The esophageal sphincters constitute the anatomical protection against pulmonary aspiration. The aim of this thesis was to study the esophageal sphincters and how they are affected by different components of emergency anesthesia using high-resolution solid-state manometry. The effect of propofol (0.3 mg/kg) was studied in young and elderly volunteers. Propofol can be given as an anxiolytic agent for manometric studies of the lower esophageal sphincter (LES) without affecting the results. However, propofol is not recommended for studies of the upper esophageal sphincter (UES). The effects of cricoid pressure (CP) and peripheral pain were studied in awake volunteers, with and without remifentanil infusion (5 ng/ml). Pain did not affect pressure in the LES, but CP or remifentanil induced a significant decrease in LES pressure. However, neither CP nor remifentanil affected the barrier pressure (LES-intra gastric pressure). When CP was applied during ongoing remifentanil infusion, no further decrease in LES pressure was measured. CP induced high pressures in the area of the UES independent of remifentanil infusion, indicating that CP is effective in preventing gastroesophageal regurgitation. Barrier pressure was also studied in anesthetized patients after rocuronium (0.6 mg/kg) administration and no decrease was measured. In addition, alfentanil (20 μ/kg) added during anesthesia induction with propofol did not decrease the barrier pressure. In conclusion, CP seems to be effective in preventing regurgitation and does not affect barrier pressure. Muscle relaxation with rocuronium does not risk gastro-esophageal integrity. In addition, opioids can be integrated, even during emergency anethesia, without increasing the risk for pulmonary aspiration.

Orientador: Angelica de F. de Assunção Braga / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T23:53:56Z (GMT). No. of bitstreams: 1 Loyola_YolandaChristinadeSousa_D.pdf: 22412843 bytes, checksum: 64766635e73a046988de0b090a234fe6 (MD5) Previous issue date: 2006 / Resumo: Os anestésicos locais comumente empregados na prática clínica podem interagir com os bloqueadores neuromusculares e potencializar seus efeitos. Muitos autores estudaram esta interação mas o mecanismo envolvido na potencialização do bloqueio neuromuscular e a ação dos anestésicos locais nos sítios pré e pós juncionais não foram completamente elucidados. Neste trabalho através de experimentos específicos na junção neuromuscular foram estudados os seguintes parâmetros: o efeito dos anestésicos locais procaína e lidocaína na transmissão neuromuscular; a sua influência no bloqueio neuromuscular produzido pela d-tubocurarina e pelo rocurônio; a eficácia da neostigmina e da 4-aminopirídina na reversão do bloqueio produzido pela associação anestésicos locais - bloqueadores neuromusculares; os efeitos dos anestésicos locais nos potenciais de membrana e potenciais de placa terminal em miniatura. Avaliou-se também em preparações diafragma de rato cronicamente desnervado e biventer cervicis de pintainho os efeitos dos anestésicos locais na ação contraturante da acetilcolina. Os resultados foram expressos em médias e desvios padrão e analisados através dos testes de Wilcoxon e Mann-Witney, adotando-se um nível de significância de 5% (p < 0,05). Nas preparações nervo frênico - diafragma de rato, sob estimulação elétrica indireta, os anestésicos locais nas concentrações empregadas, não alteraram a amplitude das respostas musculares mas potencializaram os efeitos da d- tubocurarina e do rocurônio.. Este bloqueio foi parcialmente e totalmente revertido pela neostigmina e pela 4-aminopiridina, respectivamente. A procaína e a lidocaína não causaram alteração significativa nos potenciais de membrana, não demonstrando ação despolarizante na fibra muscular. A procaína causou diminuição na amplitude e na freqüência dos potenciais de placa terminal em miniatura (pptms) e a lidocaína, ao contrário, promoveu um aumento inicial na freqüência dos pptms seguida de bloqueio. Nas preparações biventer cervicis de pintainho e diafragma de rato cronicamente desnervado, a procaína e a lidocaína promoveram diminuição significativa na resposta contraturante da acetilcolina evidenciando um efeito pós-juncional. Os resultados obtidos demonstram um sinergismo entre as drogas devido principalmente a um efeito pós-juncional / Abstract: Local anesthetics commonly used in clinical practice can interact with neuromuscular blockers and potentiate their effects. Many authors studied this interaction, but the mechanism involved in the potentiation of neuromuscular blockers and the action of local anesthetics in the pre and postjunctional sites were not completely elucidated- In this study, in specific experiments in the neuromuscular junction the following parameters were studied: the effects of the local anesthetics procaine and lidocaine in the neuromuscular transmission; its influence on the neuromuscular blockade produced by d-tubocurarine and by rocuronium; the efficacy of neostigmine and of 4-aminopyhdine in the reversion of the blockade produced by the association of local anesthetics - neuromuscular blockers; the effects of local anesthetics on the membrane potentials and miniature end - plate potentials. It was also evaluated in chronically denervated rat diaphragm preparation and chick biventer cervicis preparation the effects of local anesthetics on acetylcholine contracture. The results were expressed in average and standard deviation and analyzed through the Wilcoxon and Mann-Witney tests, adopting a level of significance of 5% (p <0.05). In rat phrenic nerve diaphragm preparations under indirect electric stimulation, local anesthetics in the concentrations used did not change the amplitude of the muscle response but potentiated the effects of d-tubocurarine and of rocuronium. This blockade was partially and totally reverted by neostigmine and by 4-aminopyridine, respectively. Procaine and lidocaine caused no significant alteration in the membrane potentials, not demonstrating depolarizing action in the muscle fiber. Procaine caused a decrease in the amplitude and frequency of the miniature end - plate potentials {meps) and lidocaine, in contrast, promoted an initial increase in the frequency of meps followed by blockade. In chick biventer cervicis preparations and chronically denervated rat diaphragm, procaine and lidocaine promoted a significant decrease in the response to acetylcholine contracture evidencing a post-junctional effect. The results obtained demonstrate a synergism among the drugs mainly due to a postjunctional effect / Doutorado / Doutor em Farmacologia

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.