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.
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Data availability
JAM and LB had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. See ESM.
References
Hammond NE, Myburgh J, Seppelt I et al (2022) 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. JAMA 328(19):1922–1934. https://doi.org/10.1001/jama.2022.19709
The SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of selective decontamination of the digestive tract on hospital mortality in critically ill patients receiving mechanical ventilation: a randomized clinical trial. JAMA. 2022;328(19):1911–1921. https://doi.org/10.1001/jama.2022.17927
Bonten MJ, Kollef MH, Hall JB (2004) Risk factors for ventilator-associated pneumonia: from epidemiology to patient management. Clin Infect Dis 38(8):1141–1149. https://doi.org/10.1086/383039
Ewig S, Torres A, El-Ebiary M et al (1999) Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med 159(1):188–198. https://doi.org/10.1164/ajrccm.159.1.9803097
The SuDDICU Investigators (2021) Protocol summary and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) crossover, cluster randomised controlled trial. Crit Care Resusc 23(2):183–193
Campbell MK, Elbourne DR, Altman DG et al (2004) CONSORT statement: extension to cluster randomised trials. BMJ 328(7441):702–708. https://doi.org/10.1136/bmj.328.7441.702
ANZICS Centre for Outcome and Resource Evaluation. APD Data Dictionary. Version 6.1. April 2022 https://www.anzics.com.au/wp-content/uploads/2021/03/ANZICS-APD-Data-Dictionary.pdf.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13(10):818–829
Knaus WA, Wagner DP, Draper EA et al (1991) The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest 100(6):1619–1636. https://doi.org/10.1378/chest.100.6.1619
World Health Organization. Defined daily dose (DDD). Accessed 3rd July, 2023. https://www.who.int/tools/atc-ddd-toolkit/about-ddd.
Kenward MGRJH (2009) An improved approximation to the precision of fixed effects from restricted maximum likelihood. Comput Stat Data Anal 53:2583–2595
Korinek AM, Laisne MJ, Nicolas MH, Raskine L, Deroin V, Sanson-Lepors MJ (1993) Selective decontamination of the digestive tract in neurosurgical intensive care unit patients: a double-blind, randomized, placebo-controlled study. Crit Care Med 21(10):1466–1473. https://doi.org/10.1097/00003246-199310000-00013
Ribaric SF, Turel M, Knafelj R et al (2017) Prophylactic versus clinically-driven antibiotics in comatose survivors of out-of-hospital cardiac arrest—a randomized pilot study. Resuscitation 111:103–109. https://doi.org/10.1016/j.resuscitation.2016.11.025
Francois B, Cariou A, Clere-Jehl R et al (2019) Prevention of early ventilator-associated pneumonia after cardiac arrest. N Engl J Med 381(19):1831–1842. https://doi.org/10.1056/NEJMoa1812379
Sirvent JM, Torres A, El-Ebiary M, Castro P, de Batlle J, Bonet A (1997) Protective effect of intravenously administered cefuroxime against nosocomial pneumonia in patients with structural coma. Am J Respir Crit Care Med 155(5):1729–1734. https://doi.org/10.1164/ajrccm.155.5.9154884
Acquarolo A, Urli T, Perone G, Giannotti C, Candiani A, Latronico N (2005) Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study. Int Care Med 31(4):510–516. https://doi.org/10.1007/s00134-005-2585-5
Vincent JL, Rello J, Marshall J et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302(21):2323–2329. https://doi.org/10.1001/jama.2009.1754
Acknowledgements
The authors and investigators wish to acknowledge the patients who were enrolled in our study and their families; the health care workers who cared for these patients; the research co-ordinators at each participating hospital; members and executive of the Australian and New Zealand Intensive Care Society Clinical Trials Group; the international independent Data and Safety Monitoring Committee; manufacturing and support staff at Verita® Pharma, Sydney, who provided the SDD drug preparations; international collaborators in Canada and the United Kingdom; and the research and support teams at The George Institute for Global Health, Sydney. This paper was endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.
SuDDICU Australia Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group: Anthony Gordon, Brian Cuthbertson, Robert Fowler, Srinivas Murthy, Natalie Pattison, Jon 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, David Sanchez, 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 Marshall, Rebecca McEldrew, Forbes McGain, Rebecca Morgan, John Mulder, Anna Tippett, Miriam Towns, Ellie Barker, Shelley Donovan, Katrina Ellis, Atul Gaur, Hannah Gibbons, Rebecca Gregory, Eloise Hair, Mary Keehan, Jess Naumoff, Elisha Turner, Gail Brinkerhoff, Dustin Bush, Federica Cazzola, Joshua Davis, Ken Havill, Paul Healey, Amber Poulter, Krishna Sunkara, Anders Aneman, 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 Grigg, Meg Harward, Cassie Jones, Josephine Mackay, Jason Meyer, Emma Saylor, Ellen Venz, James Walsham, Krista Wetzig, Nerissa Brown, Marianne Chapman, Kathleen Glasby, Samuel Gluck, Tejaswini Murthy, Stephanie O'Connor, Eamon Raith, Justine Rivett, Joannies Yap, Angela Ashelford, Frances Bass, Simon Finfer, Emily Fitzgerald, Oliver Flower, Naomi Hammond, Bernard Hudson, Pierre Janin, Elizabeth Limbrey, Sharon Mar, Anne O'Connor, Melissa Owen, Naomi Pallas, Julia Pilowsky, Veronica Roach, Elizabeth Ruse, Wade Stedman, Miyuki Tokumitsu, Elizabeth Yarad, Deborah Inskip, Theresa Jacques, Adeline Kintono, Jennene Miller, Catherine Milner, John Myburgh, Rebecca Sidoli, Samantha Bates, Gerard Fennessy, Craig French, Sathyajith Kootayi, Fiona Marshall, Rebecca McEldrew, Forbes McGain, Rebecca Morgan, John Mulder, Anna Tippett, Miriam Towns, Catherine Kurenda, Sandra Peake, Tricia Williams, Jeremy Cohen, Amanda Davie, Amy Owens, Roslyn Purcell, Bala Venkatesh, Cartan Costello, Alan Davey-Quinn, Michael Davies, Ahmed Elgendy, Wenli Geng, Veerendra Jagarlamudi, Matthew Mac Partlin, Mahadev Patil, Adam Purdon, Martin Sterba, Andrea Marshall, Anthony Delaney, Simon Finfer, Naomi Hammond, John Myburgh, Ian Seppelt, Balasubramanian Venkatesh, Maryam Correa, Fiona Goodman, Marwa Abdel-All, Hayley Clark, Natalie Espinosa, Benjamin Finfer, Miranda Hardie, Sharon Micallef, Jennene Miller, Dijlah Moungatonga, Conrad Nangla, Anne O'Connor, Fiona Osbourne, Julia Pilowsky, Tina Schneider, Isabella Schoeler, Prakriti Shrestha, Anna Tippett, Elizabeth Wilson, Laurent Billot, Manuela Armenis, Dominic Byrne, Qiang Li, Jayanthi Mysore, Amrutha Nagarajaiah, Prakash Velappan, Parisa Glass, Kate Myburgh, Philippa Smith, Martina Bachmaier, Daryll Knowles, Michael Tattersall.
Funding
No specific funding for this post hoc analysis was obtained. The SuDDICU Australia trial was supported by a Project Grant from the National Health and Medical Research Council of Australia (Project Grant number 1084244); by a Leadership Fellowship from National Health and Medical Research Council of Australia (to JAM); by Practitioner Fellowships from the National Health and Medical Research Council of Australia (to SRF); by a Career Development Fellowship from National Health and Medical Research Council (to JSD); by an Emerging Leader Investigator Grant from the National Health and Medical Research Council of Australia (to NEH); by a Clinical Practitioner Research Fellowship from the Health Research Council of New Zealand (to PJY). The George Institute for Global Health, Australia was the Principal Sponsor for this trial. SDD drug preparations were purchased and manufactured under contract with the George Institute for Global Health by Verita Pharma® (Sydney, Australia). The sponsor, funders and drug manufacturer had no input into the design and conduct of the study, collection, management, analysis and interpretation of data; preparation, review or approval of the manuscript; and the decision to submit the manuscript for publication. The Sponsor had no right of veto to publish this trial or to control the decision regarding to which journal the paper was submitted.
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Non-author collaborators: listed in the Acknowledgement section. Concept and design: LB, JSD, AD, AD, SRF, NEH, QL, JAM, IMS, BV, PJY. Acquisition, analysis and interpretation of data: LB, AD, AD, SRF, NEH, QL, SM, JAM, IMS, PJY. Drafting of the manuscript: PJY (wrote the first draft of the manuscript); LB, AD, SRF, QL, SM, JAM, IMS. Critical revision of the manuscript for important intellectual content: LB, JSD, AD, AD, SRF, NEH, QL, SM, JAM, IMS, BV, PJY. Statistical analysis: LB, AD, QL. Obtained funding: JSD, SRF, JAM, IMS, PJY. Administrative, technical or material support: LB, AD, SRF, NEH, QL, SM, JAM. Supervision: LB, SRF, NEH, QL, JAM.
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The George Institute for Global Health holds all intellectual property rights related to the SuDDICU study drugs, including component drug acquisition, manufacturing, packaging and distribution. None of the SuDDICU investigators have any direct or indirect financial or commercial interests relating to the development of the SuDDICU study drugs.
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The SuDDICU Australia Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group are listed in the Acknowledgement section.
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Young, P.J., Devaux, A., Li, Q. et al. Selective digestive tract decontamination in critically ill adults with acute brain injuries: a post hoc analysis of a randomized clinical trial. Intensive Care Med 50, 56–67 (2024). https://doi.org/10.1007/s00134-023-07261-y
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DOI: https://doi.org/10.1007/s00134-023-07261-y