A research report submitted to the Faculty of Medicine, University of Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Anaesthesia. / Spinal anaesthesia for Caesarean section is associated with an unacceptably high incidence of hypotension despite the administration of an intravenous fluid preload and the use of uterine displacement. The theoretical benefits of preventing hypotension as opposed to treating it as it occurs are the avoidance of considerable maternal discomfort, a reduced risk of serious cardiovascular or respiratory depression and the avoidance of transient foetal asphyxia. The use of prophylactic intramuscular ephedrine prior to spinal anaesthesia has been recommended but not well studied. The advantages of the intramuscular route for ephedrine administration are its simplicity and its favourable pharmacokinetic profile. Cardiovascular support is sustained throughout the surgery and into the post operative period. Opposition to the use of intramuscular ephedrine in the prevention of hypotension is based on two studies in which spinal anaesthesia was not used [1,2]. These studies showed an unacceptably high incidence of hypertension, a deleterious effect on foetal gas exchange and a lack of efficacy when intramuscular ephedrine was used in epidural and general anaesthesia respectively. This research report describes a randomised, double blind, interventional study designed to assess the safety (prevalence of hypertension, tachycardia or foetal compromise) and efficacy (prevalence of hypotension) of 37,5mg of ephedrine given prior to spinal anaesthesia for Caesarean section. Forty patients who had given informed consent were entered into the study. Blood pressures and pulse rates were recorded for 90 minutes after ephedrine administration, samples of umbilical venous blood were collected and Apgar scores assessed. This study found that giving 37,5mg of intramuscular ephedrine prior to spinal anaesthesia was safe from a maternal point of view in that it was not associated with reactive hypertension or tachycardia. When the ephedrine was given 10 minutes prior to induction of the spinal the technique proved to be effective in reducing the incidence and severity of hypotension. When used in the above manner the technique was not associated with foetal depression or acidosis. / WHSLYP2016

Made available in DSpace on 2015-07-22T20:49:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-26 / A redução da massa de anestésico local é utilizada para minimizar os efeitos da hipotensão arterial, relacionados com raquianestesia para cesariana, diminuindo a incidência de eventos adversos maternos e preservando o bem-estar fetal. Esta estratégia tem o risco de resultar em anestesia insuficiente. Por outro lado, a hipotensão associada às maiores massas de anestésico local no espaço subaracnóideo pode ser controlada com infusão contínua profilática de fenilefrina.! Objetivo: Avaliar os efeitos da infusão contínua e profilática de fenilefrina para controle pressórico sobre os eventos adversos maternos e conceptuais em cesarianas com diferentes doses de bupivacaína na raquianestesia. Métodos: Foi realizado um estudo clínico prospectivo, não-aleatório, com 60 gestantes a termo, admitidas para cesariana eletiva. Todas as pacientes receberam raquianestesia com bupivacaína hiperbárica, acrescida de 5 mcg de sufentanil e 100 mcg de morfina. Foram alocadas em dois grupos, G12 e G8, na dependência da dose de bupivacaína hiperbárica administrada, 12 ou 8 mg, respectivamente. Foi realizada hidratação com 10 ml/Kg de solução de Ringer Lactato, 10 a 15 minutos antes da realização do bloqueio. Logo após, iniciou-se infusão contínua de 100 mcg/min de fenilefrina, com o objetivo de manter a pressão arterial dentro de limites estritos. Foram avaliados níveis sensitivos de bloqueio anestésico, consumo de vasopressores, incidência de eventos adversos maternos e condições do recém-nascido. Resultados: Os dados maternos mostraram que os dois grupos foram semelhantes, quanto ao nível de bloqueio anestésico, consumo de fenilefrina por unidade de tempo e incidências de hipotensão e hipertensão arterial, bradicardia, náuseas, vômitos, dispnéia, dor e tremores. Os dados conceptuais evidenciaram que os grupos foram semelhantes quanto à gasometria de artéria e veia umbilicais e lactato arterial e venoso. Todos os RN apresentaram pH > 7,2 e apenas 1 obteve pontuação < 7 no Apgar do primeiro minuto. Conclusões: Quando a pressão arterial é mantida dentro de controle rígido, por meio da infusão profilática contínua de fenilefrina, a incidência de eventos adversos maternos e conceptuais não difere quando a raquianestesia é realizada com 12 mg ou 8 mg de bupivacaína hiperbárica. / Background: Reduced local anesthetic dose is used for minimizing hypotension changes related with spinal anesthesia for cesarean section, optimizing both maternal and fetal outcomes. This strategy can result in neuroaxial block failure. On the other hand, the higher doses associated with hypotension can be controlled with continuous prophylactic infusion of phenylephrine. The present study assessed the effects of continuous infusion of phenylephrine under strict blood pressure control and the maternal-fetal outcomes in patients under spinal anesthesia for elective cesarean section with two anesthetic solution. Methods: The number of 60 patients, scheduled for elective cesarean section, was allocated into 2 non-randomized groups (30 individuals each) for this prospective clinical study identified as Group 12 (G12), who were administered 12 mg hyperbaric bupivacaine and; Group 8 (G8), who were injected with 8 mg hyperbaric bupivacaine. In both groups, the anesthetic solution was added to sufentanyl 5 !g and morphine 100 !g. Pre-hydration with Ringer Lactate solution – 10 ml/Kg. Continuous phenylephrine infusion started at the end of the spinal block, with a infusion rate of 100 !g/min under strict blood pressure control. Comparatively, sensitive anesthetic block level, vasopressor consumption, adverse maternal and neonate outcomes were evaluated. Results: The incidence of maternal adverse effects such as nausea, vomiting, dispnea, pain, tremor, and bradicardy, necessity of atropine, hypotension and hypertension showed no significant difference between groups. In addition, other parameters were evaluated in neonates, pH, pCO2, BE and lactate of umbilical vases and the consumption of phenylephrine per time unit. All neonates showed pH higher than 7.20, as well as the Apgar score higher than 7 at 5`; only one neonate of G12 showed the Apgar score lower than 7 at 1`. Conclusion: Strict arterial blood pressure performed with prophylactic continuous infusion of phenylephrine, doesn’t change the maternal and fetal outcomes in patients scheduled for elective cesarean section under spinal anesthesia. / TEDE / BV UNIFESP: Teses e dissertações

Introdução: Os hidroxietilamidos (HES) são considerados expansores plasmáticos efetivos em pacientes submetidos a procedimentos cirúrgicos de grande porte. Entretanto, seu uso clínico é limitado principalmente por sua interferência na hemostasia, representada por alterações da função plaquetária e na coagulação. A extensão dessas alterações está relacionada ao seu ipeso molecular ou à sua substituição molar. Este estudo clínico, foi realizado durante cirurgia de artroplastia de quadril em pacientes adultos para comparar os efeitos do HES (130/0,4) e a solução de Ringer lactato em relação ao sangramento intra-operatório, parâmetros hemodinâmicos, alterações na coagulação, necessidade de transfusões e resultados clínicos. Métodos: Quarenta e oito pacientes candidatos à cirurgia de artroplastia total de quadril sob anestesia subaracnoidea foram distribuídos aleatoriamente em dois grupos 24 pacientes foram selecionados para receber HES (30 ml/kg após anestesia) e 24 pacientes para receber solução de Ringer lactato (30ml/kg). O período de observação teve início após a indução da anestesia e terminou 5 horas após o termino do procedimento cirúrgico. Durante esse período o critério para a infusão de doses adicionais de fluido (10ml/kg de Solução de Ringer lactato para ambos os grupos) foi pressão arterial sistólica inferior a 90 mmHg e/ou um decréscimo de 20% da pressão arterial inicial, frequência cardíaca acima de 100 bpm, e/ou débito urinário menor de 0,4ml/kg/h. Vasopressor foi utilizado nos casos em que a hipotensão persistiu, após a reposição de volume. Transfusão de concentrado de hemácias foi administrada nos pacientes que se mantiveram instáveis hemodinamicamente após bolus adicionais de Ringer lactato ou vasopressor, Parâmetros hemodinâmicos foram mensurados em três períodos da cirurgia; dados bioquímicos foram coletados e testes da coagulação realizados e comparados. Os pacientes foram acompanhados durante sua internação hospitalar. Resultados: Os grupos foram uniformes em relação aos dados demográficos, tipo e duração da cirurgia, assim como a doenças pré-existentes. Não foram observadas diferenças significativas em relação aos parâmetros hemodinâmicos ou temperatura corporal durante o estudo. Os testes de coagulação, função plaquetária, análise de gases sanguíneos e dados bioquímicos mostraramse semelhantes entre os grupos. Perdas sanguíneas foram significativamente maiores no grupo HES (1296x890,p=0,04), necessitou de menos unidades de concentrado de hemácias durante o período observacional (17%versus46%, p=0,029) apresentou menores taxas de infecção (0 versus 4 ,p<0,03), comparado ao grupo Ringer lactato. Conclusões: Em cirurgia de artroplastia total de quadrill, a hemodiluição com hidroxietilamido resultou em maiores taxas de sangramento, menos transfusões sanguíneas e menos infecção pós-operatória. / Introduction: Hydroxyethyl starches (HES) are considered effective plasma expanders in patients undergoing major surgeries. However, the clinical use of HES is limited mainly by their affection of hemostasis, detectable by impaired platelet function and altered coagulation. The extent of such alteration has classically been related to the molecular weight or molar substitution of the used HES solution. This prospective, randomized study was performed during hip arthroplasty in adult patients under spinal anesthesia to compare the effects of HES 130/0.4 with lactateds Ringer solution regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. Methods: Forty eight patients scheduled to hip arthroplasty after spinal anesthesia were randomized in two groups 24 patients were allocated to receive HES 130/0.4 (30 ml/Kg just after anesthesia) and 24 patients were signaled to receive lactateds Ringer solution (30 ml/Kg). The observational period started after the induction of anesthesia and finished 5 hours after the end of the surgery. During this period, the triggers for infusion of additional boluses of fluids (10 ml/Kg of lactateds Ringer for both groups) were a systolic blood pressure lower than 90 mmHg and/or a decrease of 20% from baseline, a heart rate higher than 100 bpm, and/or a urine output lower than 0.4 ml.Kg-1.h-1. Vasopressors were used if there was persistent hypotension despite of fluid reposition. Red blood cell transfusion was administered if patient remained unstable despite of additional boluses of Ringer or vasopressors, according to the preestablished triggers. Hemodynamic measurements were done in three periods of the surgery, biochemical parameters were analyzed and coagulation tests were performed and compared between groups. After surgery, patients were followed during the hospital stay. Results: The groups were well matched regarding demographic data, type of surgery, and duration of surgery, as well as preexisting diseases. No significant differences in hemodynamic or body temperature were seen during the study. Coagulation variables, platelet function, gases analysis and biochemical parameters were not different between groups. Blood losses were significantly higher in HES 130/0.4 group comparing to Ringers group (1296 x 890 ml, p= 0.046). Despite of that, HES group required less units of blood in the observational period comparing to Ringer group (17% versus 46%, p=0.029). HES group presented lower infection rate compared to Ringer group (0 versus 4 cases, p=0.03). Conclusions: During hip arthroplasty, hemodilution with hydroxyethyl starch 130/0.4 resulted in higher rates of bleeding. However, patients treated with hydroxyethyl starch required less transfusion and presented lower rate of infection.

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

Diss. Linköping : Univ., 2004.

Introdução: Os hidroxietilamidos (HES) são considerados expansores plasmáticos efetivos em pacientes submetidos a procedimentos cirúrgicos de grande porte. Entretanto, seu uso clínico é limitado principalmente por sua interferência na hemostasia, representada por alterações da função plaquetária e na coagulação. A extensão dessas alterações está relacionada ao seu ipeso molecular ou à sua substituição molar. Este estudo clínico, foi realizado durante cirurgia de artroplastia de quadril em pacientes adultos para comparar os efeitos do HES (130/0,4) e a solução de Ringer lactato em relação ao sangramento intra-operatório, parâmetros hemodinâmicos, alterações na coagulação, necessidade de transfusões e resultados clínicos. Métodos: Quarenta e oito pacientes candidatos à cirurgia de artroplastia total de quadril sob anestesia subaracnoidea foram distribuídos aleatoriamente em dois grupos 24 pacientes foram selecionados para receber HES (30 ml/kg após anestesia) e 24 pacientes para receber solução de Ringer lactato (30ml/kg). O período de observação teve início após a indução da anestesia e terminou 5 horas após o termino do procedimento cirúrgico. Durante esse período o critério para a infusão de doses adicionais de fluido (10ml/kg de Solução de Ringer lactato para ambos os grupos) foi pressão arterial sistólica inferior a 90 mmHg e/ou um decréscimo de 20% da pressão arterial inicial, frequência cardíaca acima de 100 bpm, e/ou débito urinário menor de 0,4ml/kg/h. Vasopressor foi utilizado nos casos em que a hipotensão persistiu, após a reposição de volume. Transfusão de concentrado de hemácias foi administrada nos pacientes que se mantiveram instáveis hemodinamicamente após bolus adicionais de Ringer lactato ou vasopressor, Parâmetros hemodinâmicos foram mensurados em três períodos da cirurgia; dados bioquímicos foram coletados e testes da coagulação realizados e comparados. Os pacientes foram acompanhados durante sua internação hospitalar. Resultados: Os grupos foram uniformes em relação aos dados demográficos, tipo e duração da cirurgia, assim como a doenças pré-existentes. Não foram observadas diferenças significativas em relação aos parâmetros hemodinâmicos ou temperatura corporal durante o estudo. Os testes de coagulação, função plaquetária, análise de gases sanguíneos e dados bioquímicos mostraramse semelhantes entre os grupos. Perdas sanguíneas foram significativamente maiores no grupo HES (1296x890,p=0,04), necessitou de menos unidades de concentrado de hemácias durante o período observacional (17%versus46%, p=0,029) apresentou menores taxas de infecção (0 versus 4 ,p<0,03), comparado ao grupo Ringer lactato. Conclusões: Em cirurgia de artroplastia total de quadrill, a hemodiluição com hidroxietilamido resultou em maiores taxas de sangramento, menos transfusões sanguíneas e menos infecção pós-operatória. / Introduction: Hydroxyethyl starches (HES) are considered effective plasma expanders in patients undergoing major surgeries. However, the clinical use of HES is limited mainly by their affection of hemostasis, detectable by impaired platelet function and altered coagulation. The extent of such alteration has classically been related to the molecular weight or molar substitution of the used HES solution. This prospective, randomized study was performed during hip arthroplasty in adult patients under spinal anesthesia to compare the effects of HES 130/0.4 with lactateds Ringer solution regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. Methods: Forty eight patients scheduled to hip arthroplasty after spinal anesthesia were randomized in two groups 24 patients were allocated to receive HES 130/0.4 (30 ml/Kg just after anesthesia) and 24 patients were signaled to receive lactateds Ringer solution (30 ml/Kg). The observational period started after the induction of anesthesia and finished 5 hours after the end of the surgery. During this period, the triggers for infusion of additional boluses of fluids (10 ml/Kg of lactateds Ringer for both groups) were a systolic blood pressure lower than 90 mmHg and/or a decrease of 20% from baseline, a heart rate higher than 100 bpm, and/or a urine output lower than 0.4 ml.Kg-1.h-1. Vasopressors were used if there was persistent hypotension despite of fluid reposition. Red blood cell transfusion was administered if patient remained unstable despite of additional boluses of Ringer or vasopressors, according to the preestablished triggers. Hemodynamic measurements were done in three periods of the surgery, biochemical parameters were analyzed and coagulation tests were performed and compared between groups. After surgery, patients were followed during the hospital stay. Results: The groups were well matched regarding demographic data, type of surgery, and duration of surgery, as well as preexisting diseases. No significant differences in hemodynamic or body temperature were seen during the study. Coagulation variables, platelet function, gases analysis and biochemical parameters were not different between groups. Blood losses were significantly higher in HES 130/0.4 group comparing to Ringers group (1296 x 890 ml, p= 0.046). Despite of that, HES group required less units of blood in the observational period comparing to Ringer group (17% versus 46%, p=0.029). HES group presented lower infection rate compared to Ringer group (0 versus 4 cases, p=0.03). Conclusions: During hip arthroplasty, hemodilution with hydroxyethyl starch 130/0.4 resulted in higher rates of bleeding. However, patients treated with hydroxyethyl starch required less transfusion and presented lower rate of infection.

INTRODUÇÃO: Clonidina intratecal pode prolongar a duração da raquianestesia, possivelmente com maior duração da analgesia pós-operatória em cesáreas. Neste estudo, avaliamos o uso de clonidina como medicação adjuvante na anestesia para cesárea, pelas vias intratecal e intravenosa e seus efeitos na dor pós-operatória e repercussões neonatais. MÉTODOS: em ensaio clínico prospectivo, aleatorizado, duplo-cego, controlado por placebo, 64 mulheres submetidas à cesárea eletiva sob raquianestesia foram aleatorizadas e alocadas em três grupos, a depender de como receberiam a clonidina adjuvante: clonidina intratecal 75 mcg, clonidina intravenosa 75 mcg, e solução fisiológica 0,9% (controle). O desfecho primário foi dor pós-operatória aguda. Os desfechos secundários foram dor pós-operatória tardia (após três meses), eventos adversos maternos e neonatais. RESULTADOS: não foram encontradas diferenças nos escores de dor ou no consumo de opioides no período pós-operatório precoce. Clonidina intratecal e intravenosa causaram maiores índices de sedação intraoperatória, em comparação com o grupo controle {RASS: 0 [(-1)-(0)] vs. 0 [(-1)-(-1)] vs. 0 [(-1)-(-1)] para controle, intratecal e intravenosa, respectivamente, p < 0,001}. Não houve diferença para efeitos adversos ou desfechos neonatais entre os grupos. CONCLUSÕES: clonidina intratecal e clonidina intravenosa não tiveram efeito na dor pós-operatória pós-cesárea. Ambas causaram maior sedação intraoperatória / BACKGROUND: Intrathecal clonidine may prolong the duration of spinal anesthesia, possibly with longer duration of postoperative analgesia in cesarean sections. In this study, we evaluated the use of clonidine as an intrathecal or intravenous adjuvant medication for cesarean section anesthesia and its effects on postoperative pain and neonatal outcomes. METHODS: In a prospective, randomized, double-blind, placebo-controlled clinical trial, 64 women undergoing elective cesarean section under spinal anesthesia were randomized and allocated to three groups, depending on how they would receive adjuvant clonidine: 75 mcg intrathecal clonidine, 75 mcg intravenous clonidine, and 0.9% saline solution (control). The primary outcome was acute postoperative pain. Secondary outcomes were late postoperative pain (after three months), maternal and neonatal adverse events. RESULTS: no differences were found in pain scores or opioid use in the acute postoperative period. Intrathecal and intravenous clonidine caused higher rates of intraoperative sedation compared to the control group {RASS: 0 [(-1)-(0)] vs. 0 [(-1)-(-1)] vs. 0 [(-1)-(-1)] for control, intrathecal and intravenous, respectively, p < 0.001}. There was no difference for adverse effects or neonatal outcomes among groups. CONCLUSIONS: intrathecal clonidine and intravenous clonidine had no effect on post-cesarean postoperative pain. Both caused higher intraoperative sedation

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.