About this trial
Delirium is an acute, fluctuating disturbance in attention and cognition that commonly complicates the course of critically ill patients, particularly those admitted with acute heart failure (AHF). Its occurrence in the intensive care unit (ICU) is associated with prolonged mechanical ventilation, longer ICU and hospital stays, increased morbidity and mortality, and substantial healthcare costs. In patients with AHF, the risk of delirium is amplified by factors such as cerebral hypoperfusion, systemic inflammation, sedative exposure, and multi-organ dysfunction. Therefore, effective prevention and early management of delirium in this population are critical to improving outcomes.
Dexmedetomidine, a selective α2-adrenoceptor agonist, has gained wide use in ICU sedation due to its anxiolytic and analgesic properties and minimal respiratory depression. Several randomized controlled trials and meta-analyses have demonstrated that dexmedetomidine-based sedation reduces the incidence and duration of delirium compared with traditional sedatives such as benzodiazepines or propofol. However, its use in AHF patients may be limited by dose-dependent bradycardia and hypotension, potentially compromising hemodynamic stability in an already fragile population.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, possesses unique properties that may offer an alternative approach to delirium prevention. At subanesthetic (low) doses, ketamine provides analgesia, maintains respiratory drive, and exerts sympathomimetic effects that support blood pressure and cardiac output-features that may be advantageous in AHF. Emerging evidence from cardiac surgery and critical care studies suggests that low-dose ketamine infusion might reduce delirium incidence through anti-inflammatory and neuroprotective mechanisms, although data remain limited and heterogeneous.
Given the hemodynamic fragility of AHF patients and the need for sedatives that balance safety and delirium treatment, a direct comparison between low-dose ketamine and dexmedetomidine is warranted. This study aims to evaluate and compare the efficacy and safety of these two agents in treating delirium among AHF patients admitted to the ICU. By addressing this gap, the study seeks to identify a sedation strategy that optimizes cognitive and hemodynamic outcomes in this high-risk population.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years.
Confirmed diagnosis of acute heart failure according to established clinical and echocardiographic criteria.
Positive CAM-ICU or ICDSC (score ≥4) at screening AND
RASS ≥ +1 (agitation) or RASS ≤ -1 (hypoactive) indicating a motoric subtype.
Disqualifiers
Primary neurological events (e.g., stroke, seizure, traumatic brain injury) as cause of altered mental status.
Severe hepatic dysfunction (e.g., Child-Pugh Class C) or renal impairment (eGFR < 30 mL/min/1.73m²).
Known hypersensitivity or contraindication to ketamine or dexmedetomidine.
Current or recent (within 48 hours) use of antipsychotics, benzodiazepines, or other sedatives.
Trial design
Parallel
Treatments tested in this trial
Low dose ketamine infusion
DrugPatients will receive an intravenous infusion of ketamine at a dose of 0.2 - 0.5 mg/kg/hour, titrated to achieve light sedation (RASS -2 to 0). No bolus dose will be given.
Dexmedetomidine infusion
DrugPatients will receive an intravenous infusion of dexmedetomidine 0.7 - 1.5 mcg/kg/hour, titrated similarly to maintain a RASS score of -2 to 0. No bolus dose will be given.
Treatment groups
Trial outcomes
Primary outcomes
Resolution of delirium
Resolution of delirium within 72 hours of initiating treatment, assessed twice daily using the Confusion Assessment Method for the ICU (CAM-ICU) tool, measured as the proportion of patients who transition from CAM-ICU positive to CAM-ICU negative status.
Secondary outcomes
Hemodynamic stability, measured by changes in mean arterial pressure (MAP)
Incidence of significant hypotension (Mean Arterial Pressure \< 60 mmHg or requiring initiation/increase of vasopressor support), or Incidence of significant hypertension (Systolic BP \> 180 mmHg requiring new antihypertensive therapy).
Hemodynamic stability, measured by changes in heart rate (HR)
Incidence of significant bradycardia (Heart Rate \< 40 bpm or requiring intervention \[e.g., atropine, pacing\]) or Incidence of tachycardia (Heart Rate \> 120 bpm sustained for \>10 minutes).
Duration of Delirium
Total number of days in the first 7 days with a positive CAM-ICU
ICU Length of Stay
Number of days the patient stayed in the ICU (Days from ICU admission to ICU discharge)
Sponsors and contacts
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