Gastric pH and nosocomial pneumonia: a meta-analysis
ACP J Club. 1992 Jan-Feb;116:8. doi:10.7326/ACPJC-1992-116-1-008
Cook DJ, Laine LA, Guyatt GH, Raffin TA. Nosocomial pneumonia and the role of gastric pH. A meta-analysis. Chest. 1991 Jul;100:7-13.
To evaluate the effect of drugs for prevention of stress ulceration on the rate of nosocomial pneumonia in critically ill patients, using meta-analysis.
Citations from 1966 to 1990 were retrieved from MEDLINE and EMBASE using the key and text words pneumonia, critical care, hemorrhage (gastrointestinal), and clinical trials. SCISEARCH was searched to locate additional articles. Bibliographies were also scanned to obtain additional references.
Potential articles for inclusion were randomized, controlled trials comparing rates of nosocomial pneumonia in critically ill patients receiving drugs for stress ulcer prophylaxis or placebo. Articles were identified by duplicate blind review. The full text of eligible articles was obtained for a final selection. 8 of 48 randomized, controlled trials on stress ulcer prophylaxis met the criteria, including 3 studies reported as abstracts and 1 study reported at a symposium.
2 independent reviewers evaluated the methodologic quality, sample characteristics, intervention, and outcome of each study using additional information from the authors if needed.
The 8 trials included 535 patients. Patients receiving histamine receptor antagonists or antacids in 4 trials had an increased incidence of pneumonia, whereas those receiving pH-altering drugs in the remaining 4 trials had a decreased incidence of pneumonia. The statistical test for homogeneity indicated that the results of the 8 trials could not be combined; therefore 2 hypotheses were examined: 1) Titration of prophylactic treatment to achieve a specific gastric pH alters the incidence of nosocomial pneumonia, and 2) sucralfate differs from pH-altering drugs in its effect on the incidence of pneumonia.
A sensitivity analysis of the 3 trials in which pH-altering treatment was titrated to pH ≥ 3.5 found no significant effect on the incidence of pneumonia (common odds ratio [COR], 0.66; 95% CI, 0.24 to 1.78). In trials comparing sucralfate with pH-raising drugs, there was a trend toward a decreased rate of pneumonia with sucralfate (COR, 0.55; CI, 0.28 to 1.06).
Available data suggest that stress ulcer prophylaxis with pH-altering agents has no effect on the incidence of nosocomial pneumonia. Sucralfate may be associated with a lower incidence of pneumonia as compared with pH-altering drugs.
Source of funding: No external funding.
Address for article reprint: Dr. D.J. Cook, Department of Clinical Epidemiology and Biostatistics, McMaster University Medical Centre, Hamilton, Ontario L8N 3Z5.
Stress ulcer bleeding has been found to affect mainly patients on mechanical ventilation or with coagulopathy or the multiple organ system failure syndrome. For these conditions, the pathophysiology of stress ulceration and resultant gastrointestinal (GI) bleeding may not be easily amenable to prophylaxis. Worse still, there is now concern about increased gastric microbial growth associated with alteration of gastric pH. A consequence of gastric microbial colonization is transmission of organisms to the tracheobronchial tree by aspiration, leading to nosocomial pneumonia.
Parallel to the elucidation of the mechanisms involved in nosocomial pneumonia, important advances have been made in its diagnosis in mechanically ventilated patients. In the past, nosocomial pneumonia has been diagnosed clinically with criteria of fever, leukocytosis, purulent sputum (usually with pathogens isolated by culture), and changing infiltrates on the chest radiograph. Recent studies have definitively shown that these clinical criteria are not accurate in ventilated patients (1). Accurate diagnosis requires quantitative cultures of the protected specimen brush (PSB) or bronchoalveolar lavage (BAL) in diagnosing nosocomial pneumonia (2, 3).
What has this to do with the reviewed articles? Both articles are meta-analyses relating to the efficacy and consequences of stress ulcer prophylaxis, mainly in mechanically ventilated patients. Meta-analysis is an increasingly used tool that applies statistical principles to the evaluation of quantitative results of study outcomes. These two studies nicely demonstrate what I consider to be the "up" side and "down" side of this type of analysis. Meta-analysis is often helpful when the results can indeed be quantitated. Tryba's review of 40 studies indicates that any form of prophylaxis is better than nothing, and sucralfate appears to be better than antacids or H2 antagonists for pneumonia and mortality. Cook and associates also analyzed the effect of drugs for stress ulcer prophylaxis on the development of nosocomial pneumonia. These authors have extensive experience in this type of analysis and the abstracted article reflects this experience. Unfortunately for both meta-analyses, nosocomial pneumonia was diagnosed clinically in all the studies reviewed. Therefore, although the methods of the meta-analyses may be excellent, the studies they review are flawed. The clinical diagnosis of nosocomial pneumonia is an unacceptable substitute for diagnosis using quantitative cultures of PSB or BAL. It is impossible, in my opinion, to either verify or refute the conclusions of the meta-analyses because the true frequency of nosocomial pneumonia cannot be found in the reviewed data. Therefore, I feel strongly that clinicians should not let fear of inducing nosocomial pneumonia affect decisions about stress ulcer prophylaxis on the basis of these reviews.
I heartily agree with Cook and colleagues that further information regarding the effect of stress ulcer medication on the development of nosocomial pneumonia should include studies in which appropriate diagnostic measures are used.*
Susan K. Pingleton, MD
The University of Kansas Medical Center Kansas City, Kansas
*Inaccurate diagnosis might have obscured the relationship between prophylaxis and pneumonia in the study by Cook and colleagues, but, in reply to Dr. Pingleton's commentary, Dr. Tryba points out that this is not a plausible explanation for better efficacy of sucralfate in these studies for either pneumonia or death. Thus, sucralfate may be the preferred form of stress ulcer prophylaxis.—The Editor