Selective decontamination of the digestive tract: a meta-analysis
ACP J Club. 1994 May-June;120:66. doi:10.7326/ACPJC-1994-120-3-066
Heyland DK, Cook DJ, Jaeschke R, et al. Selective decontamination of the digestive tract: an overview. Chest. 1994 Apr;105:1221-9.
To evaluate the effect of selective decontamination of the digestive tract (SDD) on pneumonia, mortality, and length of stay in the intensive care unit (ICU) in adult patients.
MEDLINE was searched for the years 1966 to 1992, using the terms decontamination, prophylaxis, intensive care units, antibiotics, prospective, random, drug therapy, prevention and control, and respiratory tract infections. Unpublished reports were searched in BIOSIS Previews, Federal Research in Progress, Conference Papers Index, National Technical Information Service database, and UNIVRES. Investigators of studies were contacted.
Randomized controlled trials of SDD in adult patients in the ICU using either oropharyngeal, nasogastric nonabsorbable antibiotics, or both with or without systemic antibiotics were included. Studies were excluded if they were duplicates of a published study, used historical controls, allocated patients nonrandomly, or included noncritically ill patients. Of 25 relevant trials identified (including 3395 patients), 20 were included in the pneumonia analysis and 24 in the mortality analysis.
Number of patients who developed pneumonia, number of deaths, and duration of ICU stay were determined for each study. The number of patients requiring treatment to prevent 1 episode of pneumonia was calculated. Assessment of studies for inclusion in the overview and methodologic quality was determined by 3 independent reviewers and was based on randomization, blinding, use of placebo, patient selection, population description, reproducibly described intervention, and outcome of all-cause mortality or pneumonia. Studies were subgrouped according to blinding, mortality rates, antibiotic regimens, and diagnostic approach to respiratory tract infections. There was 100% agreement among reviewers for study inclusion, and the kappa on agreement for methodologic quality ranged from 0.44 to 1.00.
SDD was found to reduce incidence of pneumonia compared with placebo (relative risk [RR] 0.46, 95% CI 0.39 to 0.56). 19 patients (CI 16 to 23) with a baseline risk of 10% would need to be treated to prevent 1 case of pneumonia. SDD reduced mortality (RR 0.87, CI 0.79 to 0.97). Treated patients and controls did not differ for length of ICU stay.
Selective decontamination of the digestive tract was effective in reducing the incidence of pneumonia and marginally reduced mortality in patients in the intensive care unit.
Source of funding: Not stated.
For article reprint: Dr. D.K. Heyland, Department of Clinical Epidemiology and Biostatistics, McMaster University Faculty of Health Sciences, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. FAX 905-577-0017
Nosocomial infection remains a major problem in the ICU because it may be associated with an increased incidence of organ failure and death. Evidence suggests that the organisms responsible are those that colonize the gastrointestinal and respiratory tracts of susceptible hosts. SDD is a technique designed to influence this colonization, suppressing the growth of potentially pathogenic aerobic gram-negative bacteria while allowing the continued presence of normal anaerobic bacteria in the gut.
Although many groups have reported a decrease in respiratory infections, few have reported any decrease in mortality. Several investigators concluded that this failure to show a decrease in mortality may be caused by study design. The meta-analyses by Heyland and colleagues and the Selective Decontamination of the Digestive Tract Trialists' Collaborative Group (TCG) attempted to address this problem as well as to summarize quantitatively all studies to date. Both meta-analyses used similar rigorous methods to retrieve, review, and analyze previous studies. Additionally, the TCG used intention-to-treat analysis by asking for original data from all trialists. The TCG analyzed 22 randomized clinical trials, whereas Heyland and colleagues analyzed 25. 20 were examined by both groups.
Not surprisingly, perhaps, the studies had similar results. A significant difference in respiratory infection rates existed between treatment and control groups, but neither study showed any convincing difference in mortality. Thus, neither paper has produced results that differ importantly from those of the original studies or of previous reviews. Both papers conclude that further evaluation is necessary to determine whether mortality is affected, in part because, even with these large meta-analyses, the sample size may have been insufficient. Heyland further recommends that widespread use of SDD is not warranted at the present time.
Answers to the question of whether SDD reduces mortality, therefore, continue to remain elusive. Aside from sample-size considerations, both meta-analyses are limited by the amount of information available from the original randomized controlled trials. Of most interest is the potential to decrease mortality in particular patient populations, such as young adults with trauma. Neither meta-analysis had information on the outcome of individual patients within the original studies and, therefore, could not pool outcomes for these specific patient populations.
If a clearly shown decrease in mortality is required before SDD is routinely used, then we must await the results of future research. If, on the other hand, a decrease in respiratory infection is of importance, then clinicians may wish to use SDD now. This use, however, must be with the caveat that the presumed benefit of reduced morbidity and, therefore, reduced resource utilization has not been shown. Indeed, current evidence, although based on crude proxies of resource utilization, suggests little or no benefit (1).
Both meta-analyses have suggested that future evaluation of SDD must adhere to a scrupulous clinical trial design, include adequate sample size, and address a priori the specific ICU populations to be studied. If a heterogeneous population is studied, information on individual outcomes, as shown by the TCG, should be retained to allow improved meta-analysis.
Further work also is required on the mechanism of action of SDD. Both reviews were based on the underlying premise of the randomized controlled trials that SDD reduced mortality via a reduction in respiratory infection. The gut may play a central role in the initiation and maintenance of the systemic inflammation seen in critical illness, regardless of nosocomial infection. Recent work suggests SDD may influence that inflammation by reducing gut translocation (2). As we come to better understand the role of the gut in critical illness, we may be able to better determine the value of SDD.
Derek C. Angus, MB, ChB, MPH
University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania, USA