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Three Part Question

[In adult patient presenting with acute upper GI bleed], is [erythromycin better than placebo] at [enhancing visualisation/need for second-look endoscopy/need for blood transfusion/duration of procedure/length of stay/need for emergent surgery]?

Clinical Scenario

A 40-year-old man came in to ED with suspected upper GI bleed. He was prescribed erythromycin before going for endoscopy. You wonder what was the role of erythromycin pre-endoscopy

Search Strategy

Medline via Ovid Interface 1946 to June Week 4 2016

Embase via Ovid Interface 1974 to 2016 Week 27
{exp gastrointestinal hemorrhage OR upper gastrointestinal haemorrhage.mp. OR upper gastrointestinal bleed$.mp. OR upper gastrointestinal hemorrhage.mp. OR gastrointestinal hemorrhage.mp. OR exp hematemesis OR hematemesis.mp. OR haematemesis.mp. OR exp melena OR melena.mp. OR malaena.mp.} AND {exp endoscopy OR exp endoscopy, digestive system OR exp endoscopy, gastrointestinal OR endoscopy.mp.} AND {exp erythromycin OR erythromycin.mp.}limit to humans, English language, last 10 years

{exp upper gastrointestinal bleed OR upper gastrointestinal bleed$.mp. OR exp gastrointestinal hemorrhage OR upper gastrointestinal hemorrhage.mp. OR upper gastrointestinal haemorrhage.mp. OR exp melena OR gastrointestinal haemorrhage.mp. OR malaena.mp. OR exp hematemesis OR haematemesis.mp.} AND {exp endoscopy OR exp gastrointestinal endoscopy OR exp digestive tract endoscopy OR endoscopy.mp.} AND {exp erythromycin OR erythromycin.mp.}limit to humans, English language, last 10 years.

Search Outcome

142 papers were identified from the search. 10 relevant papers were selected after screening the title and abstracts and removing duplicates. 6 meta-analyses, 3 research papers and 1 review article were found. The review article was removed as full text was not available.
Only 1 of the meta-analysis was used as it was most recent and covered all the research papers in the past. It was found as a conference abstract on Medline and the full paper was found in Annals of Gastroenterology

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Rahman et al. 2016 USA	8 RCTs involving 598 adult patients with upper gastrointestinal bleeding were randomized to receive pre-endoscopic erythromycin or control	Meta-analysis and systematic review	Gastric visualization	8 studies. Significant heterogeneity found (I2=64%, P<0.01). Erythromycin vs placebo, 76.8% vs 50.7% (OR 4.14; 95% CI: 2.01-8.53; P<0.01). Statistically significant higher odds with erythromycin. After removing one of the study, there was no significant heterogeneity. NNT=4	Variation in dose of erythromycin given across different studies. Two of the four outcomes demonstrated significant heterogeneity (gastric visualization and units of blood transfused). On sensitivity analysis, similar result was displayed in gastric visualization but not for units of blood transfused which was due to the impact of one recent RCT. Three studies utilized nasogastric lavage in both groups Gastric visualization was determined either adequate or inadequate based on the authors’ discretion
			Need for second-look endoscopy	8 studies. No significant heterogeneity ((I2 =24%, P=0.24) Erythromycin vs placebo, 15.1% vs 25.7% (OR 0.51; 95% CI: 0.34-0.77; P<0.01). NNT=9
			Units of blood transfused	6 studies. Significant heterogeneity (I2=89%, P<0.01). No significant difference (MD -1.06; 95% CI: -2.24-0.13; P=0.08) After sensitivity analysis of one study’s removal, no heterogeneity was identified (I2=0%, P=0.85), and significant decrease in amount of blood transfusion (MD -0.41; 95% CI: -0.82 to -0.01; P=0.04)
			Length of hospital stay	5 studies. No significant heterogeneity ((I2=0%, P=0.55) Significant odds of few days in hospital stay (MD -1.75; 95% CI: -2.43 to -1.06, P<0.01)
			Length of endoscopy	5 studies. Significant heterogeneity (I2 =96%, P<0.01) Length of endoscopy was not statistically significant (MD -4.94; 95% CI: -12.42-2.54; P=0.20)
			Need for emergent surgery	2 studies. No significant heterogeneity Erythromycin vs no erythromycin, 1.4% vs 5.3% (OR 1.11; 95% CI: 0.27-4.67; P=0.08)

Comment(s)

This systematic review and meta-analysis included all of the RCT to date regarding the topic. Erythromycin was shown to be effective in enhancing gastric visualization and reducing the need for second-look endoscopy as well as length of hospital stay. The author commented that the mean unit of blood transfused did not differ in this meta-analysis as it had in past analyses due to significant heterogeneity in the most recent study included. If the paper was excluded, the result would be significant without heterogeneity.

Clinical Bottom Line

Erythromycin should be given as a pro-kinetic before endoscopy

References

1. Rahman R, Nguyen DL, Sohail U, et al Pre-endoscopic erythromycin administration in upper gastrointestinal bleeding: an updated meta-analysis and systematic review Annals of Gastroenterology