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Title: Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial.
Austin Authors: Shehabi, Yahya;Serpa Neto, Ary ;Howe, Belinda D;Bellomo, Rinaldo ;Arabi, Yaseen M;Bailey, Michael;Bass, Frances E;Kadiman, Suhaini Bin;McArthur, Colin J;Reade, Michael C;Seppelt, Ian M;Takala, Jukka;Wise, Matt P;Webb, Steve A
Affiliation: Adult Critical Care, University Hospital of Wales, Cardiff, UK
Critical Care Division, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
Faculty of Medicine, University of Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia
Joint Health Command, Australian Defence Force, Canberra, Australia
Sydney Medical School-Nepean, University of Sydney, Sydney, Australia
Department of Clinical Medicine, Macquarie University, Sydney, Australia
Intensive Care Unit, Royal Perth Hospital, Perth, WA, Australia
Monash Health School of Clinical Sciences, Monash University, Clayton, VIC, 3186, Australia
Prince of Wales Clinical School of Medicine, University of New South Wales, Randwick, Sydney, 2031, Australia
Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil
Data Analytics Research and Evaluation (DARE) Centre
Intensive Care
College of Medicine, King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia..
Department of Anesthesiology and Intensive Care, IJN-UTM Cardiovascular Engineering Center, National Heart Institute, Kuala Lumpur, Malaysia..
Department of Critical Care Medicine, Auckland City Hospital, University of Auckland, Auckland, New Zealand..
Department of Intensive Care, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland..
Issue Date: 8-Mar-2021 2021-03-08
Publication information: Intensive Care Medicine 2021; online first: 8 March
Abstract: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.
DOI: 10.1007/s00134-021-06356-8
ORCID: 0000-0003-4707-7462
PubMed URL: 33686482
Type: Journal Article
Subjects: Critically ill
Mechanical ventilation
Appears in Collections:Journal articles

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