{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:12:56Z","timestamp":1792422776173,"version":"4.5.0"},"reference-count":18,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["16\/93\/01"],"award-info":[{"award-number":["16\/93\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"\n Background<\/jats:title>\n Optimising comfort and ability to communicate for mechanically ventilated intensive care unit patients is a priority for clinicians, intensive care unit patients and their relatives. Current usual care is propofol-based sedation plus an opioid analgesic. The alpha2-agonists dexmedetomidine and clonidine are potential alternative sedatives.<\/jats:p>\n <\/jats:sec>\n \n Objective(s)<\/jats:title>\n To explore whether nurses and relatives perceive patients sedated with dexmedetomidine and\/or clonidine appear more awake, comfortable and co-operative than patients receiving only propofol-based sedation.<\/jats:p>\n <\/jats:sec>\n \n Design and methods<\/jats:title>\n Substudy within an open-label, three-arm trial.<\/jats:p>\n <\/jats:sec>\n \n Setting and participants<\/jats:title>\n Forty-one intensive care units in the United Kingdom. One thousand four hundred and thirty-seven adults receiving propofol\u2005\u00b1\u2005opioid for sedation-analgesia within 48 hours of starting mechanical ventilation, expected to require \u2265\u200548 total hours of mechanical ventilation.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Light sedation was targeted in all patients unless clinicians requested deeper sedation. In intervention groups, algorithms promoted alpha2-agonist up-titration and propofol down-titration, followed by sedation primarily with allocated alpha2-agonist. Usual care was propofol-based sedation. Intervention continued until patients were successfully extubated (primary outcome), or other pre-defined end points.<\/jats:p>\n <\/jats:sec>\n \n Outcomes<\/jats:title>\n \n For each 12-hour care period, nurses responded to two \u2018yes\/no\u2019 questions:\n is the patient able to communicate pain? Is the patient able to co-operate with care?<\/jats:italic>\n When the patients\u2019 personal legal representative visited, they were asked for \u2018yes\/no\u2019 responses to three questions:\n does the patient appear awake? Does the patient appear comfortable? Does the visitor feel they can communicate with the patient?<\/jats:italic>\n <\/jats:p>\n Intervention versus propofol group responses were compared fitting a generalised linear mixed model, with results expressed as odds ratios (95% confidence intervals); odds ratios >\u20051 indicated greater probability of a \u2018yes\u2019 response.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Nurse responses were available for >\u200590% of trial patients [mean (standard deviation) 12 (12) care periods per patient]. Comparing dexmedetomidine versus propofol groups, the odds ratio for a \u2018yes\u2019 response to \u2018\n communicate pain<\/jats:italic>\n \u2019 was 1.38 (95% confidence interval 1.08 to 1.75), and for clonidine versus propofol, it was 1.13 (0.89 to 1.43). For \u2018\n co-operate with care<\/jats:italic>\n \u2019 comparing dexmedetomidine versus propofol groups, the odds ratio was 1.14 (95% confidence interval 0.98 to 1.32), and for clonidine versus propofol, it was 0.96 (95% confidence interval 0.83 to 1.12). Relative responses were available for 32\u201334% of trial patients across groups [mean (standard deviation) 3 (3) days per patient]. For the \u2018\n appear awake<\/jats:italic>\n \u2019 question, the dexmedetomidine versus propofol group odds ratio was 1.48 (95% confidence interval 1.04 to 2.10), and for clonidine versus propofol, it was 1.35 (95% confidence interval 0.95 to 1.91). For \u2018\n appear comfortable<\/jats:italic>\n \u2019, the dexmedetomidine versus propofol group odds ratio was 0.64 (95% confidence interval 0.38 to 1.09), and for clonidine versus propofol, it was 0.78 (95% confidence interval 0.45 to 1.34). For the \u2018\n feel they can communicate<\/jats:italic>\n \u2019 comparison, the dexmedetomidine versus propofol group odds ratio was 1.00 (95% confidence interval 0.68 to 1.47), and for clonidine versus propofol, it was 1.05 (95% confidence interval 0.71 to 1.54).\n <\/jats:p>\n <\/jats:sec>\n \n Limitations<\/jats:title>\n Interventions were unblinded, with risk of bias; missing data may not have been at random.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Nurses perceived patients receiving dexmedetomidine-based sedation could better communicate pain than with propofol-based sedation, and relatives perceived patients appeared more awake. No differences for the other questions were found, or for the clonidine versus propofol comparisons, although some uncertainty remains due to the wide confidence intervals.<\/jats:p>\n <\/jats:sec>\n \n Future work<\/jats:title>\n Additional mixed-methods research of sedation quality with different agents from staff and relative perspectives.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16\/93\/01.<\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/gjtw2718","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T12:31:27Z","timestamp":1752841887000},"page":"1-18","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Relative and bedside nurse assessment of comfort and communication during propofol, dexmedetomidine, or clonidine-based sedation: pre-planned analysis within the A2B RCT"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3590-8540","authenticated-orcid":true,"given":"Timothy S","family":"Walsh","sequence":"first","affiliation":[{"name":"Usher Institute, The University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2658-5022","authenticated-orcid":true,"given":"Richard A","family":"Parker","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-9090","authenticated-orcid":true,"given":"Leanne M","family":"Aitken","sequence":"additional","affiliation":[{"name":"City St George\u2019s, University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-9711","authenticated-orcid":true,"given":"Cathrine A","family":"McKenzie","sequence":"additional","affiliation":[{"name":"NIHR Southampton Biomedical Research Centre, Perioperative and Critical Care Theme, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6001-8578","authenticated-orcid":true,"given":"Robert","family":"Glen","sequence":"additional","affiliation":[{"name":"Lay Member, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6494-4903","authenticated-orcid":true,"given":"Christopher J","family":"Weir","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, 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