Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage
Adão, D., Gois, A. F., Pacheco, R. L., Pimentel, C. F., Riera, R.
The Cochrane Database of Systematic Reviews. 2023;2(2):Cd013176
BACKGROUND Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.
An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding
Chiang HC, Yang EH, Hu HM, Chen WY, Chang WL, Wu CT, Wu DC, Sheu BS, Cheng HC
BMC gastroenterology. 2022;22(1):439
BACKGROUND Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).
Clinical efficacy of norepinephrine combined with cimetidine in treatment of neonatal upper gastrointestinal hemorrhage and its adverse reactions
Dong X, Li H, Zhu T
Pakistan journal of medical sciences. 2022;38(8):2215-2219
OBJECTIVES To investigate the clinical efficacy of norepinephrine combined with cimetidine in the treatment of neonatal upper gastrointestinal hemorrhage and its adverse reactions. METHODS A total of 68 cases of neonatal upper gastrointestinal hemorrhage in Huangshi Maternal and Child Health Care Hospital from please mention dates October 2018 to February 2020 were selected and randomly divided into treatment group and control group by coin tossing, with 34 infants in each group. The control group received conventional therapy, and the treatment group was additionally treated with norepinephrine combined with cimetidine. The efficacy and safety were compared between the two groups. RESULTS The time when the bleeding stops, the time of fecal occult blood turning negative and hospital stay of the treatment group were shorter than those of the control group (P < 0.05). Superoxide dismutase (SOD) level increased while malondialdehyde (MDA) level decreased in both groups after treatment compared with those before treatment (P < 0.05). After treatment, the SOD level was higher while the MDA level was lower in the treatment group than those in the control group (P < 0.05). The effective rate of the treatment group was higher than that of the control group (P < 0.05). However, no significance was found in adverse reactions between the two groups (P > 0.05). CONCLUSION Norepinephrine combined with cimetidine in the treatment of neonatal upper gastrointestinal hemorrhage can shorten the recovery time of symptoms, improve efficacy and reduce stress reaction. It is safe, effective and worthy of use in clinical practice.
Somatostatin plus Gastroscopic Administration of Omeprazole for the Treatment of Acute Upper Gastrointestinal Bleeding: An Exploration of a Promising Alternative
Feng L, Fu J
Evidence-based complementary and alternative medicine : eCAM. 2022;2022:6329592
OBJECTIVE To analyze the efficacy and safety of somatostatin combined with gastroscopic administration of omeprazole in the treatment of acute upper gastrointestinal bleeding. METHODS Eligible 112 patients with acute upper gastrointestinal bleeding treated in our hospital from May 2019 to July 2020 were randomized at a ratio of 1 : 1 either to the control group (somatostatin) or observation group (somatostatin combined with omeprazole gastroscope administration). The treatment efficacy, the average hemostasis time, rebleeding rate, average length of hospital stay, and the incidence of adverse reactions were compared. RESULTS The study group demonstrated significantly higher total effective rate than the control group (96.45% vs. 80.36%, <0.05). The study group demonstrated superior performances compared to the control group with respect to the average hemostasis time ((14.17 ± 2.53 h) vs. (28.84 ± 4.07 h)), rebleeding rate (3.57% vs. 14.28%), and average length of hospital stay ((5.86 ± 1.26 d) vs. (9.74 ± 1.07 d)) (all p < 0.05). The chi-square test revealed a remarkably lower total incidence of adverse reactions in the study group vs. control group which was (4 (7.14%) vs. 12 (21.43%)) (p < 0.05). CONCLUSION The combination of somatostatin and gastroscopic administration of omeprazole might be a promising alternative for the treatment of acute upper gastrointestinal bleeding. It improves the clinical treatment effect and controls the symptoms of patients, with a good safety profile.
Oral Proton Pump Inhibitors May Be as Effective as Intravenous in Peptic Ulcer Bleeding: A Systematic Review and Meta-analysis
Csiki E, Szabó H, Hanák L, Szakács Z, Kiss S, Vörhendi N, Pécsi D, Hegyi E, Hegyi P, Erőss B
Clinical and translational gastroenterology. 2021;12(4):e00341
Free full text
INTRODUCTION Current guidelines recommend intravenous (IV) proton pump inhibitor (PPI) therapy in peptic ulcer bleeding (PUB). We aimed to compare the efficacy of oral and IV administration of PPIs in PUB. METHODS We performed a systematic search in 4 databases for randomized controlled trials, which compared the outcomes of oral PPI therapy with IV PPI therapy for PUB. The primary outcomes were 30-day recurrent bleeding and 30-day mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes, while weighted mean differences (WMDs) with CI were calculated for continuous outcomes in meta-analysis. The protocol was registered a priori onto PROSPERO (CRD42020155852). RESULTS A total of 14 randomized controlled trials reported 1,951 peptic ulcer patients, 977 and 974 of which were in the control and intervention groups, respectively. There were no statistically significant differences between oral and IV administration regarding 30-day rebleeding rate (OR = 0.96, CI: 0.65-1.44); 30-day mortality (OR = 0.70, CI: 0.35-1.40); length of hospital stay (WMD = -0.25, CI: -0.93 to -0.42); transfusion requirements (WMD = -0.09, CI: -0.07 to 0.24); need for surgery (OR = 0.91, CI: 0.40-2.07); further endoscopic therapy (OR = 1.04, CI: 0.56-1.93); and need for re-endoscopy (OR = 0.81, CI: 0.52-1.28). Heterogeneity was negligible in all analysis, except for the analysis on the length of hospitalization (I2 = 82.3%, P = 0.001). DISCUSSION Recent evidence suggests that the oral administration of PPI is not inferior to the IV PPI treatment in PUB after endoscopic management, but further studies are warranted.
Nonsurgical Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients: A Systematic Review and Network Meta-analysis
Jing L, Zhang Q, Chang Z, Liu H, Shi X, Li X, Wang J, Mo Y, Zhang X, Ma L, et al
Journal of clinical gastroenterology. 2020
INTRODUCTION The aim of this study was to evaluate the effectiveness of nonsurgical secondary prophylaxis interventions for esophageal varices (EV) rebleeding in cirrhotic patients using network meta-analysis. MATERIALS AND METHODS Secondary prophylaxis of EV rebleeding in cirrhosis is searched on PubMed, Embase, and the Cochrane Library databases. The quality of literatures was extracted by 2 independent investigators according to the requirements of Cochrane Handbook for Systematic Reviews of Interventions, Version 5.0.0. Meta-analysis was performed on Review Manager 5.3 software for the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality; and STATA 15.1 software was used for network meta-analysis. RESULTS In all, 57 randomized controlled trials were reviewed. Endoscopic band ligation (EBL)+argon plasma coagulation has not been recommended by guidelines, and it is rarely used; the number of existing studies and the sample size are small. Considering poor stability of the combined results, these studies were excluded; 55 literatures were included. In terms of reducing the incidence of rebleeding, transjugular intrahepatic portosystemic shunt (TIPS) surface under the cumulative ranking curve (SUCRA) (94.3%) was superior to EBL+endoscopic injection sclerotherapy (EIS) (84.4%), EIS+β-blockers (77.9%), EBL (59.8%), EBL+β-blockers+isosorbide-5-mononitrate (52.7%), EBL+β-blockers (51.4%), EIS (34.2%), β-blockers+isosorbide-5-mononitrate (23.7%), β-blockers (20.8%), and placebo (0.8%). In reducing rebleeding-related mortality, TIPS SUCRA (87.2%) was more efficacious than EBL+EIS (83.5%), EIS (47.9%), EBL+β-blockers (47.4%), β-blockers (41.8%), EBL (34.5%), and placebo (7.6%). In reducing overall mortality, TIPS SUCRA (81.1%) was superior to EBL+EIS (68.9%), EIS+β-blockers (59.2%), EBL+β-blockers (55.4%), EIS (48.8%), EBL (48.7%), β-blockers (34.2%), placebo (3.6%). CONCLUSIONS TIPS was more effective in reducing the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality in cirrhosis. Combined with the above results, TIPS is more likely to be recommended as a secondary prophylaxis intervention for EV in cirrhosis.
Prevention of recurrent idiopathic gastroduodenal ulcer bleeding: a double-blind, randomised trial
Wong GLH, Lau LHS, Ching JYL, Tse YK, Ling RHY, Wong VWS, Chiu PWY, Lau JYW, Chan FKL
OBJECTIVE Patients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have a considerable risk of recurrent ulcer complications. We hypothesised that a proton pump inhibitor (lansoprazole) is superior to a histamine 2 receptor antagonist (famotidine) for the prevention of recurrent ulcer bleeding in such patients. DESIGN In this industry-independent, double-blind, randomised trial, we recruited patients with a history of idiopathic bleeding ulcers. After ulcer healing, we randomly assigned (1:1) patients to receive oral lansoprazole 30 mg or famotidine 40 mg daily for 24 months. The primary endpoint was recurrent upper GI bleeding within 24 months, analysed in the intention-to-treat population as determined by an independent adjudication committee. RESULTS Between 2010 and 2018, we enrolled 228 patients (114 patients in each study group). Recurrent upper GI bleeding occurred in one patient receiving lansoprazole (duodenal ulcer) and three receiving famotidine (two gastric ulcers and one duodenal ulcer). The cumulative incidence of recurrent upper GI bleeding in 24 months was 0.88% (95% CI 0.08% to 4.37%) in the lansoprazole arm and 2.63% (95% CI 0.71% to 6.91%) in the famotidine arm (p=0.313; crude HR 0.33, 95% CI 0.03 to 3.16, p=0.336). None of the patients who rebled used aspirin, non-steroidal anti-inflammatory drugs or other antithrombotic drugs. CONCLUSION This 2-year, double-blind randomised trial showed that among patients with a history of H. pylori-negative idiopathic ulcer bleeding, recurrent bleeding rates were comparable between users of lansoprazole and famotidine, although a small difference in efficacy cannot be excluded. TRIAL REGISTRATION NUMBER NCT01180179; Results.
Sandwich method with or without lauromacrogol in the treatment of gastric variceal bleeding with liver cirrhosis: A meta-analysis
Wu K, Song Q, Gou Y, He S
BACKGROUND To compare the efficacy and safety of the modified sandwich method with lauromacrogol in the treatment of gastric variceal bleeding (GVB) caused by liver cirrhosis with the traditional sandwich method no accompanied by lauromacrogol via a meta-analysis. METHODS The Cochrane Library, Pubmed, the China National Knowledge Infrastructure (CNKI) database, the Chinese Wanfang database, and the Chongqing VIP database were searched to identify cohort studies comparing modified to traditional sandwich method in the treatment of GVB with liver cirrhosis. The relative risk for hemostasis rate, gastric varices (GV) remission rate, re-bleeding rate, the incidence of post-operative complications (pain, fever, ulcer or erosion, ectopic embolism), and all-cause mortality were calculated. The mean difference for average tissue adhesive dosage per case was calculated. Relevant data were analyzed with the Reviewer Manager 5.3.5. RESULTS Four cohort studies with a total of 587 patients were included in this meta-analysis. In the treatment of GVB with liver cirrhosis, compared with the traditional sandwich method, the modified sandwich method was associated with a higher GV remission rate (RR: 1.24, 95% CI: 1.09-1.42; P = .001) according to the pooled results. There were no statistically significant differences between the 2 methods in the rate of hemostasis, re-bleeding, pain, fever, ulcer or erosion, ectopic embolism, and all-cause mortality (P >== .05). CONCLUSIONS This meta-analysis indicated that the modified sandwich method with lauromacrogol is more effective than the traditional sandwich method without lauromacrogol. Due to the limited number of studies and samples, more RCT studies are needed to further validate the efficacy and safety of the modified sandwich method with lauromacrogol in the treatment of GVB with liver cirrhosis.
Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis
Chen WC, Hsin IF, Chen PH, Hsu PI, Wang YP, Cheng JS, Lin HS, Hou MC, Lee FY
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019
BACKGROUND & AIMS Gastric variceal bleeding (GVB) frequently recurs after hemostasis by gastric variceal obturation (GVO). We performed a multicenter, randomized controlled trial to determine the efficacy of carvedilol plus GVO in secondary prophylaxis of GVB. METHODS We performed a prospective study of 121 patients with cirrhosis (ages 20-80 years) with GVB proven by endoscopy within 24 hours of bleeding and stable hemodynamics for at least 3 days after initial GVO. Patients were randomly assigned into a group that underwent repeated GVO (n = 61) or a group received repeated GVO plus carvedilol (n = 60). Recurrent GVB, upper gastrointestinal bleeding (UGIB), adverse events, and survival were compared between the groups. RESULTS GVB recurred in 21 patients (34%) in the group that received repeated GVO and 14 patients (23%) in the group that received repeated GVO plus carvedilol (P = .18). Ascites (relative risk [RR], 2.69; 95% CI, 1.33-5.48; P = .006) and hepatoma (RR, 2.10; 95% CI, 1.03-4.28; P = .04) were associated with recurrent GVB. Twenty-nine patients (48%) in the group that received repeated GVO and 17 patients (28%) in the group that received repeated GVO plus carvedilol had recurrent UGIB (P = .03). Carvedilol (RR, 0.44; 95% CI, 0.24-0.80; P = .007) was associated with reduced risk of UGIB recurrence. Ascites (RR, 3.02; 95% CI, 1.59-5.73; P = .001) and hepatoma (RR, 2.07; 95% CI, 1.10-3.88; P = .02) were associated with recurrent UGIB. A higher proportion of patients in the group that received repeated GVO plus carvedilol (53%) had adverse events than the group that received repeated GVO (15%) (P < .001). Mean survival times were 21 +/- 18 months in the group that received repeated GVO vs 25 +/- 20 months in the group that received repeated GVO plus carvedilol (P = .30). CONCLUSION In a randomized controlled trial, we found that addition of carvedilol to GVO did not decrease recurrence of GVB in patients with cirrhosis but was associated with decreased recurrence of UGIB. However, carvedilol plus GVO produced significantly more adverse events. Mean survival times did not differ significantly between groups. ClinicalTrials.gov no: NCT02504723.
Pharmacological interventions for prevention and treatment of upper gastrointestinal bleeding in newborn infants
Green DS, Abdel-Latif ME, Jones LJ, Lui K, Osborn DA
The Cochrane database of systematic reviews. 2019;7:Cd011785
BACKGROUND Upper gastrointestinal bleeding is typically a mild, self-limiting condition that can affect both preterm and term neonates, although it can be severe particularly when associated with co-morbidities. Pharmacological interventions with a proton pump inhibitor (PPI), H2 receptor antagonist (H2RA), antacid, bismuth and sucralfate may have effects on both the prevention and treatment of upper gastrointestinal bleeding in infants. OBJECTIVES To assess how different pharmacological interventions (PPIs, H2RAs, antacids, sucralfate or bismuth salts) administered to preterm and term neonates for the prevention or treatment of upper gastrointestinal bleeding to reduce morbidity and mortality compare with placebo or no treatment, supportive care, or each other. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 6), MEDLINE via PubMed (1966 to 12 July 2018), Embase (1980 to 12 July 2018), and CINAHL (1982 to 12 July 2018). We also searched clinical trial databases, conference proceedings, the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials, and online for Chinese literature articles. SELECTION CRITERIA We selected randomised, quasi-randomised and cluster-randomised trials involving preterm and term neonates. Trials were included if they used a proton pump inhibitor, H2 receptor antagonist, antacid, sucralfate or bismuth either for the prevention or treatment of upper gastrointestinal bleeding. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. We conducted meta-analysis using a fixed-effect model. We used the GRADE approach to assess quality of evidence. MAIN RESULTS Eleven studies with 818 infants met the criteria for inclusion in this review.Four trials with 329 infants assessed the use of an H2 receptor antagonist for prevention of upper gastrointestinal bleeding in high-risk newborn infants. Meta-analysis of these four trials identified a reduction in any upper gastrointestinal bleeding when using an H2 receptor antagonist (typical risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.58; typical risk difference (RD) -0.20, 95% CI -0.28 to -0.11; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 9). The quality of evidence was moderate. A single trial with 53 infants assessing prevention of upper gastrointestinal bleeding reported no difference in mortality in infants assigned H2 receptor antagonist versus no treatment; however the quality of evidence was very low.Seven trials with 489 infants assessed an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) for treatment of gastrointestinal bleeding in newborn infants. Meta-analysis of two trials (131 infants) showed no difference in mortality from use of a H2 receptor antagonist compared to no treatment. The quality of evidence was low. Meta-analysis of two trials (104 infants) showed a reduction in duration of upper gastrointestinal bleeding from use of an inhibitor of gastric acid compared to no treatment (mean difference -1.06 days, 95% CI -1.28 to -0.84). The quality of evidence was very low. Meta-analysis of six trials (451 infants) showed a reduction in continued upper gastrointestinal bleeding from use of any inhibitor of gastric acid compared to no treatment (typical RR 0.36, 95% CI 0.26 to 0.49; typical RD -0.26, 95% CI -0.33, -0.19; NNTB 4, 95% CI 3 to 5). The quality of evidence was low. There were no significant subgroup differences in duration of upper gastrointestinal bleeding or of continued upper gastrointestinal bleeding according to type of inhibitor of gastric acid. A single trial (38 infants) reported no difference in anaemia requiring blood transfusion from use of a H2 receptor antagonist compared to no treatment.Although no serious adverse events were reported from the use of a H2 receptor antagonist or proton pump inhibitor, some neonatal morbidities - including necrotising enterocolitis, ventilator-associated pneumonia, duration of ventilation and respiratory support, and duration of hospital stay - were not reported. Long-term outcome was not reported. AUTHORS' CONCLUSIONS There is moderate-quality evidence that use of an H2 receptor antagonist reduces the risk of gastrointestinal bleeding in newborn infants at high risk of gastrointestinal bleeding. There is low-quality evidence that use of an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) reduces the duration of upper gastrointestinal bleeding and the incidence of continued gastric bleeding in newborn infants with gastrointestinal bleeding. However, there is no evidence that use of an inhibitor of gastric acid in newborn infants affects mortality or the need for blood transfusion. As no study reported the incidence of necrotising enterocolitis, ventilator- or hospital-associated pneumonia, sepsis, or long-term outcome, the safety of inhibitors of gastric acid secretion is unclear.