Selective digestive tract decontamination in critically ill adults with acute brain injuries: a post hoc analysis of a randomized clinical trial
Paul J. Young, Anthony Devaux, Qiang Li, Laurent Billot, Joshua S. Davis, Anthony Delaney, Simon Finfer, Naomi Hammond, Sharon Micallef, Ian Seppelt, Balasubramanian Venkatesh, John Myburgh, Anthony Gordon, Brian H. Cuthbertson, Robert Fowler, Srinivas Murthy, Natalie Pattison, Jonathan R. Iredell, Colman Taylor, Duncan Young, Tom van der Poll, Ian Roberts, Catherine Boschert, Emma Broadfield, Timothy Chimunda, Jason Fletcher, Cameron Knott, Sanjay Porwal, Julie Smith, Deepak Bhonagiri, Monique Leijten, Sandhya Narayan, D. A. Sánchez, Peta Saunders, Carli Sherriff, Jonathan Barrett, Gabrielle Hanlon, Sarah Jelly-Butterworth, Julie O’Donnell, Judith Watson, Shailesh Bihari, Julia Brown, Sharon Comerford, Russell Laver, Joanne McIntyre, Tapaswi Shrestha, Jin Xia, Samantha Bates, Gerard Fennessy, Craig French, Sathyajith Kootayi, Fiona H. Marshall, Rebecca McEldrew, Forbes McGain, Rebecca L. Morgan, John Mulder, Anna Tippett, Miriam Towns, Ellie Barker, Shelley Donovan, Katrina R. Ellis, Atul Gaur, Hannah M. Gibbons, Rebecca Gregory, Eloise Hair, Mary Keehan, Jess Naumoff, Elisha Turner, Gail Brinkerhoff, Dustin Bush, Federica Cazzola, Joshua S. Davis, Ken Havill, Paul R. Healey, Amber Poulter, Krishna Sunkara, Anders Åneman, Rachel Choit, Kelsey Dobell‐Brown, Kairui Guo, Jillian Lee, Monique Leijten, Lien Lombardo, Zachariah Manalil, Jennene Miller, Jordan Rogers, Antony Stewart, Jana Yanga, Rebecca Gresham, Julie Lowrey, Kristy Masters, Ian Seppelt, Christina Whitehead, Beverly Zaratan, Matthew J. Grigg, Meg Harward, Cassie Jones, Josephine Mackay, Jason Meyer, Emma Saylor
Abstract
PURPOSE: The aim of this study was to determine whether selective decontamination of the digestive tract (SDD) reduces in-hospital mortality in mechanically ventilated critically ill adults admitted to the intensive care unit (ICU) with acute brain injuries or conditions. METHODS: We carried out a post hoc analysis from a crossover, cluster randomized clinical trial. ICUs were randomly assigned to adopt or not to adopt a SDD strategy for two alternating 12-month periods, separated by a 3-month inter-period gap. Patients in the SDD group (n = 2791; 968 admitted to the ICU with an acute brain injury) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191; 1093 admitted to the ICU with an acute brain injury) received standard care. The primary outcome was in-hospital mortality within 90 days. There were four secondary clinical outcomes: death in ICU, ventilator-, ICU- and hospital-free days to day 90. RESULTS: Of 2061 patients with acute brain injuries (mean age, 55.8 years; 36.4% women), all completed the trial. In patients with acute brain injuries, there were 313/968 (32.3%) and 415/1093 (38%) in-hospital deaths in the SDD and standard care groups (unadjusted odds ratio [OR], 0.76, 95% confidence interval [CI] 0.63-0.92; p = 0.004). The use of SDD was associated with statistically significant improvements in the four clinical secondary outcomes compared to standard care. There was no significant heterogeneity of treatment effect between patients with and without acute brain injuries (interaction p = 0.22). CONCLUSIONS: In this post hoc analysis of a randomized clinical trial in critically ill patients with acute brain injuries receiving mechanical ventilation, the use of SDD significantly reduced in-hospital mortality in patients compared to standard care without SDD. These findings require confirmation.