Dexmedetomidine Versus Midazolam for End-of-Life Sedation: The DREAMS Non-Blinded Randomized Clinical Trial

End-of-life distress and delirium are common in palliative care inpatients, often requiring sedatives that diminish interaction. Current practices rely on clinical experience rather than evidence.

To compare the sedative efficacy of subcutaneous dexmedetomidine versus midazolam in managing end-of-life distress while maintaining responsiveness, and to evaluate comparative effect on delirium in the terminal phase.

Single center randomized non-blinded clinical trial (ACTRN12621000052831) of palliative care inpatients in an Australian Local Health District admitted for end-of-life care. Patients received dexmedetomidine (0.5 µg/kg/h) or midazolam (0.25 mg/kg/day) via subcutaneous infusion for symptom management during the terminal phase. The primary outcome was responsiveness measured by mean Richmond Agitation Sedation Score-Palliative version (RASS-PAL) compared between treatment arms over the first 72 hours. Secondary outcomes included delirium severity (memorial delirium assessment score [MDAS]) and patient comfort (Patient Comfort Assessment [PCA]).

Fifty two patients were randomized (median age 80 years [IQR 72-88]; 63% male) and included in the primary analysis. Mean RASS-PAL scores showed no significant difference between arms (dexmedetomidine vs. midazolam: day 1: -2.33 vs. -1.90; day 2: -2.44 vs. -2.86; day 3: -2.95 vs. -2.53; all P > 0.05). Dexmedetomidine showed superior early delirium severity scores (day 1 MDAS: 6.5 vs. 8.8, P = 0.05) which did not persist. Protocol withdrawal occurred earlier in the midazolam arm (5 vs. 0 patients on day 1, P = 0.025). Patient comfort scores remained mild (PCA < 3) in both arms.

Dexmedetomidine and midazolam can achieve sedative equivalence with similar RASS-PAL scores. Dexmedetomidine patients experienced lower initial delirium severity scores and fewer early withdrawals in secondary analysis. Current dosing guideline for midazolam may need revising.