Stress Ulcer, Gastritis, and Gastrointestinal Bleeding Prophylaxis in Critically Ill Pediatric Patients: A Systematic Review

Ludovic Reveiz, MD, MSc; Rafael Guerrero-Lozano, MD; Angela Camacho, MD; Lina Yara, MD; Paola Andrea Mosquera, Psi, MSc


Pediatr Crit Care Med. 2010;11(1):124-32. 

In This Article

Abstract and Introduction


Objective: To identify and evaluate the quality of evidence supporting prophylactic use of treatments for stress ulcers and upper gastrointestinal bleeding. Stress ulcers, erosions of the stomach and duodenum, and upper gastrointestinal bleeding are well-known complications of critical illness in children admitted to the pediatric intensive care unit.
Data sources: Studies were identified from the Cochrane Central Register of Controlled Trials, PUBMED; LILACS; Scirus. We also scanned bibliographies of relevant studies.
Study Selection: This systematic review of randomized controlled trials assessed the effects of drugs for stress-related ulcers, gastritis, and upper gastrointestinal bleeding in critically ill children admitted to the pediatric intensive care unit.
Data extraction and synthesis: Two reviewers independently extracted the relevant data. Most randomized controlled trials were judged as having unclear risk of bias. When pooling two randomized controlled trials, treatment was significantly more effective in preventing upper gastrointestinal bleeding (macroscopic or important bleeding) compared with no treatment (two studies = 300 participants; relative risk, 0.41; 95% confidence interval, 0.19–0.91; I2 = 12%). Meta-analysis of two studies found no significant difference in death rates among groups (two randomized controlled trials = 132 participants; relative risk, 1.39; 95% confidence interval, 0.70–2.79; I2 = 4%). The rate of pneumonia was not significantly different when comparing treatment and no treatment in one study. When comparing ranitidine with no treatment, significant differences were found in the proportion of mechanically ventilated children with normal gastric mucosal endoscopic findings by histologic specimens (one randomized controlled trial = 48 participants; relative risk, 3.53; 95% confidence interval, 1.34–9.29). No significant differences were found when comparing different drugs (omeprazole, ranitidine, sucralfate, famotidine, amalgate), doses, or regimens for main outcomes (deaths, endoscopic findings of erosion or ulcers, upper gastrointestinal bleeding, or pneumonia).
Conclusions: Although pooled data of two studies suggested that critically ill pediatric patients may benefit from receiving prophylactic treatment to prevent upper gastrointestinal bleeding, we found that high-quality evidence to guide clinical practice is still limited.


Stress ulcers of the stomach and duodenum as well as upper gastrointestinal (UGI) bleeding are well-known complications of critical illness in children admitted to a pediatric intensive care unit (ICU). The prevalence of stress ulceration in critically ill adults and children may vary depending on the severity of the illness and methods used for diagnosis. A cohort of 1006 consecutive admissions enrolled in a pediatric ICU reported that 10.2% of pediatric participants had UGI bleeding and 1.6% had clinically significant UGI bleeding.[1] Clinically important UGI bleeding has an important attributable morbidity and mortality in adults, associated with a significant risk of death (relative risk [RR], 4.1; 95% confidence interval [CI], 2.6–6.5) and an excess length of ICU stay of approximately 4 to 8 days.[2] Clinically important UGI bleeding is defined as macroscopic bleeding that results in hemodynamic instability and the need for red blood cell transfusion and may lead to complications, such as gastrointestinal perforations and surgery.[3,4]

Prophylaxis against stress ulcers has been recommended for the prevention of UGI bleeding in critically ill adults patients. A systematic review published more than one decade ago found that prophylaxis with histamine2-receptor antagonists decreases the occurrence of overt gastrointestinal bleeding (odds ratio [OR], 0.58; 95% CI, 0.42–0.79) and clinically important bleeding (OR, 0.44; 95% CI, 0.22–0.88).[5] Another study found that, among critically ill adult patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate and no significant differences were found in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.[6] However, a more recent integrative study found that ranitidine was ineffective in the prevention of UGI bleeding in patients in intensive care compared with placebo (OR, 0.72; 95% CI, 0.30–1.70) and might increase the risk of pneumonia when compared with sucralfate (OR, 1.35; 95% CI, 1.07–1.70) and that studies on sucralfate do not provide conclusive positive results.[7] A guideline on stress ulcer prophylaxis published in 2006 recommended pharmacologic intervention in adults admitted to the ICU who have coagulopathy, require mechanical ventilation for>48 hrs, have a history of gastrointestinal ulceration or bleeding within 1 yr before admission, or have at least two of the following risk factors: sepsis, ICU stay of>1 wk, occult bleeding lasting ≥6 days, and use of>250 mg of hydrocortisone or the equivalent.[8] Unfortunately, there is still conflicting evidence concerning prophylaxis for stress ulcers in children and we did not find any systematic review on this topic.

The aims of the systematic review presented here are to assess the best evidence on the effects of interventions for stress ulcer in children, to identify gaps in the literature, and to suggest further clinical investigation.


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