Chanpura and Yende Critical Care 2012, 16:322
Weighing risks and benefi ts of stress ulcer prophylaxis in critically ill patients University of Pittsburgh Department of Critical Care Medicine: Evidence-Based Medicine Journal Club, edited by Sachin Yende Expanded abstract
signifi cant gastrointestinal bleeding, hospital-acquired Citation
pneumonia, mortality, and the use of enteral nutrition.
Marik PE, Tajender Vasu T, Hirani A, Pachinburavan M:
Stress ulcer prophylaxis in the new millennium: a Results
systematic review and meta-analysis. Critical Care Med
Seventeen studies (which enrolled 1836 patients) met the 2010, 38:11.
inclusion criteria. Patients received adequate enteral nutrition in three of the studies. Overall, stress ulcer Background
prophylaxis with a histamine-2 receptor blocker reduced Recent observational studies suggest that bleeding from the risk of gastrointestinal bleeding (odds ratio 0.47; 95% stress ulceration is extremely uncommon in intensive confi dence interval, 0.29–0.76; <  0.002; Heterogeneity care unit patients. Furthermore, the risk of bleeding may [I2] = 44%); however, the treatment eff ect was noted only not be altered by the use of acid suppressive therapy. in the subgroup of patients who did not receive enteral Early enteral tube feeding (initiated within 48 h of inten- nutrition. In those patients who were fed enterally, stress sive care unit admission) may account for this obser- ulcer prophylaxis did not alter the risk of gastrointestinal vation. Stress ulcer prophylaxis may, however, increase bleeding (odds ratio 1.26; 95% confi dence interval, 0.43– the risk of hospital-acquired pneumonia and Clostridia 3.7). Overall histamine-2 receptor blockers did not increase the risk of hospital-acquired pneumonia (odds ratio 1.53; 95% confi dence interval, 0.89 –2.61; = 0.12; I2  =  41%); however, this complication was increased in Objective: A systematic review of the literature to deter- the subgroup of patients who were fed enterally (odds mine the benefi t and risks of stress ulcer prophylaxis and ratio 2.81; 95% confi dence interval, 1.20–6.56; =  0.02; the moderating eff ect of enteral nutrition.
I2 = 0%). Overall, stress ulcer prophylaxis had no eff ect on hospital mortality (odds ratio 1.03; 95% confi dence Data Sources: MEDLINE, Embase, Cochrane Register of interval, 0.78–1.37; = 0.82). Th Controlled Trials, and citation review of rele vant primary however, higher in those studies (n = 2) in which patients were fed enterally and received a histamine-2 receptor Study Selection: Randomized, controlled studies that blocker (odds ratio 1.89; 95% confi dence interval, 1.04–evaluated the asso ciation between stress ulcer prophy- 3.44; =  0.04, I2  =  0%). Sensitivity analysis and meta- regression demonstrated no relationship between the only those studies that compared a histamine-2 receptor treatment eff ect (risk of gastrointestinal bleeding) and the classifi cation used to defi ne gastrointestinal bleeding, Data Extraction: Data were abstracted on study design, the Jadad quality score or the year the study was reported.
study size, study setting, patient population, histamine-2 receptor blocker and dosage used, incidence of clinically Conclusions
e results of this meta-analysis suggest that, in those patients receiving enteral nutrition, stress ulcer prophy-laxis may not be required and, indeed, such therapy may increase the risk of pneumonia and death. However, Deprtment of Critical Care Medicine, 606D Scaife Hall, 3550 Terrace Street, University of Pittsburgh, Pittsburgh, PA 15261, USA because no clinical study has prospectively tested the Full list of author information is available at the end of the article infl uence of enteral nutrition on the risk of stress ulcer prophylaxis, those fi ndings should be considered explora- tory and interpreted with some caution.
Chanpura and Yende Critical Care 2012, 16:322
bleeding in patients who received enteral nutrition, and In 1969, Skillman et al. [1] reported a clinical syndrome these individuals had higher risk of hospital-acquired of lethal “stress ulceration” in seven of 150 (5%) pneumonia (=  0.02, n  =  9 studies) and mortality consecutive intensive care unit (ICU) patients. Th ese (= 0.04, n = 2 studies).
patients had in common respiratory failure, hypotension, e results of this meta-analysis suggest that SUP may and sepsis. Subsequent studies confi rmed this fi nding not be benefi cial in patients who are fed enterally. Th and two meta-analyses published by Cook et al. [2] strength of this review article includes the rigorous demonstrated that both histamine-2 receptor blockers attempt to identify all relevant RCTs studies, consider (H2RBs) and sucralfate decreased the risk of bleeding and evaluate for possible confounding factors, such as from stress ulceration when compared to a placebo. year of publications, defi Stress ulcer prophylaxis (SUP) becomes regarded as the bleeding, quality of randomized controlled trials, and standard of care in patients admitted to the intensive publication bias. Limitations of this article includes lack Care Unit (ICU), and this intervention is currently of homogeneity in patient population, diff erence in endorsed by Surviving sepsis campaign and American diagnostic criteria used for major end-points, and only Society of Health System Pharmacists (ASHP) guidelines. three studies had patients with enteral nutrition.
e universal use of SUP has been reinforced with the adoption of “ventilator bundles.” Currently Joint Com- Recommendation
mission and the Institute for Healthcare Improvement SUP is benefi cial in high risk patients, including those recommend universal SUP as a core “quality” measure for that are on mechanical ventilation and have coagulopathy. SUP may cause unfavorable outcomes, such as hospital- Although the Agency for Healthcare Research and acquired pneumonia and Clostridium diffi Quality recommends using SUP only in patients on and clinicians must weigh risks and benefi ts in low-risk mechanical ventilation and high bleeding risk from patients, such as those who are not requiring mechanical coagulopathies, SUP is used in all critically ill patients ventilation or are receiving enteral nutrition.
and even outside the ICU setting. For example, estimates Competing interests
indicate that approximately 90% of critically ill patients The authors declare that they have no competing interests.
admitted to the ICU receive some form of SUP [3], and up to 52% of non-ICU patients receive SUP [4,5]. SUP is Author details
1The Clinical Research, Investigation, and Systems Modeling of Acute Illness
not without risks. Acid suppressive therapy is associated (CRISMA) Center, University of Pittsburgh, Pittsburgh, PA, USA. 2Department of with increased colonization of the upper gastrointestinal Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
tract with potentially pathogenic organisms and may Published: 29 October 2012 increase the risk of hospital-acquired pneumonia [5]. Furthermore, gastric acid is an important defense against References
the acquisition of Clostridium diffi Skillman JJ, Bushnell LS, Goldman H, et al.: Respiratory failure, hypotension, sepsis and jaundice. A clinical syndrome associated with lethal hemorrhage of acid suppressive therapy has been linked to an from acute stress ulceration of the stomach. Am J Surg 1969, 117:523–530.
increased risk of Clostridium diffi cile infection [6-8]. 2. Cook DJ, Witt LG, Cook RJ, et al.: Stress ulcer prophylaxis in the critically ill: us, understanding risks and benefi ts of SUP is impor- a metaanalysis. Am J Med 1991; 91:519–527.
Daley RJ, Rebuck JA, Welage LS, et al.: Prevention of stress ulceration: tant. For example, patients receiving enteral alimentation Current trends in critical care. Crit Care Med 2004; 32:2008–2013.
have a lower incidence of stress ulceration than unfed Janicki T, Stewart S: Stress-ulcer prophylaxis for general medical patients: patients [9]. Whether routine SUP in patients who receive a review of the evidence. J Hosp Med 2007; 2:86–92.
Herzig SJ, Howell MD, Ngo LH, et al.: Acid suppressive medication use and enteral feeding is benefi cial or harmful is not known.
the risk for hospital-acquired pneumonia. JAMA 2009, 301:2120–2128.
Marik et al. [10] conducted a meta-analysis of 17 6. Cunningham R, Dale B, Undy B, et al.: Proton pump inhibitors as a risk factor randomized clinical trials and postulated that SUP may cile diarrhea. J Hosp Infect 2003, 54:243–245.
have no added benefi ts in ICU patients who receive 7. Dial S, Alrasadi K, Manoukian C, et al.: Risk of Clostridium diffi cile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and ey examined the eff ect of diff erent case-control studies. Can Med Assoc J 2004, 171:33–38.
SUP regimes on the risk of gastrointestinal bleeding, 8. Louie TJ, Meddings J: Clostridium diffi cile infection in hospitals: risk factors hospital-acquired pneumonia, and mortality, stratifying and responses. Can Med Assoc J 2004, 171:45–46.
Pingleton SK, Hadzima SK: Enteral alimentation and gastrointestinal the studies based on enteral nutrition.
bleeding in mechanically ventilated patients. Crit Care Med 1983, 11:13–16.
e meta-analysis included a total of 1836 enrolled 10. Marik PE, Vasu T, Hirani A, Pachinburavan M: Stress ulcer prophylaxis in the between the years 1980 and 2004. Overall, SUP with a millennium: a systematic review and meta-analysis. Crit Care Med 2010, 38:2222-2228.
H2RB reduced the risk of GI bleeding (< 0.002) but had no eff ect on mortality. Th noted only in the subgroup of patients who did not Cite this article as: Chanpura T, Yende S: Weighing risks and benefi ts of
stress ulcer prophylaxis in critically ill patients. Critical Care 2012, 16:322.
receive enteral nutrition. SUP did not alter the risk of GI

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