(965) Dexmedetomidine vs Haloperidol for Nocturnal Hyperactive Delirium in the Nonintubated: DEX-HD Trial

Introduction: Evidence has shown the efficacy of dexmedetomidine (DEX) for delirium of intubated patients in ICUs. However, its efficacy and safety for nocturnal hyperactive delirium of non-intubated patients in high dependency units (HDUs) are limited. We hypothesize that DEX may provide better sedation, and reduce delirium and circadian rhythm disruption the following day, compared with haloperidol (HD) in this setting.

Methods: We conducted an open-label, parallel-group, randomized controlled trial to compare DEX and HD for nocturnal hyperactive delirium of non-intubated patients at two HDUs of Kyoto University Hospital from May 2022 to July 2024. Non-intubated ones admitted to the HDUs via the emergency room were allocated 1:1 to the DEX or HD group as of admission. The allocated investigational drug will be administered when participants develop hyperactive delirium (RASS ≥1 and positive CAM-ICU) during the night. DEX is administered continuously, while HD is administered intermittently, preferably avoiding the other investigational drug use as rescue within 2h after administration. The primary outcome is to achieve the targeted sedation level (RASS between -3 and 0) 2h after administration. Secondary outcomes are the delirium prevalence and unintentional diurnal sedation (UDS) mimicking circadian rhythm disruption (diurnal RASS ≤-1) the following day, and safety. Chi-square test was used to test each outcome.

Results: Of 457 participants, 52 received DEX and 48 received HD. Compared to HD, DEX achieved more frequently targeted sedation level 2h after the administration (75.0% vs, 56.3%, P = 0.047). DEX did not reduce the prevalence of delirium (30.6% vs, 40.5% at 10 AM, P = 0.31; 40.5% vs, 52.5% at 10 PM, P = 0.27), while reducing UDS the following day (42.2% vs, 67.4% at 10 AM, P = 0.015; 26.8% vs, 51.2% at 2 PM, P = 0.022; 21.6% vs, 46.2% at 6 PM, P = 0.023). No statistical difference was found in hypotension (7.7% vs. 2.1%, P = 0.18) or bradycardia (5.8% vs 2.1%, P =0.34) between the groups.

Conclusions: Compared with HD, DEX more successfully controlled nocturnal hyperactive delirium and reduced circadian rhythm disruption the following day of non-intubated patients in HDUs without significant adverse event.