A Comparison of Dexmedetomidine and Haloperidol in Patients With Intensive Care Unit (ICU)-Associated Agitation and Delirium (Dex)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00505804
Recruitment Status : Completed
First Posted : July 25, 2007
Last Update Posted : January 24, 2013
The Alfred
Information provided by (Responsible Party):
Rinaldo Bellomo, Austin Health

Brief Summary:

The purpose of the study is to determine whether dexmedetomidine is a more effective medication than haloperidol in the treatment of agitation and delirium in patients receiving mechanical ventilation in an intensive care unit. Haloperidol is a medication conventionally used for this purpose.

The investigators will study only patients who have recovered from their illness to the point that, were it not for agitation and delirium, they would no longer require mechanical ventilation.

The investigators hypothesize that patients receiving dexmedetomidine will be able to discontinue mechanical ventilation earlier than those receiving haloperidol.

Condition or disease Intervention/treatment Phase
Delirium Agitation Ventilator Weaning Respiration, Artificial Intensive Care Drug: dexmedetomidine Drug: haloperidol Phase 2

Detailed Description:

Up to 80% of patients undergoing intensive care have delirium. Early in the ICU stay, delirium and agitation are usually prevented using analgesic and sedative drugs which essentially render the patient unconscious. This is appropriate in the context of aggressive treatment of pathophysiological instability, which often requires multiple painful procedures. However, after the underlying pathophysiological problem has resolved, patients sometimes remain delirious and agitated. This often requires ongoing heavy sedation, which in turn necessitates continued mechanical ventilation, and can worsen the (temporarily masked) delirium. Prolonged mechanical ventilation increases the risk of ventilator associated pneumonia and other life threatening complications.

The drug most commonly used to treat delirium is haloperidol, which reduces hallucinations and unstructured thought patterns, but also reduces the interaction with the environment. Haloperidol has significant side effects, including extrapyramidal reactions (in 1-10% of patients), neuroleptic malignant syndrome (in which it is the cause in 50% of cases), and prolonged QT syndrome (which can precipitate fatal arrhythmias).

An ideal sedative agent in this context would have fewer side effects, relieve agitation without causing excessive sedation, and be easily titrated. An analgesic action might allow less opioid use, also lessening delirium. Early studies in other contexts suggest dexmedetomidine has all these properties.

The investigators hypothesise that patients with ICU-associated delirium after the resolution of their underlying pathological process who receive dexmedetomidine will be able to be extubated earlier than those who receive haloperidol.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Open Label Pilot Study of the Efficacy of Dexmedetomidine and Haloperidol in Ventilated Patients With ICU-associated Agitation and Delirium
Study Start Date : January 2005
Actual Primary Completion Date : November 2008
Actual Study Completion Date : November 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1 Drug: dexmedetomidine
Dexmedetomidine IV infusion of 0.0 to 0.7 mg/kg/min for as long a deemed necessary by the treating clinician.
Active Comparator: 2 Drug: haloperidol
Haloperidol IV loading dose of 2.5mg, followed by a continuous infusion of 0.0 to 2mg/hr for as long as deemed necessary by the treating clinician

Primary Outcome Measures :
  1. Time from the commencement of treatment to extubation [ Time Frame: days ]
    the tiem taken to extubate the patient

Secondary Outcome Measures :
  1. Time taken to achieve a satisfactory sedation score (score 3 or 4 on the Riker scale) [ Time Frame: hours ]
    time to sedation score

  2. The need for supplemental sedative and analgesic medication (morphine, midazolam or propofol, as clinically indicated) [ Time Frame: During delivery of trial medication ]
  3. Average Riker score for agitation [ Time Frame: During delivery of trial medication ]
  4. Average RASS score for agitation [ Time Frame: During delivery of trial medication ]
  5. Need for re-intubation [ Time Frame: During the same ICU admission ]
  6. Average Bergeron ICDSC score for delirium [ Time Frame: During delivery of trial medication ]
  7. Duration of ICU stay [ Time Frame: days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients will be eligible for the study if, in the opinion of the treating clinician, they continue to require mechanical ventilation only because their degree of agitation requires such a high dose of sedative medication (midazolam or propofol, the only commonly used specific sedatives in our unit) that extubation is not possible.

Exclusion Criteria:

  • Patients who could not be extubated even if delirium or agitation were corrected. This will include:

    • Patients receiving high dose opioid analgesia (>20 m/morphine/day)
    • Patients shortly to return to the operating theatre
    • Patients undergoing repeated invasive procedures, in whom it is desirable to maintain deep sedation.
    • Patients likely to require ongoing airway protection or control, or ventilatory support (for example, spinal patients with an inadequate vital capacity)
  • Known allergy to haloperidol or alpha2 agonists

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00505804

Sponsors and Collaborators
Austin Health
The Alfred
Principal Investigator: Rinaldo Bellomo, MD FJFICM Austin Health, University of Melbourne
Study Director: Michael C Reade, MBBS FJFICM Austin Health, University of Melbourne

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Rinaldo Bellomo, Prof, Austin Health Identifier: NCT00505804     History of Changes
Other Study ID Numbers: H2004/02026
First Posted: July 25, 2007    Key Record Dates
Last Update Posted: January 24, 2013
Last Verified: January 2013

Keywords provided by Rinaldo Bellomo, Austin Health:

Additional relevant MeSH terms:
Psychomotor Agitation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Psychomotor Disorders
Haloperidol decanoate
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Autonomic Agents
Gastrointestinal Agents