Propofol has been gaining increased attention as a sole agent in providing procedural sedation due to its predictable pharmacokinetics and favorable amnestic properties. Oral and maxillofacial surgical procedures are unique in duration and concomitant use of local anesthesia making it difficult to evaluate data obtained from other specialties. The purpose of our study is to evaluate the safety, efficacy and satisfaction among surgeons and patients using propofol only, for procedural sedation during the extraction of third molars. Propofol 10mg/ml was administered using an induction dose of 0.5 to 1mg/kg over 60 seconds followed by bolus doses of 10 – 20mg every minute to achieve a Ramsay sedation score of at least 3. Respiratory compromise was identified in 15% of patients. Hemodynamic compromise was identified in 15%. Patient and surgeon satisfaction was high however propofol does not represent the ideal drug as a sole agent for procedural sedation in oral surgery due to the frequent need for hand restraint (40%).

Electroretinoraphic signals (ERGs) are affected when recorded under isoflurane anesthesia in the operating room. We explored the effect of isoflurane and propofol in ex vivo guinea pig retinal preparations using a multielectrode array to record simultaneously ERGs and retinal ganglion cell (RGC) activity. The viability and light-response characteristics of the model were documented. In the presence of isoflurane, the ERG and RGC activity was reduced in a dose-dependent manner, even at sub-clinical doses; the OFF responses were consistently more affected. Propofol had minimal effects: at subclinical doses, a small excitation was measured while a concentration a hundred times stronger than the clinical concentration was required to measure a significant decline in EGR and RGC signals. This study confirms the usefulness of the guinea pig model to study clinically relevant retinal issues and shows that propofol is a better anesthetic to use in the operating room when retinal investigations are required.

TÁVORA, R. V. Análise dos efeitos do 2,6-Diisopropilfenol sobre a eletrofisiologia cardíaca em pacientes com ectopias de via de saída ventricular. 2017. 113 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2017. / Submitted by Erika Fernandes (erikaleitefernandes@gmail.com) on 2017-03-31T12:25:10Z No. of bitstreams: 1 2017_dis_rvtavora.pdf: 4606208 bytes, checksum: baf37b23409e42125bc3d22338f7b29f (MD5) / Approved for entry into archive by Erika Fernandes (erikaleitefernandes@gmail.com) on 2017-03-31T12:25:30Z (GMT) No. of bitstreams: 1 2017_dis_rvtavora.pdf: 4606208 bytes, checksum: baf37b23409e42125bc3d22338f7b29f (MD5) / Made available in DSpace on 2017-03-31T12:25:30Z (GMT). No. of bitstreams: 1 2017_dis_rvtavora.pdf: 4606208 bytes, checksum: baf37b23409e42125bc3d22338f7b29f (MD5) Previous issue date: 2017-01-25 / Propofol is an effective hypnotic agent for the induction and maintenance of anesthesia. Recent studies have demonstrated that this drug exerts effects on the cardiac conduction system having both pro-arrhythmic and antiarrhythmic effects in a concentration-dependent manner. These effects seem to be more important when the mechanism involved in arrhythmias is hyperautomatism with few effects on reentrant arrhythmias. The mechanisms involved in such effects remain poorly defined, but possibly involve ion channels such as sodium, calcium, and potassium as well as modulations in the autonomic nervous system. However, we have not found in the literature studies on the effects of propofol on post-potency-triggered arrhythmias that represent one of the most frequent types of ventricular arrhythmias. The suspicion that the infusion of this agent can suppress this type of arrhythmia causes propofol to be deferred as sedative drug in electrophysiological study procedures that aim at the ablation of foci of this arrhythmic disorder. Such practice is based on individual observations and has no backing in scientific publications. The objective of this work is to propose a study model for the evaluation of the interference of 2,6-diisopropylphenol in cardiac electrophysiological variables and to analyze the effects of propofol on arrhythmias that conceptually have as a mechanism the activities triggered by late post-potentials. Ten patients with ventricular outflow tract arrhythmias without structural heart disease were selected and indicated for the treatment of ablation. All patients had an expressive number of ventricular extrasystoles (> 10% of total beats) detected on holter / 24h examination. Diagnostic catheters were positioned in the coronary sinus, right ventricle and anteroseptal region of the tricuspid ring for atrial, ventricular and HIS potentials, respectively. At baseline and under programmed atrial and ventricular pacing, data were collected from 17 (seventeen) cardiac electrophysiological variables: heart rate, QRS complex duration, atrial and ventricular command threshold, atrial conduction time, AH and HV intervals, Ventricular-atrial conduction, anterograde and retrograde Wenckebach points, effective retrograde anterograde and retrograde atrioventricular refractory periods, effective refractory periods of the right atrium and ventricle, coupling interval, and number of extrasystoles recorded within 5 minutes. These variables were collected before and during the intravenous infusion of propofol aiming to achieve a target sedation titrated by bispectral index (BIS) between 40 and 60. Analysis of the data presented showed that the infusion of propofol in doses titrated by the bispectral index did not seem to interfere in the Expression of ventricular arrhythmias triggered by late post-potentials when these were manifested as ventricular extrasystoles. / O propofol é um agente hipnótico eficaz para a indução e manutenção da anestesia. Estudos recentes demonstraram que este medicamento exerce efeitos sobre o sistema de condução cardíaco possuindo tanto efeitos pro-arrítmicos quanto anti-arrítmicos de forma concentração-dependente. Esses efeitos parecem ser mais importantes quando o mecanismo implicado nas arritmias é o hiperautomatismo com poucos efeitos em arritmias reentrantes. Os mecanismos implicados em tais efeitos permanecem mal definidos, mas possivelmente envolvem canais iônicos como sódio, cálcio e potássio além de modulações no sistema nervoso autônomo. Entretanto, não encontramos na literatura estudos sobre os efeitos do propofol em arritmias desencadeadas por “pós-potenciais tardios” que representam um dos tipos mais frequentes de arritmias ventriculares. A suspeita de que a infusão deste agente possa suprimir este tipo de arritmia, faz com que o propofol seja preterido como droga sedativa em procedimentos de estudo eletrofisiológicos que objetivam a ablação de focos deste distúrbio arrítmico. Tal prática é baseada em observações individuais e não tem respaldo em publicações científicas. O objetivo deste trabalho é propor um modelo de estudo para a avaliação da interferência do 2,6-diisopropilfenol em variáveis eletrofisiológicas cardíacas além de analisar os efeitos do propofol sobre arritmias que conceitualmente têm por mecanismo atividades deflagradas por pós-potenciais tardios. Foram selecionados dez pacientes com arritmias de trato de saída ventricular sem cardiopatia estrutural identificada e com indicação para o tratamento de ablação. Todos os pacientes apresentavam um número expressivo de extra-sístoles ventriculares (>10% do total de batimentos) detectados em exame de holter/24h. Cateteres diagnósticos foram posicionados em seio coronariano, ventrículo direito e região ântero-septal do anel tricúspide para o registro de potenciais atriais, ventriculares e de HIS respectivamente. Em estado basal e sob estimulação atrial e ventricular programadas, foram coletados dados de 17 (dezessete) variáveis eletrofisiológicas cardíacas: frequência cardíaca, duração do complexo QRS, limiar de comando atrial e ventricular, tempo de condução atrial, intervalos AH e HV, tempo de condução ventrículo-atrial, pontos de Wenckebach anterógrado e retrógrado, períodos refratários efetivos anterógrado e retrógrado do nodo-atrioventricular, períodos refratários efetivos do átrio e ventrículo direitos, intervalo de acoplamento e número de extrassístoles registradas em 5 minutos. Tais variáveis foram coletadas antes e durante a infusão endovenosa de propofol objetivando atingir uma sedação alvo titulada pelo índice bispectral (BIS) entre 40 e 60. A análise dos dados apresentados mostrou que a infusão de propofol em doses tituladas pelo índice bispectral não pareceu interferir na expressão de arritmias ventriculares deflagradas por pós-potenciais tardios quando estas eram manifestas na forma de extra-sístoles ventriculares.

Made available in DSpace on 2014-06-11T19:35:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-10Bitstream added on 2014-06-13T19:24:22Z : No. of bitstreams: 1 000740869.pdf: 1028761 bytes, checksum: cc4c4888304f1ac5407453c12d423e7c (MD5) / O propofol é um dos fármacos mais utilizados na prática clínica do anestesiologista. O principio ativo do propofol é insolúvel em água, portanto, para permitir sua difusão nos compartimentos biológicos sem o comprometimento das propriedades anestésicas, utilizou-se, inicialmente, como veículo, óleo vegetal. Nesta emulsão o propofol fica dissolvido na fase-óleo sob a forma de pequenas partículas formando uma dispersão coloidal. As complicações resultantes são: dor a injeção, acidose metabólica, hipertrigliceridemia, e possível rabdomiólise com insuficiência renal. Uma nova formulação do propofol com finalidade de proporcionar maior conforto ao paciente, na busca de superar ou minimizar estes efeitos indesejáveis, principalmente o da dor à injeção, foi proposta, baseada em microemulsões, em substituição à emulsão lipídica. Comparar a incidência de inflamação após a infusão de propofol em dose única e em infusão contínua com o diluente emulsão lipídica (EL) ou com diluente em microemulsão (ME). Estudar o efeito do propofol com ambos os diluentes sobre os bioquímicos, a pressão arterial média (PAM), a pressão venosa central (PVC), o Sódio e o Potássio plasmáticos. Os animais foram divididos em sete grupos de 6 animais, sendo: Grupo SHA – 6 coelhos que receberam apenas o tratamento cirúrgico; Grupo Controle-Infusão em bolus (CRB) – 6 coelhos que receberam solução fisiológica 3mL EV; Grupo Controle-Infusão Contínua (CRI) – 6 coelhos que receberam 3 mL de solução fisiológica, seguida da infusão contínua no volume de 0,05 mL/kg/min, por 60 minutos EV; Grupo Propofol EL em bolus (PEB) – 6 coelhos que receberam propofol em emulsão lipídica (3 mg/kg) em bolus EV; Grupo Propofol ME em bolus (PMB) – 6 coelhos que receberam propofol em microemulsão (3 mg/kg) em bolus EV; Grupo Propofol EL contínuo (PEC) – 6 coelhos que receberam propofol em... / Propofol is currently the agent of choice for both induction and maintenance of general anesthesia. This study compared the incidence of endothelial injury after single-dose or continuous propofol infusion in conventional lipid-based emulsion (EL) versus microemulsion (ME), and also assessed the inflammatory effects caused by both propofol formulations. Forty-two rabbits (2.5-4.5 Kg) were randomly allocated into 7 groups of 6 animals each and treated as follows: SHAM– surgical treatment alone; Bolus Control Group –3 mL-intravenous (IV) bolus of saline; Continous Infusion Control Group–3 mL- IV bolus of saline followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Bolus LE Propofol Group –IV bolus of LE propofol (3 mg/kg); Bolus ME Propofol Group–IV ME propofol bolus (3 mg/kg); Continuous LE Propofol Group– IV LE propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Continuous ME Propofol Group– IV ME propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min. Hemodynamic and blood parameters were recorded at 4 time points. The groups investigated were found to be homogeneous with regard to the parameters assessed, except for IL-6 plasma concentration, which differed among them when propofol microemulsion was used. Under the experimental conditions of this study, no statistically significant difference was observed among groups when saline, lipid emulsion or microemulsion solvents were used. However, the group receiving propofol in microemulsion tended to show a greater number of damaged cells.

Made available in DSpace on 2015-04-09T12:28:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-20Bitstream added on 2015-04-09T12:48:14Z : No. of bitstreams: 1 000814861.pdf: 726105 bytes, checksum: 6bc0095c4ea15ec2fed2a0387f54f45f (MD5) / Avaliaram-se, comparativamente, os efeitos do tiopental e do propofol sobre os parâmetros cardiovasculares, respiratórios, hemogasométricos, nível glicêmico, cinética celular e período de recuperação. Para tanto, utilizaram-se 20 coelhos da raça Nova Zelândia Branco, adultos, machos ou fêmeas, com peso médio de 3,67±0,43 Kg. Após seleção aleatória, estes foram distribuídos em dois grupos de 10 animais, denominados grupo propofol (GP) e grupo tiopental (GT). Para o GP, foi induzida a anestesia geral pela administração intravenosa (IV) de propofol (10 mg/Kg) e em seguida, iniciou-se a infusão contínua na dose inicial 1 mg/Kg/min, a qual, havendo necessidade, foi reajustada de modo a que o índice biespectral estivesse situado entre 65 e 75. Para o GT empregou-se a mesma metodologia, substituindo-se o propofol pelo tiopental. As observações das variáveis de interesse em ambos os grupos, tiveram início 20 minutos após a indução anestésica (M0) e novas mensurações foram realizadas em intervalos de 15 minutos, por um período de 60 minutos. A avaliação da recuperação teve início 30 minutos (MR30) após o término da infusão dos fármacos e novas avaliações foram realizadas em intervalos de 60 minutos. Os dados foram submetidos à análise de variância de duas vias (Two-way ANOVA) e uma via (One-way ANOVA), seguidas pelo teste de Bonferroni (p<0,05). Para a análise da recuperação, os escores foram analisados e os grupos comparados pelo teste não paramétrico de Wilcoxon de 2 amostras independentes (p<0,05). No GP, a pressão parcial de oxigênio (PaO2) o dióxido de carbono (PaCO2) e a saturação da oxihemoglobina (SaO2) no sangue arterial aumentaram a partir do M30 e no M60, respectivamente. O volume corrente (VT), no M60, e o índice respiratório (IR), no M0, foram menores no GP, enquanto o conteúdo arterial de oxigênio (CaO2), no M0, foi maior no GP que no GT. A pressão de oxigênio alveolar ... / The effects of thiopental and propofol were comparatively evaluated about its influence on cardiovascular and respiratory parameters, blood gas, blood glucose levels, cell kinetics and recovery period in 20 rabbits of New Zealand White, adults, male and female, with weight between 3,67±0,43 Kg. After a random selection, they were shared into two groups of 10 animals, called propofol group (GP) and thiopental group (GT). For GP, general anesthesia was induced by intravenous (IV) administration of propofol (10 mg/Kg) and then began continuous infusion at an initial dose 1 mg/Kg/min, and then was adjusted as necessary to the bispectral index values vary between 65 and 75. The same method was employed for GT, using thiopental instead propofol, at the dose of 10 mg/Kg for induction followed the initial dose of 1 mg/Kg/min. Data collection of the variables of interest in both groups began 20 minutes after induction of anesthesia (M0) and new measurements were made at 15 minutes intervals for a period of 60 minutes. The assessment of recovery began 30 minutes (MR30) after the infusion of agents and new evaluations were made at intervals of 60 minutes. Data were analysed using to analysis of variance, two-way (two-way ANOVA) and route (One-way ANOVA) followed by Bonferroni test (p<0,05). For recovery assessment, the scores were analyzed and the groups were compared by non parametric Wilcoxon test for 2 independent samples (p<0,05). In GP, the partial pressure of oxygen (PaO2), carbon dioxide (PaCO2) and oxyhemoglobin saturation (SaO2) in arterial blood increased from M30 and M60, respectively. The tidal volume (VT) in M60, and respiratory index (IR) in M0, were lower in the GP, while the arterial oxygen content (CaO2) at M0 was greater in GP than in GT. The alveolar oxygen tension (PAO2), alveolar-arterial oxygen difference (P(A-a)O2), IR, arterial-alveolar ratio (PaO2/PAO2) and ratio of partial pressure of arterial oxygen to fraction of ...

Orientador: Luiz Antonio Vane / Banca: Norma Sueli Pinheiro Módolo / Banca: José Mariano Soares de Moraes / Resumo: O propofol é um dos fármacos mais utilizados na prática clínica do anestesiologista. O principio ativo do propofol é insolúvel em água, portanto, para permitir sua difusão nos compartimentos biológicos sem o comprometimento das propriedades anestésicas, utilizou-se, inicialmente, como veículo, óleo vegetal. Nesta emulsão o propofol fica dissolvido na fase-óleo sob a forma de pequenas partículas formando uma dispersão coloidal. As complicações resultantes são: dor a injeção, acidose metabólica, hipertrigliceridemia, e possível rabdomiólise com insuficiência renal. Uma nova formulação do propofol com finalidade de proporcionar maior conforto ao paciente, na busca de superar ou minimizar estes efeitos indesejáveis, principalmente o da dor à injeção, foi proposta, baseada em microemulsões, em substituição à emulsão lipídica. Comparar a incidência de inflamação após a infusão de propofol em dose única e em infusão contínua com o diluente emulsão lipídica (EL) ou com diluente em microemulsão (ME). Estudar o efeito do propofol com ambos os diluentes sobre os bioquímicos, a pressão arterial média (PAM), a pressão venosa central (PVC), o Sódio e o Potássio plasmáticos. Os animais foram divididos em sete grupos de 6 animais, sendo: Grupo SHA - 6 coelhos que receberam apenas o tratamento cirúrgico; Grupo Controle-Infusão em bolus (CRB) - 6 coelhos que receberam solução fisiológica 3mL EV; Grupo Controle-Infusão Contínua (CRI) - 6 coelhos que receberam 3 mL de solução fisiológica, seguida da infusão contínua no volume de 0,05 mL/kg/min, por 60 minutos EV; Grupo Propofol EL em bolus (PEB) - 6 coelhos que receberam propofol em emulsão lipídica (3 mg/kg) em bolus EV; Grupo Propofol ME em bolus (PMB) - 6 coelhos que receberam propofol em microemulsão (3 mg/kg) em bolus EV; Grupo Propofol EL contínuo (PEC) - 6 coelhos que receberam propofol em ... / Abstract: Propofol is currently the agent of choice for both induction and maintenance of general anesthesia. This study compared the incidence of endothelial injury after single-dose or continuous propofol infusion in conventional lipid-based emulsion (EL) versus microemulsion (ME), and also assessed the inflammatory effects caused by both propofol formulations. Forty-two rabbits (2.5-4.5 Kg) were randomly allocated into 7 groups of 6 animals each and treated as follows: SHAM- surgical treatment alone; Bolus Control Group -3 mL-intravenous (IV) bolus of saline; Continous Infusion Control Group-3 mL- IV bolus of saline followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Bolus LE Propofol Group -IV bolus of LE propofol (3 mg/kg); Bolus ME Propofol Group-IV ME propofol bolus (3 mg/kg); Continuous LE Propofol Group- IV LE propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Continuous ME Propofol Group- IV ME propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min. Hemodynamic and blood parameters were recorded at 4 time points. The groups investigated were found to be homogeneous with regard to the parameters assessed, except for IL-6 plasma concentration, which differed among them when propofol microemulsion was used. Under the experimental conditions of this study, no statistically significant difference was observed among groups when saline, lipid emulsion or microemulsion solvents were used. However, the group receiving propofol in microemulsion tended to show a greater number of damaged cells. / Doutor

Made available in DSpace on 2014-06-11T19:30:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2013Bitstream added on 2014-06-13T20:20:40Z : No. of bitstreams: 1 deschk_m_me_araca.pdf: 1043151 bytes, checksum: 98566e693ca4c0ab17fc2c38ada17bfc (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O estudo teve por objetivo avaliar o índice bispectral, efeitos hemodinâmicos e respiratórios da infusão contínua de diferentes taxas de propofol em bezerros. Foram utilizados 8 animais de seis a 12 meses de idade, holandeses, pesando de 84 a 124 kg. Os animais foram induzidos à anestesia com propofol na dose de 5 mg/kg IV e posicionados em decúbito lateral direito, onde permaneceram respirando espontaneamente ar ambiente. Ato contínuo, a manutenção anestésica foi realizada pela infusão contínua de propofol, administrado por meio de bomba de infusão em duas diferentes taxas 0,6 mg/kg/minuto IV (G06) e 0,8 mg/kg/minuto IV, (G08) durante 60 minutos. Os 8 animais foram anestesiados duas vezes, com uma semana de intervalo entre uma anestesia e outra. As variáveis hemodinâmicas (FC, PAS, PAD, PAM, DC, PVC, PAPm, PAPOm, IC, IS, IRVS e IRVP), respiratórias (ETCO, f, SpO, 2 2 V, V, e PFI), hemogasométricas (PaO, PaCO, SaO, DB, pH e HCO -) e TE ME 2 2 2 3 índice bispectral (BIS, EMG e IQS) foram avaliadas antes da indução anestésica (M ), e 15, 30, 45 e 60 minutos após o início da infusão contínua do B propofol (M15, M30, M45 e M60, respectivamente). Já a colheita das amostras para a dosagem plasmática do propofol foi realizada aos M15, M30, M45 e M60 minutos durante a infusão contínua do propofol e as demais colheitas foram realizadas após o termino da infusão com intervalos de 10 minutos por um período de 50 minutos (M70, M80, M90, M100 e M110 respectivamente). A infusão contínua de diferentes taxas de propofol não alterou as variáveis do BIS ao longo do tempo durante a infusão, também não causou alterações hemodinâmicas importantes, porém o G08 apresentou acidose respiratória indicando uso de ventilação controlada / The aim of this study was to evaluate the bispectral index, hemodynamic and respiratory effects of continuous infusion of different rates of propofol in calves. Eight Holstein calves aging between six and 12 months and weighing 84-124 kg were used. They were induced to anesthesia with propofol at a dose of 5 mg / kg IV and positioned in right lateral recumbency, where they remained spontaneously breathing ambient air. Immediately thereafter, the anesthesia was maintained by continuous infusion of propofol administered with the aid of an infusion pump in two different rates 0.6 mg / kg / minute, IV (G06) and 0.8 mg / kg / minute, IV, (G08), during 60 minutes. The 8 animals were anesthetized twice, with one-week interval between anesthesia. The measurements of hemodynamic (HR, SAP, DAP, MAP, CO, CVP, mPAP, mPAPO, CI, SI, SVRI and PVRI), and respiratory parameters (ETCO2, f, SpO2, VTE, VME, and PFI), arterial blood gases (PaO2, PaCO2, SaO2, BE, pH and HCO3-) and bispectral index (BIS, EMG and SQI) were assessed before induction of anesthesia (MB), and 15, 30, 45 and 60 minutes after the start of continuous infusion of propofol (M15 , M30, M45 and M60, respectively). Sampling to measure plasma propofol was performed M15, M30, M45 and M60 minutes during continuous infusion of propofol and other samples were harvested after the end of infusion with 10-minute intervals during a period of 50 minutes (M70, M80, M90, M100 and M110 respectively). Continuous infusion of propofol at different rates did not alter the variables BIS over time and also did not cause significant hemodynamic changes, but the G08 had respiratory acidosis suggesting the use of controlled ventilation

Class of 2011 Abstract / OBJECTIVES: To compare the use of propofol to dexmedetomidine hydrochloride (Precedex®) in patients undergoing pain pump placements at University Physicians Hospital. METHODS: A retrospective chart review was performed evaluating anesthesia charts from December 2009 through February 2011. Heart rate (HR), blood pressure (BP), respiratory rate (RR), surgery time, and length of stay in the PACU were collected for both treatment groups. Demographic variables were also collected including age, sex, medical condition for which they are having a procedure performed, other co-morbid conditions and concurrent medications. RESULTS: Charts were reviewed for 8 dexmedetomidine patients and 16 propofol patients. There was no statistical difference among the groups with regard to demographics. The groups had similar procedural average systolic blood pressures, diastolic blood pressures, and heart rate (p = 0.93; p = 0.56, p = 0.37 respectively). The procedure time and recovery time in the PACU were similar between the dexmedetomidine group and propofol group (p = 0.52; p = 0.25, respectively). The endpoint respiratory rate was significantly lower in the propofol group (p = 0.05). There was no difference in additional sedative-analgesic medication use. CONCLUSION: Dexmedetomidine does not offer any clinical advantages to propofol when used as anesthesia for pain pump placement.

Objective To compare the anaesthetic and cardiopulmonary effects of alfaxalone in comparison to propofol when used for total intravenous anaesthesia (TIVA) during ovariohysterectomy in dogs. Animals Fourteen healthy female crossbred dogs between 6 months and 5 years, with body weight between 16 - 42 kg. Methods All dogs were premedicated with acepromazine 0.01 mg/kg and morphine 0.4 mg/kg subcutaneously. Anaesthesia was induced and maintained with either Group 1- propofol (6 mg/kg followed by 0.3-0.5 mg/kg/min intravenously) or Group 2 alfaxalone (2 mg/kg followed 0.10-0.12 mg/kg/min intravenously). Quality of induction and recovery were determined. Dogs were spontaneously breathing 100 % oxygen. Respiratory and cardiovascular parameters were measured: Respiratory rate (RR), end tidal CO2 (ETCO2), tidal volume (TV). Heart rate (HR), systolic (SAP), diastolic (DAP), and mean arterial blood pressure (MAP). Arterial blood samples were collected during and after the surgery to determinate arterial PH, PaCO2, PaO2. Results Smooth and rapid induction followed by satisfactory maintenance and good recovery quality was observed with both anaesthetic agents. Cardiopulmonary effects were similar for both groups with notable respiratory depression and fair hemodynamic parameters. Conclusions and Clinical Relevance The administration of alfaxalone used as TIVA in premedicated dogs produced satisfactory anaesthesia with the same quality as that produced by propofol during ovariohysterectomy. Hypoventilation was the most prominent adverse effect from both anaesthetic agents suggesting a need for ventilatory support during prolonged TIVA periods with either anaesthetic agent. / Dissertation (MSc)--University of Pretoria, 2010. / Companion Animal Clinical Studies / unrestricted

Since the introduction of the lipid emulsion formulation in 1986, propofol has become established for induction as well as for maintenance of anaesthesia in veterinary practice1 including cats2;3-8. Propofol is rapidly metabolized by hepatic glucuronidation in most species and it has also been shown to undergo extrahepatic metabolism9-13, so that total body clearance may exceed liver blood flow in certain species. Because of their highly carniverous diet, cats are little exposed to antiherbivory compounds so that they have become deficient in UGP-glucuronosyltransferase (UGT)14. Consequently, a number of drugs are eliminated slowly15;16, often giving rise to prolonged half-lives of the parent drugs. Cats are therefore sensitive to the adverse effects of many drugs and toxins that are normally glucuronidated before elimination. It is therefore likely that the disposition of propofol may differ markedly from that of humans and other animal species17. Adam et al18 reported that for the cremophor propofol formulation in cats, volumes of distribution were smaller and elimination halflives were longer than those of pigs, rats and rabbits. In addition, pulmonary uptake has been demonstrated to occur in cats,19 however propofol’s pharmacokinetics have not been studied formally. The purpose of this study was to determine the pharmacokinetic behaviour of propofol after single intravenous injections. In comparison with man, the apparent central volume of distribution in domestic cats is small (0.56L.kg-1 body weight vs. 0.228L.kg-1) for the human pharmacokinetic parameter set of Marsh et al20 and the clearance (0.0086 L.kg-1.min-1 vs. 0.027 L.kg- 1.min-1) is approximately 2½ times slower in cats when compared with humans. Slow clearance should not influence recovery from anaesthesia following standard induction doses, because the early decreases in blood concentrations are predominantly due to redistribution of drug to various tissues (similar to the disposition of thiopentone which exhibits a slow total body clearance21. However it is possible that drug may accumulate within the body after prolonged infusions, resulting in delayed recovery times. This phenomenon is best described by calculating “context-sensitive” decrement-times by computer simulation22-24. Computer software♣ were used to calculate the 20%, 50% and 80% context-sensitive decrement times for the cat pharmacokinetic model. For comparative purposes, similar calculations were performed for an adult human male (weight 70 kg) using the pharmacokinetic parameter-set of Marsh et al20. Assuming that recovery from anaesthesia occurs after a 50% decrease in blood concentrations has taken place, it is apparent from the 50% context-senstive decrement-time graph that for infusions lasting up to 20 minutes (during which concentrations are kept constant), recovery can be expected to be rapid and predictable. However if infusions are administered for longer than 20 minutes, the recovery times of the “average” cat increase rapidly, reaching a plateau of 36 minutes, while recovery times of the human remain short, albeit increasing slowly. Awakening times become dramatically prolonged and unpredictable in both cats and humans if propofol concentrations are required to decrease by 80% for recovery to occur. Under these circumstances the 80% decrement time after a two-hour infusion is approximately two hours in cats and 45 minutes in humans. On the other hand, if dosing is conservative, so that blood concentrations need to decrease by only 20% for awakening to occur, then recovery times are short and predictable, being only a few minutes, regardless of the duration of the preceding infusion. These findings are in accordance with those of Pascoe et al25 who reported that cats took longer to recover after a short (30 min) infusion than after a long (150 min) infusion. In their crossover study, the propofol infusion rates were adjusted so that the cats were maintained at a light level of anaesthesia at which they responded sluggishly to pedal stimulation. It is therefore likely that propofol concentrations were kept steady and were similar during the 30-minute as well as during the 150-minute infusions. Delayed recovery has also been reported when propofol was administered to cats on consecutive days26. Conclusions and clinical relevance: We recommend that propofol infusions be administered to cats only for fairly short procedures and that for prolonged surgery, maintenance of anaesthesia should be accomplished using other drugs. In order to decrease the propofol dose, premedication and analgesic supplements should be co-administered to provide “balanced” anaesthesia. ♣ TIVA Trainer version 8, author Frank Engbers, Leiden University Medical Centre Copyright / Dissertation (MMedVet)--University of Pretoria, 2009. / Companion Animal Clinical Studies / unrestricted