrathecal route, and diluting to a final volume of 1 mL/7,5 Kg bodyweight with NaCl0,9% solution. The parameters were evaluated at baseline (M0), after instrumentation of the animals while held in right lateral recumbeny; 5 minutes after administration of detomidine (M1); 5 minutes after anesthetic induction (M2); 10 minutes after performing spinal anesthesia and positioning of the animal into dorsal recumbency (M3); immediately after osteotomy of the right hindlimb (M4); 30 minutes after the spinal anesthesia and positioning of the animal into dorsal recumbency (M5); immediately after osteotomy of the left hindlimb (M6); and at the end of surgery/anesthesia (M7). There was a 40% reduction in heart rate in M1 in both groups, remaining on average 23% reduced to M7. Mean arterial pressure rose in 16% in GISO at M2, 12 but decreasing from M3 to M7, like at in the GPRO. The average EtISO was 0,57 V% and average infusion rate of propofol was 0,24 mg.Kg-1.min-1. Spinal block was 100% effective in all animals. We registered a respiratory acidosis in M2, and a posterior metabolic alkalosis in M3 to M7, in both groups. Reduction of potassium levels and sustained hyperglycemia were observed in M2 to M7 in both groups. A 20% decrease ocurred in hematocrit and hemoglobin were observed in both groups from M1. The total time of surgery, anesthesia and extubation were 66±9,8, 92±7,0 and 13,8±1,5 minutes in GISO and 56±2,4, 82,9±4,6 and 5,4±1,5 minutes in GPRO. We conclude that sedation provided with the association of morphine and detomidine promoted adequate sedation depth, quality of induction promoted by propofol or ketamine diazepam was excellent and the protocol of spinal anesthesia was effective in preventing the nociception during surgical stimulation, not requiring rescue analgesia. The maintenance anesthesia with propofol or isoflurane produced similar depth of anesthesia with minimal cardiovascular and hemogasometric alterations, which are well tolerated in healthy animals / O objetivo deste estudo foi comparar a eficácia e segurança da pré medicação com detomidia e morfina em ovinos mantidos sob anestesia geral inalatória com isofluorano ou anestesia total intravenosa com propofol, ambas associadas à anestesia subaracnóidea lombo-sacra. Foram utilizados 14 ovinos, fêmeas, adultas, com peso médio 27,2±2,4 Kg. Todos os animais foram pré medicados com 0,3 mg.Kg-1 de morfina pela via IM, e 5 minutos após receberam 20 mcg.Kg-1 de detomidina pela via IV. Posteriormente foram alocados em dois grupos: GISO (n=7), onde foram induzidos com 0,5 mg.Kg-1 de diazepam e 5 mg.Kg-1 de cetamina IV, e manutenção anestésica realizada através de isofluorano diluído em 100% de oxigênio; no GPRO (n=7), os animais foram induzidos com 4 mg.Kg-1 de propofol, e a manutenção foi realizada com infusão contínua de propofol na taxa inicial de 0,3 mg.Kg-1.min-1 sendo posteriormente ajustada de acordo com o plano anestésico. Todos os animais foram mantidos sob ventilação mecânica ajustada para manter normocapnia. Todos os animais foram submetidos à osteotomia bilateral de tíbia, para tanto, receberam 0,5 mg.Kg-1 de ropivacaína 0,75% associado a 0,1 mg.Kg-1 de morfina pela via subaracnóidea, diluindo-se para um volume final de 1 mL/7,5 Kg com solução NaCl 0,9%. Os parâmetros foram avaliados no momento basal (M0), este ocorrido após a instrumentação dos animais, enquanto mantidos em decúbito lateral direito; 5 minutos após a administração da detomidina (M1); 5 minutos após a indução anestésica (M2); 10 minutos após a realização da anestesia subaracnóidea e posicionamento do animal em decúbito dorsal (M3); imediatamente após a realização da osteotomia do membro pélvico direito (perfuração da cortical) (M4); 30 minutos após a realização da anestesia subaracnóidea e posicionamento do animal em decúbito dorsal (M5); imediatamente após a realização da osteotomia do membro pélvico esquerdo (perfuração da cortical) (M6); e ao término da 10 cirurgia/anestesia (M7). Houve redução de 40% nos valores médios de frequência cardíaca em M1 em ambos os grupos, permanecendo em média 23% reduzidos até M7. A pressão arterial média elevou-se 16% em M2 no GISO, mas reduzindo-se de M3 até M7, assim como no GPRO. A EtISO média foi de 0,57V% e a taxa média de infusão do propofol foi de 0,24 mg.Kg-1.min-1. O bloqueio subaracnóideo foi 100% eficaz em todos os animais. Registrou-se acidose respiratória em M2, e posterior alcalose metabólica de M3 à M7, em ambos os grupos. Redução dos valores de potássio e hiperglicemia sustentada ocorreram de M2 a M7, em ambos os grupos. Decréscimo significativo de 20% nos valores de hematócrito e hemoglobina foram observados nos dois grupos a partir de M1. Os tempos totais de cirurgia, anestesia e para extubação foram de 66±9,8, 92±13,8 e 7,0±1,5 minutos no GISO e 56±2,4, 82,9±4,6 e 5,4±1,5 minutos no GPRO. Conclui-se que a sedação promovida pela associação de morfina e detomidina promoveu sedação adequada, a qualidade de indução promovida pelo propofol ou associação de cetamina diazepam foi excelente, o protocolo de anestesia subaracnóidea foi eficaz em prevenir a nocicepção durante o estímulo cirúrgico, não requerendo resgate analgésico trans operatório. A manutenção anestésica com isofluorano ou propofol promoveu plano anestésico similar com mínimos efeitos cardiovasculares ou hemogasométricos, os quais são bem tolerados em animais hígidos

Fragestellung: Es wird untersucht, ob die isolierte hypertherme Extremitätenperfusion (ILP) mit TNF-alpha und Melphalan eine akute systemische inflammatorische Reaktion (SIRS) auslöst. Weiterhin soll der Einfluß von zwei verschiedenen total intravenösen Narkoseverfahren sowie der Zusammenhang der unabhängig voneinander bestimmten Meßgrößen Herzindex/Sauerstoffverbrauchsindex (HI/VO2I) und Sauerstoffverbrauchsindex/Sauerstoffangebotsindex (VO2I/DO2I) beim Entstehen eines SIRS analysiert werden. Methodik: 73 Patienten, die sich einer ILP mit TNF-alpha und Melphalan in Allgemeinanästhesie unterzogen, wurden in diese klinische, retrospektive Untersuchung eingeschlossen. Ein erweitertes kardiopulmonales Monitoring, bestehend aus kontinuierlicher Thermodilution, kontinuierlicher indirekter Kalorimetrie, invasiver Blutdruckmessung sowie arterieller und gemischtvenöser Blutgasanalysen ermöglichte die Analyse von hämodynamischen, metabolischen und gasanalytischen Parametern an 8 definierten Zeitpunkten im Verlauf der ILP mit TNF-alpha und Melphalan. 21 Patienten erhielten eine Narkose mit Etomidate/Midazolam/Sufentanil/Pancuroniumbromid (N1), und bei 52 Patienten wurde die Narkose mit Propofol/Remifentanil/Cis-Atracurium (N2) durchgeführt. Ergebnisse: Während der ILP mit TNF-alpha und Melphalan kam es bei folgenden Parametern zu signifikanten Veränderungen in der systemischen Reperfusionsphase gegenüber den Ausgangswerten vor der extrakorporalen Zirkulation: Herzfrequenz, Herzindex, Temperatur, Gesamtsauerstoffaufnahme, pulmonale Sauerstoffaufnahme, Sauerstoffangebot, systemischer Gefäßwiderstand, pulmonalarterieller Mitteldruck, kardiale Füllungsdrücke, gemischtvenöser Kohlendioxid- und Sauerstoffpartialdruck, arterieller Kohlendioxid- und Sauerstoffpartialdruck, gemischtvenöse Sauerstoffsättigung, arterieller und gemischtvenöser Sauerstoffgehalt sowie arterieller pH- und Laktatwert. Bezüglich der Narkoseverfahren zeigte die Narkose N2 versus N1 signifikant geringere Herzfrequenzen und Herzindices, sowie signifikant erhöhte pulmonalarterielle Mitteldrücke, pulmonale und systemische Gefäßwiderstände. Die Korrelationen von HI/VO2I und VO2I/DO2I sind in der prä-Bypass-Phase gering, nehmen im Verlauf der ILP zu und erreichen zum Zeitpunkt der systemischen Reperfusion jeweils ihren Maximalwert. Schlußfolgerungen: Die ILP mit TNF-alpha und Melphalan kann als dynamisches in-vivo Modell für das Entstehen einer SIRS-Reaktion aufgefaßt werden. Die inflammatorische Antwort ist in ihrem Ausmaß eher gering und erreicht nach Aufhebung der extrakorporalen Zirkulation mit systemischer Reperfusion der behandelten Extremität ihr Maximum. Die Überwachung der Teilkreisläufe, ein erweitertes hämodynamisches Monitoring sowie forcierte intravenöse Volumentherapie in der Reperfusionsphase lassen dieses Behandlungsverfahren für die Patienten in Allgemeinanästhesie sicher erscheinen. Beide beschriebenen Narkoseverfahren sind für diese operative Therapie geeignet. Der Zusammenhang von HI/VO2I sowie VO2I/DO2I ist im Verlauf der ILP gering, kann sich aber mit Zunahme der inflammatorischen Reaktion verstärken. / objective: To determine whether the isolated hyperthermic limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha) and melphalan causes an acute systemic inflammatory response syndrome (SIRS)? Also analysed will be the influence of two total intravenous anaesthesias and the correlation of independent measured values cardiac index/oxygen consumption index (HI/VO2I) and oxygen consumption index/oxygen delivery index (VO2I/DO2I). design: Retrospective review of hemodynamic, metabolic and blood gas values from 73 patients, undervented isolated hyperthermic limb perfusion of leg with TNF-alpha and Melphalan in general anaesthesia. methods: Cardiopulmonary monitoring consisted of continuous thermodilution, continuous calorimetry, arterial pressure and arterial as well as admixed blood-gas analyses. Values were measured on 8 time points in the course of ILP. In 21 patients anaesthesia was carried out with drug-combination of Etomidate/Midazolam/Sufentanil/Pancuroniumbromid (N1), and 52 patients were given anaesthesia with Propofol/Remifentanil/Cis-atracurium (N2). results: The following values changed significantly after limb-reperfusion compared with the baseline: heart rate, cardiac index, temperature, oxygen consumption, pulmonary oxygen consumption, oxygen delivery, systemic vascular resistance, mean pulmonary arterial pressure, precardial pressures, admixed carbon dioxide pressure, admixed oxygen pressure, arterial carbon dioxide pressure, arterial oxygen pressure, admixed oxygen saturation, arterial and admixed oxygen content as well as arterial pH- and lactat. conclusions: The isolated hyperthermic limb perfusion with TNF-alpha and melphalan may be used as a dynamic in-vivo model for the development of an SIRS. The inflammatory response is slight and reached the maximum after reperfusion of treated limb. Monitoring of the two circulations, extended cardiopulmonary monitoring and intravenous volumetherapie in the reperfusion time makes this cancer treatment in general anaesthesia safe. Both anaesthesia are suitable. The correlations of HI/VO2I as well as VO2I/DO2I are low in the beginning and rise with the increase of the inflammatory response.