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Rahman R, Nguyen DL, Sohail U, Almashhrawi AA, Ashraf I, Puli, SR, Bechtold ML. Pre-endoscopic erythromycin administration in upper gastrointestinal bleeding: an updated meta-analysis and systematic review. Annals of Gastroenterology. 2016 Jul-Sep; 29(3): 312-7.

Study Population: 598 adults from 8 randomized controlled trials, primarily in ICU settings

Efficacy Endpoints

Need for 2nd endoscopy, hospital length of stay, units of packed red blood cells (PRBC) transfused, and visualization of gastric mucosa

Harm Endpoints

Gastrointestinal discomfort, cardiac arrhythmias

Narrative

Upper gastrointestinal (GI) bleeding is a medical emergency that accounts for more than 500,000 hospital admissions each year and has a significant mortality of 5-10% with standard medical therapy.2 Urgent endoscopy with adequate visualization of the gastric mucosa is often essential for identifying the source of bleeding and treatment of these lesions. Traditionally, nasogastric lavage has been used to improve visualization, but this technique causes significant patient discomfort (pain and nausea) and risk (misplaced tube, risk of clot dislodgment). Erythromycin, a macrolide antibiotic, facilitates the motility of the gastric antrum and duodenum, thereby accelerating gastric emptying. For this reason, intravenous erythromycin has been proposed as a pre-endoscopy aid in visualization and treatment of upper GI bleeding.

This meta-analysis includes eight trials (n = 598) involving adult patients with upper GI bleeding. All were randomized, controlled trials (RCTs) comparing erythromycin administration versus no erythromycin administration prior to endoscopy, but two of the studies were not blinded. All studies evaluated the primary endpoints of adequate visualization of the gastric mucosa and need for a second-look endoscopy.

Gastric visualization was assessed in each study as a dichotomous outcome and reported as adequate or inadequate visualization of gastric mucosa. Adequate gastric visualization was observed in 77% patients who received erythromycin before endoscopy and 51% who received no erythromycin or placebo (odds ratio [OR]: 4.14; 95% CI: 2.01-8.53). Erythromycin administration also resulted in a statistically significant decrease in the need for second-look endoscopy (OR 0.51; 95% CI: 0.34-0.77). Among secondary outcomes, there was a statistically significant decrease in hospital length of stay (5 trials, n = 375, mean difference [days]: MD -1.75; 95% CI: -2.43 to -1.06). No statistically significant difference was observed in duration of endoscopy (5 studies, n = 503) or need for emergent surgery (2 trials, n = 146). Administration of erythromycin was not associated with a statistically significant decrease in packed red blood cell (PRBC) transfusions (6 trials, n = 544, significant heterogeneity). However, a sensitivity analysis in which one study was removed showed significantly reduced heterogeneity and found that erythromycin administration decreased the number of blood transfusions compared to no erythromycin (mean difference [number of units]: -0.41; 95% CI: -0.82 to -0.01).

This meta-analysis did not explore harm outcomes, but several individual studies monitored for adverse effects. The medication was generally well tolerated, with only a few minor adverse reactions reported (GI discomfort).

Caveats

Two of the eight studies were not blinded, which introduced a risk of bias. However, a sensitivity analysis in which these two studies were removed the results remained similar in all measured outcomes. In addition, there was considerable variation of the erythromycin dose among the included trials, though studies have suggested an effect with as little as 70 mg of erythromycin,3 well below even the lowest doses used in these trials. As the authors point out, given the small number of patients in the included trials, mortality could not be fully assessed in this meta-analysis.

Statistically significant heterogeneity was found in two outcomes (gastric visualization and procedural duration), but sensitivity analysis did not change the overall results. This heterogeneity may have been due to differences in study population, particularly in the percentage of the population with acute variceal bleeding. The authors suggest that erythromycin may be less effective in variceal bleeding, though this was not specifically addressed in the meta-analysis. Finally, three of the studies utilized nasogastric lavage, a significant potential confounder, before the administration of erythromycin. One prospective, randomized, multicenter trial4 compared intravenous erythromycin infusion without NG lavage, NG lavage without erythromycin, and the combination of both erythromycin and NG lavage. No statistically significant difference was seen among the three groups, suggesting that erythromycin and NG lavage may be similar in efficacy and that combining the two adds no significant benefit.

In light of these limitations, there appears to be a definite need for further research in this area. However, because of the reported benefits of improved visualization of gastric mucosa, decreased need for second-look endoscopy, and decreased hospital length of stay as well as low frequency of serious adverse effects, we recommend this intervention in adult patients with acute upper GI bleeding, particularly in those for whom nasogastric lavage prior to endoscopy is contraindicated or less desirable. We give it a rating of Green.

Author

Brian Resler, MD; Gary Green, MD

Supervising Editor: Allan Wolfson, MD; Michael Ritchie, MD

Published/Updated

June 5, 2018