Do proton pump inhibitors increase the incidence of nosocomial pneumonia and related infectious complications when compared with histamine-2 receptor antagonists in critically ill trauma patients?

doi:10.1016/j.cursur.2004.03.014

Current Surgery

Volume 61, Issue 5, September–October 2004, Pages 452-458

https://doi.org/10.1016/j.cursur.2004.03.014 Get rights and content

Abstract

Background

Proton pump inhibitors (PPI) may increase the risk of nosocomial pneumonia caused by profound irreversible gastric acid suppression. The study purpose was to characterize differences in nosocomial pneumonia and related infections in trauma patients administered either histamine₂-receptor antagonists (H2RA) or PPI.

Methods

Observational evaluation of consecutive critically ill adult trauma patients administered either omeprazole or famotidine during a 22-month period. Nosocomial infection was evaluated daily based on published CDC definitions.

Results

Eighty of 269 patients fulfilled study criteria. The PPI group (n = 40) exhibited increased baseline risk for infection, demonstrated by higher ISS (p = 0.020), more chest tube placements (p = 0.031), and increased chest trauma (p = 0.025). Overall number of patients infected per group included 33% and 40% of patients administered PPI and H2RA, respectively (p = 0.64). Despite baseline differences, the incidence of nosocomial infection was similar (p = 0.87), and extrapolation of pneumonia based on 1000 patient days revealed a ratio 51.7 vs 52.2 in the PPI vs H2RA groups, respectively, which was not significant (p = 0.99).

Conclusions

Proton pump inhibitor administration does not increase risk of nosocomial pneumonia or other nosocomial infections compared with H2RA therapy in the critically ill trauma patient.

Introduction

Trauma patients with severe injury require prolonged mechanical ventilation and often develop additional risk factors such as coagulopathy, acute renal failure, or sepsis, which increase the risk for development of stress ulceration. However, the incidence of stress-related gastrointestinal (GI) bleeding has declined substantially during the past 20 years, related in part to improved resuscitation measures and therapeutic prophylactic agents. In fact, the incidence of stress-related GI bleeding ranges from 2.8% to 6% in the acutely ill,1, 2, 3 with registry data specific to trauma patients indicating an even lower frequency of less than 1%.4 Although evidence suggests antisecretory agents used for prevention including histamine₂-receptor antagonists (H2RA) and proton pump inhibitors (PPI) are effective,3, 5, 6 they are overprescribed and often patients are unnecessarily discharged on the antisecretory therapy administered during hospitalization.7, 8, 9

The prevention of stress-related GI bleeding is important in the high-risk trauma patient. Concerns and controversy surrounding the potential complications of gastric acid suppression have been described. Areas of concern have been identified with respect to their impact on the rates of pneumonia and other infectious complications in patients receiving H2RA or PPI therapies. The purpose of prescribing these agents is to maintain gastric pH above 4, which is a surrogate measure for reduction in GI bleeding risk.6, 10 Several small studies have indicated superior gastric acid suppression with PPI compared with the H2RA.6, 10, 11, 12 This is related, in part, to tolerance demonstrated with H2RA and irreversible acid suppression associated with PPI.6, 10, 11, 12 It is suggested that the higher the gastric pH, the greater the risk of developing nosocomial pneumonia because of microbial growth favoring an alkaline environment.3, 6, 13Therefore, it has been proposed that PPI therapy may result in a greater incidence of pneumonia, although data exclusive to the trauma population is limited to evaluate this theory. Importantly, pneumonia is the most common infectious process in the acute trauma population and is associated with increased mortality.14, 15 The objective of the current study was to characterize differences in the frequency of nosocomial pneumonia and other related infectious complications in critically ill trauma patients administered either a H2RA or a PPI.

Section snippets

Study population

This was a nonrandomized, observational study to evaluate nosocomial infection in patients receiving a PPI or H2RA. All patients admitted to the intensive care unit of a level-I regional trauma center secondary to a traumatic event who received antisecretory therapy with either a H2RA or a PPI were screened for study eligibility. Patients who received H2RA, famotidine 20 mg intravenously or orally twice daily, were evaluated for nosocomial infection retrospectively from September 2000 to June

Results

Two hundred sixty-nine patients were evaluated for inclusion into the study. Eighty patients were included (n = 40 omeprazole, n = 40 famotidine); 189 patients were eliminated from analysis because of exclusion criteria (intensive care unit admission less than 48 hours, n = 120; antisecretory therapy, n = 55; incomplete data, n = 5; burn injury, n = 4; immunocompromised, n = 3; pregnancy, n = 1; and chronic antibiotics, n = 1). The majority of patient demographics, vital signs, and severity of

Discussion

This observational study is the first to directly compare the potential for infectious complications of PPI and H2RA in critically ill trauma patients. We postulated that a higher incidence of nosocomial pneumonia would occur in PPI patients because of the greater elevation of gastric pH. The lack of significant data regarding these agents in critically ill trauma patients already at increased risk of infection required further evaluation. Our study reports the incidence of nosocomial pneumonia

References (29)

R.J. Nardino et al.
Overuse of acid-suppressive therapy in hospitalized patients
Am J Gastroenterol
(2000)
H.S. Merki et al.
Do continuous infusions of omeprazole and ranitidine retain their effect with prolonged dosing?
Gastroenterology
(1994)
L. Lachman et al.
Twenty-four-hour intragastric pHTolerance within 5 days of continuous ranitidine administration
Am J Gastroenterol
(2000)
P. Netzer et al.
Effect of repeated injection and continuous infusion of omeprazole and ranitidine on intragastric pH over 72 hours
Am J Gastroenterol
(1999)
J.S. Garner et al.
CDC definitions for nosocomial infections, 1988
Am J Infect Control
(1988)
E.W. Hanisch et al.
A randomized, double-blind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia
Am J Surg
(1998)
D. Yildizdas et al.
Occurrence of ventilator-associated pneumonia in mechanically ventilated pediatric intensive care patients during stress ulcer prophylaxis with sucralfate, ranitidine, and omeprazole
J Crit Care
(2002)
ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board...
D. Cook et al.
Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group
Crit Care Med
(1999)
D. Cook et al.
A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation
N Engl J Med
(1998)

R.K. Simons et al.

A risk analysis of stress ulceration after trauma

J Trauma

(1995)

M.R. Lasky et al.

A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients

J Trauma

(1998)

M.J. Levy et al.

Comparison of omeprazole and ranitidine for stress ulcer prophylaxis

Dig Dis Sci

(1997)

J.F. Barletta et al.

Stress ulcer prophylaxis in trauma patients

Crit Care

(2002)

Cited by (35)

Ventilator-associated pneumonia: The potential critical role of emergency medicine in prevention
2012, Journal of Emergency Medicine
Citation Excerpt :
Meta-analyses of stress ulcer prophylaxis studies have shown that prophylaxis with sucralfate or histamine-2 receptor antagonists is associated with minimal risk of VAP, although there is still controversy about which is optimal (48–50). Two groups that examined the effect of proton pump inhibitors on nosocomial pneumonia found no significant differences in pneumonia rates compared to histamine-2 receptor antagonists or sucralfate (51,52). However, in a very recent, large, prospective pharmacoepidemiologic cohort study in hospitalized (but not ICU patients), Herzig et al. found that the incidence of hospital-acquired pneumonia was higher in patients exposed to acid-suppressive medication than in the unexposed group (4.9% vs. 2.0%, respectively; odds ratio [OR], 2.6; 95% confidence interval [CI], 2.3–2.8) (53).
Delivery of critical care within a certain window of opportunity is paramount in many disease states, and providing the right care to these patients at the right time in the Emergency Department (ED) can significantly reduce mortality. However, aggressive treatment of these patients often requires endotracheal intubation and mechanical ventilation either in the pre-hospital or ED phase of care. Care of mechanically ventilated patients in the ED is not trivial or without potential complications, including ventilator-associated pneumonia (VAP).
This article summarizes the epidemiology, pathophysiology, and specific risk factors associated with VAP and provides evidence-based recommendations for its prevention. We emphasize practices that are particularly important in the early stages of care of intubated, mechanically ventilated patients; thus, they should be instituted in the ED.
Specifically, we recommend continuous backrest elevation of 30–45°, chlorhexidine application to the oral cavity after intubation and every 12 h thereafter, orotracheal intubation with a tube that enables continuous subglottic suctioning, and cuff pressure assessments after intubation and every 4 h thereafter to maintain pressure between 20 and 30 cm H₂O.
In-hospital gastric protection with proton pump inhibitors: Adverse effects beyond (over)utilization?
2010, Italian Journal of Medicine
Proton pump inhibitors (PPIs) have provided important benefits in the management of gastroesophageal reflux disease (GERD), peptic ulcer disease and in the prevention of non steroidal antiinflammatory drugs and aspirin-related ulcer complications. PPIs are also the most commonly used medications for stress ulcer prophylaxis, despite little evidence to support their use in non-intensive care unit.
Considering the widespread use of PPIs, these agents’ overall safety profile is unquestionable. However, there is growing evidence that PPIs use may be associated with an increased risk of enteric infections, pneumonia, hip fractures, vitamin B12 deficiency. Overall, until now, none of these adverse effects have discouraged the PPIs treatment. Recently attention has been placed on a more important potential adverse effect of PPIs, their interaction with clopidogrel to which they are associated for the prophylaxis of gastrointestinal bleeding. Preliminary results of laboratory tests suggest that omeprazole reduces clopidogrel's antiplatelet effect. The interaction seems to involve the competitive inhibition of the CYP2C19 isoenzyme. The effect appears to be clinically important, as some retrospective studies have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. Some studies indicate that pantoprazole and esomeprazole are not associated with impaired response to clopidogrel. However, the available data for PPIs other than omeprazole do not allow definitive conclusions to be drawn about whether is a class effect.
Specifically designed and randomized clinical studies are needed to define the interaction between PPIs and clopidogrel. Moreover, alternative treatment strategies with histamine-2 receptor antagonists that are not dependent on cytochrome p450 2C19 should be tested in future studies.
Do proton-pump inhibitors increase the risk for nosocomial pneumonia in a medical intensive care unit?
2008, Journal of Critical Care
Citation Excerpt :
These differences may account for the conflicting results because our cohort was at a higher risk of NP development. It has been proposed that gastric colonization may be induced by PPIs due to their capacity to maintain a pH of 4 or higher for a longer time than H2 blockers and to the fact that tachyphylaxis does not develop with prolonged use as it does with H2 blockers [12]. In addition to an increase in gastric colonization secondary to pH modification, PPIs may also impair neutrophil function and natural killer cell activity by decreasing extracellular and intracellular oxygen intermediate production [19].
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.
Retrospective cohort study in a medical intensive care unit of a 554-bed, university-affiliated, academic medical center.
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).
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.
NSAIDs, Risks, and Gastroprotective Strategies: Current Status and Future
2008, Gastroenterology
Association between gastric acid suppressants and Clostridium difficile colitis and community-acquired pneumonia: analysis using pharmacovigilance tools
2007, International Journal of Infectious Diseases
Citation Excerpt :
In addition, five epidemiological investigations (case–control, nested case–control, prospective cohort, cross-sectional) have reported an increased risk of community-acquired/nosocomial pneumonia and community-acquired C. difficile disease in patients receiving PPIs and/or H2 receptor antagonists.4–8 Two other epidemiological studies either did not find H2 receptor antagonists and PPIs as risk factors for community-acquired pneumonia9 or did not find an association between PPIs and nosocomial pneumonia when compared to H2 receptor antagonists in patients in a trauma unit.10 These nine studies were published in the years 2003–2005.
Recent epidemiological studies identifying an association between some classes of gastric acid suppressants and Clostridium difficile colitis and community-acquired pneumonia prompted our analysis. Our objective was to retrospectively apply data mining algorithms (DMAs) to the Food and Drug Administration (FDA) drug safety database to see if they might have directed/redirected attention to the reported association of gastric acid suppressive drugs with C. difficile colitis and community-acquired pneumonia, prior to the published epidemiological findings that supported the association.
Two statistical DMAs, proportional reporting ratios (PRRs) and multi-item gamma Poisson shrinker (MGPS), were applied to a spontaneous reporting system (SRS) database to identify signals of disproportionate reporting (SDRs).
SDRs related to community-acquired pneumonia were observed for two proton pump inhibitors (lansoprazole and omeprazole), two H₂ antagonists (famotidine and roxatidine), and one antacid (magnesium silicate hydroxide). For C. difficile colitis, an SDR was generated for one proton pump inhibitor (lansoprazole).
Although our analysis suggests that there may be an association between the SDRs using SRS data and the epidemiological findings, these results may not have alerted public health professionals in advance of published studies to an association between proton pump inhibitors/gastric acid suppressants and C. difficile colitis or community-acquired pneumonia. However, the analysis reveals the potential utility of DMAs to direct attention to more subtle indirect drug adverse effects in SRS databases that as yet are often identified from epidemiological investigations.
Prophylactic acid- suppressive therapy in hospitalized adults: Indications, benefits, and infectious complications
2017, Critical Care Nurse
Acid-suppressive therapy for prophylaxis of stress ulcer bleeding is commonly prescribed for hospitalized patients. Although its use in select, at-risk patients may reduce clinically significant gastrointestinal bleeding, the alteration in gastric pH and composition may place these patients at a higher risk of infection. Although any pharmacologic alteration of the gastric pH and composition is associated with an increased risk of infection, the risk appears to be highest with proton pump inhibitors, perhaps owing to the potency of this class of drugs in increasing the gastric pH. With the increased risk of infection, universal provision of pharmacologic acid suppression to all hospitalized patients, even all critically ill patients, is inappropriate and should be confined to patients meeting specific criteria. Nurses providing care in critical care areas may be instrumental in screening for appropriate use of acid-suppressive therapy and ensuring the drugs are discontinued upon transfer out of intensive care or when risk factors are no longer present.

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Original reportDo proton pump inhibitors increase the incidence of nosocomial pneumonia and related infectious complications when compared with histamine-2 receptor antagonists in critically ill trauma patients?

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Am J Gastroenterol

Gastroenterology

Am J Gastroenterol

Am J Gastroenterol

Am J Infect Control

Am J Surg

J Crit Care

Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group

Crit Care Med

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation

N Engl J Med

A risk analysis of stress ulceration after trauma

J Trauma

A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients

J Trauma

Comparison of omeprazole and ranitidine for stress ulcer prophylaxis

Dig Dis Sci

Stress ulcer prophylaxis in trauma patients

Crit Care

Original report
Do proton pump inhibitors increase the incidence of nosocomial pneumonia and related infectious complications when compared with histamine-2 receptor antagonists in critically ill trauma patients?