ACID-SUPPRESSION HELPS ULCERS HEAL
Acid and pepsin interfere with the healing of ulcers and other nonvariceal upper GI lesions. Further, an acidic environment promotes platelet disaggregation and fibrinolysis and impairs clot formation.16 This suggests that inhibiting gastric acid secretion and raising the gastric pH to 6 or higher may stabilize clots. Moreover, pepsinogen in the stomach is converted to its active form (pepsin) if the pH is less than 4. Therefore, keeping the pH above 4 keeps pepsinogen in an inactive form.
Histamine-2 receptor antagonists
Histamine-2 receptor antagonists were the first drugs to inhibit acid secretion, reversibly blocking histamine-2 receptors on the basolateral membrane of parietal cells. However, these drugs did not prove very useful in managing upper GI bleeding in clinical trials.17,18 In their intravenous form, they often fail to keep the gastric pH at 6 or higher, due to tachyphylaxis.19 The use of this class of drugs has declined in favor of proton pump inhibitors.
Proton pump inhibitors
Proton pump inhibitors reduce both basal and stimulated acid secretion by inhibiting hydrogen-potassium adenosine triphosphatase, the proton pump of the parietal cell.
Multiple studies have shown that proton pump inhibitors raise the gastric pH and keep it high. For example, an infusion of omeprazole (Prilosec) can keep the gastric pH above 6 for 72 hours without inducing tachyphylaxis.20,21
Started after endoscopy. Randomized controlled trials have found proton pump inhibitors to be effective when given in high doses intravenously for 72 hours after successful endoscopic treatment of bleeding ulcers with high-risk endoscopic signs, such as active bleeding or nonbleeding visible vessels.22,23
A meta-analysis indicated that these drugs decrease the incidence of recurrent peptic ulcer bleeding, the need for blood transfusions, the need for surgery, and the duration of hospitalization, but not the mortality rate.24,25 These studies also illustrate the benefit of following up endoscopic treatment to stop the bleeding with an intravenous infusion of a proton pump inhibitor.
The recommended dose of omeprazole for patients with high-risk findings on endoscopy is an 80-mg bolus followed by an 8-mg/hour infusion for 72 hours. After the patient’s condition stabilizes, oral therapy can be substituted for intravenous therapy. In patients with low-risk endoscopic findings (a clean-based ulcer or flat spot), oral proton pump inhibitors in high doses are recommended.
In either case, after the initial bleeding is treated endoscopically and hemostasis is achieved, a proton pump inhibitor is recommended for 6 to 8 weeks, or longer if the patient is also positive for Helicobacter pylori or is on daily treatment with aspirin or a nonsteroidal anti-inflammatory drug (NSAID) that is not selective for cyclo-oxygenase 2 (see below).
Started before endoscopy, these drugs reduced the frequency of actively bleeding ulcers, the duration of hospitalization, and the need for endoscopic therapy in a randomized controlled trial.26 A meta-analysis found that significantly fewer patients had signs of recent bleeding on endoscopy if they received a proton pump inhibitor 24 to 48 hours before the procedure, but it did not find any significant difference in important clinical outcomes such as death, recurrent bleeding, or surgery.27 Nevertheless, we believe that intravenous proton pump inhibitor therapy should be started before endoscopy in patients with upper GI bleeding.
Octreotide (Sandostatin), an analogue of the hormone somatostatin, decreases splanchnic blood flow, decreases secretion of gastric acid and pepsin, and stimulates mucus production. Although it is beneficial in treating upper GI bleeding due to varices, its benefit has not been confirmed in patients with nonvariceal upper GI bleeding.
A meta-analysis revealed that outcomes were better with high-dose intravenous proton pump inhibitor therapy than with octreotide when these drugs were started after endoscopic treatment of acute peptic ulcer bleeding.28 Nevertheless, octreotide may be useful in patients with uncontrolled nonvariceal bleeding who are awaiting endoscopy, since it is relatively safe to use.
ALL PATIENTS NEED ENDOSCOPY
All patients with upper GI bleeding need an upper endoscopic examination to diagnose and assess the risk posed by the bleeding lesion and to treat the lesion, reducing the risk of recurrent bleeding.
How urgently does endoscopy need to be done?
Endoscopy within the first 24 hours of upper GI bleeding is considered the standard of care. Patients with uncontrolled or recurrent bleeding should undergo endoscopy on an urgent basis to control the bleeding and reduce the risk of death.
However, how urgently endoscopy needs to be done is often debated. A multicenter randomized controlled trial compared outcomes in patients who underwent endoscopy within 6 hours of coming to the emergency department vs within 24 hours after the initial evaluation. The study found no significant difference in outcomes between the two groups; however, the group that underwent endoscopy sooner needed fewer transfusions.29
For a better view of the stomach
Gastric lavage improves the view of the gastric fundus but has not been proven to improve outcome.30
Promotility agents such as erythromycin and metoclopramide (Reglan) are also used to empty the stomach for better visualization.31–35 Erythromycin has been shown to improve visualization, shorten the procedure time, and prevent the need for additional endoscopy attempts in two randomized controlled studies.33,34 Furthermore, a cost-effectiveness study confirmed that giving intravenous erythromycin before endoscopy for acute upper GI bleeding saved money and resulted in an increase in quality-adjusted life-years.35