Intravenous Infusion of Low Dose Ketamine Versus Dexmedetomedine for Delirium Treatment in Acute Heart Failure

Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorAlexandria University

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 volunteers

Qualifiers

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

Design model

Parallel

Treatments tested in this trial

  • Low dose ketamine infusion

    Drug

    Patients 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

    Drug

    Patients 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

150 Participants
are divided into 2 treatment groups
Group A: Ketamine ArmActive comparator 1 intervention
Group B: Dexmedetomidine ArmActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
72 hours from initiating treatment

Secondary outcomes

1

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).

Time frame
During active infusion (Baseline, and at 1, 2, 4, 8, 12, and 24 h); and for 6 hours post-infusion cessation.
2

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).

Time frame
During active infusion (Baseline, 1, 2, 4, 8, 12, and 24 h); and for 6 hours post-infusion cessation.
3

Duration of Delirium

Total number of days in the first 7 days with a positive CAM-ICU

Time frame
7 days after admission
4

ICU Length of Stay

Number of days the patient stayed in the ICU (Days from ICU admission to ICU discharge)

Time frame
From ICU admission to discharge. Censored at Day 30.

Other outcomes

Sponsors and contacts

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