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Review: Selective digestive decontamination reduces mortality more than chlorhexidine in general ICU patients

Question In patients in general intensive care units (ICUs), what is the relative efficacy of selective digestive tract decontamination (SDD), selective oropharyngeal decontamination (SOD), and topical oropharyngeal chlorhexidine for preventing mortality? Review scope Included studies compared SDD (poorly absorbable antibiotics applied to the oropharynx and stomach plus empirical IV antibiotics), SOD (poorly absorbable antibiotics applied to the oropharynx only), or topical oropharyngeal chlorhexidine (chlorhexidine applied to the oropharynx) with placebo or usual care in adults in general ICUs. Studies that included children only or specialized populations (such as cardiac surgery); assessed combinations of oropharyngeal plus gastric application of antibiotics, or gastric or subglottic application; or delivered active topical drugs to both groups or empirical IV antibiotics to the control group were excluded. The outcome was mortality. Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Register of Clinical Trials (all 1984 to Dec 2012); published meta-analyses and congress abstracts (2005 to 2012); and controlled-trials.com were searched for randomized controlled trials (RCTs). 29 RCTs {n =14723}* met the selection criteria. 14 RCTs assessed SDD, 3 assessed SOD, 11 assessed chlorhexidine, and 1 assessed SDD and SOD. Sequence generation was adequate in 18 RCTs, and allocation concealment was adequate in 20 RCTs. Main results A generalized linear modelling framework was used for analysis of mixed treatment comparisons that combined data from direct and indirect comparisons. Mixed treatment comparisons are shown in the Table. Conclusion In patients in general intensive care units, selective digestive tract decontamination reduces mortality more than chlorhexidine or placebo or usual care; selective oropharyngeal decontamination reduces mortality more than chlorhexidine. Mixed treatment comparisons for mortality in patients in general intensive care units Comparisons Odds ratio (95% credible interval) SDD vs placebo or usual care 0.74 (0.63 to 0.86) SDD vs chlorhexidine 0.61 (0.47 to 0.78) SOD vs placebo or usual care 0.82 (0.62 to 1.02) SDD vs SOD 0.91 (0.70 to 1.19) SOD vs chlorhexidine 0.67 (0.48 to 0.91) Chlorhexidine vs placebo or usual care 1.23 (0.99 to 1.49) SDD = selective digestive tract decontamination (poorly absorbable antibiotics applied to the oropharynx and stomach plus empirical IV antibiotics); SOD = selective oropharyngeal decontamination (poorly absorbable antibiotics applied to the oropharynx only). Commentary Of all the questions that have been addressed by RCTs in critical care, none has shown a more consistent result, nor engendered more controversy, than that of the utility of SDD. The rationale for SDD dates back 40 years to the work of van der Waaij and colleagues, who described a key role for the anaerobic gut flora in preventing pathologic colonization by gram-negative organisms, such as Pseudomonas species (1). Anaerobes vastly outnumber aerobes in the healthy gastrointestinal tract and play important roles in gut development, absorptive capacity, and mucosal antibacterial defenses. SDD selectively targets aerobic gram-negative organisms and fungi, leaving the anaerobic and gram-positive flora intact. SDD is not gut sterilization but rather ablation of pathologic overgrowth and support of the normal indigenous flora. Chlorhexidine exerts much broader antimicrobial activity, including against anaerobes. Although the systematic review by Price and colleagues included small individual studies, their pooled conclusions are consistent and congruent with the conclusions of other trials that did not meet the inclusion criteria of the systematic review. The lingering concern with SDD is that it might result in the emergence of resistant organisms. Systematic reviews have not shown this (2), but the long-term effects of broad adoption of this prophylactic strategy are uncertain. The available evidence argues compellingly that we should abandon routine use of chlorhexidine and adopt SDD as a more efficacious alternative. Yet, there is a disconnect between the evidence and what clinicians are comfortable doing. The most productive resolution of this remarkably durable controversy could be a well-designed RCT that addresses not only individual patient benefit but also communal microbial ecology.