RATIONALE: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing. METHODS: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions. RESULTS: The results are measured as beyond use date (BUD) defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for cisatracurium diluted to 10x and 100x is 96 hours. Higher dilutions (1,000x to 100,000x) should be used immediately following preparation (within less than 24 hours). Vecuronium at 10x and 100x also has a BUD of 96 hours, and the 1,000x dilution is stable for 24 hours. The 10,000x dilution should be used immediately. Rocurium at 10x to 1,000x has a BUD of 48 hours, yet higher dilutions (10,000x and 100,000x) should be used immediately. CONCLUSIONS: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.

Made available in DSpace on 2014-06-11T19:29:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-11-24Bitstream added on 2014-06-13T19:37:58Z : No. of bitstreams: 1 moro_et_me_botfm.pdf: 465770 bytes, checksum: 4a10047a2171b9c6542fe3eba27f15c5 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / Justificativa e Objetivos: o início de ação dos agentes bloqueadores neuromusculares pode ser influenciado por fatores que incluem a distância do músculo ao coração, o fluxo sangüíneo muscular e o débito cardíaco. O propofol pode causar hipotensão arterial, principalmente quando associado a um opióide, o que diminuiria o fluxo sangüíneo muscular e, portanto tem sido citado como um fator responsável pelo aumento do tempo de latência dos bloqueadores neuromusculares. O objetivo deste estudo foi avaliar a eficácia da efedrina na prevenção dos efeitos hipotensores arteriais induzidos pela associação do propofol e do remifentanil, assim como os efeitos sobre o tempo de latência do cisatracúrio. Método: foram selecionados 60 pacientes com idade entre 18 e 52 anos, estado físico ASA I ou II, que seriam submetidos à cirurgia eletiva sob anestesia geral e divididos em 3 grupos, de modo aleatório. A distribuição dos pacientes foi realizada de acordo com a solução empregada durante a indução da anestesia como segue: G I (n=20) - Propofol 1 %; G II (n=20) - Propofol 1% + efedrina 0,5 mg.ml-1 e G III (n=20) - Propofol 1% + efedrina 1,0 mg.ml-1. Após a pré-oxigenação com O2 a 100% em máscara facial, foi administrado remifentanil em infusão contínua, por via venosa (0,5 mg.kg-1.min-1), por 90 segundos. Em seguida foi administrado o propofol 1% (associado ou não à efedrina), com velocidade de infusão igual a 180 ml.h-1, até a perda da resposta ao estímulo auditivo e dos reflexos palpebral e corneano e cisatracúrio na dose de 0,15 mg.kg-1 . Foram registrados os dados demográficos, os sinais vitais (PAS, PAM, PAD, FC e SpO2) e o tempo de latência do cisatracúrio pelo método da aceleromiogarfia (T1< 5% do controle). O nível de significância utilizado foi de 5%. Resultados: os grupos foram homogêneos com relação aos dados demográficos. Houve diminuição... / Justification and Objectives: the beginning of action of neuromuscular blocking agents may be influenced by factors including the distance from the muscle to the heart, muscle blood flow and cardiac output. Propofol may cause systemic hypotension, particularly when associated with an opioid, which would decrease muscle blood flow and, hence, it has been cited as a factor responsible for the increase in the onset time of neuromuscular blocking agents. This study aimed at evaluating the efficacy of ephedrine in the prevention of systemic hypotensive effects induced by the association of propofol and remifentanil as well as the effects on the onset time of cisatracurium. Method: sixty patients were selected. They were 18 to 52 years old, exhibited ASA physical status I or II and would be submitted to elective surgery under general anesthesia. The patients were randomly allocated into three groups. The distribution of patients was carried out according to the solution used during anesthesia induction, as follows: G I (n=20) - 1% propofol; G II (n=20) - 1% propofol + 0.5 mg.ml-1 ephedrine and G III (n=20) - 1% propofol + 1.0 mg.ml-1 ephedrine. Following pre-oxygenation with O2 at 100% by facial mask, remifentanil was administered by venous continuous infusion (0.5 mg.kg-1.min-1) for 90 seconds. Next, 1% propofol was administered (associated with ephedrine or not), at an infusion rate equal to 180 ml.h-1 until the response to auditory stimuli and palpebral and corneal reflexes could not be detected; a dose of 0.15 mg.kg-1 of cisatracurium was also administered. Demographic data, vital signs (SBP, MBP, DBP, HR and SpO2) and the onset time of cisatracurium were recorded by the acceleromiography method (T1< 5% of the control). The level of significance used was of 5%.Results: the groups were homogeneous as regards the demographic data. There was a statistically significant... (Complete abstract click electronic access below)

Orientador: Norma Sueli Pinheiro Módolo / Banca: Eliana M. Ganem / Banca: Angélica de Fátima Assunção Braga / Resumo: Justificativa e Objetivos: o início de ação dos agentes bloqueadores neuromusculares pode ser influenciado por fatores que incluem a distância do músculo ao coração, o fluxo sangüíneo muscular e o débito cardíaco. O propofol pode causar hipotensão arterial, principalmente quando associado a um opióide, o que diminuiria o fluxo sangüíneo muscular e, portanto tem sido citado como um fator responsável pelo aumento do tempo de latência dos bloqueadores neuromusculares. O objetivo deste estudo foi avaliar a eficácia da efedrina na prevenção dos efeitos hipotensores arteriais induzidos pela associação do propofol e do remifentanil, assim como os efeitos sobre o tempo de latência do cisatracúrio. Método: foram selecionados 60 pacientes com idade entre 18 e 52 anos, estado físico ASA I ou II, que seriam submetidos à cirurgia eletiva sob anestesia geral e divididos em 3 grupos, de modo aleatório. A distribuição dos pacientes foi realizada de acordo com a solução empregada durante a indução da anestesia como segue: G I (n=20) - Propofol 1 %; G II (n=20) - Propofol 1% + efedrina 0,5 mg.ml-1 e G III (n=20) - Propofol 1% + efedrina 1,0 mg.ml-1. Após a pré-oxigenação com O2 a 100% em máscara facial, foi administrado remifentanil em infusão contínua, por via venosa (0,5 mg.kg-1.min-1), por 90 segundos. Em seguida foi administrado o propofol 1% (associado ou não à efedrina), com velocidade de infusão igual a 180 ml.h-1, até a perda da resposta ao estímulo auditivo e dos reflexos palpebral e corneano e cisatracúrio na dose de 0,15 mg.kg-1 . Foram registrados os dados demográficos, os sinais vitais (PAS, PAM, PAD, FC e SpO2) e o tempo de latência do cisatracúrio pelo método da aceleromiogarfia (T1< 5% do controle). O nível de significância utilizado foi de 5%. Resultados: os grupos foram homogêneos com relação aos dados demográficos. Houve diminuição... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Justification and Objectives: the beginning of action of neuromuscular blocking agents may be influenced by factors including the distance from the muscle to the heart, muscle blood flow and cardiac output. Propofol may cause systemic hypotension, particularly when associated with an opioid, which would decrease muscle blood flow and, hence, it has been cited as a factor responsible for the increase in the onset time of neuromuscular blocking agents. This study aimed at evaluating the efficacy of ephedrine in the prevention of systemic hypotensive effects induced by the association of propofol and remifentanil as well as the effects on the onset time of cisatracurium. Method: sixty patients were selected. They were 18 to 52 years old, exhibited ASA physical status I or II and would be submitted to elective surgery under general anesthesia. The patients were randomly allocated into three groups. The distribution of patients was carried out according to the solution used during anesthesia induction, as follows: G I (n=20) - 1% propofol; G II (n=20) - 1% propofol + 0.5 mg.ml-1 ephedrine and G III (n=20) - 1% propofol + 1.0 mg.ml-1 ephedrine. Following pre-oxygenation with O2 at 100% by facial mask, remifentanil was administered by venous continuous infusion (0.5 mg.kg-1.min-1) for 90 seconds. Next, 1% propofol was administered (associated with ephedrine or not), at an infusion rate equal to 180 ml.h-1 until the response to auditory stimuli and palpebral and corneal reflexes could not be detected; a dose of 0.15 mg.kg-1 of cisatracurium was also administered. Demographic data, vital signs (SBP, MBP, DBP, HR and SpO2) and the onset time of cisatracurium were recorded by the acceleromiography method (T1< 5% of the control). The level of significance used was of 5%.Results: the groups were homogeneous as regards the demographic data. There was a statistically significant... (Complete abstract click electronic access below) / Mestre

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Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Thesis (MMed)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: Introduction: Of the volatile anaesthetic agents, desflurane causes the greatest degree of potentiation of the neuromuscular blocking drugs (NMB). The purpose of this study was to determine whether desflurane prolongs the effects of 3xED95 doses of rocuronium and cisatracurium to the same degree. The two NMB represent potent and less potent classes respectively. Methods: Informed, written consent was obtained from 63 adult patients scheduled for routine surgery. They were randomly allocated to one of four groups to receive either desflurane-sufentanil (end-tidal partial pressure 4.0 kPa) or propofol-sufentanil anaesthesia and either rocuronium (0.9mg/kg) or cisatracurium (0.15mg/kg). All patients received a target-controlled sufentanil infusion (0.5 ng/ml). Neuromuscular blockade was recorded using accelerometry (TOFGUARD ®, Organon) while patients recovered spontaneously to a Train-of-Four ratio of 0.9 (TOFR0.9). Data were analysed using one- and two-way analysis of variance. The main effects were the types of anaesthetic and NMB on indices of recovery. Results: Compared with propofol-sufentanil anaesthesia, mean times to recovery to T125% and TOFR0.9, were prolonged by desflurane-sufentanil (p<0.01). There were no interactions. Mean prolongation of time to TOFR0.9 was 41 min (SD 36) for cisatracurium and 26.6 min (SD 39) for rocuronium. Discussion: Whereas previous studies did not reveal prolongation of the duration of action of rocuronium by desflurane, we demonstrated a statistically significant prolongation of the spontaneous recovery times of both rocuronium and cisatracurium by desflurane. From the data we could not conclude that there was a difference between the two NMB. A power study revealed that in order to detect a difference between times to recovery to TOF0.9, a sample size of 101 subjects per group would be required. Conclusion: Desflurane prolongs the mean time to spontaneous recovery from neuromuscular blockade after 3xED95 doses of both cisatracurium (a potent NMB) and rocuronium (a less potent NMB). There was wide inter-individual variation in times to spontaneous recovery. Any difference in the mean prolongations between the different types of NMB is unlikely to be of clinical importance. / AFRIKAANSE OPSOMMING: Inleiding Van al die vlugtige narkosemiddels veroorsaak desfluraan die grootste mate van potensiasie van die neuromuskulêre blokkeermiddels. Die doel van hierdie studie was om vas te stel of desfluraan wel die effek van driedubbel die ED95 dosis van rokuronium en cisatrakurium tot dieselfde mate sal verleng. Metodiek Geskrewe ingeligte toestemming is verkry van 63 pasiënte wat voorgedoen het vir roetiene chirurgiese prosedures. Pasiënte is lukraak in een van vier groepe ingedeel om of desfluraansufentaniel (eind-gety parsieële druk 4.0 kPa) of propofol-sufentaniel narkose en of rokuronium (0.9 mg/kg) of cisatrakurium (0.15 mg/kg) te ontvang. Alle pasiënte het 'n teiken-beheerde sufentaniel infusie (0.5 ng/ml). Neuromuskulêre blokkade is waargeneem met behulp van aksellerometrie (TOF-GUARD, Organon) terwyl pasiënte spontaan herstel het tot “reeks-van-vier” verhouding (Engels “Train-of-four” ratio) 0.9 (TOFR0.9). Data analise is gedoen met behulp van een- en tweerigting analise van variansie. Resultate Desfluraan-sufentaniel het die gemiddelde hersteltyd tot T125% en TOFR0.9 verleng in vergelyking met propofol-sufentaniel. Geen interaksies is waargeneem nie. Gemiddelde verlenging van TOFR0.9 vir cisatrakurium was 41 minute (standaardafwyking 36) en vir rokuronium 26.6 minute (standaardafwyking 39). Bespreking Vorige studies kon nie vasstel of desfluraan die werkingsduur van rokuronium verleng nie. Ons het in hierdie studie vasgestel dat desfluraan wel 'n statisties beduidende verlenging in die hersteltyd van beide rokuronium en cisatrakurium veroorsaak. Ons kon egter nie 'n verskil tussen die twee neuromuskulêre agente aandui nie. 'n onderskeidingsvermoëstudie het getoon dat ten minste 101 pasiënte per groep benodig sou word om 'n beduidende verskil tussen die hersteltye tot TOFR0.9 te verkry. Gevolgtrekking Desfluraan verleng die gemiddelde hersteltyd tot spontane herstel van neuromuskulêre blokkade na driedubbele ED95 dosisse van beide cisatrakurium en rokuronium. Daar was egter groot interindividuele variasie ten opsigte van spontane hersteltyd. Enige verskille in die gemiddelde verlenging is onwaarskynlik van kliniese belang.

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing. Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions. Results: The results are measured as beyond use date (BUD) defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for cisatracurium diluted to 10x and 100x is 96 hours. Higher dilutions (1,000x to100,000x) should be used immediately following preparation (within less than 24 hours). Vecuronium at 10x and 100x, also has a BUD of 96 hours, and the 1,000x dilution is stable for 24 hours. The 10,000x dilution should be used immediately. Rocuronium at 10x to 1,000x has a BUD of 48 hours, yet higher dilutions (10,000x and 100,000x) should be used immediately. Conclusions: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.