Is routine stress ulcer prophylaxis of benefit for patients undergoing cardiac surgery?

Department of Cardiothoracic Surgery, John Radcliffe Hospital, Oxford, UK.
Interactive Cardiovascular and Thoracic Surgery (Impact Factor: 1.11). 02/2012; 14(5):622-8. DOI: 10.1093/icvts/ivs019
Source: PubMed

ABSTRACT A best evidence topic in cardiac surgery was written according to a structured protocol. We address whether routine pharmacological stress ulcer prophylaxis is of benefit for patients undergoing cardiac surgery. One hundred and fifty-six papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group, study type, relevant outcomes and results of these papers were tabulated. The results show that the incidence of stress ulcers following cardiac surgery is low (0.45%), but remains associated with significant morbidity and mortality. Five of the 7 studies demonstrated suppression of acid secretion or decreased incidence of gastric complications in patients given pharmacological stress ulcer prophylaxis, with the remaining two suggesting no clinical benefit. One prospective study of 210 patients, randomized equally between a proton pump inhibitor (PPI), histamine antagonist and teprenone, found that PPIs were the most effective at reducing gastric complications after cardiac surgery, including ulcer formation and upper gastrointestinal bleeding (UGIB). However, a separate retrospective study suggested no difference in the outcomes between the use of a PPI and a histamine antagonist. Of the studies focused on histamine antagonists, one randomized control trial (RCT) showed that cimetidine can reduce surgical stress, augment the immune system and reduce the intubation time after cardiac surgery, although no direct association with UGIB was made. A second prospectively randomized study of histamine antagonists demonstrated superior pH control with famotidine and ranitidine, when compared with cimetidine. Furthermore, haematological and neurological side-effects were noted only with the use of cimetidine. A recent meta-analysis and systematic review of the literature associated gastric acid suppression with an increased risk of pneumonia. Two prospective cohort studies that examined the use of PPI in conjunction with clopidogrel in patients with coronary artery disease concluded that there was no association with an increase in major adverse cardiovascular events with the use of PPIs. We conclude that the current evidence is marginally in favour of the use of prophylactic PPIs. However, this is associated with an increased risk of hospital-acquired pneumonia.

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    ABSTRACT: A best evidence topic was written according to a structured protocol. The question addressed was what is the optimum prophylaxis against gastrointestinal haemorrhage for patients undergoing adult cardiac surgery: histamine receptor antagonists (H(2)RA) or proton-pump inhibitors? A total of 201 papers were found; of which, 8 represented the best evidence. The authors, date, journal, study type, population, main outcome measures and results were tabulated. Only one randomized controlled trial (RCT) with relevant clinical outcomes was identified. The rest of the studies consisted of five prospective studies and two retrospective studies. In the RCT, there were no reported cases of gastrointestinal haemorrhage in the proton-pump inhibitor cohort, whereas 4 patients taking H(2)RA developed it. The rate of active gastrointestinal ulceration was higher in the H(2)RA cohort in comparison with the proton-pump inhibitor cohort (21.4 vs 4.3%). A prospective study followed 2285 consecutive patients undergoing cardiac surgery who received either no prophylaxis, or a proton-pump inhibitor. Chi-squared analysis showed the risk of bleeding to be lower in those receiving the proton-pump inhibitor (P < 0.05). Another study of 6316 patients undergoing coronary artery bypass grafting demonstrated a reduced risk of gastrointestinal bleed with prophylactic intravenous omeprazole (odds ratio = 0.2; confidence intervals = 0.1-0.8; P < 0.05). One study successfully showed that proton-pump inhibitors are effective in adequately suppressing gastric acid levels, regardless of Helicobacter pylori infection status; conversely, this study suggested that H(2)RAs were not. The evidence for H(2)RAs is marginal, with no study showing a clear benefit. One study showed that ulcer prophylaxis with H(2)RA did not correlate with the clinical outcome. Another study demonstrated gastric ulceration to be a common gastrointestinal complication in spite of regular H(2)RA use. There is also evidence to suggest that acid suppression increases the risk of nosocomial pneumonia, although open heart surgery may be a confounding factor in this association. Two RCTs showed that H(2)RAs may augment the immune system and reducing stress following cardiac surgery. Proton-pump inhibitors appear to be the superior agent for prophylaxis against gastrointestinal bleed in patients undergoing cardiac surgery, although rigorous comparative data are sparse. Furthermore, level-I evidence would confirm this.
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    ABSTRACT: The widespread use of clopidogrel alone or in combination with aspirin may result in gastrointestinal mucosal injury, clinically represented as recurrent ulceration and bleeding complications. Our recent work suggested that clopidogrel significantly induced human gastric epithelial cell (GES-1) apoptosis and disrupted gastric mucosal barrier, and that a p38 MAPK inhibitor could attenuate such injury. However, their exact mechanisms are largely unknown. The GES-1 cells were used as a model system, the effects of clopidogrel on the whole gene expression profile were evaluated by human gene expression microarray and gene ontology analysis, changes of the mRNA and protein expression were determined by real-time PCR and Western blot analysis, and cell viability and apoptosis were measured by MTT assay and flow cytometry analysis, respectively. Gene microarray analysis identified 79 genes that were differentially expressed (P<0.05 and fold-change >3) when cells were treated with or without clopidogrel. Gene ontology analysis revealed that response to stress and cell apoptosis dysfunction were ranked in the top 10 cellular events being affected, and that the major components of endoplasmic reticulum stress-mediated apoptosis pathway - CHOP and TRIB3- were up-regulated in a concentration- and time-dependent manner when cells were treated with clopidogrel. Pathway analysis demonstrated that multiple MAPK kinases were phosphorylated in clopidogrel-treated GES-1 cells, but that only SB-203580 (a p38-specific MAPK inhibitor) attenuated cell apoptosis and CHOP over-expression, both of which were induced by clopidogrel. Increased endoplasmic reticulum stress response is involved in clopidogrel-induced gastric mucosal injury, acting through p38 MAPK activation.
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