Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis
ABSTRACT To assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU).
We performed a systematic review using meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane Collaboration methodology was used. Risk ratios/relative risks (RR) with 95 % confidence intervals (CI) were estimated. The predefined outcome measures were all-cause mortality, GI bleeding, and hospital-acquired pneumonia.
Twenty trials (n = 1,971) were included; all were judged as having a high risk of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95 % CI 0.84-1.20; P = 0.87; I (2) = 0 %) or hospital-acquired pneumonia (random effects: RR 1.23, 95 % CI 0.86-1.78; P = 0.28; I (2) = 19 %) between SUP patients and the no prophylaxis/placebo patients. These findings were confirmed in the TSA. With respect to GI bleeding, a statistically significant difference was found in the conventional meta-analysis (random effects: RR 0.44, 95 % CI 0.28-0.68; P = 0.01; I (2) = 48 %); however, TSA (TSA adjusted 95 % CI 0.18-1.11) and subgroup analyses could not confirm this finding.
This systematic review using meta-analysis and TSA demonstrated that both the quality and the quantity of evidence supporting the use of SUP in adult ICU patients is low. Consequently, large randomised clinical trials are warranted.
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ABSTRACT: Introduction: Histamine-2 receptor antagonists (H2RA) and proton pump inhibitors (PPI) are frequently used to prevent stress-related mucosal bleeding (SRMB). A paucity of data implicates these agents with pneumonia and Clostridium difficile infection (CDI). Areas covered: This review comparatively evaluates the effectiveness of H2RAs and PPIs and delineates their associations with these infectious complications. A literature review through 30 September 2014 was performed. Expert opinion: The rate of SRMB is declining, likely due better resuscitation strategies and the early provision of enteral nutrition. Therefore, gastric acid-suppressing therapies arguably reduce SRMB. However, they may contribute to pneumonia and CDI. The risks of these infectious complications depend on the extent of acid suppression and may vary by patient population. PPIs are associated with the greatest hazard for these infections, likely because they provide stronger acid suppression. Intermittent administration of H2RAs has theoretical advantages over continuous H2RA or PPI therapies as this dosing strategy does not fully suppress gastric acid and may limit infection risk. Placebo-controlled studies are warranted because clinical equipoise exists as the detrimental outcomes of these infections may outweigh the benefit of preventing SRMB given the infrequent occurrence of SRMB.Expert Opinion on Drug Safety 11/2014; 14(2):1-12. DOI:10.1517/14740338.2015.986456 · 2.74 Impact Factor