Elsevier

Journal of Critical Care

Volume 23, Issue 4, December 2008, Pages 513-518
Journal of Critical Care

A Focus on Sepsis
Do proton-pump inhibitors increase the risk for nosocomial pneumonia in a medical intensive care unit?

https://doi.org/10.1016/j.jcrc.2007.11.003Get rights and content

Abstract

Purpose

The aim of this study was to determine whether the use of gastric acid-suppressive agents increases the risk of nosocomial pneumonia (NP) in a medical intensive care unit population.

Materials and Methods

Retrospective cohort study in a medical intensive care unit of a 554-bed, university-affiliated, academic medical center.

Results

A total of 924 medical records were included in the database during the study period of which 787 patients were included in the study. Out of this cohort,104 patients (13.2%) eventually developed a NP. The risk for patients who received proton-pump inhibitors (adjusted hazard ratio [AHR] 0.63; 95% CI 0.39-1.01) was not significantly different than in non exposed patients. Variables most strongly associated with NP were the administration of sedatives or neuromuscular blockers for at least 2 consecutive days (AHR 3.39;95% CI 1.99-5.75), an Acute Physiology and Chronic Health Evaluation II (APACHE II) severity score greater than 15 (AHR, 3.34; 95% CI 1.82-6.50), and presence of a central venous catheter (AHR, 1.76; 95% CI 1.12-2.76).

Conclusions

Prior use of a proton-pump inhibitor did not correlate with a significant increase in the risk of developing NP. This risk was higher with the administration of sedatives or neuromuscular blockers, increased disease severity, and placement of a central venous catheter.

Introduction

Nosocomial pneumonia (NP) is the most frequent hospital acquired infection and is associated with considerable morbidity and mortality, accounting for 25% of all infections in the intensive care unit (ICU) [1]. Patients receiving mechanical ventilation are particularly prone to developing this complication as ventilator associated pneumonia develops in 9% to 27% of all intubated patients [2]. The main mechanism for acquisition is through the aspiration of oropharyngeal secretions into the lower bronchial tree [3]. Many risk factors have been identified including male sex, age, admission for burns, trauma or central nervous diseases, history of respiratory or cardiac diseases, immunosuppression, supine patient positioning, presence of an artificial airway, enteral and parenteral nutrition, sedatives and analgesics, blood transfusions, and hyperglycemia [4]. Stress ulcer prophylaxis with both antacids and histamine type 2 (H2) blockers has also been identified as a risk factor for ICU acquired pneumonia [5]. Increase in gastric colonization secondary to pH modification has been shown and may cause retrograde colonization of the pharynx [6]. In a landmark trial comparing ranitidine to sucralfate, there was a trend towards an increase in the incidence of pneumonia in the ranitidine group [7].

Proton-pump inhibitors (PPIs) are increasingly used in the ICU for both stress ulcer prophylaxis and gastrointestinal (GI) bleeding [8]. As these agents are more efficacious in elevating gastric pH, the risk of gastric colonization and subsequent pharyngeal colonization may be higher. In one study, bacterial overgrowth, which was defined as more than 105 cfu/ml, was significantly more present in patients treated with omeprazole than with cimetidine (53% vs 17%; P < .05) [9]. Recently, observational studies in the community setting have associated the use of PPIs with a significant increase in the risk of community-acquired pneumonia in both adults and children [10], [11]. In the hospital setting, one small prospective observational study failed to show an increase in the risk of NP with PPIs compared to H2 blockers [12]. One randomized trial has shown a trend towards an increased risk associated with PPI use, whereas another small trial has reported a protective effect compared to H2 blockers [13], [14]. However, these findings were not corroborated by the largest trial comparing PPIs to H2 blockers [15]. Hence, the objective of the present study was to determine whether the use of PPIs increases the risk of nosocomial pneumonia in a medical intensive care unit (MICU) population after adjusting for other confounding factors.

Section snippets

Study design

This retrospective cohort study included all patients admitted to the MICU of the Hôpital du Sacré-Coeur de Montréal between March 14, 2002, and May 31, 2004. The date of admission to the unit was considered the index date. For patients who had multiple stays in the MICU during the study period, only the first admission was considered. Patients were considered as having an NP if there was a clinical diagnostic for NP between their second day of admission to the MICU and until MICU discharge.

Study sample

The

Baseline characteristics

A total of 924 medical records were included in the IMPACT database during the study period. After excluding 83 readmission records, 14 records with missing data, and 40 prevalent NP cases, 787 patients who were at their first admission in the MICU from the beginning of the selection process were included in the cohort. From this cohort, 104 (13.2%) patients eventually developed NP. The cumulative mortality incidence within 30 days of NP diagnostic was 23.1% (24 of the 104 patients). Mean and

Discussion

In this cohort of MICU patients exposed to multiple risk factors for NP, the hypothesis that gastric acid suppression may predispose to development NP has not been confirmed despite sufficient power to detect such a difference. In fact, use of PPIs tended toward a protective effect, whereas use of H2 blockers seemed to have no effect on the incidence of NP. The elevated exposure to important risk factors such as older age, high APACHE score, and tracheal intubation and the fact that the

Acknowledgments

The authors thank Catherine Cellini for the bibliographical research and Philippe Rico for coordinating the local IMPACT Project and providing access to the database.

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