O uso concomitante da enzima hialuronidase (H) ao anestésico local (AL) é muito utilizado para melhorar a eficácia anestésica em oftalmologia; em odontologia, no entanto, não mostrou vantagens. Um novo protocolo foi testado com o objetivo de prolongar a anestesia local sem a realização de complementação anestésica. Esta possibilidade seria especialmente interessante para pacientes que apresentam restrição de dose máxima recomendada de AL ou vasoconstritor (ex. cardiopatas). Utilizou-se cloridrato de lidocaína 2% com epinefrina para bloqueio sensitivo, motor e proprioceptivo no nervo ciático em ratos (Truant,1958). Hialuronidase 75 UTR (unidade de turbidade reduzida) foi injetada no mesmo local 30 minutos após o início da analgesia (antes do término do efeito anestésico), utilizando-se a pata contralateral como controle (injeção de solução anestésica e veículo da hialuronidase solvente). A duração do bloqueio sensitivo foi avaliada através da ausência do reflexo de retirada da pata, utilizando-se um analgesímetro. O bloqueio motor foi avaliado pela duração da claudicação e da ausência do reflexo de estiramento da pata, enquanto o bloqueio proprioceptivo foi avaliado pela perda dos reflexos de salto e do reposicionamento da pata (Thalhammer et al., 1995). Foi também estudada a alteração tecidual induzida pela hialuronidase nos períodos de 1 h, 24 h, 48 h e 72 h pós-injeção. Foram avaliados os grupos: (1) falso operado (Sham); (2) AL +H; (3) AL+ solvente (Solv) e (4) Solv+Solv. Concluiu-se que a hialuronidase prolonga a duração de ação anestésica local quando injetada isoladamente antes da regressão do bloqueio de condução do nervo ciático de rato. Em todos os grupos analisados, exceto o grupo falso-operado, observou-se reação inflamatória após as injeções. Esta inflamação foi mais acentuada no grupo hialuronidase, que mostrava sinais de regressão após 72 horas. É possível que o mecanismo de ação da hialuronidase envolva a desorganização do tecido conjuntivo na região da injeção, facilitando a difusão da solução anestésica residual até o nervo. / The concomitant use of the enzyme hyaluronidase (H) and local anesthetics (LA) is widely employed in ophthalmology in order to improve the effectiveness of anesthesia; in dentistry, however, this association did not seem advantageous. A new protocol was tested with the aim of drawing out local anesthesia without supplementary anesthesia. This possibility is especially interesting for patients with restriction of maximum recommended dose of LA or vasoconstrictor due to pathological conditions (e.g. heart disease). We used 2% lidocaine hydrochloride with epinephrine for sensitive, motor and proprioceptive blockade of the sciatic nerve in rats (Truant, 1958). Hyaluronidase 75 UTR was injected 30 minutes after the beginning of the anesthesia (before the recovery of the sensory function), using the contralateral limb as control (injection of LA plus the H vehicle solvent). The duration of the sensitive blockade was evaluated through the absence of the paw withdrawal reflex, using an analgesymeter. The motor blockade was evaluated by the duration of claudication (complete absence of extensor postural thrust) and by the absence of the paw stretching reflex, while the proprioceptive blockade was evaluated by the absence of hopping and tactile placing response (Thalhammer et al., 1995). Histological changes induced by H were analyzed 1h, 24h, 48h, and 72 h after the injection in the following groups: (1) Sham; (2) LA + H; (3) LA + H solvent (solv) and (4) Solv + Solv. We concluded that H draws out local anesthesia when injected before the recovery of the sciatic nerve blockade in the rat. In all groups studied, with the exception of the Sham, there was an inflammatory reaction after the injections. Inflammation was more intense after H injection, showing signs of regression after 72 hours. It is possible that the mechanism of action of H involves disorganization of the connective tissue, thus facilitating the diffusion of the residual anesthetic solution to the nerve.

Esta pesquisa é um estudo de caso, com natureza exploratória, descritiva e comparativa de campo, transversal e com abordagem quantitativa. Tem como objetivo classificar as cirurgias em categorias, segundo a necessidade de horas de enfermagem em salas de operações, subsidiando o dimensionamento de pessoal de enfermagem em centro cirúrgico. Foi realizada em um Hospital geral, de grande porte, da rede privada da cidade de São Paulo. A amostra foi constituída de 140 pacientes, divididos em 14 grupos, sendo 10 pacientes em cada grupo. Para a formação dos grupos foi considerado a condição física do paciente, segundo Americam Society of Anestesiologists (ASA), o porte anestésico segundo a Associação Médica Brasileira (AMB), o tipo de procedimento anestésico-cirúrgico, invasivo ou minimamente invasivo (MI) e cirurgias eletivas. Quanto à condição física do paciente, os grupos foram formados com ASA1, ASA2 e ASA3; a ASA4 foi excluída por não apresentar casos, ASA 5 e 6 foram excluídos por serem cirurgias de urgência ou emergência. Quanto ao porte anestésico, as cirurgias foram classificadas em pequeno porte, médio porte, grande porte e porte especial. Desta forma os grupos ficaram simbolizados como: 1P, 1M, 1G, 1E, 2P, 2M, 2G, 2E, 3M, 3G, 3E, 1PMI, 1MMI e 2MMI. A coleta de dados foi realizada dentro das salas de operações, por meio de observação estruturada, a qual foi utilizado um roteiro com itens referentes à caracterização da cirurgia, recursos humanos, condição física do paciente e procedimentos anestésicos-cirúrgicos. O tratamento dos dados foi feito segundo a caracterização do paciente cirúrgico, horas utilizadas pelos recursos humanos e pelo paciente, procedimentos realizados e recursos materiais utilizados. Na comparação entre os grupos, a caracterização do paciente cirúrgico permitiu os seguintes resultados: quanto ao sexo, 83 (59,29%) do sexo feminino e 57 (40,71%) masculino, a maior frequência de idade foi entre 30 e 40 anos, em 34 (24,29%) dos pacientes. As especialidades cirúrgicas de maior frequência foram otorrinolaringologia em 23 (16,43%), ginecologia e obstetrícia 21 (15%) e ortopedia e traumatologia 21 (15%). A anestesia geral prevaleceu com 75 (53,58%) dos pacientes. Quanto aos distúrbios sistêmicos que caracterizaram a ASA, as doenças cardiovasculares prevaleceram em 52 (65%) dos pacientes, sendo 40 (50%) com hipertensão arterial sistêmica e 16 (20%) com diabetes Mellitus. Quanto às horas utilizadas, as média das horas utilizadas por paciente foram: 3,40 horas de enfermagem (HE); 0,10 horas de enfermeira (HEn); 3,28 horas de técnico/auxiliar de enfermagem (HT/A); 6,14 horas da equipe médica (HEM); 1,12 horas de cirurgia (HC); 1,95 horas de salas de operações (HSO); 0,21 horas de preparo para anestesia (HPA) e 0,16 horas de preparo para cirurgia (HPC). Para uma hora de cirurgia (HC), as médias de horas utilizadas em cada paciente foram: 3,54 HE; 0,14 HEn; 3,40 HT/A; 5,77 HEM e 1,90 HSO. Para uma hora de sala de operações (HSO), as médias de horas utilizadas em cada paciente foram: 1,81 HE; 0,06 HEn; 1,75 HT/A; 3,08 HEM e 0,54 HC. Quanto aos procedimentos realizados, as médias dos invasivos foi de 2,04 procedimentos e não invasivos de 5,70 procedimentos; com total de 7,74 procedimentos. A média de recursos materiais utilizados para anestesia foi de 4,19 equipamentos e para a cirurgia de 2,76 equipamentos; com total de 6,95 equipamentos. Na análise estatística dos grupos, referentes às ASA, segundo os portes anestésicos; os resultados demonstraram que os portes anestésicos pequeno e médio não diferiram significativamente entre si, sendo inferiores aos portes grande e especial, nas variáveis HE, HT/A, HEM; quanto aos portes anestésicos, segundo às ASA; os resultados demonstraram que quase não houve diferenças entres as ASA. Os grupos de cirurgias minimamente invasivas, houve diferença apenas nos recursos materiais, sendo superiores conforme o porte anestésico e a análise entre os grupos de cirurgias invasivas e minimamente invasivas, com portes anestésicos e ASA semelhantes, os resultados demonstraram que os grupos de cirurgias invasivas apresentaram - se significativamente inferiores nas variáveis estudadas em relação aos grupos de cirurgias minimamente invasivas. Desta forma, conclui-se com este estudo, que as HE estão relacionadas aos portes anestésicos, onde quanto mais complexo o procedimento anestésico-cirúrgico, mais horas de enfermagem são utilizadas, não foi observado relação das HE utilizadas com a condição física do paciente. Assim, foi elaborado uma classificação das cirurgias em categorias, segundo a necessidade de horas de enfermagem, para uma hora de sala de operações, sendo: cuidados padrão de enfermagem, com 1,41 horas; cuidados complexos de enfermagem, com 1,99 horas e cuidados diferenciados de enfermagem, com 1,78 horas / This is a case study with exploratory character, descriptive and comparative, and a fieldwork with a quantitative approach. It aims to classify the surgeries in categories according to the number of nursing hours in operating rooms, subsidizing the dimensioning of the nursing staff in operating rooms. It was performed in a large general private Hospital in São Paulo. The sample was constituted of 140 patients, divided into 14 groups, 10 patients on each group. To organize the groups it was taken on account the patient\'s physical condition, according to the American Society of Anesthesiologists (ASA), the anesthetic complexity, according to the Brazilian Medical Association (BMA), the sort of surgical anesthetic procedure: invasive, or minimally invasive (MI) and elective surgeries. According to the patient\'s physical condition, groups were constituted with ASA1, ASA2 and ASA3. ASA 4 was put away because there were no cases, and ASA 5 and ASA 6 were put away because they were urgency or emergency surgeries. As to the anesthetic complexity, surgeries were classified as presenting small complexity, mean complexity, large complexity and special complexity. Therefore groups were symbolized as: 1S, 1M, 1L, 1S, 2S, 2M, 2L, 2S, 3M, 3L, 3S, 1SMI, 1MMI AND 2AMI. Data were collect inside the operating rooms, by means of organized observation, according to a guide presenting items referring to the surgery characteristics, human resources, patient\'s physical condition and surgical anesthetic procedures. Data analysis was performed according to the surgical patient\'s characteristics, hours taken by human resources and by the patient, procedures and material resources employed. In the comparison among groups, the characterization of the surgical patient led to the following results: as to gender, 83 (59,29%) female and 57 (40,71%) male, the higher age frequency was between 30 and 40 years in 34 (24,29%) of the patients. The most frequent surgical specialties were otorhinolaryngology and traumatology in 23 (16,43%), gynecology and obstetrics in 21 (15%) and orthopedics and traumatology in 21 patients (15%). General anesthesia prevailed in 75 (53,58%) of the patients. Concerning the systemic disorders that characterize the ASA, cardiovascular disorders prevailed in 52 (65%) of the patients, 40 (50%) presenting systemic arterial hypertension and 16 (20%) presenting diabetes Mellitus. As to the hours taken, the average hours taken by patients was: 3,40 hours of nursing (NH); 0,10 hours of nurse (NeH); 3,28 hours of nursing assistant (NaH); 6,14 hours of medical staff (MSH); 1,12 hours of surgery (SH), 1,95 hours of operating room (ORH); 0,21 hours of anesthetic preparation (APH) and 0,16 hours of surgery preparation (SPH). For one SH, the average hours taken for each patient was: 3,54 NH; 0,14 NeH; 3,40 NaH; 3,08 MSH and 0,54 SH. Concerning to the procedures taken, the average of invasive procedures was 2,04 and non-invasive procedures 5,70; total procedures 7,74. The average material resources used for anesthesia was 4,19 equipment and for surgery 2,76 equipment; total 6,95 equipment. In the statistical analysis of groups referring to the ASA, according to the anesthetic complexity, results evidenced that small and mean anesthetic complexity presented no significant difference, and were inferior to large and special complexity in variables NH, NaH and MSH; as to the anesthetic complexity according to the ASA the results evidenced that there were almost none difference among the ASA. In the group of minimally invasive surgeries, there was difference only in the material resources, that were superior according to the anesthetic complexity and in the analysis comparing groups of invasive and minimally invasive surgeries with similar anesthetic complexity and ASA the results evidenced that groups of invasive surgeries were significantly inferior in the studied variables in relation to groups of minimally invasive surgeries. Therefore, this study concludes that the NH are related to the anesthetic complexity, and the more complex the anesthetic surgical procedure, the more nursing hours are taken. The relation of NH taken with the patient\'s physical condition was not observed. Thus a classification of surgeries in categories was done, according to the necessary nursing hours for one hour of operating room, that is: standard nursing cares, 1,41 hours; complex nursing cares, 1,99 hours and differentiate nursing cares, 1,78 hours

Postoperativ shivering (PAS) definieras som en serie ofrivilliga muskelrörelser som ökar den metabola värmeproduktionen i kroppen. Förekomsten av postoperativ shivering är ett problem inom den perioperativa vården. Det finns flera orsaker till shivering. Termoregulativa och icke termoregulativa. PAS förekommer i ca 5-65% av alla anestesier, men frekvensen har under åren minskat. Det är tidigare känt att anestesi sätter termoregulationen ur spel. Konsekvenserna kan leda till vårdlidande för patienten och högre kostnader för samhället. Syftet med studien är att undersöka orsaken till shivering. Arbetet utgår från en kvantitativ metod. I samarbete med SÄS utarbetades ett datainsamlingsformulär. Studien som genomfördes på tre sjukhus i västra delen av Sverige inkluderade 350 patienter >18 år. Materialet analyserades i SPSS, version 19. Resultatet visade att ålder, kön, operationstid (knivtid) och vissa typer av operationsingrepp (öron- ögon- hals- käk- näs- och endoskopisk kirurgi), hade signifikans för uppkomsten av PAS. Övriga variabler som undersöktes (anestesimetod, temperatur och övriga undersökta operationsingrepp) hade ingen signifikans. Resultatet talar delvis emot tidigare forskning, som visar att anestesimetod har betydelse för uppkomsten av PAS. Studien överensstämmer med tidigare forskning gällande signifikans för kön, ålder, operationstid och temperatur. Genom identifiering av olika faktorer, som kan leda till postoperativ shivering, kan vi, som anestesisjuksköterskor, förebygga fenomenet och ge patienten en trygg och säker vård samt minska vårdlidande. / Program: Specialistsjuksköterskeutbildning med inriktning mot anestesisjukvård

The glycine receptor (GlyR) is a ligand-gated ion channel member of the cys-loop receptor superfamily, responsible for inhibitory neurotransmission in the brain and spinal cord. Both glycine and the partial agonist taurine act as endogenous ligands of the GlyR. Taurine-activated GlyR may have a role in the rewarding effects of drugs of abuse, such as ethanol. As a partial agonist, taurine has a decreased efficacy relative to glycine, resulting in a decreased maximum response. We investigated the effects of ethanol, anesthetics, inhalants, and zinc to determine if these allosteric modulators could increase the efficacy of the taurine-activated GlyR. Whole cell recordings of wild type GlyR revealed that each of the allosteric modulators potentiated currents generated by saturating concentrations of taurine but not glycine, implying an increase in efficacy. Zinc is found at GlyR-potentiating concentrations throughout the nervous system, so we examined the combinatorial effects of these allosteric modulators with zinc to mimic in vivo conditions. Whole cell recordings revealed that zinc potentiation of saturating taurine-generated currents decreased further potentiation by another allosteric modulator, indicating no synergistic effects on efficacy. We next investigated the actions of ethanol and isoflurane on the taurine-activated GlyR at the single channel level, finding that both allosteric modulators stabilized the channel open state, increasing the efficacy of the taurine-activated GlyR. We previously identified a mutation in the ligand-binding domain of the GlyR (D97R) that produces spontaneously activating channels, on which taurine has increased efficacy. We identified a residue, R131, as a possible binding partner of D97 in forming an electrostatic interaction that holds the channel in the closed state. We found that disruption of this interaction results in greatly increased taurine efficacy, indicating that efficacy for partial agonists may be determined by agonist ability to break this bond early in the activation process following binding. Thus we find differential mechanisms of allosteric modulation and efficacy determinations for the GlyR when activated by taurine vs. glycine. / text

The glycine receptor (GlyR) is a ligand-gated ion channel member of the cys-loop receptor superfamily, responsible for inhibitory neurotransmission in the brain and spinal cord. Both glycine and the partial agonist taurine act as endogenous ligands of the GlyR. Taurine-activated GlyR may have a role in the rewarding effects of drugs of abuse, such as ethanol. As a partial agonist, taurine has a decreased efficacy relative to glycine, resulting in a decreased maximum response. We investigated the effects of ethanol, anesthetics, inhalants, and zinc to determine if these allosteric modulators could increase the efficacy of the taurine-activated GlyR. Whole cell recordings of wild type GlyR revealed that each of the allosteric modulators potentiated currents generated by saturating concentrations of taurine but not glycine, implying an increase in efficacy. Zinc is found at GlyR-potentiating concentrations throughout the nervous system, so we examined the combinatorial effects of these allosteric modulators with zinc to mimic in vivo conditions. Whole cell recordings revealed that zinc potentiation of saturating taurine-generated currents decreased further potentiation by another allosteric modulator, indicating no synergistic effects on efficacy. We next investigated the actions of ethanol and isoflurane on the taurine-activated GlyR at the single channel level, finding that both allosteric modulators stabilized the channel open state, increasing the efficacy of the taurine-activated GlyR. We previously identified a mutation in the ligand-binding domain of the GlyR (D97R) that produces spontaneously activating channels, on which taurine has increased efficacy. We identified a residue, R131, as a possible binding partner of D97 in forming an electrostatic interaction that holds the channel in the closed state. We found that disruption of this interaction results in greatly increased taurine efficacy, indicating that efficacy for partial agonists may be determined by agonist ability to break this bond early in the activation process following binding. Thus we find differential mechanisms of allosteric modulation and efficacy determinations for the GlyR when activated by taurine vs. glycine. / text

Der heute noch gängige Einsatz von Injektionsanästhetika bei Laborratten basiert zum großen Teil auf empirischen Daten. Auf der Grundlage des deutschen Tierschutzgesetzes sind Wissenschaftler verpflichtet, das nach dem derzeitigen Kenntnisstand schonendste Betäubungsmittel zu verwenden. Die wissenschaftlichen Daten zur intra- und postoperativen Belastung bei vielen Anästhetika sind lückenhaft. Daher wurden in dieser Studie im Sinne des „Refinements“ von Tierversuchen verschiedene Injektionsnarkosen bei 69 männlichen und weiblichen 6-8 Wochen alten Sprague-Dawley-Ratten im Rahmen einer stereotaktischen Gehirnoperation (OP) verglichen, bei der zumeist Injektionsnarkosen Verwendung finden. Die Ratten wurden entweder mit Chloralhydrat (CH: 3,6 %, 430 mg/kg intraperitoneal [i.p.] KGW), mit der vollständig antagonisierbaren Anästhesie (Medetomidin 0,15 mg/kg Körpergewicht [KGW], Midazolam 2 mg/kg KGW, Fentanyl 0,005 mg/kg KGW intramuskulär [i.m]) ohne (VAA-Gruppe) bzw. mit Antagonisierung (sog. VAA+A-Gruppe) zum OP-Ende (Atipamezol 0,75 mg/kg, Flumazenil 0,2 mg/kg, Naloxon 0,12 mg/kg subcutan [s.c.]) anästhesiert und nach Erreichen des Stadiums der chirurgischen Toleranz (cT), gekennzeichnet durch den Ausfall des Zwischenzehenreflexes an des Hintergliedmaße (ZZR hi.), einer 60-minütigen OP unterzogen. Eine weitere Gruppe erhielt eine i.p.-Bolusinjektion Propofol in einer Dosis von 120 mg/kg KGW, die sich im Rahmen von Vorversuchen als geeignet herausgestellt hatte, um bei Ratten eine Hypnose zu bewirken. Anschließend wurde Propofol zu Erzeugung und Aufrechterhaltung einer cT per Dauerinfusion i.v. (4 - 6 mg/kg/h) verabreicht. Kontrolltiere erhielten eine Injektion mit isotoner Kochsalzlösung (i.p.) ohne OP. Die Erfassung des KGWs erfolgte 3 Tage vor bis 2 Tage nach der OP. Im Vorfeld wurde jedes Tier über 3 Tage an das Tragen eines Pulsoximeterclips am Hals gewöhnt. Dies diente der Ermittlung von Basiswerte für die Atemfrequenz (AF), Herzfrequenz (AF) und die periphere Sauerstoffsättigung (SpO2)am wachen, freibeweglichen Tier am Tag der Anästhesie mittels MouseOx®-Pulsoximeter. In Narkose wurden die Tiere mittels Pulsoximeter, Reflextests (ZZR hi., Lid- [LR] und Cornealreflex [CR]) und Rektalthermometer überwacht. Die externe Wärmezufuhr wurde über eine elektrische Wärmeplatte (37 °C) vorgenommen Zu zwei Zeitpunkten erfolgten Blutabnahmen zur Bestimmung der Adrenalin- (A) und Noradrenalinwerte (NA) mittels HPLC. Der Verlust der cT wurde anhand festgelegter Kriterien bestimmt (ZZR hi. positiv, Zuckungen, lautes Vokalisieren, Zähneknirschen) und die Tiere ggf. nachdosiert. Prä- und postoperativ wurde immunreaktives Corticosteron (iCS) mittels ELISA aus Kotproben ermittelt. Zudem wurde die prä- vs. postoperative Belastung durch Etablierung eines nummerischen Scoresystems und Videoüberwachung der Tiere bewertet. 48 h nach der OP wurden die Ratten euthanasiert und relevante Organe und Gewebe für die histopathologische und immunhistochemische Untersuchung entnommen, um mögliche Anästhetika bedingte Irritationen sowie eine stressinduzierte Aktivierung von c-Fos-Proteinen in schmerz-assoziierten Gehirnregionen zu analysieren. Eine weitere Gruppe erhielt eine Inhalationsnarkose mit 3 % Isofluran (ISO) ohne OP und diente der Ermittlung von A und NA Basiswerten. Die AF lag bei 104 ± 1,05 Atemzüge/min, die HF bei 396 ± 2,10 Herzschläge/min und die SpO2 bei 95,7 ± 0,09 % (Angaben als Mittelwerte ± Standardfehler). Die Verwendung des MouseOx®-Pulsoximeters erwies sich als geeignete Methode zur Ermittlung von Wachwerten bei freibeweglichen Ratten. Alle CH-anästhesierten Tiere erreichten das cT-Stadium. Die Dauer der cT lag bei 49,14 ± 4,48 min, die Narkosedauer bei 155,66 ± 8,21 min. Während der Narkose zeigten die Tiere Tachykardie, Tachypnoe sowie eine geringgradig erniedrigte SpO2 und eine leichte Hypothermie. Erhöhte A/NA-Spiegel wiesen auf eine deutlich höhere intraoperative Stressbelastung in der CH-Gruppe hin. Auch iCS war in der CH-Gruppe im Vergleich zu VAA/VAA+A signifikant erhöht. Vom Tag der Anästhesie/OP auf den Folgetag verloren CH-Tiere durchschnittlich 9,4 g KGW. Postoperativ waren bei den Tieren keine bis geringe Anzeichen für Schmerz und/oder Disstress zu erkennen. Histopathologisch zeigten alle Ratten eine Peritonitis und Perihepatitis, 44 % der Tiere multifokale, akute Lebernekrosen und 22 % eine Perisplenitis. 95 % der mittels VAA anästhesierten Tiere erreichten die cT mit einer Dauer von 47,83 ± 7,05 min (VAA) bzw. 44,77 ± 5,27 min (VAA+A). Bei VAA-Tieren betrug die gesamte Narkosedauer 182,23 ± 20,58 min. Bei der VAA-Anästhesie insgesamt waren signifikante geschlechtsspezifische Unterschiede in der Latenzzeit bis zum Erreichen der 1. cT, der cT-Dauer und der Narkosedauer festzustellen. Die VAA-Anästhesie führte zu einer mittelgradiger Atemdepression und milden Hypothermie bei signifikant niedrigeren A/NA-Werten im Vergleich zu CH. Eine Nachdosierung ging mit einem vorrübergehenden signifikanten Abfall der SpO2 einher. Tiere der VAA+A-Gruppe erwachten 3,05 ± 0,21 min nach der s.c. Antagonisierung aus der Narkose. Anschließend zeigten sie starke Aufregung und Unruhe und ein verändertes Aktivitätsmuster, eine Stunde später teils Piloerektion sowie Ataxien. Die Körperkerntemperatur (KT) der VAA+A-Tiere sank innerhalb 1. Stunde nach der Antagonisierung signifikant ab. Einige Tiere wiesen eine Myositis als Folge der i.m. Applikation auf. Nach PROP-Anästhesie erreichten nur 36 % der Tiere das cT. Im Narkoseverlauf kam es bei diesen Tieren zu einer starken Beeinträchtigung der Atemfunktion. PROP-Tiere wiesen einen signifikanten Abfall der KT und Anzeichen verlängerter Sedation nach Wiedererwachen sowie die höchsten iCS-Gehalte auf. Insgesamt verstarben 4 von 11 Tieren wegen starker Atemdepression intra- oder postoperativ. Interessanterweise waren die nach ISO-Anästhesie ermittelten A/NA-Konzentrationen signifikant höher gegenüber allen Injektionsanästhesie-Gruppen. Die Ergebnisse dieser Studie belegen, dass die CH-Anästhesie mit gesteigerter Stresshormonfreisetzung einherging. Die Verwendung 3,6 %iger CH-Lösungen ist insbesondere wegen der massiven histopathologischen Befunde abzulehnen, obwohl die Tiere subjektiv ein scheinbar gutes Wohlbefinden aufwiesen. Die i.p. Applikation von Propofol erzeugte nur eine oberflächliche Anästhesie. Aufgrund der starken postanästhetischen Exzitationen sollte sie nur bedingt für kurze, nicht schmerzhafte Manipulation verwendet werden. Die initiale i.p. Propofol-Gabe mit anschließender i.v.-Infusion ist der reinen i.v. Gabe unterlegen und nicht empfehlenswert. Die VAA-Anästhesie ist für Ratten für stereotaktische OPs hingegen gut geeignet. Dabei ist eine exogene Wärmezufuhr auch nach der Antagonisierung zwingend notwendig, da das Thermoregulations-vermögen nach Wiedererwachen nicht ausreichend wiedererlangt wurde. Auf eine Belastung durch die unerwünschten Wirkungen der Antagonisierung wie Aufregung und Unruhe sowie durch die postanästhetische Hypothermie konnte nur anhand subjektiver Kriterien geschlossen werden. Hier sind weitere Untersuchungen nötig. Sofern kein Anästhesienotfall besteht, kann allerdings auf die Antagonisierung verzichtet werden, da in der Nachschlafzeit unter externer Wärmezufuhr (37 - 38 °C) kein wesentliches Risiko einer lebensbedrohlichen Hypothermie bzw. Kreislauf- und Atemdepression besteht. / Injectable anesthetics are still commonly used today, but mainly this is based on empirical data. In line with the German Animal Welfare Act, researches have to choose the least stressful anesthetic. However, scientific data about pain and distress during and after anesthesia are rare. To contribute to the refinement of animal experiments, we therefore investigated the suitability of different injectable anesthetics during a stereotactic surgery, for which kind of surgery injectable anesthetics are mostly used, in 69 male and female, 6 - 8 weeks old Sprague-Dawley rats. Rats were anesthetized with either chloral hydrate (CH: 3.6 %, 430 mg/kg intraperitoneal [i.p.]), with a complete reversible anesthesia (medetomidine 0.15, midazolam 2, fentanyl 0.0005 mg/kg intramuscular [i.m]) without (MMF) and with reversal (MMF with reversal) at the end of surgery (atipamezole 0.75, flumazenile 0.2, naloxone 0.12 mg/kg subcutaneous [s.c.]) or with propofol (PROP). The PROP-group received an i.p. bolus injection of propofol (120 mg/kg), shown to generate hypnosis in proceedings, followed by constant intravenous infusion (4 - 6 mg/kg/h) to achieve and maintain surgical tolerance (st). After reaching surgical anesthesia, indicated by loss of the pedal withdrawal reflex of the hind limb, a 60 minute surgery was undertaken. Rats with saline injection and without surgery served as control. Body weight of each rat was assessed 3 days before the surgery until 2 days after surgery. Over 3 days prior anesthesia and surgery, rats were adapted to wear a collar clip for MouseOx® pulse oximeter, used to gain basal of respiratory rate (RR), heart rate (HR) and peripheral oxygen saturation (pO2) values in awake and freely moving rats. During narcosis, monitoring was conducted via pulse oximeter, reflex tests (pedal withdrawal reflex, corneal and palpebral reflex) and rectal thermometer. All animals were placed on an electrical heating pad (37 °C). Levels of adrenalin and noradrenalin (A/NA) were analyzed at two designated time points via HPLC. Movement of the body or the extremities, audible vocalizations and teeth grinding were classified as defined criteria for the loss of st. If animals lost st during surgery, they received an additional anesthetic dose. Immunoactive corticosteron (iCS) in feces was determined by ELISA immunoassay before and after surgery. Moreover, different signs of pain and distress were scored by using a numerical pain scale and including video recordings. Rats were sacrificed 48 h after surgery for histopathological and immunhistochemical examination to analyze potential irritation on abdominal organs and tissue as well as stress-induced activation of c-Fos-protein in brain regions associated with pain. Furthermore, 5 rats were deeply anesthetized with 3 % isoflurane (ISO) and immediately sacrificed for reference values of A and NA. The RR assessed by MouseOx® pulse oximeter was 104 ± 1.05 brpm with a HR of 396 ± 2.10 bpm and an pO2 of 95.7 ± 0.09 % (results present the mean ± standard error). The MouseOx® pulse oximeter was found in the present study to be suitable to measure accurate values for awake and freely moving rats. All rats undergoing CH anesthesia reached st. The duration of the st was 49.14 ± 4.48 min, duration of narcosis was 155.66 ± 8.21 min. During the whole narcosis animal showed tachypnoea, tachycardia as well as minimal depressed pO2-levels and a slightly hypothermia. Elevated levels of A/NA indicated a high intraoperative distress. In addition, iCS levels were significantly elevated in comparison to the MMF-group. CH-rats lost 9.4 g of bodyweight from day of surgery to the following day. Overall, post-surgical little or no signs of pain and distress were observed after awakening from anesthesia, but all CH-rats exhibited peritonitis and perihepatitis, 44 % acute multifocal liver necrosis and 22 % perisplenitis. 95 % in the MMF-group reached satisfactory surgical anesthesia with duration of 47.83 ± 7.05 min (MMF) or 44.77 ± 5.27 min (MMF with reversal). Without reversal, MMF anesthesia lasted 182.23 ± 20.58 min. Gender-differences were noted in the latency to st, duration of st as well as duration of narcosis. Rats undergoing MMF anesthesia showed moderate depression of respiratory function and mild hypothermia. The A/NA levels were lower than in the CH-rats. Rats that received additional doses of MMF to maintain st showed a transient significant decrease of pO2. Core body temperature decreased significantly during 1 h after reversal. Post-mortem examination revealed myositis in some of the MMF-rats. MMF-rats with reversal awaked from anesthesia after 3.05 ± 0.31 min. Afterwards the rats were restless and agitated. After 1 h some of the rats exhibited piloerection and ataxic movements. Only 36 % of PROP-rats reached sufficient surgical anesthesia, accompanied by a pronounced respiratory depression. PROP-rats exhibited a significant decrease of core body temperature and signs of prolonged sedation after awakening from anesthesia. 4 of 11 rats died from respiratory failure during or after surgery. Surprisingly, levels of A/NA after ISO inhalation anesthesia were significantly higher compared to the injection groups. The results of this study indicate that CH anesthesia is associated with an increased liberation of stress hormones. The use of a 3.6 % solution of CH has to be refused especially because of the pathohistological findings, despite animals showed subjectively a good well-being. Propofol administered as an i.p. bolus produced only hypnosis. Therefore, i.p. injections are marely useful for short and non-painful procedures. However, post-anesthetic excitations represent limitations. The initial i.p. propofol bolus followed by intravenous infusion is therefore less suitable than an absolute intravenous administration. Thus, i.p. injections cannot be recommended. The complete reversible combination MMF is considered as suitable for stereotactic surgeries of Sprague-Dawley rats. There is an urgent need to continue heating after awakening, because thermoregulation is insufficiently restored after reversal of MMF anesthesia. Distress through the undesirable effects of the reversal like agitation and restlessness and through hypothermia was presumed only by subjective criteria. Further investigations are needed here. If there is no emergency situation, reversal should be avoided. In case of permanent external heating (37 - 38 °C) there is no major risk of life-threatening hypothermia or depression of respiratory or cardiovascular function during sleeping time.

Orientador: Newton Nunes / Banca: Paulo Sérgio Patto dos Santos / Banca: Celina Tie Nishimori Duque / Resumo: Para avaliar os efeitos da infusão contínua de naloxona ou tramadol sobre a resposta à hipovolemia aguda foram utilizados 40 coelhos adultos distribuídos em cinco grupos: grupo naloxona (GN), grupo tramadol 1 (GT1), grupo tramadol 3 (GT3), grupo tramadol 5 (GT5) e grupo controle (GC). Os animais foram induzidos (2,5 CAM) e mantidos (1,5 CAM) à anestesia com isofluorano e após 60 minutos receberam bolus de solução de NaCl a 0,9% (GC), de naloxona (GN) ou de diferentes doses de tramadol (GT1, GT3 e GT5), seguido de infusão contínua dos mesmos fármacos. Decorridos dez minutos, os coelhos foram induzidos à hipovolemia por meio da retirada de sangue arterial no volume total de 15 ml/kg, o qual foi reinfundido após uma hora. Os parâmetros avaliados foram frequência cardíaca, eletrocardiografia, pressão venosa central, pressões arteriais (PA), pressão de perfusão coronariana (PPC), frequência respiratória, saturação de oxiemoglobina e tensão parcial de dióxido de carbono ao final da expiração. Os dados foram submetidos à análise de variância seguida pelo teste de Tukey (p<0,05). Houve diminuição significativa das médias de PA e PPC após a retirada sanguínea, em todos os grupos, com posterior retorno aos valores iniciais durante a reinfusão do sangue, com exceção do GT5 que apresentou médias estáveis durante a hipovolemia e reinfusão. O GC e GT1 apresentaram médias de PA e PPC menores que as do GT5 vinte minutos após a remoção sanguínea. As demais variáveis não apresentaram diferença significativa ao longo do período experimental. Concluiu-se que a administração do tramadol, na dose de 5 mg/kg seguida por infusão contínua de 0,025 mg/kg/min, é indicada na terapia da hipovolemia aguda, pois possui ações benéficas na PA e na PPC, sem alterar os demais parâmetros estudados. / Abstract: To evaluate the effects of continuous infusion of naloxone or tramadol on the answer to acute hypovolemia, forty adult rabbits were assigned into five groups: naloxone group (NG), tramadol group 1 (TG1), tramadol group 3 (TG3), tramadol group 5 (TG5) and control group (CG). General anesthesia was induced (2.5 CAM) and maintained (1.5 CAM) with isoflurane and, after sixty minutes, the bolus of NaCl to 0.9% (CG), of naloxone (NG) or the several doses of tramadol (TG1, TG3 e TG5) followed by continuous infusion of the same drugs were administered. After 10 minutes, the rabbits were induced to hypovolemia by withdrawing arterial blood in total volume of 15 ml/kg, which was reinfused after one hour. Heart rate, electrocardiogram, venous central pressure, arterial pressures (AP), coronary perfusion pressure (CPP), respiratory rate, pulse oxygen saturation and end-tidal carbon dioxide were evaluated. Numerical data were submitted to analyses of variance followed by Tukey test (p<0.05). The AP and CPP decreased significantly, after blood withdrawal, in all groups. During blood reinfusion, these parameters came back to the initial values, except in TG5, because these variables were stable during hypovolemia and blood reinfusion. The CG and TG1 showed mean of AP and CPP lower than the TG5 at twenty minutes after the withdrawal of blood. It was concluded that tramadol administration, at dose of 5 mg/kg followed by continuous infusion of 0.025 mg/kg/min, is indicated in therapy of acute hypovolemia, because it has useful action on AP and on CPP, besides this drug does not impair the other evaluated parameters. / Mestre

Made available in DSpace on 2014-06-11T19:23:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-02Bitstream added on 2014-06-13T19:50:49Z : No. of bitstreams: 1 moro_jv_me_jabo.pdf: 306522 bytes, checksum: 44cb74f16669bfd812909add5b4a1dc0 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Para avaliar os efeitos da infusão contínua de naloxona ou tramadol sobre a resposta à hipovolemia aguda foram utilizados 40 coelhos adultos distribuídos em cinco grupos: grupo naloxona (GN), grupo tramadol 1 (GT1), grupo tramadol 3 (GT3), grupo tramadol 5 (GT5) e grupo controle (GC). Os animais foram induzidos (2,5 CAM) e mantidos (1,5 CAM) à anestesia com isofluorano e após 60 minutos receberam bolus de solução de NaCl a 0,9% (GC), de naloxona (GN) ou de diferentes doses de tramadol (GT1, GT3 e GT5), seguido de infusão contínua dos mesmos fármacos. Decorridos dez minutos, os coelhos foram induzidos à hipovolemia por meio da retirada de sangue arterial no volume total de 15 ml/kg, o qual foi reinfundido após uma hora. Os parâmetros avaliados foram frequência cardíaca, eletrocardiografia, pressão venosa central, pressões arteriais (PA), pressão de perfusão coronariana (PPC), frequência respiratória, saturação de oxiemoglobina e tensão parcial de dióxido de carbono ao final da expiração. Os dados foram submetidos à análise de variância seguida pelo teste de Tukey (p<0,05). Houve diminuição significativa das médias de PA e PPC após a retirada sanguínea, em todos os grupos, com posterior retorno aos valores iniciais durante a reinfusão do sangue, com exceção do GT5 que apresentou médias estáveis durante a hipovolemia e reinfusão. O GC e GT1 apresentaram médias de PA e PPC menores que as do GT5 vinte minutos após a remoção sanguínea. As demais variáveis não apresentaram diferença significativa ao longo do período experimental. Concluiu-se que a administração do tramadol, na dose de 5 mg/kg seguida por infusão contínua de 0,025 mg/kg/min, é indicada na terapia da hipovolemia aguda, pois possui ações benéficas na PA e na PPC, sem alterar os demais parâmetros estudados. / To evaluate the effects of continuous infusion of naloxone or tramadol on the answer to acute hypovolemia, forty adult rabbits were assigned into five groups: naloxone group (NG), tramadol group 1 (TG1), tramadol group 3 (TG3), tramadol group 5 (TG5) and control group (CG). General anesthesia was induced (2.5 CAM) and maintained (1.5 CAM) with isoflurane and, after sixty minutes, the bolus of NaCl to 0.9% (CG), of naloxone (NG) or the several doses of tramadol (TG1, TG3 e TG5) followed by continuous infusion of the same drugs were administered. After 10 minutes, the rabbits were induced to hypovolemia by withdrawing arterial blood in total volume of 15 ml/kg, which was reinfused after one hour. Heart rate, electrocardiogram, venous central pressure, arterial pressures (AP), coronary perfusion pressure (CPP), respiratory rate, pulse oxygen saturation and end-tidal carbon dioxide were evaluated. Numerical data were submitted to analyses of variance followed by Tukey test (p<0.05). The AP and CPP decreased significantly, after blood withdrawal, in all groups. During blood reinfusion, these parameters came back to the initial values, except in TG5, because these variables were stable during hypovolemia and blood reinfusion. The CG and TG1 showed mean of AP and CPP lower than the TG5 at twenty minutes after the withdrawal of blood. It was concluded that tramadol administration, at dose of 5 mg/kg followed by continuous infusion of 0.025 mg/kg/min, is indicated in therapy of acute hypovolemia, because it has useful action on AP and on CPP, besides this drug does not impair the other evaluated parameters.

Was aimed at evaluating the effects of lidocaine and bupivacaine via the spine in turtles of the species Podocnemis expansa in promoting motor and sensitive blockages in the tail/cloaca and pelvic members, as well as the existence of significant differences in the effects produced by the two drugs. Was used 20 animals with average weights of 1.15 kg, which were divided into two anesthetic protocols: 4.6 mg/kg of lidocaine 2% and 1.15 mg/kg of bupivacaine 0.5% deposited in the spinal region in the sacro-coccigeal area. Was evaluated the latency period, the reasonable period for anesthesia and the recovery period. For the latency period of the tail/cloaca we obtained (Lca) 54±34.05 seconds (sec) and 54±18.97sec as mean values for lidocaine and bupivacaine respectively. The latency period of the pelvic member (LMp) was in average 264±75.89 seconds for lidocaine and 180±126.49 sec for bupivacaine. Then the reasonable period for anesthesia on the tail/cloaca (Hca) was 36±9.43 minutes (min) and 60.8±32.10 min for the anesthetics in the same sequence. The averages for the reasonable period in pelvic members (HMp) were 24.6±10.83 min and 58.7±33.82 min for the respective drugs. Finally, the recovery period (Rec) was 33.5±16.33 min for lidocaine and 77.5±33.27 min for bupivacaine. The average times found for bupivacaine were significantly higher except during periods of latency of the tail/cloaca and pelvic members. The heart rate remained within the range considered normal for the testudines. Was conclude that the use of lidocaine and bupivacaine via the spine is safe and effective in the promotion of anesthesia in the region of the tail/cloaca and in pelvic limbs, and that the reasonable times for anesthesia are enough to perform simple and ordinary surgical procedures. / Objetivou-se avaliar os efeitos da lidocaína e bupivacaína por via espinhal em cágados da espécie Podocnemis expansa na promoção de bloqueios motor e sensitivo nas regiões da cauda/cloaca e membros pelvinos, bem como a existência de diferenças nos efeitos produzidos pelos dois fármacos. Foram utilizados 20 animais com massa corporal média de 1,15 kg de ambos os gêneros, estes foram distribuidos em dois protocolos anestésicos: 4,6 mg/kg de lidocaína 2% e 1,15 mg/kg de bupivacaína 0,5%, depositadas na região espinhal no espaço interarcual sacro-coccígeo. Foram avaliados o período de latência, período hábil de anestesia e o período de recuperação. Foram obtidos, para período de latência da cauda/cloaca (Lca) 54±34,05 segundos (seg) e 54±18,97 seg como valores médios para lidocaína e bupivacaína respectivamente. O período de latência do membro pelvino (LMp) teve como média 264±75,89 seg para lidocaína e 180±126,49 seg para bupivacaína. Já o período hábil de anestesia em cauda/cloaca (Hca) foi de 36±9,43 minutos (min) e 60,8±32,10 min para os anestésicos na mesma sequencia. As médias para o período hábil nos membros pelvinos (HMp) foram de 24,6±10,83 min e 58,7±33,82 min para os respectivos fármacos. Por fim, o período de recuperação (Rec) foi de 33,5±16,33 min para lidocaína e 77,5±33,27 min para bupivacaína. As médias de tempo encontradas para bupivacaína foram significativamente maiores exceto nos períodos de latência de cauda/cloaca e de membros pelvinos. A freqüência cardíaca permaneceu dentro do intervalo considerado normal para os testudines. Conclui-se que a utilização de lidocaína e bupivacaína por via espinhal é segura e eficaz na promoção de anestesia na região de cauda/cloaca e nos membros pelvinos, e que os tempos hábeis de anestesia são suficientes para execução de procedimentos cirúrgicos mais simples e rotineiros. / Mestre em Ciências Veterinárias

The purpose of this study was to compare the ability to induce palatal mucosa anesthesia and the anesthetic efficacy after superior alveolar posterior nerve block of two anesthetic solutions: 4% articaine with epinephrine 1:100,000 (Articaine-DFL) and 2% lidocaine with epinephrine 1:100,000 (Alphacaine-DFL), in a double-blind crossover manner. Eighteen healthy volunteers, aged 14 to 26 years, with non-irrupted superior third molar removal indications were selected. All procedures were executed in the morning at once, by the same oral and maxillofacial surgeon. The diffusion ability and the efficacy of anesthetic solutions were verified by the 11-Point Box Scale, administered two times for each solution: after incision and detachment and after suture. The anxiety degree was evaluated by Corah Dental Anxiety Scale. Data were analyzed trough Wilcoxon´s test (α= 0.05). All the median values for the 11-Point Box Scale were similar. Besides that there were no significant statistical differences between articaine and lidocaine solutions after incision and detachment (p= 0.329) neither after the surgical procedures (p= 0.393). Results showed that in healthy patients, both anesthetic solutions had the same diffusion to palatal mucosa, and 2% lidocaine with epinephrine 1:100,000 and 4% articaine with epinephrine 1:100,000 presented similar clinical behavior, thus choosing either solution does not change the quality of the non-irrupted superior third molars removal. / Este estudo randomizado e duplo-cego avaliou comparativamente a capacidade das soluções anestésicas articaína a 4% e lidocaína a 2%, ambas associadas à epinefrina 1:100.000, quanto à capacidade de promover anestesia na mucosa palatina e eficácia anestésica após bloqueio do nervo alveolar superior posterior. A amostra foi constituída por dezoito indivíduos de ambos os sexos, com idade entre 14 e 26 anos, saudáveis, sem uso de medicação sistêmica e com indicação de remoção dos terceiros molares superiores não-irrompidos. Os procedimentos cirúrgicos foram realizados por um único cirurgião dentista, especialista e mestrando em Cirurgia e Traumatologia Buco Maxilo Facial, em sessão única e sempre no período matutino. A capacidade de difusão e a eficácia das soluções foram avaliadas através de Escalas de Onze Pontos em Caixa (EC), aplicadas após incisão e descolamento e após a sutura. O grau de ansiedade do voluntário foi avaliado através da Escala de Ansiedade Dental de Corah (EADC). Os dados foram submetidos ao teste de Wilcoxon, nível de significância de 5%. Os valores medianos obtidos pela EC de ambas as soluções anestésicas mostraram-se bastante próximos e não apresentaram diferença estatisticamente significante após incisão e descolamento (p= 0,329) e nem ao término do procedimento cirúrgico (p= 0,393). Os resultados demonstraram que as soluções lidocaína a 2% com epinefrina 1:100.000 e articaína a 4% com epinefrina 1:100.000 não apresentaram diferenças na capacidade de difusão e eficácia do anestésico, consequentemente não alteram a qualidade dos procedimentos de exodontias de terceiros molares não-irrompidos na maxila. / Mestre em Odontologia