Combination of midazolam and flumazenil in upper gastrointestinal endoscopy, a doubleblind randomized study

We evaluated the clinical usefulness of flumazenil (formerly Ro15-1788), a benzodiazepine antagonist, in combination with midazolam in upper gastrointestinal endoscopy. Thirty outpatients were randomized into two groups: those receiving flumazenil and those receiving placebo after endoscopy. For sedation, only midazolam was used. Performances pre-sedation and post-sedation (at 30 and 60 min) were analyzed using the Trieger test, Number Connection test, and Digit Symbol test. Patients receiving flumazenil were fully alert and able to ambulate 5 min after injection with this medication. Performances at 30 min in the Trieger, Number Connection, and Digit Symbol tests were significantly better in the group receiving flumazenil, p less than 0.005, p less than 0.025, and p less than 0.01, respectively. No phlebitis, nausea, vomiting, or anxiety were noted. No resedation events were documented. We conclude that flumazenil can dramatically shorten the recovery period following sedation with midazolam in upper gastrointestinal endoscopy, and its use is not associated with major side effects.     

The effect of the benzodiazepine antagonist flumazenil on the sequels of diazepam given before upper gastrointestinal endoscopy. A double-blind randomized trial

The prolonged sedation of benzodiazepines may be inconvenient for the patient. Reversal of sedation, therefore, would be desirable. Accordingly, we assessed the efficacy of the benzodiazepine antagonist flumazenil in a placebo-controlled randomized trial including 40 adults undergoing upper gastrointestinal endoscopy under diazepam (Diazemuls) sedation. We found no significant differences between groups with regard to either performance (two tests) or duration (within 240 min) of sedation. There were no noticeable side effects.     

上消化道胶囊内镜发展与创新北大核心CSCD

上消化道疾病高发,传统插管式胃镜是检查上消化道疾病最常用的检查方法和"金标准"。为了更舒适无创的检查上消化道黏膜,多项研究提出了上消化道胶囊内镜的概念,但是由于上消化道各部位解剖与生理结构的差异,目前可以使用的胶囊内镜如单纯被动式、磁控式、线控式、磁控联合线控式以及侧视胶囊内镜都存在一定的局限性,无法实现对上消化道整体黏膜情况的观察。文章试图通过介绍适用于食管、胃以及十二指肠检测的胶囊内镜,分析各内镜的诊断效能及其不足,探讨未来上消化道胶囊内镜可能的发展方向。     

老年人上消化道癌393例临床、内镜及病理分析

目的探讨老年人上消化道癌的早期诊断、早期治疗。方法对内镜检查确诊老年人上消化道癌３９３例,就其临床、内镜及病理检查进行分析。结果老年人上消化道癌发病率最高是胃癌,其次为食道及贲门,十二指肠癌少见。临床症状主要是上腹部及胃部疼痛,缺少特异性。癌发生部位则以胃体癌多见,胃窦部癌少于青年人,老年男性多于女性,与青年人相反,两者之间有显著差异（Ｐ＜０．０１）。内镜下则以Ｂｏｒｍａｎｎ型分类Ⅱ～Ⅲ型为多,病理是以腺癌为主,其次为鳞状细胞癌和印戒细胞癌。结论内镜与病理诊断符合率为９４．６６％。     

OMOM胶囊内镜在胃肠道疾病诊治中的应用

目的评价胶囊内镜对胃肠道疾病的诊断价值。方法对24例诊断不明的胃肠道疾病患者进行胶囊内镜检查。结果24例患者检查过程中均无任何不适。共检出病变19例，包括糜烂性胃炎2例，十二指肠炎2例，克罗恩病5例，小肠血管畸形7例，小肠息肉1例，小肠黏膜下占位1例（手术及病理证实为小肠肿瘤），升结肠憩室1例。余未见异常。阳性检出率79．2％。结论胶囊内镜检查操作简单、安全、有效，对消化道疾病尤其是小肠疾病有较高的诊断价值。     

Intravenous midazolam sedation in pediatric diagnostic upper digestive endoscopy. A prospective study in a general hospital

The positive role of benzodiazepines (Midazolam) in conscious sedation in pediatric patients is widely known. However, problems concerning the role of sedation in diagnostic upper endoscopy are a matter for debate as little is known about dosage and timing. We prospectively evaluated the efficacy, safety and optimal intravenous sedation dosage of midazolam in 257 consecutive patients, aged 2 months to 18 years old, who underwent upper endoscopy of the gastrointestinal tract. The initial midazolam dosage was 0.2 mg/kg Bw (Body weight) i.v. for 1 minute and, if necessary, another 0.1 mg/kg Bw was administered 5 minutes later. If sedation was sufficient, the procedure would be started 4-5 minutes later; if not, another 0.1 - 0.2 mg/kg Bw would be administered. All procedures were performed by a pediatrician together with a gastroenterologist. No serious complications occurred in any of the procedures. Oxygen saturation (OS) was maintained at over 90%, if necessary with blowby oxygen. Flumazenil was administered to 7 children (OS < 90%). Endoscopy could not be completed in 1 child. All endoscopies were completed within 10 minutes. No unexpected hospital admissions were necessary. The mean midazolam dosage was 0.4 mg/kg Bw in patients up to 6 years, for the over 6 years-olds the mean dosage was decreased to 0,2 mg/kg Bw. Particular attention was paid to the importance of informing patients before the procedure. Endoscopic diagnostic procedures can be performed safely and effectively in children with intravenous sedation in a well equipped pediatric endoscopy unit.     

Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans

If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible to induce ameliorations of the syndrome by pharmacologically antagonizing a component of the GABA/benzodiazepine receptor complex. To test this possibility we administered the benzodiazepine receptor antagonist flumazenil by intravenous injection to 14 patients with hepatic encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements of the mental status in 71% of the patients. The degree of encephalopathy improved from stage IV to stage II in 4 patients and from stage IV to stage III in 2 patients. The mental status of all patients with less advanced encephalopathy (3 with stage III, 1 with stage II) also improved, but these responses were clinically less impressive. The arousal effect occurred within minutes after the injection and lasted for 1 to 2 h. Furthermore, it was associated with a significant increase of the mean electroencephalographic frequency from 4.2 to 5.2 cycle/s. Of the 8 patients who were ultimately discharged from the hospital, 7 had responded to flumazenil. No patient who died within 48 h of receiving flumazenil had shown any arousal effect. These findings strongly favor a prominent pathogenetic role of increased GABAergic tone in hepatic encephalopathy in humans and suggest that a positive response to flumazenil might be of prognostic value in predicting short-term survival in encephalopathic patients with liver disease.     

Clinical significance of changes of flora in the upper digestive tract

Summary Dysbiosis does not necessarily mean disease. Typical clinical picture of disease caused by metabolic activity of dysbiotic microflora is the microbial over-growth syndrome. We studied case histories of 434 patients without consideration of their basic illnesses and correlated them with types of dysbioses of duodenal juice. 55% of 314 patients with gastrointestinal disorders revealed a dysbiosis. A dysbiosis could also be found in up to 64% of pancreatic diseases, whereas intestinal dysfunctions and chronic inflammatory diseases usually show normal colonization. These cases express alteration of milieu conditions and disturbed interorganic connections. We only treated cases with objective pathological findings, obtaining best results with chemotherapeutic treatment of dysbioses with only one species.

---

Klinische Bedeutung veränderter Darmflora im oberen Intestinaltrakt

Zusammenfassung Dysbiosis bedeutet nicht unbedingt Erkrankung. Typisches klinisches Bild von Krankheiten bei metabolischer Aktivität einer dysbiotischen Mikroflora ist das mikrobielle Overgrowth-Syndrom. Wir werteten die Anamnesen von 434 Patienten ohne Rücksicht auf ihre Grunderkrankung aus und suchten Korrelate mit den Dysbiosetypen des Duodenalsaftes. 55% von 314 Patienten mit gastrointestinalen Erkrankungen zeigten eine Dysbiosis. Diese konnte auch in bis zu 64% der Erkrankungen des Pankreas gefunden werden, während intestinale Störungen und chronisch-entzündliche Erkrankungen meist eine normale Besiedlung aufwiesen. Diese Fälle deuten auf eine Änderung des Milieus und auf gestörte zwischenorganische Verbindungen hin. Nur Fälle mit objektiven pathologischen Befunden werden behandelt. Die besten chemotherapeutischen Erfolge erzielten wir bei der Behandlung der Dysbiosis mit nur einer Spezies.

---

---

Supporting companies: Bayer AG, Leverkusen, Becton Dickinson GmbH, Heidelberg, Boehringer Mannheim GmbH, Mannheim, Hoechst AG, Frankfurt, Hoffmann-La Roche AG, Grenzach-Wyhlen, Pfizer GmbH, Karlsruhe, Shionogi & Co., Düsseldorf.     

Comparison between the two systems to evaluate the appropriateness of endoscopy of the upper digestive tract

OBJECTIVES: The aim of this study was to compare the diagnostic performance of the two systems for the evaluation of the appropriateness of upper digestive endoscopy suggested by the American Society of Gastrointestinal Endoscopy (ASGE) and by the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE). METHODS: Patients referred for the upper digestive endoscopy (EGD) to a University Outpatients Clinic of Northeastern Italy were consecutively included in this prospective observational study. Before the EGD, the endoscopist assigned the patients to one of the ASGE appropriateness classes; another endoscopist then identified the detailed clinical scenario for the patients, which corresponds to scenarios examined by EPAGE by using a nine-point scale: 1-3 inappropriate; 4-6 uncertain; and 7-9 appropriate. The relationship between the appropriateness of use and the presence of relevant endoscopic lesions (neoplasms, ulcers, esophagitis, erosive gastritis/duodenitis, stenosis, and varices) was assessed, calculating the sensitivity and the specificity for each of the ASGE criteria, and each of the EPAGE scores, and plotting them to form a receiver operating characteristic (ROC) curve. The area under the ROC curve (AUC) provides a summary measure of test performance, and can vary from a minimum of 0.5 to a maximum of 1.0. We compared the AUC of the ROC curve derived from the ASGE criteria against that derived from the EPAGE criteria. RESULTS: A total of 2,300 consecutive patients were included in the study (42% men; mean age: 57.3; range: 12-99); comparison of appropriateness criteria according to the ASGE and EPAGE could be made for 2,000 patients. The AUC of the ROC curve derived from the ASGE criteria was 0.553 (95% CI: 0.527-0.579), significantly higher than the AUC of the ROC curve derived from the EPAGE score: 0.523 (95% CI: 0.497-0.549; p < 0.05). CONCLUSIONS: We suggest that the diagnostic yield for relevant endoscopic findings obtained by both the systems (ASGE and EPAGE) is low; slightly better results could be accomplished by the ASGE criteria.     

Paradoxical reaction to midazolam in patients undergoing endoscopy under sedation: Incidence,risk factors and the effect of flumazenil

BackgroundThe incidence, risk factors and management strategy of paradoxical reaction to midazolam during endoscopy are yet to be clarified.MethodsThis single center prospective study included 4140 adult patients (2263 males, mean age of 57.7 ± 12.6) undergoing endoscopy under sedation with midazolam and pethidine between September 2011 and December 2011. The characteristics of patients with and without paradoxical reaction were compared. For patients who experienced paradoxical reaction and received flumazenil, their endoscopic images were reviewed to assess whether European Society of Gastrointestinal Endoscopy guidelines were met as quality indicator of endoscopy.ResultsThe incidence of paradoxical reaction was 1.4%. In multivariate analyses, male gender, unsuccessful sedation in previous endoscopy, upper endoscopy, higher dose of midazolam, and lower dose of pethidine were identified as independent risk factors for paradoxical reaction. Despite paradoxical reaction, endoscopic procedures were successfully completed in 93.3% of cases when flumazenil was administered. The rates of meeting quality indicator of endoscopy were 92.3% in patients receiving flumazenil for paradoxical reaction and 97.6% in patients without paradoxical reaction.ConclusionsFor patients with risk factors for paradoxical reaction, active use of pethidine with a dose reduction of midazolam might be helpful to prevent the occurrence of paradoxical reaction. Administration of flumazenil might be positively considered in cases of paradoxical reaction.     

消化内镜技术在消化道黏膜病变中的应用和进展

内镜是消化道疾病常用的的检查方法，传统的白光内镜对黏膜病变的发现存在局限性，容易漏诊、误诊，先进的内镜技术则有利于提高病灶与周围黏膜的视觉效果，使黏膜表面及微血管的细小变化更容易被发现，本文就胃镜技术在上消化道黏膜病变中的临床诊断应用进行综述。     

善得定治疗癌性上消化道出血临床观察

目的为观察善得定治疗恶性肿瘤所致上消化道出血的疗效及副作用方法选用恶性肿瘤所致上消化道出血６６例，随机分为善得定治疗组和垂体后叶素对照组，治疗组病人先用善得定０１ｍｇ＋０．９％ＮＳ２０ｍｌ静推，后用善得定以每小时２５微克滴速静滴维持２４～４８小时，对照组用垂体后叶素以每小时２～５Ｕ滴速静滴维持２４～４８小时，同时给硝酸甘油０．５ｍｇ吞下含服。结果治疗组总有效率为８８２３％（３０／３４），对照组总有效率为６２５０％（２０／３２），两组差异有显著意义（Ｐ＜００５），治疗组每例平均输血量为７００８０±３２７１８ｍｌ，对照组输血量平均每例为１１７６００±３２４１２ｍｌ，两组差异显著（Ｐ＜０００１）。两组均无严重副作用。结论癌性上消化道出血是晚期肿瘤常见并发症及致死原因之一，善得定较传统的垂体后叶素治疗具有止血快、止血率高，副作用少等优点，且可减少输血量，值得临床广泛推广使用。     

Preoperative evaluation of chronic alcoholics assessed for surgery of the upper digestive tract

BACKGROUND: Alcoholics are at risk of developing major complications in the postoperative period. Adequate prophylactic treatment, as well as preoperative abstinence, can significantly decrease the rate of complications. However, the preoperative diagnosis of alcoholism is difficult to establish. The purpose of this study was to assess whether three preoperative visits, an alcohol-related questionnaire (CAGE), and the laboratory markers carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) would increase the rate of detection of chronic alcoholics. METHODS: The study included the Departments of ENT, Facial and Maxillofacial Surgery, and General Surgery of a university hospital; 705 male patients were assessed for tumor surgery of the upper digestive tract and were allocated to 5 different groups. All patients were seen three times, and five different strategies were used to detect chronic alcoholics. The gold standard was the diagnosis of alcohol misuse made by an experienced (blinded) investigator according to the DSM-III-R. The main outcome measurements were the detection rates of the different test strategies. RESULTS: By clinical routine alone, only 16% were detected during the first visit and 34% after three visits. If the CAGE questionnaire was added, sensitivity increased to 64%. The further addition of GGT or CDT led to 80 and 85% detections, respectively. A combination of all tests had a sensitivity of 91%. CONCLUSIONS: To detect more alcoholic patients at risk for major complications, patients should be seen more often, and additional diagnostic tools such as the CAGE, CDT, and GGT should be used before surgery.