Authors' objectives: Most mechanically ventilated intensive care unit patients require sedation and analgesia for comfort. Current usual care is propofol-based sedation plus an opioid analgesic. The alpha2 agonists dexmedetomidine and clonidine are potential alternative sedatives, but their clinical and cost-effectiveness are uncertain. To evaluate the clinical and cost-effectiveness and safety of alpha2 agonists (dexmedetomidine and clonidine) compared with propofol for sedating adult intensive care unit patients.

Authors' results and conclusions: Mean (standard deviation) patient age was 59.2 (14.9) years; 901 (65%) male. The sub-distribution hazard ratio for time to successful extubation for dexmedetomidine versus propofol was 1.09 (95% confidence interval 0.96 to 1.25; p = 0.20) and for clonidine versus propofol was 1.05 (0.95 to 1.17; p = 0.34), with hazard ratio > 1 favouring alpha2 agonist. Median (95% confidence interval) hours from randomisation to successful extubation was: propofol 162 (136 to 170); dexmedetomidine 136 (117 to 150); and clonidine 146 (124 to 168). There was no effect interaction with age, sepsis status, median Sequential Organ Failure Assessment Score, or median Prediction of Delirium in intensive care unit patients' delirium risk score. Delirium rates were similar, but agitation occurred at higher rate than propofol with both alpha2 agonists [dexmedetomidine vs. propofol risk ratio (95% confidence intervals) 1.54 (1.21 to 1.97); clonidine vs. propofol 1.55 (1.22 to 1.97)]. Rates of severe bradycardia (rate

Authors' methods: Pragmatic open-label three-arm trial. Embedded process and economic evaluation. Forty-one intensive care units in the UK. Recruitment from December 2018 to October 2023. Participants were 1437 adults within 48 hours of starting mechanical ventilation expected to require ≥ 48 hours of mechanical ventilation [analysis population: propofol (N = 471), dexmedetomidine (N = 457), and clonidine-based (N = 476) sedation]. Median time from intubation to randomisation was 21.0 (first, third quartile: 13.2, 31.3) hours. In all groups, bedside algorithms targeted a Richmond Agitation Sedation Scale of −2 to + 1 unless clinicians requested deeper sedation. Intervention groups’ algorithms supported alpha2-agonist up-titration and propofol down-titration followed by sedation primarily with allocated alpha2 agonist. Supplemental propofol was permitted if required. This was a pragmatic unblinded trial, with associated risk of performance and ascertainment bias.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR136089

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/published-articles/GJTW3820

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/GJTW3820

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk