Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: Systematic review of randomized controlled trials L. Silvestri, H. K. F. van Saene, D. F. Zandstra, J. C. Marshall, D. Gregori, A. Gullo M ultiple organ dysfunction syndrome (MODS) is the leading cause of morbid- ity and mortality in the intensive care unit (ICU) and is respon- sible for up to 80% of deaths in the ICU (1, 2). MODS is commonly associated with occult or uncontrolled infection (3, 4), although in approximately half of the patients the infectious focus is dif- ficult to identify (5, 6). More than a half a century ago, Jacob Fine (7) hypothesized that gut over- growth of abnormal flora, particularly aerobic Gram-negative bacilli (AGNB), is a crucial event in the initiation of organ dysfunction. Translocation of AGNB and/or absorption of endotoxin released by the AGNB promote a gener- alized inflammatory state that may lead, via cytokinemia, to tissue damage of one or more organs (8). Gut over- growth of abnormal flora, defined as 10 5 AGNB per mL of ileal fluid or per gram of feces (9), is common in criti- cally ill patients requiring long-term treatment in the ICU (10). Recently, AGNB overgrowth has been shown to be associated with high fecal endotoxin load, i.e., 10 mg of endotoxin per gram of feces (11). Selective decontamination of the di- gestive tract (SDD) using parenteral and enteral antimicrobials reduces se- vere infections of lower airway (12) and blood (13) in the critically ill. Paren- teral antimicrobials aim to control pri- mary endogenous infections, whereas enteral antimicrobials are administered in throat and gut to control secondary endogenous infections of lower airways and blood, respectively (14). Addition- ally, the enteral antimicrobials poly- myxin/tobramycin prevent and, if al- ready present, eradicate gut overgrowth of abnormal flora (15) and reduce the fecal endotoxin load by a factor of 10 4 (16, 17). The gut hypothesis predicts that SDD, through prevention of infection, gut overgrowth, AGNB translocation, and en- dotoxin absorption, can reduce the sever- ity of the MODS. We performed a system- atic review and meta-analysis of randomized controlled trials (RCTs) of SDD to examine whether SDD can atten- uate MODS. From Department of Emergency (LS), Unit of Anesthesia and Intensive Care, Presidio Osped- aliero, Gorizia, Italy; School of Clinical Sciences (HKFvS), University of Liverpool, Liverpool, UK; De- partment of Intensive Care (DFZ), Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands; De- partment of Critical Care, Trauma, and General Sur- gery (JCM), St. Michael’s Hospital, Toronto, Ontario, Canada; Department of Environmental Medicine and Public Health (DG), University of Padova, Padova, Italy; Department of Anesthesia and Intensive Care (AG), Policlinico University Hospital, Catania, Italy. Supplemental digital content is available for this ar- ticle. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.ccmjournal.com). The authors have not disclosed any potential con- flicts of interest. For information regarding this article, E-mail: lucianosilvestri@yahoo.it Copyright © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3181d9db8c Objective: We examined the impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome. Data Sources: We searched MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, previous meta-analyses, and meet- ings proceedings. Study Selection: We included all randomized trials comparing both oropharyngeal and intestinal administration of antibiotics in selective decontamination of the digestive tract with or without a parenteral component, with placebo or standard therapy used in the controls. Data Extraction: Two reviewers independently applied selec- tion criteria, performed quality assessment, and extracted the data. The primary end point was the number of patients with multiple organ dysfunction syndrome developing during intensive care unit stay. Secondary end points were overall mortality and multiple organ dysfunction syndrome-related mortality. Odds ra- tios were pooled with the random effect model. Data Synthesis: We identified seven randomized trials includ- ing 1270 patients. Multiple organ dysfunction syndrome was found in 132 of 637 patients (20.7%) in the selective decontam- ination of the digestive tract group and in 219 of 633 patients (34.6%) in the control group (odds ratio, 0.50; 95% confidence interval, 0.34 – 0.74; p < .001). Overall mortality for selective decontamination of the digestive tract vs. control patients was 119 of 637 (18.7%) and 145 of 633 (22.9%), respectively, demon- strating a nonsignificant reduction in the odds of death (odds ratio, 0.82; 95% confidence interval, 0.51–1.32; p  .41). In five studies including 472 patients, multiple organ dysfunction syn- drome-related mortality was demonstrated in 31of 239 (13%) patients in selective decontamination of the digestive tract group and 37 of 233 (15.9%) in the controls (odds ratio, 0.84; 95% confidence interval, 0.48 –1.41; p  .54). Conclusions: Selective decontamination of the digestive tract reduces the number of patients with multiple organ dysfunction syndrome. Mortality was not significantly reduced, probably be- cause of the small sample size. (Crit Care Med 2010; 38:000 – 000) KEY WORDS: multiple organ failure; prevention; control; bacterial translocation; antibacterial agents; therapeutic use; infection con- trol; gastrointestinal tract; selective digestive decontamination 1 Crit Care Med 2010 Vol. 38, No. 5