Trial reportHealth technology assessment (Winchester, England)2026
Alpha2 agonists for sedation to produce better outcomes for adults with critical illness: a synopsis of the A2B RCT with cost-effectiveness and process evaluation.
Trial report in Health technology assessment (Winchester, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
28 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: 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. Objective(s): 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. Design and methods: Pragmatic open-label three-arm trial. Embedded process and economic evaluation. Setting and participants: 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 ( Interventions: 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. Outcomes: Primary outcome was time to successful extubation, analysed allowing for death as a competing risk. Secondary outcomes included mortality, sedation quality, rates of delirium and cardiovascular adverse events. Long-term outcomes included: experience of intensive care unit care; anxiety, depression and post-traumatic stress; cognitive function; health-related quality of life. Results: 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; Limitations: This was a pragmatic unblinded trial, with associated risk of performance and ascertainment bias. Future work: Future trials should explore the effectiveness of alpha2 agonists as sedatives in other populations, for example paediatric critical care and acute brain injury. Conclusions: In mechanically ventilated critically ill patients, neither dexmedetomidine- nor clonidine-based sedation was superior for major clinical outcomes or more cost-effective compared with propofol-based sedation. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/93/01.
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