New drug cocktail aims to soothe ICU delirium and prevent breathing tubes

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Age ≥18 years and ≤80 years at the time of randomization; 2. Hospitalized in the ICU (with an expected ICU stay \>24 hours); 3. Patients with hyperactive delirium: meeting criteria for Confusion Assessment Method for the ICU (CAM-ICU)\[19\] positivity (i.e., acute onset or fluctuating course plus inattention, and at least one secondary criterion-disorganized thinking or altered level of consciousness) and having agitation which is diagnosed if the Richmond Agitation-Sedation Scale (RASS) score\[20\] is superior or equal to +1. (The RASS and CAM-ICU are used to assess sedation and delirium levels. Hyperactive delirium is defined as CAM-ICU positive with RASS \> +1); 4. Receiving non-invasive respiratory support (eg. high-flow nasal cannula, CPAP, or non-invasive ventilation) at least for \>24 hours. Exclusion Criteria: 1. Known or suspected allergy or Contraindications to any of the study drugs; 2. Severe arrhythmias (e.g., ventricular fibrillation, second- or third-degree atrioventricular block, sick sinus syndrome, ventricular tachycardia, QTc interval ≥470 ms, severe bradycardia (heart rate \<40 beats per minute), etc.), or left ventricular ejection fraction (LVEF) \<30%; 3. Recent administration of esketamine, dexmedetomidine or haloperidol within previous 72 hours. 4. Pregnancy or lactation; 5. Conditions that may affect efficacy assessment or cognitive function testing, such as blindness, deafness, aphasic, or coma patients; 6. History of epilepsy or seizures; 7. Patients with an estimated survival period of less than 48 hours as judged by the investigator; 8. Neuropsychiatric conditions per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) that may introduce bias (e.g., active substance use disorder, psychosis, etc.), including alcoholism, drug abuse, or use of psychotropic medications; 9. Patients receiving non-invasive respiratory support via a tracheostomy; 10. Patients with untreated or inadequately treated hyperthyroidism; 11. Severe hepatic insufficiency (Child-Pugh grade C); 12. Severe renal dysfunction, defined as: chronic renal insufficiency with a glomerular filtration rate (GFR) ≤ 29 mL/min/1.73 m²; or subjects on long-term maintenance hemodialysis or peritoneal dialysis; 13. A history of sleep disorders requiring medical intervention within the past month; 14. Patients or their legally authorized representatives (family members) who are unable to cooperate or unwilling to provide written informed consent; 15. Other conditions deemed unsuitable for inclusion by the investigators.