NEW YORK (Reuters Health) - In mechanically ventilated patients, treatment with a proton pump inhibitor (PPI) carries a greater risk of gastrointestinal bleeding, pneumonia and Clostridium difficile infection than treatment with a histamine-2 receptor antagonist (H2RA), hints a large observational study.
But in JAMA Internal Medicine online February 17, the investigators caution that more study is needed before any change in practice is warranted.
"Comparative studies of adequate sample size are definitely needed and they must include assessments of infectious outcomes in addition to the prevention of clinically significant hemorrhage," first author Dr. Robert MacLaren from University of Colorado in Aurora, told Reuters Health by email.
The co-authors of a commentary published with the study agree, saying several "threats" to the study's conclusions are evident.
PPIs and H2RAs are often used for stress ulcer prophylaxis in the ICU. The more potent acid suppression of PPIs may reduce the rate of bleeding but boost infectious complications such as pneumonia and C. difficile infection (CDI).
To test this hypothesis, Dr. MacLaren's team performed a large retrospective cohort study using billing data on mechanically ventilated patients who received a PPI (21,873 patients) or H2RA (13,439 patients) for at least 48 hours while intubated.
They used propensity score-adjusted and propensity-matched multivariate regression models to control for potentially confounding factors.
Consistent with their hypothesis, pneumonia and CDI were more frequent in those receiving a PPI (38.6% and 3.8%, respectively) compared with those receiving an H2RA (27% and 2.2%, respectively).
Unexpectedly, however, the risk of GI hemorrhage was higher (not lower) in those receiving a PPI (5.9% vs 2.1%).
After adjusting for propensity score and covariates, PPI therapy was associated with an increased odds ratio of GI hemorrhage (2.24), pneumonia (1.2) and CDI (1.29). Similar results were obtained in the propensity-matched models of 8,799 patients in each cohort.
The investigators note that their findings go against a recent systematic review and meta-analysis comparing PPIs and H2RAs for stress-related muscosal damage, which found that PPIs cut the risk of bleeding by 64%.
"Ultimately, the findings from this study are provocative and represent the best efforts of the authors with the data and statistical techniques at hand to evaluate the intended and unintended consequences of stress ulcer prophylaxis in the intensive care unit," Dr. Richard Kim and Dr. Christopher Goss of the University of Washington in Seattle, write in their commentary.
"While well-designed randomized clinical trials remain the gold standard for determining efficacy, observational cohort studies provide key insights into clinical effectiveness in real-world settings. The primary challenges to interpreting the results of MacLaren and colleagues is the absence of a clear biologic model to explain the results and the potential for persistent indication bias away from the null hypothesis," they note.
"Additional studies will be needed to determine if the increased risk of pneumonia, CDI and acute GI hemorrhage in mechanically ventilated ICU patients in this study is due to the administration of a PPI instead of an H2RA or a result of residual indication bias," Dr. Kim and Dr. Goss conclude.
SOURCE: http://bit.ly/MIiOl1 and http://bit.ly/1l5wm8s
JAMA Intern Med 2014.
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