Elsevier

The Lancet

Volume 350, Issue 9079, 6 September 1997, Pages 692-696
The Lancet

Articles
Randomised trial of single and repeated fibrin glue compared with injection of polidocanol in treatment of bleeding peptic ulcer

https://doi.org/10.1016/S0140-6736(97)03233-9Get rights and content

Summary

Background

Although injection treatments for ulcer haemostasis seem to be effective, recurrent bleeding remains a serious problem. Large randomised clinical trials are required to show differences between treatment modalities for gastrointestinal bleeding. The aim of this study was to compare the safety and efficacy of repeated endoscopic injection of fibrin glue (FG) with that of single endoscopic injection of polidocanol in the prevention of recurrent bleeding.

Methods

854 patients with active gastroduodenal bleeding (spurting, oozing), or ulcers with a visible non-bleeding vessel, were randomly assigned one of three endoscopic treatments: single application of polidocanol 1%, single application of FG, or daily repeated application of FG until the visible vessel had disappeared. All patients were pretreated with local injection of epinephrine (1/10000), and had daily repeat endoscopies until the vessel observed at initial endoscopy was no longer visible.

Findings

Recurrent bleeding rates among the 790 patients in whom the rates could be assessed were 58 (22·8%) of 254 in the polidocranol group, 51 (19·2%) of 266 in the FG-single group, and 41 (15·2%) of 270 in the FG-repeated group. The difference between FG-repeated treatment and polidocanol was significant (p=0·036). Treatment failed, making other treatments (including surgery) necessary, in 34 (13·0%) of 261 in the polidocanol group, 34 (12·4%) of 274 in the FG-single group, and 21 (7·7%) of 274 in the FG-repeated group. The difference between FG-repeated treatment and polidocanol was significant (p=0·046). The 30-day-mortality rates were low in all three treatment groups (polidocanol 4·7%, FG-single treatment 5·3%, FG-repeated treatment 4·3%), The safety profiles of the three treatment strategies were similar.

Interpretation

Repeated injection with FG glue is significantly more effective than injection with polidocanol 1% in the treatment of bleeding from gastroduodenal ulcers. Lancet 1997; 350: 692–96

Introduction

Upper gastrointestinal haemorrhage is a life-threatening emergency that occurs with an estimated annual incidence of 100 per 100000 people.1, 2 In about 60% of cases, the site of bleeding is a peptic ulcer.3, 4 Persistent or recurrent bleeding occurs in about 20% of these patients3, 4, 5 with a mortality rate of 11–14%.3, 6 Mortality and morbidity rates are higher in patients with spurting bleeding, oozing, or a non-bleeding visible vessel on endoscopy.7, 8, 9 These patients account for the majority of cases that require additional interventions and urgent surgery.10 In patients with persistent bleeding, the mortality rate is much higher.3, 4 Endoscopic therapy improves the outcome in patients with active bleeding from peptic ulcers, and in patients with non-bleeding visible vessels.11, 12 However, the number of patients enrolled in such studies is generally small, and whether any treatment modality is better than another is therefore not known.13 Of the endoscopic treatments, injection therapy is particularly attractive because it is easy to do, the equipment is cheap and widely available, and the intervention is effective.14

In Europe, the most widely used injection treatment for bleeding gastroduodenal ulcers entails infiltration with epinephrine followed by sclerotherapy with polidocanol 1%. 10–20% of patients in whom haemostasis occurs after injection of polidocanol, however, will experience further bleeding,15 and sclerotherapy has caused occasional gastric and duodenal infarction and other serious complications both in animal models16, 17 and in patients.18, 19, 20, 21, 22 Recurrent bleeding is especially common in patients with spurting arterial bleeding, and less common in those with oozing bleeding; for patients with non-bleeding visible vessels, the isk is intermediate. Endoscopic therapies reduce the frequency of recurrent bleeding but do not change this risk ratio.3, 12

At present, the optimum strategy for management of patients with recurrent bleeding from peptic ulcers is not known; despite several trials,23, 24, 25 physicians do not know whether repeat endoscopy or referral for surgery carries a better overall risk-benefit ratio in the event of rebleeding. The use of prophylactic retreatment after initial successful haemostasis is also controversial.26

Injection of fibrin glue (FG) into actively bleeding peptic ulcers is a new treatment modality that has been studied both as single-injection therapy,27, 28, 29 and as repeated-injection therapy.27, 30 The results have so far been encouraging,28, 29, 30, 31 especially those of prophylactic retreatment to prevent further bleeding from peptic ulcers that show persistent signs of fresh bleeding.27, 28, 29, 30, 31 FGcauses only limited tissue damage and can therefore be repeated; it also provides a natural matrix for wound healing, whereas sclerosants cause thrombosis, fibrosis, scarring, and necrosis,30 and are thus routinely used only for single treatment of acute and recurrent bleeding. A 1996 trial showed that injection therapy with epinephrine plus thrombin is more effective than epinephrine alone for haemostasis.32

We undertook a randomised trial to compare the safety and efficacy of repeated FG injection and of single endoscopic injection of polidocanol in the prevention of recurrent bleeding. Our hypothesis was that repeated FG would prove superior to single-injection of polidocanol.

Since any benefit from repeated FG treatment might result either from the superiority of FG over polidocanol, or from its repeated injection, a section with single-injection therapy of FG was added to the study. We did not aim to detect significant differences between FG-single and polidocanol-single therapy.

Section snippets

Design

This study was a randomised, stratified, open-label, multicentre trial preceded by a pilot study, which allowed physicians and endoscopy assistants to familiarise themselves with the technique of FG injection. Patients aged 18 years or older admitted to hospital with a bleeding gastroduodenal ulcer were classified prospectively at endoscopy according to the presence of spurting bleeding, oozing bleeding, or a non-bleeding visible vessel. They were randomly assigned to one of three treatment

Results

854 patients were enrolled in the study and randomly assigned treatment (figure 1). Four patients did not receive treatment for the initial bleeding. After randomisation, injection treatment turned out to be impossible. The three treatment groups were similar in their demographic and clinical characteristics (table 1). There were no clinically relevant differences at baseline for haemoglobin, blood pressure, and pulse, irrespective of treatment group or signs of initial bleeding.

Recurrent

Discussion

Our results show a clinically significant benefit from the use of FG as repeated application compared with the use of standard therapy with a sclerosing agent. The benefit is evident in recurrent bleeding rates and in other endpoints. In prospectively stratified subgroups, the significant benefit was shown in the group with non-bleeding visible vessels (p=0·025). For patients with the worst endoscopic appearance (spurting bleeding), we found a 90% chance of no rebleeding with repeated FG

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