Randomized controlled trial of hemostatic powder versus endoscopic clipping for non-variceal upper gastrointestinal bleeding.

BACKGROUND AND AIMS: Despite advances in pharmacological and endoscopic management of non-variceal upper gastrointestinal bleeding (NVUGIB), mortality is still relevant. TC-325 (Hemospray-Cook Medical) is a mineral powder with adsorptive properties, designed for endoscopic hemostasis. There are still no comparative trials studying this new hemostatic modality. The objective of this research was to compare the use of TC-325 (associated with epinephrine injection) with the combined technique of endoscopic clipping and epinephrine injection for the treatment of patients with NVUGIB. METHODS: We conducted a pilot randomized controlled trial with patients that presented NVUGIB with an actively bleeding lesion at the endoscopic evaluation. Patients were randomized either to the Hemospray or Hemoclip group. The randomization list was generated by a computer program and remained unknown throughout the entire trial. All patients underwent second-look endoscopy. RESULTS: Thirty-nine patients were enrolled. Peptic ulcer was the most frequent etiology. Primary hemostasis was achieved in all Hemospray cases and in 90% of Hemoclip group (p = 0.487). Five patients in Hemospray group underwent an additional hemostatic procedure during second-look endoscopy, while no patient in the Hemoclip group needed it (p = 0.04). Rebleeding, emergency surgery and mortality rates were similar in both groups. No toxicity, allergy events, or gastrointestinal obstruction signs were observed in Hemospray group. CONCLUSIONS: TC-325 presents similar hemostatic results when compared with conventional dual therapy for patients with NVUGIB. Hemospray's excellent primary hemostasis rate certifies it as a valuable tool in arduous situations of severe bleeding or difficult location site.

Are higher doses of proton pump inhibitors better in acute peptic bleeding? / ¿Vale la pena utilizar dosis altas de inhibidores de la bomba de protones en la hemorragia péptica aguda?

Although there is broad consensus about the benefits of proton pump inhibitors in acute upper peptic bleeding, there is still controversy over their optimal dosing. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 27 randomized trials addressing this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded high-dose proton pump inhibitors probably result in little or no difference in re-bleeding rate or mortality. The risk/benefit and cost/benefit balance probably favor use of low-doses.

Si bien existe consenso acerca de la utilidad de los inhibidores de la bomba de protones en la hemorragia digestiva péptica aguda, persiste la controversia sobre cuál es la dosis óptima. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen 27 estudios aleatorizados evaluando esta pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que las dosis altas de inhibidores de la bomba de protones probablemente resultan en poca o nula diferencia en el riesgo de resangrado y mortalidad. El balance riesgo/beneficio y costo/beneficio son probablemente desfavorables a la utilización de dosis altas.

Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: Peptic ulcer represents the most common cause of upper gastrointestinal bleeding. Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this review is to compare the different modalities of endoscopic therapy. METHODS: Studies were identified by searching electronic databases MEDLINE, Embase, Cochrane, LILACS, DARE, and CINAHL. We selected randomized clinical trials that assessed contemporary endoscopic hemostatic techniques. The outcomes evaluated were: initial hemostasis, rebleeding rate, need for surgery, and mortality. The possibility of publication bias was evaluated by funnel plots. An additional analysis was made, including only the higher-quality trials. RESULTS: Twenty-eight trials involving 2988 patients were evaluated. Injection therapy alone was inferior to injection therapy with hemoclip and with thermal coagulation when evaluating rebleeding and the need for emergency surgery. Hemoclip was superior to injection therapy in terms of rebleeding; there were no statistically significant differences between hemoclip alone and hemoclip with injection therapy. There was considerable heterogeneity in the comparisons between hemoclip and thermal coagulation. There were no statistically significant differences between thermal coagulation and injection therapy, though their combination was superior, in terms of rebleeding, to thermal coagulation alone. CONCLUSIONS: Injection therapy should not be used alone. Hemoclip is superior to injection therapy, and combining hemoclip with an injectate does not improve hemostatic efficacy above hemoclip alone. Thermal coagulation has similar efficacy as injection therapy; combining these appears to be superior to thermal coagulation alone. Therefore, we recommend the application of hemoclips or the combined use of injection therapy with thermal coagulation for the treatment of peptic ulcer bleeding.

Role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage in rats.

BACKGROUND AND PURPOSE: Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage. EXPERIMENTAL APPROACH: Rats were treated with L-NAME (1 or 3 mg kg(-1), i.p.) or with L-arginine (200 mg kg(-1), i.p.) + L-NAME (3 mg kg(-1), i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg(-1), i.p.), glibenclamide (0.1, 0.3, 1 or 3 mg kg(-1), i.p.) or with glibenclamide (1 mg kg(-1), i.p.) + diazoxide (3 mg kg(-1), i.p.). After thirty minutes, the rats received sildenafil (1 mg kg(-1), by gavage), followed by intragastric instillation of absolute ethanol (4 ml kg(-1)) to induce gastric damage. One hour later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a planimetry programme. Samples of stomach were also taken for histopathological assessment and for assays of tissue glutathione and haemoglobin. KEY RESULTS: Sildenafil significantly reduced ethanol-induced gastric damage in rats. L-NAME alone, without L-arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol-induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil. CONCLUSIONS: Sildenafil had a protective effect against ethanol-induced gastric damage through the activation of the NO/cGMP/K(ATP) pathway.

[Predictors of operative treatment in patients sustaining bleeding peptic ulcers]. / Fatores preditivos do tratamento operatório na úlcera péptica hemorrágica.

OBJECTIVE: To analyze the predictors of operative treatment in patients sustaining bleeding peptic ulcers. METHODS: Retrospective analysis of the patients admitted owing to bleeding peptic ulcers from 1998 to 2001. Vital signs upon admission, associated diseases, endoscopy data, evolution and definitive care were evaluated. Patients who underwent surgery were compared with the others in order to identify the predictors of the operative treatment. Student's t and chi squared test were employed for statistical analysis, considering p< 0,05 as significant. RESULTS: Two hundred patients were included in the study group. The age ranged between 17 and 97 years (mean 52 + 18), and 153 patients (76.5%) were male. Shock upon admission was present in 27 (13.5%). The endoscopic exam performed at admission showed that 101 patients sustained ulcers in the duodenum and 99 in the stomach, which were classified as Forrest Ia in 5 (2.5%), Ib in 20 (10%), IIa in 48 (24%) and IIb in 48 (24%). Twenty five (12.5%) patients needed operation, and 23 (92%) were submitted to gastrectomy with Billroth's II reconstruction. The operative treatment were more frequently performed in patients sustaining chronic alcoholic intake (p=0.002), cigarette smoking (p=0.02), diabetes mellitus (p=0.01), chronic peptic disease (p=0.05), shock upon admission (p<0.001) and spurting activity at the endoscopy (p<0.001). Forrest IIb lesions which did not receive any form of endoscopic treatment at admission were more likely to rebleed (p=0.012). CONCLUSIONS: The predictors of operative treatment were chronic alcoholic intake, smoke addiction, diabetes mellitus, chronic peptic disease, shock upon admission and Forrest Ia ulcers.