雷莫司琼预防化疗药物所致胃肠道反应的临床观察

目的　观察盐酸雷莫司琼 (奈西雅 )注射剂治疗化疗药物所引起的胃肠反应和毒副作用 ,并与恩丹西酮 (欧贝 )比较 ,观察两药的疗效和安全性。方法　采用前瞻性随机对照研究的方法 ,将入院患者随机分为奈西雅组 (A组 )和欧贝组 (B组 ) ,分别观察化疗后 3d内食欲不振、恶心、呕吐和其他毒副反应。结果　收治的 89例患者 ,可评价疗效 85例 ,在化疗后 0～ 6h、6～ 12h、2 4～ 4 8h、4 8～ 72h奈西雅对食欲不振、恶心、呕吐的完全控制率和有效率与欧贝相比较略有优势 ,但差异无显著意义。而在 12～ 2 4h奈西雅组在食欲不振、恶心、呕吐方面的完全控制率 (分别为 4 1 9%、32 6 %、5 3 5 % )和有效率 (分别为 76 7%、75 1%、83 7% )均明显优于对照组 (完全控制率分别为 31 0 %、2 6 2 %、4 2 9% ;有效率分别为 4 0 5 %、4 2 9%、5 4 8% ) ,结果有显著的差异 (P <0 0 5 )。说明奈西雅的作用时间较欧贝长 ,其有效率奈西雅组高于后者。奈西雅不良反应较轻 ,主要为头痛、口干、便秘等 ,与欧贝比价差异无显著意义。结论　奈西雅能有效地治疗化疗所致的胃肠道反应 ;其疗效与欧贝相似 ,但作用持续时间较欧贝长 ,毒副反应轻 ,是新一代 5 HT3 受体拮抗剂。     

恩丹西酮和地塞米松预防小儿术后恶心呕吐的临床研究

目的:研究恩丹西酮和地塞米松预防小儿术后恶心呕吐(PONV)的临床效果。方法:选择120例手术患儿分4组,每组30例。Ⅰ组:静注生理盐水;Ⅱ组:地塞米松0.1mg/kg;Ⅲ组:恩丹西酮0.1mg/kg;Ⅳ组:地塞米松0.1mg/kg加恩丹西酮0.1mg/kg。比较各组患儿PONV的发生率。结果Ⅱ、Ⅲ、Ⅳ组PONV发生率明显低于Ⅰ组(P<0.005),Ⅳ组也明显低于Ⅱ、Ⅲ组(P<0.005),Ⅱ、Ⅲ组间无明显差异(P0.005)。结论:恩丹西酮和地塞米松均可有效预防小儿PONV,两药联合应用效果更佳。     

恩丹西酮Ⅲ期临床试验

恩丹西酮（Ｏｎｄａｎｓｅｔｏｎ）治疗抗癌药物引起的恶心、呕吐反应７２例，分三组观察。第１组为非顺氯铵铂（ＤＤＰ），含ＡＤＭ、ＣＴＸ组。于化疗前给恩丹西酮，静注，８ｍｇ，次日口服恩丹西酮４ｍｇ，每日２次，共用１天。其疗效第１天１００％；第２～３天为８１．８％，９６．９％；第４～５天为１００％。第２组为含ＤＤＰ组，输ＤＤＰ之日静注恩丹西酮８ｍｇ，次日口服本药４ｍｇ，１日２次，连服２天，其疗效第１～３天分别为７５．７％，８１．８％，９６．９％，第４～５天为１００％。第３组亦为含有ＤＤＰ加氟美松１０ｍｇ，用法同第２组，其止吐疗效第１～３天为９０．９％，第４～５天为１００％。结果，恩丹西酮加氟美松的效果９０．９％，比单用恩丹西酮组的疗效７５．５％～９６．９％优越。     

恩丹西酮和胃复安预防顺铂化疗呕吐反应的疗效分析

采用自身对照方法，观察了１０６例恶性肿瘤病人以顺铂为主联合化疗，于第１，２周期分别使用胃复安，恩丹西酮。预防恶心呕吐反应，有效率分别为：４３．３９％，９２．４５％，二者差异显著。胃复安组８例发生椎体外系反应，恩丹西酮均未出现椎体外系症状。     

恩丹西酮预防化疗所致呕吐Ⅲ期临床研究

作观察了经顺铂类和非顺铂类药物化疗的95例患应用恩丹西酮的止吐作用。顺铂组共68例。顺铂40mg／次×3天(23例)，50mg／次×3天(27例)。80mg／次×2天(18例)；非顺铂组27例．均系接受含环磷酰胺和／或阿霉素联合方案化疗用胃复安后出现呕吐患，A组后接受同一方案治疗。结果显示，恩丹西酮对控制顺铂不同剂量组所致急性呕吐的CR率依次为87.0％，85.2％和66.7%，总有效率分别为91．3％，96．3％和94．4％;而对非顺铂组控制急性呕吐的CR率为88．9%。有效率为96.3％。上述结果表明恩丹西酮对控制顺铂类和非顺铂类药物所致的呕吐反应均有较强的止吐作用。     

Ephedrine versus ondansetron in the prevention of hypotension during cesarean delivery: a randomized,double-blind,placebo-controlled trial

BackgroundMaternal hypotension is common after spinal anesthesia for cesarean delivery. We compared the effects of prophylactic ephedrine with ondansetron on post-spinal blood pressure.MethodsOne hundred and sixty-eight term, singleton parturients were enrolled in this prospective, double-blind, placebo-controlled trial. Patients were randomized to receive either prophylactic intravenous ephedrine 10 mg (Group E), ondansetron 8 mg (Group O) or normal saline (Group P) immediately after spinal anesthesia. The primary outcome was maternal blood pressure between spinal block and delivery; secondary outcomes were nausea and vomiting scores, Apgar scores, numbers requiring intraoperative vasoconstrictors and the dose of vasoconstrictors required.ResultsFifty-six patients were recruited to each group, but two in Group P were excluded from the analysis owing to protocol violations. There were no significant differences between the groups in maternal systolic, diastolic or mean arterial pressures, or the proportion of patients experiencing hypotension. The proportion of patients in Group E requiring intraoperative ephedrine or any vasoconstrictor (ephedrine and/or norepinephrine) was significantly lower than that in Group P (P=0.023 and 0.034, respectively). The proportion of patients in Group O requiring intraoperative norepinephrine was significantly lower than that in Group P (P=0.02). There was no difference in the proportions of patients in Groups E and O requiring any vasoconstrictors (P=0.34).ConclusionsThere was no significant difference in maternal blood pressure in women administered prophylactic ephedrine or ondansetron after spinal anesthesia for cesarean delivery compared with placebo. Ephedrine reduced the proportion of patients requiring a rescue vasoconstrictor before delivery.     

Evidence thatm-chlorophenylpiperazine-induced hyperthermia in rats is mediated by stimulation of 5-HT2C receptors

Intraperitoneal administration ofm-chlorophenylpiperazine (m-CPP) to Wistar rats produced hyperthermia with a peak effect at 30 min. Pretreatment with low doses of metergoline (5-HT₁/5-HT₂ antagonist), mesulergine and mianserin (5-HT_2C/5-HT_2A antagonists) blockedm-CPP-induced hyperthermia. Pretreatment with propranolol (-adrenergic receptor antagonist that also has binding affinity for 5-HT_1A, 5-HT_1B and 5-HT_2B sites), yohimbine (₂-noradrenergic antagonist that also has binding affinity for 5-HT_2B sites), MDL-72222 or ondansetron (5-HT₃ antagonists) did not attenuatem-CPP-induced hyperthermia. Only high doses of ketanserin, LY-53857 and ritanserin (5-HT_2A/5-HT_2C antagonists) as well as spiperone (5-HT_1A/5-HT_2A/D₂ antagonist) attenuatedm-CPP-induced hyperthermia. Daily administration ofm-CPP produced complete tolerance to its hyperthermic effect by day 5. However, there was no cross-tolerance to 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT_2A agonist that also has high affinity for 5-HT_2C receptors)-induced hyperthermia.m-CPP-induced increases in temperature were found to be significantly less in the Fawn-Hooded (FH) rat strain as compared to the Wistar rat strain; in prior studies, FH rats have been found to be subsensitive to other 5-HT_2C-mediated pharmacologic responses. Altogether, these findings suggest thatm-CPP-induced hyperthermia in rats is mediated by selective stimulation of 5-HT_2C receptors.     

Efficacy of evidence-based institutional protocol for prevention of postoperative nausea and vomiting: A prospective observational study

BackgroundPostoperative nausea and vomiting (PONV) is the second most common complaint in the postoperative period, often resulting in increased post anaesthesia care unit (PACU) and hospital stay. Translation of knowledge into consistent practice was considered a major gap. Hence, the present study was undertaken to test the efficacy of locally developed evidence-based institutional protocol for prevention of PONV.MethodsPhase I consisted of determining the baseline incidence of PONV before introduction of the institutional protocol for PONV prophylaxis. In phase II, educational sessions for anaesthesiologists for PONV prevention and treatment were conducted, after which an institutional protocol was introduced. In phase III, this protocol was implemented, and the incidence of PONV was recorded using the same methodology as in phase I. The rate of adherence to the institutional protocol was also recorded.ResultsThe incidence of postoperative nausea (PON) dropped significantly from 32.5% in phase I to 20% in phase III (p = 0.033). Similarly, the incidence of postoperative vomiting (POV) decreased from 20.5% in phase I to 9.1% in phase III (p = 0.016). Of all anaesthesiologists, 78.18% were noted to adhere to the protocol in phase III. Incidence of PON and POV was significantly less in patients in whom PONV prophylaxis was administered in adherence to protocol (8.3% vs 57.7%, p < 0.001; 3.6% vs 26.9%, p < 0.001, respectively).ConclusionEvidence-based institutional protocols are effective in significantly reducing the incidence of PONV in adults undergoing noncardiac surgery under anaesthesia.Clinical trial number and registry URLThe trial was registered with Clinical Trials Registry of India (http:/ctri.nic.in) (CTRI/2015/12/006432).     

Prediction of serotonergic treatment efficacy using age of onset and Type A/B typologies of alcoholism

Background: Previously, we reported that ondansetron was efficacious at treating early‐onset (≤25‐years old) but not late‐onset (≥26‐years old) alcoholics in a double‐blind, randomized, placebo‐controlled clinical trial (n = 321 enrolled patients, 271 of them randomized). Randomized participants underwent 11 weeks of treatment with ondansetron (1, 4, or 16 μg/kg twice daily; n = 67, 77, and 71, respectively) or identical placebo (n = 56), plus weekly standardized group cognitive behavioral therapy. Methods: For this study, we reanalyzed the original sample to determine whether the Type A/B typological classification predicts ondansetron treatment response. In this comparative analysis, k‐means clustering was applied to 19 baseline measures of drinking behavior, psychopathology, and social functioning, similar to those used by Babor in the original typological derivation. A 2‐factor solution described robustly 2 groups phenomenologically consistent with Type A/B classification. Subjects were subdivided into early‐ and late‐onset alcoholics. Results: Seventy‐two percent of Type B subjects had early‐onset alcoholism (EOA); 67% of Type A subjects had late‐onset alcoholism (LOA). The A/B typology better discriminated 2 clusters based upon baseline severity of alcoholism. There was a significant effect (p < 0.05) for Type B alcoholics to respond to ondansetron (4 μg/kg); however, Type A alcoholics receiving ondansetron showed no beneficial effect. Early‐onset vs. late‐onset classification predicted ondansetron response substantially better than Type A/B classification, which did not add to the prediction of treatment outcome. Further analyses showed that ondansetron was effective in the 33% of Type A alcoholics with EOA but ineffective in the 28% of Type B alcoholics with LOA. Conclusions: Type A/B classification best discriminates alcoholic subtypes based upon baseline severity. Early‐ vs. late‐onset classification is, however, a better predictor of response to ondansetron treatment because it might be more closely related to fundamental neurobiological processes associated with the underlying pathophysiology of alcoholism.     

Acute and anticipatory emesis in breast cancer patients

A group of 90 breast cancer patients undergoing chemotherapy were assessed prospectively to estimate the prevalence of acute (post-treatment) and anticipatory emesis in the 1990s. For this purpose, two protocols of chemotherapy were analysed separately: cyclophosphamide/methotrexate/5-fluorouracil (CMF) and 5-fluorouracil/doxorubicin/cyclophosphamide (FAC). All patients were treated with antiemetic therapy, which included one corticoid plus ondansetron (in the FAC regimen), or one corticoid plus thiethylperazine (in the CMF regimen). For at least one cycle of chemotherapy 86.1% and 91.7% patients in the FAC protocol presented vomiting and nausea respectively; 11.1% had anticipatory vomiting and 30.6% had anticipatory nausea. In the CMF protocol, 79.6% had post-chemotherapy vomiting and 71.7% had post-chemotherapy nausea associated with at least one cycle. In this group, 7.4% had anticipatory vomiting and 16.6% had anticipatory nausea. A high proportion of patients suffered anticipatory anxiety in both groups (75% in FAC, 74.1% in CMF). The stimuli most frequently associated with the appearance of anticipatory emesis were olfactory stimuli and cognitive stimuli. In summary, as a result of the advances made in antiemetic control during the last decade, the severity of chemotherapy-induced emesis seems to have significantly decreased, but the prevalence of these symptoms along the course of the treatment still remains high.