| Tuberculosis (TB) is a common clinical chronic infectious disease caused by mycobacterium tuberculosis. For the world with a high incidence of TB in our country, there are more than 400 millions infected persons, of which about 10% of TB bacterium infected people will develop into TB. The disease may be involved in multiple organs, but 80% occur in the lungs. Early, united, appropriate amount, regular, and an entire treatment can cure most TB, but for the intractable TB patients, an appropriate surgery is an effective way for relieving illnesses. Vecuronium bromide, which have a short onset time, exact muscle relaxant effect, and little effect on circulation system, is a common non-depolarizing muscle relaxant in clinical practice, and its metabolic required enzymes mainly depend on the synthesis in liver. The commonly used anti-tuberculosis drugs may cause liver function and (or) peripheral nerve, and muscle system damage, or may block the neuromuscular junction postsynaptic acetylcholine receptors, yielding curare like skeletal muscle relaxation, interfering the muscle relaxant effect, thus anesthesiologists should monitor the muscle relaxation level timely during the operation period in TB patients. Or else, insufficient or muscle relaxation effect in surgery or residual muscle relaxation in anesthesia recovery period may occur, which may cause the anesthesia risk increasing. Therefore the establishment of TB patients commonly used non-depolarizing muscle relaxant vecuronium’s dose-response curve, and the establishment of its 95% effective dose (ED95) value and pharmacodynamic parameters have important clinical significance, which can be use to guide the rational application of vecuronium in these patients, thereby reducing the occurrence of the adverse reactions rate. This research take a single dose method for the determination of vecuronium administration by weight, to detect its ED95 value and common pharmacodynamic parameters of TB patients, and compare with the ordinary patients study, then providing a reference for clinical reasonable application of vecuronium in TB patients.Part one Detection of dose-response relationship of vecuronium in TB patientsObjective To establish the dose-response curve of vecuronium and to evaluate the ED95 value of vecuronium in TB and ordinary patients.Methods One hundred and sixty ASA grade Ⅰ or Ⅱ patients were enrolled in this study, of which eighty for TB surgery (group T) and eighty for non-tuberculosis surgery (group N). All patients were randomly divided into four equal subgroups, each subgroup singly received an intravenous bolus of 20μg/kg,30μg/kg,40μg/kg or 50μg/kg of vecuronium respectively under midazolam-propofol-fentanyl anesthesia. After patients’consciousness disappeared, the neuromuscular block (NMB) was measured by neuromuscular transmit (NMT) monitor which belonged to GE Datex-Ohmeda S/5 ADU anesthesia work station, and the responses were defined in terms of the percentages of maximum suppression at the first twitch response (T1) of the train-of-four stimulation (TOF) of the adductor pollicis muscle. According to log-probit transformation of the data of dose and response, the dose-response curve of vecuronium was established through linear regression. The ED50, ED75, ED90 and ED95 value of vecuronium were calculated, and the onset time was also observed in TB and ordinary patients. SPSS 17.0 were used to analyze the data. All data are reported as the mean±standard deviation. Comparisons between groups were made by student t-test, while comparisons among group were made by one-way analysis of variance and, comparisons between gender was made by the chi-square test. Differences were considered significant at P<0.05.Results No significant difference were found in general situation among all subgroups (P> 0.05). The percentages of maximal suppression of T1 rised when increasing the dose of vecuronium (P< 0.05). Compared to non-tuberculosis patients, the onset time of vecuronium in TB patients were longer and statistical difference was found at a single dose of 40μg/kg (P< 0.05). The ED50,ED75,ED90 and ED95 value of vecuronium were 26.6μg/kg,31.6μg/kg,37.0μg/kg and 40.5μg/kg respectively in TB patients, while 25.9μg/kg,30.8μg/kg,36.1μg/kg and 39.7μg/kg respectively in ordinary patients.Conclusion The ED95 value of vecuronium was 40.5μg/kg in TB patients, similar to 39.7μg/kg in non-tuberculosis patients, while the onset time prolonged with a single dose corresponded to 1 times of the ED95 value of the drug.Part two Compare of dose-response relationship of vecuronium in TB patients with different genderObjective To compare the dose-response curve of vecuronium in TB and ordinary patients with different gender.Methods Three hundred and twenty ASA grade Ⅰ or Ⅱ patients were enrolled in this study, of which one hundred and sixty for TB surgery (group T) and one hundred and sixty for non-tuberculosis surgery (group N). All patients were divided into male and female group, which continually divided into four equal subgroups randomly. Each subgroup singly received an intravenous bolus of 20μg/kg,30μg/kg, 40μg/kg or 50ug/kg of vecuronium respectively under midazolam-propofol-fentanyl anesthesia. The NMB was measured, and the responses were defined in terms of the percentages of maximum suppression at T1 of TOF of the adductor pollicis muscle. According to log-probit transformation of the data of dose and response, the dose-response curve of vecuronium was established through linear regression. The ED50, ED75, ED90 and ED95 value of vecuronium was calculated, and the onset time was also observed in TB and ordinary patients with different gender. SPSS 17.0 were used to analyze the data. All data are reported as the mean±standard deviation. Comparisons between groups were made by student t-test, while comparisons among group were made by one-way analysis of variance. Differences were considered significant at P<0.05.Results No significant difference were found in general situation among all subgroups (P>0.05). The percentages of maximal suppression of T1 rised when increasing the dose of vecuronium, and the onset time in male TB patients is statistically longer at a single dose of 40μg/kg (P<0.05). The ED50, ED75, ED90 and ED95 value of vecuronium in male TB patients were 27.6μg/kg,32.7μg/kg,38.3μg/kg and 42.0μg/kg respectively, while 26.0μg/kg,31.0μg/kg,36.3μg/kg and 39.9μg/kg respectively in female TB patients. The ED50, ED75, ED90 and ED95 value of vecuronium in male ordinary patients were 26.3μg/kg,31.4μg/kg,36.9μg/kg and 40.6μg/kg respectively, while 25.7μg/kg,30.8μg/kg,36.3μg/kg and 40.0μg/kg respectively in female ordinary patients.Conclusions The ED95 value of vecuronium in TB patients was 42.0μg/kg (male) or 39.9μg/kg (female), close to that in non-tuberculosis patients. The onset time prolonged with a single dose corresponded to 1 times of the ED95 value of the drug in male TB patients.Part three Detection of pharmacodynamics of vecuronium in TB patientsObjective To detect the pharmacodynamic parameters of vecuronium in TB and ordinary patients.Methods Forty ASA grade Ⅰ or Ⅱ patients received selective general anesthesia were enrolled in this study, of which twenty for TB surgery (group T) and others for non-tuberculosis surgery (group N). Each patient received an intravenous of midazolam, fentanyl, and propofol. The NMB was measured after patients’ consciousness disappeared. With an intravenous 0.1mg/kg of vecuronium, the responses were defined in terms of the percentages of maximum suppression at T1 of TOF of the adductor pollicis muscle. Endotracheal intubation was conducted when T1 fell to its lowest and repeated no less than 3 times. The onset time, the maximum inhibition of T1, the clinical effect time, the recovery index, the pharmacological effect time and the endotracheal intubation conditions were recorded. Mean pressure (MAP) and heart rate (HR) were measured before anesthesia induction (to), after general anesthesia for 5 min (t1),15 min (t2),30 min (t3),45 min (t4), and 1 h (t5). SPSS 17.0 were used to analyze the data. All data are reported as the mean±standard deviation. Comparisons between groups were made by student t-test except hemodynamic changes, which were made by variance analysis of repeated measurement data and, comparisons between gender was made by the chi-square test. Differences were considered significant at P< 0.05.Results No significant differences were found in general, hemodynamic changes, endotracheal intubation conditions, the maximum inhibition of T1, the onset time, the recovery index, and the pharmacological effect time between two groups (P> 0.05). The clinical effect time of vecuronium in TB patients was shorter than ordinary patients (P< 0.05).Conclusion With a single intravenous 0.1 mg/kg of vecuronium, the maximum inhibition of T1, the onset time, the recovery index and the pharmacological effect time in TB patients were similar to those in non-tuberculosis patients, while the clinical effect time was shorter, thus the additional interval should be shorten appropriately.Part four Compare of pharmacodynamics of vecuronium in TB patients with different genderObjective To compare the pharmacodynamic parameters of vecuronium in TB and ordinary patients with different gender.Methods Eighty ASA grade I or II patients received selective general anesthesia were enrolled in this study, of which forty for TB surgery (group T) and others for non-tuberculosis surgery (group N), which continually divided into male and female subgroups with 20 cases each. Each patient received an intravenous of midazolam, fentanyl, and propofol. The NMB was measured after patients’ consciousness disappeared. With an intravenous 0.1mg/kg of vecuronium, the responses were defined in terms of the percentages of maximum suppression at T1 of TOF of the adductor pollicis muscle. Endotracheal intubation was conducted when T1 fell to its lowest and repeated no less than 3 times. The onset time, the maximum inhibition of T1, the clinical effect time, the recovery index, the pharmacological effect time and the endotracheal intubation conditions were recorded. MAP and HR were measured before and after anesthesia induction. SPSS 17.0 were used to analyze the data. All data are reported as the mean±standard deviation. Comparisons between groups were made by student t-test except hemodynamic changes, which were made by variance analysis of repeated measurement data. Differences were considered significant at P< 0.05.Results No significant differences were found in general, hemodynamic changes, endotracheal intubation conditions, the maximum inhibition of T1, the onset time, the recovery index, and the pharmacological effect time among groups (P> 0.05). The clinical effect time of vecuronium in TB patients was shorter than ordinary patients (P<0.05). However, regarding to the clinical effect time, there’s no statistical difference between different gender in group T (P> 0.05), while significant statistical difference was found between different gender in group N (P< 0.05).Conclusion With a single intravenous 0.1mg/kg of vecuronium, the commonly used pharmacodynamic parameters were similar to each other between different gender in TB patients. Thus anesthesiologists could neglect the consequence of blocking aging of vecuronium in tuberculosis patients with different gender. |
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