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Abstract

Background
Optimising comfort and ability to communicate for mechanically ventilated (MV) intensive care (ICU) patients is a priority for clinicians, ICU patients and their relatives. Current usual care is propofolbased sedation plus an opioid analgesic. The alpha2-agonists dexmedetomidine and clonidine are potential alternative sedatives.

Objective(s)
To explore whether nurses and relatives perceive patients sedated with dexmedetomidine and/or clonidine appear more awake, comfortable, and cooperative than patients receiving only propofolbased sedation.

Design and methods
Sub-study within an open-label three-arm trial.

Setting and participants
41 ICUs in the United Kingdom. 1437 adults receiving propofol ±opioid for sedation-analgesia within 48 hours of starting MV, expected to require ≥48 total hours of MV.

Interventions
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.

Outcomes
For each 12-hours care period nurses responded to two ‘yes/no’ questions: Is the patient able to communicate pain? Is the patient able to cooperate with care? When the patients’ personal legal representative visited, they were asked for ‘yes/no’ responses to three questions: does the patient appear awake? Does the patient appear comfortable? Does the visitor feel they can communicate with the patient? Intervention versus propofol group responses were compared fitting a generalised linear mixed model, with results expressed as Odds Ratios (OR; 95% confidence intervals); ORs >1 indicated greater probability of a ‘yes’ response.

Results
Nurse responses were available for >90% of trial patients (mean (SD) 12 (12) care periods per patient). Comparing dexmedetomidine versus propofol groups, the OR for a ‘yes’ response to ‘communicate pain’ was 1.38 (1.08 to 1.75), and for clonidine versus propofol was 1.13 (0.89 to 1.43). For ‘cooperate with care’ comparing dexmedetomidine versus propofol groups, OR was 1.14 (0.98 to 1.32), and for clonidine versus propofol 0.96 (0.83 to 1.12). Relative responses were available for 32-34% of trial patients across groups (mean (SD) 3 (3) days per patient). For the ‘appear awake’ question, the dexmedetomidine versus propofol group OR was 1.48 (1.04 to 2.10), and clonidine versus propofol 1.35 (0.95 to 1.91). For ‘appear comfortable’ the dexmedetomidine versus propofol group OR was 0.64 (0.38 to 1.09), and for clonidine versus propofol 0.78 (0.45 to 1.34). For the ‘feel they can communicate’ comparison the dexmedetomidine versus propofol group OR was 1.00 (0.68 to 1.47), and for clonidine versus propofol 1.05 (0.71 to 1.54).

Limitations
Interventions were unblinded, with risk of bias; missing data may not have been at random.

Conclusions
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.

Future work
Additional mixed methods research of sedation quality with different agents from staff and relative perspectives.

Study registration:
NCT03653832

Publication Type:	Article
Additional Information:	Copyright © 2025 Walsh T et al. This work was produced by Walsh et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.
Publisher Keywords:	Critical Care; intensive care units; hypnotics and sedatives; respiration, artificial; adrenergic alpha-2 receptor agonists; dexmedetomidine; clonidine
Subjects:	R Medicine > RT Nursing
Departments:	School of Health & Medical Sciences
SWORD Depositor:	Symplectic Administrator

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