Meta Analysis Stress ulcer prophylaxis in the new millennium: A systematic review and meta-analysis
This review may be edited
Summary
Posted By:	Elizabeth Sweetman
E-Mail:	esweetman@med.usyd.edu.au
Posted Date:	15.09.11
Title:	Stress ulcer prophylaxis in the new millennium: A systematic review and meta-analysis
Authors:	Marik PE, Vasu T, Hirani A, Pachinburavan M.
Reference:	Crit Care Med. 2010 Nov;38(11):2222-8.
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	BACKGROUND: Recent observational studies suggest that bleeding from stress ulceration is extremely uncommon in intensive care unit patients. Furthermore, the risk of bleeding may not be altered by the use of acid suppressive therapy. Early enteral tube feeding (initiated within 48 hrs of intensive care unit admission) may account for this observation. Stress ulcer prophylaxis may, however, increase the risk of hospital-acquired pneumonia and Clostridia difficile infection. OBJECTIVE: A systematic review of the literature to determine the benefit and risks of stress ulcer prophylaxis and the moderating effect of enteral nutrition. DATA SOURCES: MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. STUDY SELECTION: Randomized, controlled studies that evaluated the association between stress ulcer prophylaxis and gastrointestinal bleeding. We included only those studies that compared a histamine-2 receptor blocker with a placebo. DATA EXTRACTION: Data were abstracted on study design, study size, study setting, patient population, the histamine-2 receptor blocker and dosage used, the incidence of clinically significant gastrointestinal bleeding, hospital-acquired pneumonia, mortality, and the use of enteral nutrition. DATA SYNTHESIS: Seventeen studies (which enrolled 1836 patients) met the inclusion criteria. Patients received adequate enteral nutrition in three of the studies. Overall, stress ulcer prophylaxis with a histamine-2 receptor blocker reduced the risk of gastrointestinal bleeding (odds ratio 0.47; 95% confidence interval, 0.29-0.76; p < .002; I = 44%); however, the treatment effect was noted only in the subgroup of patients who did not receive enteral nutrition. In those patients who were fed enterally, stress ulcer prophylaxis did not alter the risk of gastrointestinal bleeding (odds ratio 1.26; 95% confidence interval, 0.43-3.7). Overall histamine-2 receptor blockers did not increase the risk of hospital-acquired pneumonia (odds ratio 1.53; 95% confidence interval, 0.89-2.61; p = .12; I = 41%); however, this complication was increased in the subgroup of patients who were fed enterally (odds ratio 2.81; 95% confidence interval, 1.20-6.56; p = .02; I = 0%). Overall, stress ulcer prophylaxis had no effect on hospital mortality (odds ratio 1.03; 95% confidence interval, 0.78-1.37; p = .82). The hospital mortality was, however, higher in those studies (n = 2) in which patients were fed enterally and received a histamine-2 receptor blocker (odds ratio 1.89; 95% confidence interval, 1.04-3.44; p = .04, I = 0%). Sensitivity analysis and meta-regression demonstrated no relationship between the treatment effect (risk of gastrointestinal bleeding) and the classification used to define gastrointestinal bleeding, the Jadad quality score nor the year the study was reported. CONCLUSIONS: The results of this meta-analysis suggest that, in those patients receiving enteral nutrition, stress ulcer prophylaxis may not be required and, indeed, such therapy may increase the risk of pneumonia and death. However, because no clinical study has prospectively tested the influence of enteral nutrition on the risk of stress ulcer prophylaxis, our findings should be considered exploratory and interpreted with some caution.
Are the Results Valid?
1. Did the overview address a focused clinical question?
	Yes. The authors describe their intent to investigate the effect of stress ulcer prophylaxis (SUP) specifically H2RBs in patients receiving EN vs patients receiving no EN, inadequate EN, PN or oral diet. The primary outcome of this meta-analysis was risk of GI bleeding and secondary outcomes included incidence of hospital acquired pneumonia(HAP)and mortality.
2. Were the criteria used to select articles for inclusion appropriate?
	Yes. The authors stated that they were only going to include randomised, placebo controlled studies that evaluated the role of histamine-2 receptor blockers (H2RB) in preventing bleeding from stress ulceration.
3. Is it unlikely that important, relevant studies were missed?
	The authors undertook a comprehensive search with some aspects stronger than others. For example, the initial Medline search only revealed 56 citations. It is unlikely however, due to the authors searching the bibliographies of selected articles and current review papers on this topic that any relevant studies were missed. A QUOROUM flow diagram would be useful in this paper as it would allow readers to follow the RCT selection process.
4. Was the validity of the included studies appraised?
	Yes. The authors independently assessed allocation concealment and the likelihood of bias in all included RCTs. The authors used the Jadad 5-point scale to assess each trial.
5. Were assessments of studies reproducible?
	Yes. All four authors independently reviewed all of the studies considered for this meta-analysis and also independently assessed the methodological quality of all included papers. Any disagreement between authors was resolved by consensus.
6. Were the results similar from study to study?
	The authors report I2 and P values for heterogeneity for all analyses. Although I2 is uniformably below 50%, the P value (P = 0.03)for heterogeneity suggests significant heterogeneity for the primary analysis.
What are the Results?
1. What are the overall results of the overview?
	Primary Outcome; Stress Ulcer Prophylaxis (SUP) with H2RBs did reduce GI bleeding (OR 0.47; 95% CI, 0.29-0.76; p < 0.02; I2 = 44%). Secondary Outcomes; SUP with H2RBs did not increase the risk of hospital acquired pneumonia (OR 1.53; 95% CT 0.89-2.61; p = 0.12). SUP with H2RBs had no effect on hospital mortality compared to placebo (OR 1.03; 95% CI 0.78-1.37; p = 0.82). We report only the primary analyses here. The Authors report a number of hypothesis generating sub-group analyses however these are not adjusted for multiple comparisons and should be interpreted with caution.
2. How precise were the results?
	Please see above for 95% CIs.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
	The overall results are interesting but not novel. We are concerned that the sub-group analysis was not conducted using conservative statistical tests such as a test of interaction. If we apply a conservative Bonferroni correction the sub-group analyses are no longer significant.
2. Were all clinically important outcomes considered?
	Yes all important clinically important outcomes were considered.
3. Are the benefits worth the harms and costs?
	H2RBs are cheap and readily used in clinical practice. No confirmed harms are documented for H2RBs. Clinicians use of H2RBs should not be influenced by this papers sub-group analysis.
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