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Therapeutics

Endoscopic injection reduced further bleeding and need for surgery in patients with bleeding duodenal ulcers

ACP J Club. 1992 Sept-Oct;117:39. doi:10.7326/ACPJC-1992-117-2-039

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Source Citation

Moretó M, Zabella M, Suárez MJ, et al. Endoscopic local injection of ethanolamine oleate and thrombin as an effective treatment for bleeding duodenal ulcer: a controlled trial. Gut. 1992 Apr;33:456-9.


Abstract

Objective

To determine whether endoscopic injection of thrombin and ethanolamine oleate is an effective treatment for adults with duodenal ulcers that are actively bleeding or have nonbleeding visible vessels.

Design

Randomized controlled trial completed before hospital discharge.

Setting

A university hospital in Spain.

Patients

All adults hospitalized with upper gastrointestinal hemorrhage had endoscopy within 16 hours of admission. Patients were included if they had received ≥ 3 units of blood and had a duodenal ulcer with active bleeding or a nonbleeding visible vessel. 6 patients were excluded: 5 had excessive bleeding in the duodenum or had duodenal deformity; 1 had a stroke. 38 patients were included (mean age, 56 y; 35 men).

Intervention

19 patients received injection therapy: 1 mL of 5% ethanolamine oleate alternating with 1 mL (10 U) of bovine thrombin in 4 to 5 sites around the vessel and then into the vessel itself. If bleeding continued, an additional dose of sclerosant was given. The mean volume of ethanolamine oleate used was 7.7 mL (range 4 to 15 mL). All patients with serious continuing bleeding received additional injection treatment. All patients received standard medical care including ranitidine and cimetidine, and they were followed by gastroenterologists who were blinded to injection status.

Main outcome measures

Rebleeding (hematemesis or melena, or both, with signs of shock or confirmative endoscopy, or both), need for surgery or transfusion, and death.

Main results

Bleeding continued in 3 patients (16%) in the injection group and 11 (58%) in the control group (P < 0.005). {This absolute risk reduction [ARR] of 42% means that 3 patients would need to be treated [NNT] with injection (rather than standard medical care) to prevent 1 additional patient from rebleeding 95% CI 2 to 8; the relative risk reduction (RRR) was 73%, CI 27% to 91%.}* No serious complications occurred. 1 patient in the injection group and 8 patients in the control group had emergency surgery (P < 0.05): {ARR 37%; NNT 3, CI 2 to 9; RRR 88%, CI 34% to 98%}.* Patients in the injection group required a mean of 1.9 units of blood and the control group needed a mean of 5.3 units after endoscopy (P < 0.002). After 1 week, 1 patient in the injection group (5%) and 11 in the control group (58%) had further bleeding (P < 0.005): {ARR 53%; NNT 2, CI 1 to 4; RRR 91%, CI 55% to 98%}.* The groups did not differ for death although both patients who died were in the control group.

Conclusion

Injection therapy using thrombin and ethanolamine oleate reduced further bleeding and the need for surgery in patients with bleeding duodenal ulcers or nonbleeding ulcers with visible vessels.

Source of funding: Not stated.

Address for article reprint: Dr. M. Moretó, Lertegui 14, Baja C, 48930-Getxo (Vizcaya), Spain.

*Numbers calculated from data in article.


Commentary

Endoscopic injection reduced rebleeding in bleeding peptic ulcers

The mortality rate from bleeding ulcers has remained stable over the last 30 years and ranges from 6% to 10% (1). Because no medical therapy is effective for the acute treatment of bleeding ulcers, nonsurgical means of controlling bleeding have been sought. Various endoscopic forms of hemostatic therapy that use heat to stop bleeding have been assessed. On the basis of several randomized trials, a 1989 National Institutes of Health Consensus Conference concluded that bipolar electrocoagulation and heater probe were the treatments of choice in patients with bleeding ulcers (1).

Recently, the use of injection therapy has been evaluated. A major attraction of injection therapy is its simplicity: An injection catheter is the only equipment required. A number of injection solutions (absolute alcohol, polidocanol, epinephrine [1:10 000], saline) have been used with success. At least 7 previous trials have shown some benefit of injection therapy when compared with standard management of patients with bleeding ulcers. The trials by Oxner and colleagues and Moretó and colleagues further support the use of injection therapy.

The clinical and endoscopic entry criteria must be examined carefully when assessing therapeutic trials for bleeding ulcers. Clinical evidence of major bleeding (e.g., hemodynamic instability, transfusions) increases the likelihood of further bleeding, surgery, and death (1). Endoscopic features provide even better prognostic information. Patients with active bleeding or nonbleeding visible vessels have much higher rates of further bleeding and need urgent intervention more often than those with clots, flat pigmented spots, or clean-based ulcers (2). Patients without high-risk features generally do well with standard management alone and should not be included in therapeutic trials. It should be noted that patients with high-risk features are in the minority: fewer than 20% of those suspected of gastrointestinal hemorrhage in the Oxner study.

The study by Oxner and colleagues had no specific clinical entry criteria other than suspected upper gastrointestinal hemorrhage, and only half the patients had hemodynamic instability. All patients had visible vessels, and 5% had spurting vessels (the highest risk endoscopic feature). Rebleeding was significantly decreased with injection therapy. Unfortunately, the authors treated rebleeding episodes in the control group with injection therapy so that the relative effect of treatment on the more important and less subjective parameters such as surgery, hospital days, and transfusions cannot be properly assessed.

As in most trials of endoscopic therapy, the 2 trials under discussion failed to show a significant decrease in mortality with treatment. This finding may relate to the relatively small size of the individual studies. Recent meta-analyses have shown a significant decrease in mortality, evident only in patients with active bleeding or non-bleeding visible vessels, providing further justification for the use of endoscopic therapy (3).

Most articles now suggest that endoscopic hemostatic therapy should be used in patients with bleeding ulcers who have clinical and endoscopic features predicting a high risk for further bleeding or death (1). At present, bipolar electrocoagulation, heater probe, and injection therapy can be considered comparable in safety and efficacy for the treatment of bleeding ulcers.

Loren Laine, MD
University of Southern California Medical CenterLos Angeles, California, USA


References

1. N.I.H. Consensus Conference. Therapeutic endoscopy and bleeding ulcers. JAMA. 1989;262:1369-72.

2. Laine L, Cohen H, Brodhead J, et al. Prospective evaluation of immediate versus delayed refeeding and prognostic value of endoscopy in patients with upper gastrointestinal hemorrhage. Gastroenterology. 1992;102:314-6.

3. Cook DJ, Guyatt GH, Salena BJ, Laine LA. Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Gastroenterology. 1992;102:139-48.