Orientador: Norma Sueli Pinheiro Módolo / Resumo: Introdução: histerectomia abdominal é cirurgia amplamente realizada no mundo, e raquianestesia com adição de morfina é considerada a técnica anestésica de escolha devido a melhor qualidade de recuperação e adequado controle da dor pós-operatória. No entanto, náuseas e vômitos pós-operatórios (NVPO) são problemas frequentes quando morfina é utilizada no neuroeixo. Palonosetrona é um antagonista serotoninérgico potente e com longa duração de ação, efetivo na prevenção de NVPO após anestesia geral. O seu efeito após anestesia no neuroeixo ainda não foi estabelecido. Nós comparamos palonosetrona com ondansetrona para profilaxia de NVPO quando raquianestesia com morfina foi usada em pacientes com alto risco para NVPO. A hipótese é que a palonosetrona promove melhor controle de NVPO quando comparada com ondansetrona nesse contexto. Métodos: após aprovação do Comitê de Ética em Pesquisa, foram incluídas no estudo 140 pacientes elegíveis para histerectomia abdominal sob raquianestesia com adição de morfina. Todas receberam anestesia subaracnóidea com administração de 15 mg de bupivacaína hiperbárica e 0,1 mg de morfina. Dexametasona 8 mg foi administrada por via endovenosa em todas as pacientes como uma abordagem multimodal para prevenção de NVPO. As pacientes foram divididas aleatoriamente em dois grupos para receber 0,075 mg de palonosetrona ou 4 mg de ondansetrona antes do início da cirurgia. O desfecho primário avaliado foi a incidência global de NVPO nas 48h após a cirurgia. Adi... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Orientador: Eliana Marisa Ganem / Resumo: Introdução: O parecoxibe, um pró-fármaco hidrolisado à valdecoxibe, é um antagonista da COX-2 com intensa atividade anti-inflamatória e analgésica. Embora muitos estudos tenham sido realizados indicando a eficácia dos antagonistas da COX em aliviar o processo da dor, quase nada foi estudado sobre a toxicidade desses fármacos no neuroeixo. Objetivos: O objetivo desta pesquisa foi avaliar os efeitos que diferentes doses de parecoxibe, administrado pela via subaracnoidea, em punção única, determinariam sobre a medula espinal e as meninges de coelhos. Metodologia: Após aprovação pela Comissão de Ética no Uso de Animais, 30 coelhos adultos jovens, da raça grupo genético de Botucatu, com pesos entre 2510 g e 3560 g, fornecidos pelo Biotério da Faculdade de Medicina de Botucatu, foram randomizados em três grupos: grupo S – solução salina a 0,9%, grupo P4 – parecoxibe (dose: 4 mg) e grupo P8 – parecoxibe (dose: 8 mg). Após a anestesia intravenosa com xilazina e cetamina os animais foram submetidos à punção subaracnoidea guiada por ultrassom, com agulha de Quincke 25G, no espaço entre primeira e a segunda vértebras sacrais e realizada a injeção de uma das soluções previamente sorteadas em volume de 0,4 mL (10 µL por centímetro de medula espinal medida entre a base do crânio e o espaço lombossacral). Após a recuperação da anestesia e por 21 dias, os animais foram avaliados quanto à sensibilidade e à motricidade. Em seguida, foram sacrificados por decapitação e retiradas as porções lomb... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Parecoxib, a pro-drug that is hydrolyzed to valdecoxib, is a COX-2 antagonist with strong anti-inflammatory and analgesic activity. Although many studies have demonstrated the efficacy of COX antagonists in relieving pain, almost nothing is known about the toxicity of these drugs when administered into the neuraxis. Objectives: The aim of this study was to evaluate the effects of a single injection of different doses of parecoxib into the subarachnoid space on the spinal cord and meninges of rabbits. Methods: After approval by the Ethics Committee on Animal Use, 30 young adult rabbits of the Botucatu genetic group weighing 2,510 to 3,560 g, were randomized into three groups: group S - 0.9% saline; group P4 – parecoxib (dose: 4 mg); group P8 – parecoxib (dose: 8 mg). After intravenous anesthesia with xylazine and ketamine, the animals underwent ultrasound-guided subarachnoid puncture with a Quincke 25G needle in the space between the first and second sacral vertebrae and the injection of one of the previously established solutions was performed in a volume of 0.4 mL (10 µL per cm of spinal cord measured from the skull base to the lumbosacral space). After recovery from anesthesia, the animals were evaluated regarding sensitivity and motor function for 21 days. After this period, the animals were sacrificed by decapitation and the lumbar and sacral portions of the spinal cord and the roots of the cauda equina were removed for histological examination by light micros... (Complete abstract click electronic access below) / Doutor

Submitted by CAIO JOSÉ XAVIER ABIMUSSI null (caioabimussi@fmva.unesp.br) on 2016-01-17T16:54:36Z No. of bitstreams: 1 TESE_VERSÃO FINAL_CORRIGIDA.pdf: 2286468 bytes, checksum: 496c8f6ffc7595636c5c52c061679bc7 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-01-18T15:52:49Z (GMT) No. of bitstreams: 1 abimussi_cjx_dr_araca.pdf: 2286468 bytes, checksum: 496c8f6ffc7595636c5c52c061679bc7 (MD5) / Made available in DSpace on 2016-01-18T15:52:49Z (GMT). No. of bitstreams: 1 abimussi_cjx_dr_araca.pdf: 2286468 bytes, checksum: 496c8f6ffc7595636c5c52c061679bc7 (MD5) Previous issue date: 2015-12-14 / Não recebi financiamento / Objetivou-se avaliar a anestesia raquidiana com ropivacaína em cães alterando a baricidade do anestésico local, investigando as alterações hemodinâmicas e complicações. Foram utilizados seis cães, Beagle, 4 anos, submetidos a anestesia inalatória com isofluorano e aos tratamentos: Ghipo = anestesia raquidiana hipobárica (0,5 mL NaCl 0,9% + 0,5 mL ropivacaína 0,75%); Giso = anestesia raquidiana isobárica (0,5 mL NaCl 1,53% + 0,5 mL ropivacaína 0,75%); Ghiper = anestesia raquidiana hiperbárica (0,5 mL glicose 10% + 0,5 mL ropivacaína 0,75%). Após indução anestésica e manutenção com isofluorano, os animais foram posicionados em decúbito lateral direito para a passagem de um cateter de artéria pulmonar pela veia jugular esquerda. Após esse procedimento, a punção subaracnóide foi realizada entre L5-L6 com uma agulha espinhal 22G, seguida da administração de 1 mL de anestésico local em 1 min. Os animais foram mantidos por 60 minutos anestesiados em decúbito ventral. A FC, f, PAM, DC, PAPm e TºC apresentaram aumento progressivo em todos os grupos enquanto que a PCPm, apenas no GHIPO, aumentou ao longo de todos os momentos. O IRPT no GISO apresentou valores significativamente superiores no M1, M5 e M10 comparado aos demais grupos, exceto no M5, em que o GISO diferiu somente do GHIPER. O IRVP no GISO aumentou no M5 em comparação ao MB. Foram observados efeitos adversos como déficit motor unilateral, atonia vesical, excitação, dor aguda e quemose. Conclui-se que as alterações hemodinâmicas não foram relevantes, embora a anestesia inalatória com isofluorano tenha influído sobre os resultados obtidos. / The aim of the study was to assess spinal anesthesia with ropivacaine in dogs altering the local anesthetic agent’s baricity in order to investigate hemodynamic changes and complications. Six beagle dogs aged 4 years old were anesthetized with isoflurane and subjected to the treatments: Ghypo = spinal anesthesia with hypobaric ropivacaine (0.5 mL of 0.9% NaCl + 0.5 mL ropivacaine at 0,75%); Giso = isobaric spinal anesthesia (0.5 mL of 0,906% NaCl + 0.5 mL ropivacaine at 0,75%); Ghyper = hyperbaric spinal anesthesia (0.5 mL of 10% glucose + 0.5 mL ropivacaine at 0.75%). After induction to anesthesia and maintenance with isoflurane, animals were positioned in right lateral recumbency for pulmonary artery catheterization through the left jugular vein. Rightafter, spinal anesthesia was performed between L5-L6 using a 22G Quincke tip needle, followed by administration of 1 mL of local anesthetic during 1 minute. Animals were maintained under anesthesia for 60 minutes in ventral recumbency. HR, FR, MAP, CO, mPAP and body temperature progressively increased in all groups. whereas PCWP increased only in GHYPO at all time points. The TPRI showed significantly higher values in GISO at M1, M5 and M10 compared to the other groups, except for M5, during which GISO differed only from GHYPER. The PVRI increased at M5 compared to MB in GISO. Side effects such as unilateral motor deficit, bladder atony, excitation, acute pain and chemosis were observed. In conclusion, the hemodynamic changes were not relevant, although inhalation anesthesia with isoflurane might have influenced the results.

Bakgrund: Kejsarsnitt har blivit vanligare, orsaken kan vara medicinska indikationer, men också förlossningsrädsla. Att kvinnor som föder barn vaginalt får en bättre upplevelse om de får stöd av en medmänniska är välkänt. Studier av kvinnor som föder barn med planerade kejsarsnitt visar att de också behöver stöd. Detta stöd ges framför allt av anestesisjuksköterskor eftersom barnmorskan är sterilklädd. Syfte: Syftet var att beskriva hur anestesisjuksköterskan ger stöd till den födande kvinnan vid planerat kejsarsnitt i spinalanestesi. Metod: En empirisk, deskriptiv studie med kvalitativ ansats genomfördes. Fem anestesisjuksköterskor intervjuades. Deras berättelser analyserades med kvalitativ innehållsanalys. Resultat: I resultatet framkom fem olika teman och tio subkategorier. Resultatet visar hur anestesisjuksköterskorna ger stöd. Temana var främja delaktighet (kommunicera, involvera närstående), värna integritet (stå bakom, dela födelsen), inge trygghet (vara närvarande, utstråla kompetens, teamarbete) och skapa relation (emotionellt engagemang, använda personligheten, känna in den unika patienten). Det femte temat produktionskrav beskriver de tidspressade förhållanden som gäller där anestesisjuksköterskorna ger stödet. Slutsats: Att ge stöd vid kejsarsnitt innebär att anestesisjuksköterskorna pendlar mellan närhet och distans till patienten, utifrån den unika patientens behov. Målet för stödet var att den blivande modern skulle kunna föda sitt barn lugn och trygg, tillsammans med sin närstående. Arbetsmiljö med flera kejsarsnitt per dag påverkar anestesisjuksköterskornas möjligheter att ge stöd. Klinisk betydelse: Denna studie avser att öka kunskapen om anestesisjuksköterskans stöd vid planerade kejsarsnitt. Detta är en pilotstudie som det kan vara värdefullt att reflektera kring som kliniskt verksam anestesisjuksköterska. / Background: Caesarean section has become more common, the cause may be medical indications, but also fear of childbirth. It is well known that women who give birth vaginally have a better experience if they are supported by a fellow human being. Studies of women who give birth with planned caesarean section shows that they also need support. The purpose was to describe how the nurse anesthetist provides support to the woman in labor at elective caesarean section in spinal anesthesia. Method: An empirical, descriptive study with qualitative approach was conducted. Five nurse anesthetists were interviewed. Their stories were analyzed using qualitative content analysis. Results: The results revealed five different themes and ten subcategories. The results show how a nurse anesthetist provides support. Nurse anesthetists provide support by promoting participation, protect integrity, provide safety and build relationships. The fifth theme, which is called the production requirements, describes the time-strained circumstances of the place where nurse anesthetists provide support. Conclusion: Nurse anesthetists were prepared to provide support so that the mother could give birth to the baby while feeling safe and calm. Working environment with multiple caesarean sections per day affects nurse anesthetist capacity to provide support. Clinical significance: This study intends to increase awareness of the nurse anesthetist support for this form of childbirth. This is a pilot study that it may be useful for the clinically active nurse anesthetist to reflect on.

INTRODUÇÃO: O Brasil ocupa o primeiro lugar entre os países com maiores taxas de cesariana no mundo. Pouco se sabe a respeito das consequências futuras deste procedimento, sobre a saúde materna. Este estudo investigou a influência da técnica anestésico-cirúrgica e analgesia pós-operatória, no aparecimento de dor crônica após a cesariana. Procuramos também identificar os fatores de risco de dor crônica pós-cesariana. MÉTODO: Este estudo prospectivo com distribuição aleatória foi conduzido em 443 pacientes que foram submetidas à cesariana (eletivas e emergenciais), com diferentes doses de bupivacaína 0,5% hiperbárica e opioides na raquianestesia, bem como uso de anti-inflamatórios não esteroidais peri-operatório. Os grupos foram: G8SMA- 8 mg bupivacaína hiperbárica + 2,5 mcg sufentanil + 100 mcg morfina; G10SMA- 10 mg bupivacaína hiperbárica + 2,5 mcg sufentanil + 100 mcg morfina; G12,5MA- 12,5 mg bupivacaína hiperbárica + 100 mcg morfina; G15MA- 15 mg bupivacaína hiperbárica + 100 mcg morfina; G12,5M - 12,5 mg bupivacaína hiperbárica + 100 mcg morfina. Somente as pacientes do grupo G12,5M não receberam AINE no peri-operatório. Dor em repouso e em movimento foram avaliadas no pós-operatório imediato. Fatores peri-operatórios, cirúrgicos e obstétricos foram investigados. Contato telefônico foi realizado, após três e seis meses do procedimento cirúrgico, para identificação das pacientes com dor crônica. RESULTADOS: A incidência de dor crônica nos grupos foi: G8SMA= 20%, G10SMA= 13%; G12,5MA= 7,1%; G15MA= 2,2% e G12,5M= 20,3%. Pacientes que apresentaram escores de dor mais elevados no período pós- operatório imediato, que referiram doenças crônicas em tratamento, que apresentaram maior tempo em trabalho de parto sem analgesia, tiveram maior incidência de dor crônica (p<0,05). CONCLUSÃO: A incidência de dor crônica diminui com emprego de doses maiores de anestésicos locais e uso de anti-inflamatórios não esteroidais. Escores mais elevados de dor no período pós-operatório imediato tiveram associação com aparecimento de dor crônica após a cesariana. Os fatores de risco encontrados foram: doença crônica em tratamento, maior tempo em trabalho de parto sem analgesia e escores de dor elevados no pós- operatório imediato / INTRODUCTION: Brazil holds first place in cesarean section rate in the world. Little is known about the consequences upon maternal health. This study investigated the influence of anesthetic, surgical techniques and postoperative analgesia on chronic pain after cesarean section. We also tried to identify risk factors for chronic pain after cesarean section. METHODS: A prospective randomized study was conducted among 443 patients who underwent elective or emergency cesarean section with different doses of hyperbaric bupivacaine 0.5% and opioids in spinal anesthesia, associated or not to non steroidal anti-inflamatory drugs. The groups were: G8SMA- 8mg hyperbaric bupivacaine + 2.5 mcg sufentanil + 100 mcg morphine; G10SMA- 10 mg hyperbaric bupivacaine + 2.5 mcg sufentanil + 100 mcg morphine; G12.5MA- 12.5 mg hyperbaric bupivacaine + 100 mcg morphine; G15MA- 15 mg hyperbaric bupivacaine + 100 mcg morphine; G12.5M- 12.5 mg hyperbaric bupivacaine + 100 mcg morphine (only in this group, non-steroidal anti-inflammatory drug was not used). Pain at rest and during movement were evaluated on the first two postoperative days using the verbal numerical rating scale. Perioperative, surgical and obstetric factors were investigated. Phone survey was conducted after three and six months to identify patients with chronic pain RESULTS: Incidences of chronic pain in groups were: G8SMA= 20%, G10SMA= 13%; G12.5MA= 7.1%; G15MA= 2.2% and G12.5M= 20.3 %. Patients with co-morbidities, and who had been more than 15 hours in labor before the cesarean (without analgesia) had more chance to have chronic pain than those who did not have pain. Patients who had higher pain scores on the two postoperative days were associated to chronic pain (p<0.05).!! CONCLUSION: The incidence of chronic pain decreases with higher doses of local anesthetic and the use of non-steroidal anti-inflammatory drugs. Patients who had higher pain scores in the immediate postoperative period were more likely to develop chronic pain. The only predictors of chronic pain were: previous history of disease, longer time in labor, intensity of postoperative pain and the use of lower doses of local anesthetic in spinal anesthesia

INTRODUÇÃO: O Brasil ocupa o primeiro lugar entre os países com maiores taxas de cesariana no mundo. Pouco se sabe a respeito das consequências futuras deste procedimento, sobre a saúde materna. Este estudo investigou a influência da técnica anestésico-cirúrgica e analgesia pós-operatória, no aparecimento de dor crônica após a cesariana. Procuramos também identificar os fatores de risco de dor crônica pós-cesariana. MÉTODO: Este estudo prospectivo com distribuição aleatória foi conduzido em 443 pacientes que foram submetidas à cesariana (eletivas e emergenciais), com diferentes doses de bupivacaína 0,5% hiperbárica e opioides na raquianestesia, bem como uso de anti-inflamatórios não esteroidais peri-operatório. Os grupos foram: G8SMA- 8 mg bupivacaína hiperbárica + 2,5 mcg sufentanil + 100 mcg morfina; G10SMA- 10 mg bupivacaína hiperbárica + 2,5 mcg sufentanil + 100 mcg morfina; G12,5MA- 12,5 mg bupivacaína hiperbárica + 100 mcg morfina; G15MA- 15 mg bupivacaína hiperbárica + 100 mcg morfina; G12,5M - 12,5 mg bupivacaína hiperbárica + 100 mcg morfina. Somente as pacientes do grupo G12,5M não receberam AINE no peri-operatório. Dor em repouso e em movimento foram avaliadas no pós-operatório imediato. Fatores peri-operatórios, cirúrgicos e obstétricos foram investigados. Contato telefônico foi realizado, após três e seis meses do procedimento cirúrgico, para identificação das pacientes com dor crônica. RESULTADOS: A incidência de dor crônica nos grupos foi: G8SMA= 20%, G10SMA= 13%; G12,5MA= 7,1%; G15MA= 2,2% e G12,5M= 20,3%. Pacientes que apresentaram escores de dor mais elevados no período pós- operatório imediato, que referiram doenças crônicas em tratamento, que apresentaram maior tempo em trabalho de parto sem analgesia, tiveram maior incidência de dor crônica (p<0,05). CONCLUSÃO: A incidência de dor crônica diminui com emprego de doses maiores de anestésicos locais e uso de anti-inflamatórios não esteroidais. Escores mais elevados de dor no período pós-operatório imediato tiveram associação com aparecimento de dor crônica após a cesariana. Os fatores de risco encontrados foram: doença crônica em tratamento, maior tempo em trabalho de parto sem analgesia e escores de dor elevados no pós- operatório imediato / INTRODUCTION: Brazil holds first place in cesarean section rate in the world. Little is known about the consequences upon maternal health. This study investigated the influence of anesthetic, surgical techniques and postoperative analgesia on chronic pain after cesarean section. We also tried to identify risk factors for chronic pain after cesarean section. METHODS: A prospective randomized study was conducted among 443 patients who underwent elective or emergency cesarean section with different doses of hyperbaric bupivacaine 0.5% and opioids in spinal anesthesia, associated or not to non steroidal anti-inflamatory drugs. The groups were: G8SMA- 8mg hyperbaric bupivacaine + 2.5 mcg sufentanil + 100 mcg morphine; G10SMA- 10 mg hyperbaric bupivacaine + 2.5 mcg sufentanil + 100 mcg morphine; G12.5MA- 12.5 mg hyperbaric bupivacaine + 100 mcg morphine; G15MA- 15 mg hyperbaric bupivacaine + 100 mcg morphine; G12.5M- 12.5 mg hyperbaric bupivacaine + 100 mcg morphine (only in this group, non-steroidal anti-inflammatory drug was not used). Pain at rest and during movement were evaluated on the first two postoperative days using the verbal numerical rating scale. Perioperative, surgical and obstetric factors were investigated. Phone survey was conducted after three and six months to identify patients with chronic pain RESULTS: Incidences of chronic pain in groups were: G8SMA= 20%, G10SMA= 13%; G12.5MA= 7.1%; G15MA= 2.2% and G12.5M= 20.3 %. Patients with co-morbidities, and who had been more than 15 hours in labor before the cesarean (without analgesia) had more chance to have chronic pain than those who did not have pain. Patients who had higher pain scores on the two postoperative days were associated to chronic pain (p<0.05).!! CONCLUSION: The incidence of chronic pain decreases with higher doses of local anesthetic and the use of non-steroidal anti-inflammatory drugs. Patients who had higher pain scores in the immediate postoperative period were more likely to develop chronic pain. The only predictors of chronic pain were: previous history of disease, longer time in labor, intensity of postoperative pain and the use of lower doses of local anesthetic in spinal anesthesia

I found that 2.6ml of 0.5% levobupivacaine had similar clinical characteristics as the same volume of 0.5% bupivacaine in spinal anaesthesia. Both were effective for spinal anaesthesia in urological surgery, when a sensory block up to at least T10 dermatome was required. In comparing the use of levobupivacaine alone and levobupivacaine with fentanyl, there were no significant differences in haemodynamic changes and quality of sensory and motor block, when 2.6ml of levobupivacaine alone or 2.3ml of levobupivacaine with fentanyl 15mcg (0.3ml) were used in spinal anaesthesia. Both were effective for spinal anaesthesia in urological surgery. In comparing the use of ropivacaine 10mg and bupivacaine 10mg, both with fentanyl 15mcg in spinal anaesthesia for urological surgery, all the patients achieved adequate level of sensory block up to T10 dermatome or higher. The two drugs were similar in the onset time of motor block, the characteristics of sensory block and haemodynamic changes; however, the duration of motor block was shorter with ropivacaine. I concluded that both studied solutions, ropivacaine-fentanyl and bupivacaine-fentanyl, were effective for spinal anaesthesia in urological surgery and the duration of motor block was shorter with the ropivacaine-fentanyl solution. The dose-response relationship of ropivacaine in spinal anaesthesia for lower limb surgery requiring a sensory block up to at least the T12 dermatome was defined. Anaesthesia was successful in 0, 0, 42, 83 and 100% when ropivacaine at doses of 2, 4, 7, 10 and 14mg respectively were given. The derived values for ED50 and ED95 were 7.6mg and 11.4mg respectively. The cephalic level of sensory block and the degree of motor block increased with larger doses of ropivacaine. Finally, the median effective dose (ED50) of bupivacaine, levobupivacaine and ropivacaine in spinal anaesthesia for lower limb surgery were defined as 5.50mg (95% CI: 4.90--6.10mg), 5.68mg (95% CI: 4.92--6.44mg), and 8.41mg (95% CI: 7.15--9.67mg) respectively. The relative potency ratios were 0.97 (95% CI: 0.81--1.17) for levobupivacaine/bupivacaine, 0.65 (95% CI: 0.54--0.80) for ropivacaine/bupivacaine and 0.68 (95% CI: 0.55--0.84) for ropivacainellevobupivacaine. / In this series of studies, I have shown that levobupivacaine and ropivacaine are effective local anaesthetic agents for spinal anaesthesia in lower limb and urological surgery. This proved my hypothesis. Both are suitable alternatives to bupivacaine for spinal anaesthesia. Furthermore, these studies showed that ropivacaine is less potent than levobupivacaine and bupivacaine and the potency is similar between levobupivacaine and bupivacaine at median effective dose. / Levobupivacaine and ropivacaine are two relatively new local anaesthetics which were developed in view of their potential for less cardiotoxicity in comparison with bupivacaine, the most common local anaesthetic used in spinal anaesthesia for many years. Both are produced in pure S(-) enantiomer form in contrast to bupivacaine which is a racemic mixture. They have been shown to be effective in peripheral nerve blocks, and epidural analgesia and anaesthesia; nevertheless, experience of their use in spinal anaesthesia is limited. The objective of this thesis was to evaluate their use in spinal anaesthesia for surgery in non-obstetric patients. My hypothesis was that levobupivacaine and ropivacaine are effective local anaesthetic agents for spinal anaesthesia in lower limb and urological surgery. In order to test this hypothesis, I conducted five clinical studies on 269 patients who had urological surgery or lower limb surgery under spinal or combined spinal-epidural anaesthesia. First, I investigated the efficacy and clinical characteristics of levobupivacaine and the mixture of levobupivacaine with fentanyl in spinal anaesthesia. Next, I compared the use of ropivacaine-fentanyl with bupivacaine-fentanyl in spinal anaesthesia. Finally, I defined the dose-response relationship of ropivacaine in spinal anaesthesia using traditional dose-response methodology and defined the relative potency among levobupivacaine, ropivacaine and bupivacaine by comparing the defined ED50 in spinal anaesthesia using up-down sequential allocation method. / Lee, Ying Yin. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 133-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

Introduction: Hysterectomy is the most common major gynecological operation in the Western World and approximately 5000 benign hysterectomies are performed in Sweden every year. Consequently it is a surgical procedure that affects many women. The procedure comprises challenges concerning perioperative health care, perceived postoperative symptoms, quality of life aspects and health economics. The concept of fast track is a multimodal strategy to reduce hormonal surgical stress response and achieve an enhanced postoperative recovery and is today considered to be evidence based in relation to colorectal surgery. Spinal anesthesia, as an important part of fast track, provides benefits of extended effect on analgesia and reduced postoperative morbidity. It is reasonable to believe that employing the strategies of fast track including spinal anesthesia could also provide substantial benefits for women requiring surgical removal of the uterus. Aims: To determine whether duration of hospital stay, presence and intensity of postoperative symptoms, duration of sick leave and cost-effectiveness differ between women undergoing benign fast track abdominal hysterectomy in spinal anesthesia with intrathecal morphine (SA) and in standard general anesthesia (GA). Material &amp; Methods: 180 women participated in this open randomized multicenter study with five participating hospitals in the southeast region of Sweden. One hundred and sixty two completed the study; 82 women were randomized to SA and 80 to GA. A fast track model comprising premedication without sedatives, intravenous fluid regulation, analgesics based on non-opioids, pre-emptive antiemetic therapy, early enteral nutrition and mobilization and standard criteria for discharge were used. End points were duration of hospital stay, use of analgesics, perceived postoperative symptoms, occurrence of postoperative complications, duration of sick leave and health economic evaluations. Results: Duration of hospital stay did not differ between the two modes of anesthesia. Vomiting and pruritus occurred significantly more often after SA. Complication rates did not differ between groups. Women with SA experienced less overall discomfort and had a reduced need for opioids postoperatively. Abdominal pain, drowsiness and fatigue occurred less often and with lower intensity among the women in the SA group. Health related quality of life improved faster and the duration of sick leave was shorter in women after SA. Total costs (hospital costs plus costs for productivity loss) were lower for the SA group. Within the first 29 days after hysterectomy the women in the SA group gained more QALYs than women in the GA group. Conclusions: The duration of hospitalisation after fast track abdominal hysterectomy was less than 50 hours and mode of anesthesia did not influence this. SA displayed considerable advantages regarding postoperative symptoms and recovery. SA was considered cost-effective in comparison with GA due to lower total costs and more QALYs gained. Our study indicates that SA should be recommended as the first choice of anesthesia in benign abdominal hysterectomy.

Activation of spinal N-methyl-D-aspartate (NMDA) receptors stimulates cyclooxygenase and nitric oxide pathways. Compounds that block the activity of these NMDA receptor systems reduce pain hypersensitivity. However, their usefulness is limited by the side effects they produce. One way of reducing side effects is by combining drugs that produce the same overt effect by different mechanisms, which hopefully increase the net effect. In these series of studies, drugs that interact with NMDA receptor systems and their combinations were screened in vitro to identify spinal antinociceptive synergistic combinations that could be assessed in vivo. Based on developmental changes in thresholds, conduction velocities and blocking actions of the local anaesthetic lignocaine in neonatal rat L4/L5 dorsal root potentials, it was decided to use spinal cord in vitro preparation from 5- to 7-day-old rat pups. In single drug studies, the NMDA receptor channel blocker ketamine (1-50 µM) and the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (200-600 µM), but not the NSAID salicylate (1000 µM) and the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 1-100 µM), reduced spinal NMDA receptor-mediated transmission. Ketamine also depressed non-NMDA receptor-mediated transmission. Using isobolographic and composite additive line analyses, fixed-ratio combinations of ketamine and ketoprofen, ketamine and L-NAME, and ketopofen and L-NAME synergistically depressed NMDA receptor-mediated transmission. The two former combinations had a subadditive effect on non-NMDA receptor-mediated transmission, and the latter had no significant effect. These studies identified that all combinations synergistically reduced both nociceptive transmission and potential side effects. In free-moving sheep implanted with indwelling cervical intrathecal catheters, 100 µ1 subdural administration of ketamine (25-400 µM) and ketoprofen (200-3200 µM) alone and in a fixed-ratio combination (873.95-3350.78 µM, 0.045:0.955) did not raise nociceptive thresholds as assessed by mechanical stimulation of one foreleg. Subdural administration of NMDA (2 mM) decreased mechanical nociceptive thresholds, and this was prevented by the highest concentrations of ketamine and ketoprofen alone and in combination. These findings demonstrated that NMDA receptor channel blockers and NSAIDs alone or in combination had no direct hypoalgesic effects when given onto the spinal cord of sheep, but they prevented NMDA-induced pain hypersensitivity. Simultaneous blockade of NMDA receptor systems could have important clinical implications.

Three clinical investigations together with a combined editorial and review of the cardiovascular physiology of spinal anaesthesia in normal and preeclamptic pregnancy form the basis of a thesis to be submitted for the degree of Doctor of Medicine at the University of St Andrews. First, the longstanding consensus that spinal anaesthesia could cause severe hypotension in severe preeclampsia was examined using three approaches. The doses of ephedrine required to maintain systolic blood pressure above predetermined limits were first compared in spinal versus epidural anaesthesia. The doses of ephedrine required were then similarly studied during spinal anaesthesia in preeclamptic versus normal control subjects. The principal outcome of these studies, that preeclamptic patients were resistant to hypotension after a spinal anaesthetic, was then further investigated by studying pulse transit time (PTT) changes in normal versus preeclamptic pregnancy. PTT was explored both as beat-to-beat monitor of cardiovascular function and also as an indicator of changes in arterial stiffness. The cardiovascular physiology of obstetric spinal anaesthesia was then reviewed in the light of the three clinical investigations, developments in reproductive vascular biology and the regulation of venous capacitance. It is argued that the theory of a role for vena caval compression as the single cause of spinal anaesthetic induced hypotension in obstetrics should be revised.