INTRODUCTION: Pharmacotherapy for upper gastrointestinal bleeding has been difficult to evaluate because clinical end points are infrequent and affected by other factors. AIMS: To evaluate whether blood in the stomach at endoscopy reflected severity of bleeding, predicted clinical outcomes, and could be altered by therapeutic agents. METHODS: We studied 414 consecutive admissions with suspected upper gastrointestinal bleeding. Patients were randomised to receive lansoprazole 60 mg followed by 30 mg four times daily, tranexamic acid 2 g followed by 1 g four times daily, both drugs, or placebo for four days, until discharge or a clinical end point occurred. Logistic regression analysis was used to determine predictors of endoscopic changes and clinical outcomes, and to investigate the effects of drug treatments on blood in the stomach. RESULTS: Of 414 patients with suspected upper gastrointestinal bleeding, 379 were endoscoped. Upper gastrointestinal bleeding was confirmed in 316. Sixteen required surgery within 30 days and 16 died on the index admission. Trial treatments were evaluable on a per protocol basis in 228 patients. The amount of blood in the stomach was found to reflect initial risk, with significant associations with high risk categorisation (odds ratio 3.7 (95% confidence interval 1.5-9.4) for more than a trace v none/trace), age (1.5 (1.1-1.9) per decade), and initial pulse (1.02 (1.00-1.04) per beat), and to predict rebleeding (9.2 (4.6-18.7)) and surgery (8.2 (2.9-22.9)). Other stigmata were less significant in these respects. The amount of blood in the stomach at endoscopy was reduced significantly by both lansoprazole (0.22 (0.07-0.63)) and tranexamic acid (0.27 (0.09-0.81)), although there was no evidence of synergy. CONCLUSIONS: Blood in the stomach reflects clinical features in patients with acute upper gastrointestinal bleeding and is reduced by treatment with lansoprazole and tranexamic acid.
In this prospective, randomized, double-blind study the effect of the antifibrinolytic drug tranexamic acid was compared with that of placebo in 154 patients bleeding from verified benign lesions in the stomach and/or duodenum. Three out of 72 patients receiving tranexamic acid underwent emergency surgery, in contrast to 15 out of 82 in the placebo group (p = 0.010). Nineteen patients receiving placebo rebled during admission, as compared with 10 in the treatment group (p = 0.097). The blood transfusion requirement was significantly reduced by tranexamic acid (p = 0.018). Side effects were seen in six patients, of which an uncomplicated deep venous thrombosis was the most severe. It was concluded that tranexamic acid reduces the blood transfusion requirement and the need for emergency surgery in patients bleeding from a benign gastric or duodenal lesion.
A prospective randomised double blind study examined the effect of the antifibrinolytic drug tranexamic acid compared with placebo in 154 patients bleeding from verified benign lesions in the stomach or duodenum or both. Three out of 72 patients receiving tranexamic acid underwent emergency surgery compared with 15 out of 82 given placebo (p = 0.010). Nineteen patients receiving placebo rebled during their admission as compared with 10 in the active treatment group (p = 0.097). Blood transfusion requirements were significantly reduced by tranexamic acid (p = 0.018). Side effects occurred in six patients, of which an uncomplicated deep venous thrombosis was the most severe. Tranexamic acid reduces the blood transfusion requirement and need for emergency surgery in patients bleeding from a benign gastric or duodenal lesion.
We studied the effects of tranexamic acid (an antifibrinolytic agent) and cimetidine on acute upper-gastrointestinal-tract bleeding in a double-blind randomized placebo-controlled trial in 775 patients with hematemesis or melena or both. Mortality was significantly reduced in patients receiving either tranexamic acid (mortality, 6.3 per cent) or cimetidine (7.7 per cent), as compared with patients receiving placebo (13.5 per cent) (P = 0.0092 for tranexamic acid vs. placebo, P = 0.045 for cimetidine vs. placebo). Ninety-nine patients were withdrawn before the code was broken, mainly because their primary illness was considered not to be due to acute upper-gastrointestinal-tract bleeding. Mortality among those withdrawn was high (22 per cent), and their exclusion reduced death rates to 4 per cent in those given tranexamic acid, 8 per cent in those given cimetidine, and 11 per cent in those given placebo (P = 0.0072 for tranexamic acid vs. placebo, P greater than 0.50 for cimetidine vs. placebo). The reduced mortality associated with tranexamic acid was detectable at both participating hospitals and in most of the main subgroups of patients classified according to site of bleeding. However, treatment with this agent was not associated with any decrease in the rate of rebleeding or the need for operation.
The effect or oral tranexamic acid on massive upper gastrointestinal hemorrhage was evaluated in a randomized double-blind study. Totally 50 patients entered the trial and seven were excluded, leaving 22 placebo treated and 21 tranexamic acid treated for analysis. The groups were comparable regarding sex, age, diagnosis, and initial laboratory data. Transfusions requirements and operation frequency did not differ. Mortality was slightly reduced and death delayed in tranexamic acid treated patients.
In a double-blind trial of tranexamic acid in massive upper gastrointestinal haemorrhage, 76 patients were treated with the active drug and 73 patients with placebo. The doses were 1 g intravenously six times daily for a maximum of 3 days, followed by 1.5 g orally four times daily for a maximum of 4 days. The treatment group and the placebo group were comparable with respect to mean age, diagnoses and laboratory tests but differed slightly with respect to sex and alcohol consumption. The transfusion requirement in the treatment group was less than in the placebo group during the first days after admission, the difference being significant on the second day after admission. Ten patients in the treatment group and 18 patients in the placebo group were operated on. Eleven patients in the treatment group and 12 patients in the placebo group died. In the tranexamic-acid-treated group fewer operations were performed and significantly less blood was needed. It therefore seems highly likely that tranexamic acid has a beneficial effect, although small.
The efficacy of antifibrinolytic therapy in the management of acute upper gastrointestinal haemorrhage has been investigated in a double-blind clinical trial. Two-hundred patients were studied using tranexamic acid, a potent antifibrinolytic agent. Of these, 103 were in the treatment group and 97 in the control group. Patients were analysed to determine severity of initial blood loss, transfusion requirements, together with the incidence of recurrent bleeding, surgical intervention, and death. Final diagnosis as to the site of bleeding was arrived at using endoscopy, barium studies, and the findings at operation and necropsy. The groups were well matched as regards severity of initial haemorrhage, age, sex, aetiological diagnosis, and precipitating factors. A significant difference was observed in the requirement for surgical intervention to control continuing or recurrent haemorrhage. Twenty-three of 97 in the control group and seven of 103 in the treatment group required surgery. There appeared to be a reduction in the transfusion rate after the first three days of hospitalization in the treatment group. There were no significant differences in mortality or in side-effects between the two groups.
