盐酸托烷思琼预防脑动脉瘤栓塞术后恶心呕吐的观察

目的:观察盐酸托烷思琼对预防脑动脉瘤栓塞术患者术后恶心呕吐(PONV)的有效性和安全性。方法:选择行颅内动脉瘤栓塞术患者45例,随机分为3组,每组15例,于手术结束前30分钟A组患者缓慢静注盐酸托烷思琼5mg,B组患者缓慢静注盐酸托烷思琼3mg,C组患者给予生理盐水。术后观察并记录以下指标:(1)术后24h内恶心呕吐发生率及强度;(2)术后2、8h镇静评分(OAA/S);(3)术后2、8h平均动脉压(MAP),心率(HR);(4)各组不良反应的发生情况。结果:术后24h内两治疗组恶心呕吐发生率显著低于对照组,差异有统计学意义(P<0.05或P<0.01)。托烷思琼5mg组恶心呕吐发生率略低于3mg组,但差异无统计学意义(P>0.05)。结论:托烷思琼可降低脑动脉瘤栓塞术患者术后恶心呕吐的发生率。托烷思琼3mg不仅可以减少药物用量,而且能减少副作用的发生,是一种经济、有效、安全的止吐方法。     

5-Hydroxytryptamine-induced increase in left ventricular dP/dtmax does not suggest the presence of ventricular 5-HT4 receptors in the pig

Summary Although 5-hydroxytryptamine (5-HT) increases porcine atrial force and rate via 5-HT₄ receptors, its effect on left ventricular contractility is not known. Therefore, using the maximum rate of rise of left ventricular pressure (LVdP/dt_max) as an index of cardiac contractility, we have attempted to analyze the possible role of ventricular 5-HT₄ receptors in the anaesthetized pig. The full agonists at 5-HT₄ receptors, 5-HT and 5-methoxytryptamine (each 3, 10 and 30 g · kg^–1), and the -adrenoceptor agonist, isoprenaline (0.01, 0.03 and 0.1 g · kg^–1), increased heart rate, LVdP/dt_max and cardiac output. For a given degree of tachycardia, the increase in LVdP/dt_max by isoprenaline was substantially more than that observed with either 5-HT or 5-methoxytryptamine. The 5-HT₄ receptor partial agonist, renzapride (3, 10, 30, 100 and 300 g · kg^–1), also increased heart rate and LVdP/dt_max dose-dependently. When the heart was paced at 150 beats · min^–1, increases in LVdP/dt_max as well as cardiac output (except with the highest doses) by 5-HT, 5-methoxytryptamine and isoprenaline were clearly attenuated. However, the magnitude of attenuation of LVdP/dt_max responses by cardiac pacing was more marked in the case of 5-HT and 5-methoxytryptamine than with isoprenaline.The effects of renzapride (300 g · kg^–1) and tropisetron (0.3 and 3 mg · kg^–1) on increases in heart rate and LVdP/dt_max by 5-HT, 5-methoxytryptamine and isoprenaline were also studied. In the absence of atrial pacing, both renzapride and tropisetron (3 mg · kg^–1) effectively antagonized the responses to 5-HT and 5-methoxytryptamine; except for some decrease in the LVdP/dt_max response by tropisetron, the effect of isoprenaline remained essentially unchanged after the antagonists. During atrial pacing, renzapride significantly antagonized the responses to the first two doses of 5-HT, but the responses to the highest 5-HT dose and to 5-methoxytryptamine remained unaffected. Though, particularly after its higher dose, tropisetron reduced the responses to 5-HT and 5-methoxytryptamine, isoprenaline responses were also affected.The above results show that a significant part of the increase in LVdP/dt_max by 5-HT receptor agonists in the anaesthetized pig is a consequence of tachycardia elicited by these compounds via 5-HT₄ receptors. Since the increase in LVdP/dt_max, compared to tachycardia, was much less with 5-HT and 5-methoxytryptamine than with isoprenaline, and since the antagonism by renzapride and tropisetron against 5-HT and 5-methoxytryptamine during atrial pacing was relatively weaker and/or unspecific, it appears unlikely that the increase in LVdP/dt_max, during atria] pacing is mediated by ventricular 5-HT₄ receptors. This view is substantiated by our recent in vitro experiments where 5-HT (0.01 to 100 mol/l) failed to significantly increase contractions of porcine left ventricular trabeculae.Correspondence to P. R. Saxena at the above address     

国产盐酸托烷司琼治疗顺铂化疗所致恶心、呕吐的疗效与安全性评价

目的:比较国产与进口盐酸托烷司琼在治疗顺铂化疗所致恶心、呕吐的疗效和安全性。方法:采用多中心、双盲、随机对照方法,128例接受顺铂化疗的恶性肿瘤患者随机分为进口盐酸托烷司琼组和国产盐酸托烷司琼组,于化疗前1d应用盐酸托烷司琼,5mg/次,1次/d,连用6d,观察并记录用药1wk内患者食欲减退、恶心、呕吐及其他不良反应。结果:128例患者按研究要求完成观察,2组在治疗恶心、呕吐方面及发生其他不良反应方面均无显著性差异(P>0.05)。结论:国产盐酸托烷司琼在治疗顺铂化疗所致恶心、呕吐的疗效和安全性与进口盐酸托烷司琼相当。     

The neuroprotective effect of tropisetron on vincristine-induced neurotoxicity

Vincristine (VCR) peripheral neuropathy is a dose-limiting side effect. Several studies have shown that tropisetron, a 5-HT₃ receptor antagonist, exerts anti-inflammatory and immunomodulatory properties. Current study was designed to investigate a suppressive effect of tropisetron on VCR-induced neuropathy and whether this effect exerts through the 5-HT₃ receptor or not.Neuropathy was induced in rats by administration of vincristine (0.5 mg/kg, 3 intraperitoneal injections on alternate days) and in treatment group, tropisetron (3 mg/kg); m-chlorophenylbiguanide (mCPBG), a selective 5-HT₃ receptor agonist (15 mg/kg); tropisetron (3 mg/kg) plus mCPBG (15 mg/kg); granisetron, another selective 5-HT₃ receptor antagonist (3 mg/kg) were administered intraperitoneally 1 h prior to vincristine injection. Hot plate, open field tests (total distance moved, mean velocity and percentage of total duration of the movement) and motor nerve conduction velocity (MNCV) were performed to evaluate the sensory and motor neuropathy. Further, plasma levels of tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) and the level of TNF-α in sciatic nerve were assessed as well as histological examination.In only VCR-treated rats hot plate latencies were significantly increased, total distance moved, mean velocity, total duration of the movement and sciatic MNCV significantly decreased compared with control. In tropisetron and tropisetron plus mCPBG groups, one injection of tropisetron prior to each VCR injection robustly diminished TNF-α and IL-2 levels, and also prevented mixed sensory-motor neuropathy, as indicated by less mortality rate, better general conditions, behavioral and electrophysiological studies. Moreover, pathological evidence confirmed the results obtained from other findings. But granisetron and mCPBG had no significant effect on the mentioned parameters.In conclusion, these studies demonstrate that tropisetron significantly suppressed VCR-induced neuropathy and could be a neuroprotective agent for prevention of VCR-induced neuropathy via a receptor-independent pathway.     

3种止吐药物在晚期食管癌患者化疗中的药物经济学评价

目的：前瞻性研究本院帕洛诺司琼、阿扎司琼和托烷司琼对化疗引起恶心和呕吐的影响及对不同止吐方案进行成本-效果分析。方法：选取2018年1月~2019年12月间124例采用多西他赛+顺铂（DP）方案化疗的晚期食管癌患者作为研究对象,均签署知情同意书。将其随机分为3组（帕洛诺司琼组、阿扎司琼组和托烷司琼组）。在化疗前,分别给予相应药物预防止吐,通过MAT量表与FLIE量表对化疗相关恶心呕吐（CINV）情况进行评估,并基于医疗提供者角度,开展成本-效果分析。结果：3组抑制急性呕吐与恶心、延迟性呕吐与恶心方面,疗效比较无统计学差异（P>0.05）。住院期间抑制呕吐与恶心的药物成本,三种方案有统计学差异（P<0.05）。采用最小成本法,帕洛诺司琼成本最低,具有经济性。敏感性分析结果显示：缓解恶心和呕吐,帕诺洛司琼具有经济性概率始终最高。结论：帕诺洛司琼具有较好的经济性。     

酒石酸布托啡诺、地佐辛与盐酸托烷司琼在镇痛泵内配伍的稳定性考察

目的:考察酒石酸布托啡诺、地佐辛、盐酸托烷司琼在0.9%氯化钠注射液中的配伍稳定性。方法:模拟临床实际用药的配伍浓度和使用环境,检测0,1,4,6,24,48,72 h外观、pH、相对百分含量的变化。结果:酒石酸布托啡诺、地佐辛与盐酸托烷司琼的配伍液在72 h内pH未出现明显变化,外观稳定,各药品成分相对百分含量也没有明显变化。结论:在室温条件下,酒石酸布托啡诺、地佐辛与盐酸托烷司琼在0.9%氯化钠注射液中72 h内保持稳定。因此,酒石酸布托啡诺(6 mg)、地佐辛(20 mg)与盐酸托烷司琼(10 mg)可以配伍使用,在镇痛泵内配伍稳定。     

Serotonin mediates PGE<Subscript>2</Subscript> overexpression through 5-HT<Subscript>2A</Subscript> and 5-HT<Subscript>3</Subscript> receptor subtypes in serum-free tissue culture of macrophage-like synovial cells

Serotonin antagonists show impressive analgesic efficacy in rheumatoid arthritis, osteoarthritis (OA) or fibromyalgia; however, this effect is not well understood. We examined the mechanism of serotonin-induced inflammation and its antagonists in OA. Serotonin receptor subtypes and COX-2 were analysed by RT-PCR from synovial tissue. Serum-free cultures were stimulated with 10 muM serotonin and/or the antagonists ketanserin (5-HT(2A)), tropisetron (5-HT(3)) and parecoxib (COX-2). Prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and leukotriene B4 (LTB4) were measured by an immunoassay in the supernatants. RT-PCR results showed mRNA for 5-HT(2A) and 5-HT(3) receptors, and COX-2. PGE(2) in the supernatants increased by 261.2% +/- 56.7 (mean +/- SEM; P = 0.007) in response to serotonin. TNF-alpha, IL-1beta and LTB4 levels did not change. Ketanserin, tropisetron and parecoxib suppressed PGE(2). The serotonin-induced PGE(2) overexpression appeared thus to be mediated by 5-HT(2A) and 5-HT(3) receptors. This activation might involve COX-2. The findings may explain the potent benefit of 5-HT(3) antagonists.     

盐酸托烷司琼和氟哌利多预防吗啡硬膜外自控镇痛引起的恶心呕吐效果观察

目的探讨盐酸托烷司琼和氟哌利多预防术后吗啡硬膜外自控镇痛（PCEA）引起恶心呕吐的效果和不良反应？方法选择硬膜外麻醉下行开腹妇科手术患者120例，ASAⅠ～Ⅱ级，分3组各40例，A组用盐酸托烷司琼5mg，B组用氟哌利多5mg，两组的药物分别将药加入PCEA药盒注入硬膜外腔，C组PCEA药液不加其他药物。术毕行吗啡PCEA镇痛，镇痛方法采用负荷量＋连续量，负荷量为吗啡2mg，连续量为2ml／h，自控量为0．5ml／15min，PCEA药液为吗啡8mg＋布比卡因150mg＋生理盐水至100ml。术后连续监测BP、RR、ECG、SpO2，定时观察记录视觉模拟评分法（VAS）的评分、恶心、呕吐发生率。结果3组患者手术后镇痛效果满意，组间比较差异无显著性（P〉0．05），恶心呕吐发生率，A、B组明显低于C组，差异有显著性意义（P〈0．05），A组与B组相比：A组明显低于B组，差异有显著性意义（P〈0．05）。结论盐酸托烷司琼较氟哌利多能更有效地预防术后吗啡PCEA引起的恶心呕吐。     

托烷司琼联合长托宁预防吗啡硬膜外镇痛恶心、呕吐的临床研究

目的:观察托烷司琼术后经患者硬膜外自控镇痛(PECA)泵持续输注结合长托宁术前肌注对直肠癌术后吗啡PECA所致的恶心呕吐的影响。方法:选择硬膜外麻醉下行直肠癌手术患者120例随机均分为A、B、C三组,A组术前抗胆碱药采用阿托品,B、C组采用长托宁,术后PECA均采用吗啡,术毕A组不用止呕药,B组托烷司琼5mg于术毕单次静注,C组托烷司琼5mg加入PECA泵中持续泵入。镇痛方法采用连续输注,连续量为2 mL/h,自控量为0.5 mL/15min,PCEA药液为吗啡5mg+托烷司琼5 mg+布比卡因150 mg+生理盐水至100 mL。于连接PECA泵即刻,观察各组术后2,12,24和48 h镇痛评分(VAS);Ramsay镇静评分(RSS);恶心、呕吐例数;因严重恶心、呕吐而要求终止PCA的例数。结果:(1)术后各时间点的VAS评分无明显差异,(2)A组各时点RSS明显低于B、C组(P<0.01)。(3)术后恶心、呕吐例数及要求终止PCA的例数A组明显多于B组、C组(P<0.05,P<0.01),恶心、呕吐例数B组亦明显多于C组(P<0.05)。结论:托烷司琼术后经患者PECA泵持续输注结合长托宁术前肌注能明显减少直肠癌术后吗啡PECA所致的恶心、呕吐,且有较好的术后镇静效果。     

托烷司琼不同时间给药预防术后恶心呕吐的临床观察

目的观察托烷司琼不同时间给药预防术后恶心呕吐的效果。方法将120例择期在全凭静脉麻醉下行腹腔镜胆囊切除术(LC)的病人随机分为3组,每组40例。A组病人麻醉诱导前静脉注射托烷司琼5mg;B组病人手术结束后静脉注射托烷司琼5mg;C组为不给托烷司琼及其他抗呕吐药物的对照组。观察并记录病人术后24h恶心呕吐的发生情况。结果A、B组术后恶心呕吐的发生率明显低于C组(P<0.05),其中A组发生率比B组更低(P<0.05)。结论托烷司琼术前和术后不同时间给药,均能有效减少病人术后恶心呕吐的发生,术前预防性用药效果更佳。