Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis

Abstract

Importance: The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain.

Objective: To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care.

Data sources: The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022.

Study selection: Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo.

Data extraction and synthesis: Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework.

Main outcomes and measures: The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms.

Results: There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty.

Conclusions and relevance: Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.

Figure 1.. Flow Diagram of Search Strategy and Included Studies

^aOne study identified in previous meta-analyses was not able to be located from primary sources.

Figure 2.. Forest Plot for Hospital Mortality for the Comparison Between Selective Decontamination of the Digestive Tract (SDD) Compared With Standard Care

The dark blue boxes represent point estimates, and the sizes of the boxes are propotional to the weight. The whiskers represent confidence intervals. For the diamonds, the width represents all trials’ pooled estimate confidence interval and the middle point, the point estimate. ^aCredible intervals for bayesian estimates.

Figure 3.. Cumulative Incidence Plot for the Posterior Probability of the Risk Ratio (RR) for Mortality for Selective Decontamination of the Digestive Tract Compared With Standard Care

A, The cumulative posterior distribution of the estimated RR, with the y-axis corresponding to the probability the RR is less than or equal to the value on the x-axis. The blue area is related to the intervention being beneficial while the orange area is related to an RR greater than 1 (ie, the intervention associated with higher mortality vs the comparator). The bold vertical line indicates the median. B, The full posterior distribution of the estimated RR, with the bold vertical line indicating the median value and the area highlighted in blue indicating the percentile-based 95% credible interval. The dotted lines at an RR of 1 indicate no treatment effect. These panels demonstrate that the probability that selective decontamination of the digestive tract is associated with reduced mortality (to any extent) compared with standard care is more than 99%.

Figure 4.. Primary Outcome, Secondary Outcomes, and Subgroup Analyses for the Comparison of Selective Decontamination of the Digestive Tract (SDD) vs Standard Care

Subgroup and secondary outcomes are presented based on calculations using vague priors. Full details of the priors are presented in eAppendix 1 in the Supplement. ICU indicates intensive care unit. ^aConfidence interval. ^bTotal number of trials is 31 because the de Smet et al study contributes both intravenous (IV) and non-IV data. Participant numbers for the control group have been split evenly between the IV and non-IV groups so they remain the same as the main publication (ie, not double counted). ^cNo data in medical ICUs. ^dThe effect size is the log of the risk ratio. The exponent of the values provides the estimated risk ratio, also shown in eFigure 17 in the Supplement. ^eMedian duration of ventilation was 11.8 days (IQR, 8.7-15.1) in the SDD group and 12.5 days (IQR, 8.7-18.0) in the control group. ^fMedian intensive care unit length of stay was 17.2 days (IQR, 12.2-22.0) in the SDD group and 18.9 days (IQR, 12.6-27.0) in the control group. ^gMedian hospital length of stay was 27 days (IQR, 26.3-30.0) in the SDD group and 29 days (IQR, 27-31) in the control group.