Chanpura and Yende Critical Care 2012, 16:322 http://ccforum.com/content/16/5/322 J O U R N A L C LU B C R I T I Q U E
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; P < 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; P = 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; P = 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; P = 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; P = 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 Th
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 Commentary
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 (P = 0.02, n = 9 studies) and mortality consecutive intensive care unit (ICU) patients. Th
ese (P = 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
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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 (P < 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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