Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

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Article Reviewed:

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Effectiveness and Cost of Selective Decontamination of the Digestive Tract in Critically Ill Intubated Patients. A randomized, double-blind, placebo-controlled, multicenter trial

Sanchez Garcia MS, Cambronero Galache JA, Diaz JL, et al.

Am J Respir Crit Care Med 1998;158: 908-916. [abstract] [full-text for subscribers only]

Reviewed by Paulette Johnson, MD and Barry Markovitz, MD, Washington University and St. Louis Children's Hospital

Review posted March 5, 1999

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I. What is being studied?:

The study objective:

To determine if selective decontamination of the digestive tract (SDD) could be used to decrease morbidity and cost of care in critically ill intubated patients.

The study design:

Randomized, double-blind, placebo controlled trial

The patients included:

271 adults in 5 ICU's in Madrid expected to be intubated for 48 hrs

The patients excluded:

Pregnant, allergies to the study drugs, organ transplantation, and no need for nasogastric (ng) tube.

The interventions compared:

Two sets of comparisons were made. In patients not infected (and not already receiving intravenous antibiotics) at the start of the trial, oral gentamicin, polymyxin E, and amphotericin B with ng gentamicin, polymyxin E, and amphotericin B, with intravenous ceftriaxone was compared with placebo. In patients considered infected already at the trial's onset, only the topical (oral and ng) components were compared with placebo.

The outcomes evaluated:

Early (< 5 days) or late (> 5 day) pneumonia (defined as a compatible, new and persistent infiltrate on chest x-ray, with at least three of the following: fever (temperature > 38°C), peripheral leukocytosis (> 12,000/mm3), or leukopenia (< 3,000/mm3), purulent tracheal aspirate, and growth of a potentially pathogenic microorganism in lower-airway sections), costs (total), and mortality.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes. A computer generated random number table was used, stratified by center.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes. All patients were followed to trial completion.

Were patients analyzed in the groups to which they were randomized?

Yes. No patients crossed over to the other group.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

Yes. Treatment and placebo preparations, prepared by the pharmacy, were indistinguishable. Treatment codes were maintained in sealed envelopes.

4. Were the groups similar at the start of the trial?

Yes. Except for more patients with chronic renal failure and impaired consciousness on admission in the SDD group, there were no differences in age, gender, underlying condition, diagnoses, APACHE II scores, and adjunctive treatments, e.g., enteral feeding, antibiotics.

5. Aside from the experimental intervention, were the groups treated equally?

Except for noting that patients were "openly randomized to receive sucralfate or alkalinizing agents to balance gut-protection medication" (and there was no difference between groups in the use of these medications), no mention is made regarding other aspects of patient care.

III. What were the results?

1. How large was the treatment effect?

Category 1: IV Ceftriaxone + SDD vs Placebo + Placebo (patients not infected at outset of trial)

Early onset pneumonia

1. Relative Risk: 0.28 (0.12, 0.66)*
2. Relative Risk Reduction: 72% (88%, 44%)
3. Absolute Risk Reduction: 0.37 (0.17, 0.57)
4. Number needed to treat (NNT): 2.7 (2, 6)

Ventilator Associated Pneumonia

1. Relative Risk: 0.342 (0.12, 0.95)
2. Relative Risk Reduction: 0.66 (78%, 5%)
3. Absolute Risk Reduction: 0.219 (0.04, 0.40)
4. NNT: 4.6 (2, 25)

Category 2: Antibiotics + SDD vs Antibiotics + Placebo (patients already infected at outset of trial)

Early onset pneumonia

1. Relative Risk: 0.73 (0.43, 1.24)
2. Relative Risk Reduction: 0.27 (67%, -24%)
3. Absolute Risk Reduction: 0.07 (0.19, -0.05)
4. NNT: 14 (5-infinity)

Ventilator Associated Pneumonia

1. Relative Risk: 0.41 (0.22, 0.78)
2. Relative Risk Reduction: 0.59 (78%, 22%)
3. Absolute Risk Reduction: 0.162 (0.05, 0.27)
4. NNT: 6 (4, 20)

Totals for VAP (SDD vs. Placebo, both categories combined)

1. Relative Risk: 0.39 (0.23, 0.67)
2. Relative Risk Reduction: 0.61 (77%, 33%)
3. Absolute Risk Reduction: 0.18 (0.27, 0.09)
4. NNT: 6 (4, 11)

*Numbers shown in parenthesis indicate the confidence intervals

Significant reductions in numbers of patients on antibiotics (108 vs 128, p = 0.04), days on antibiotics (12 vs 20, p = 0.015), and duration of intubation for survivors (8.5 days vs 12 days, p = 0.01) was demonstrated. There was a 21% reduction of total cost per survivor in the SDD treated group.

There was no statistically significant difference in mortality between the groups (38.9 vs 47.1%). This may reflect the lack of a direct cause and effect relationship established between VAP and death.

2. How precise was the estimate of the treatment effect?

The confidence intervals reported above tell us, for example, that we can be 95% certain that the absolute risk reduction in VAP overall was between 9% and 27%.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

This study provides rather impressive evidence that ventilator-associated pneumonia can be reduced in critically ill, mechanically ventilated adults by the use of selective decontamination of the digestive tract. The obvious question for pediatric critical care is whether the pathobiology of VAP is similar enough in children compared to adults to suggest such therapy would be useful for us. This issue is uncertain.

2. Were all clinically important outcomes considered?

Yes. They also reported information regarding the microbiology of their patients, as selecting for resistant organisms with this treatment could be raised as a concern. Indeed, in the SDD patients carriage of gram positive cocci increased significantly over time compared to placebo treated patients.

3. Are the likely treatment benefits worth the potential harms and costs?

The treatment benefit appears significant with little or no harm identified and at a low cost. In addition, the results of this trial are consistent with other investigations and systematic reviews of randomized controlled trials evaluating SDD. It is clear that SDD decreases VAP. However, whether reducing VAP leads to decreased morbidity, mortality and cost is unproven. Most RCT's failed to show a decrease in mortality.

References

1. Kollef MH. The role of selective digestive tract decontamination on mortality and respiratory tract infections. A meta-analysis. Chest 1994; 105:1101-08. [abstract]
2. Misset B, Artigas A, Bihari D et al. Short-term impact of the European Consensus Conference in the use of Selective Decontamination in the Digestive tract with antibiotics in ICU patients. Intensive Care Med 1996; 22:981-84. [abstract]
3. Liberati A, D'Amico R, Pifferi S, Leonetti C, Torri V, Brazzi L, Tinazzi A. Antibiotic prophylaxis for respiratory tract infections in adult patients in intensive care units. The Cochrane Database of Systematic Reviews. 1998 Volume (3). [abstract]

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