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

A Randomised Open Label Pilot Study of the Efficacy of Dexmedetomidine and Haloperidol in Ventilated Patients With ICU-associated Agitation and Delirium

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.

Study Overview

• Status: Completed
• Conditions: Delirium; Agitation; Intensive Care; Respiration, Artificial; Ventilator Weaning
• Intervention / Treatment: Drug: dexmedetomidine; Drug: haloperidol

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
• Enrollment (Actual): 20
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from the commencement of treatment to extubation	the tiem taken to extubate the patient	days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time taken to achieve a satisfactory sedation score (score 3 or 4 on the Riker scale)	time to sedation score	hours
The need for supplemental sedative and analgesic medication (morphine, midazolam or propofol, as clinically indicated)		During delivery of trial medication
Average Riker score for agitation		During delivery of trial medication
Average RASS score for agitation		During delivery of trial medication
Need for re-intubation		During the same ICU admission
Average Bergeron ICDSC score for delirium		During delivery of trial medication
Duration of ICU stay		days

Collaborators and Investigators

• Sponsor: Austin Health
• Collaborators: The Alfred
• Investigators: Principal Investigator: Rinaldo Bellomo, MD FJFICM, Austin Health, University of Melbourne; Study Director: Michael C Reade, MBBS FJFICM, Austin Health, University of Melbourne

Publications and helpful links

General Publications

• Reade MC, O'Sullivan K, Bates S, Goldsmith D, Ainslie WR, Bellomo R. Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit Care. 2009;13(3):R75. doi: 10.1186/cc7890. Epub 2009 May 19.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: July 23, 2007
• First Submitted That Met QC Criteria: July 24, 2007
• First Posted (Estimate): July 25, 2007

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: dexmedetomidine; haloperidol
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Dyskinesias; Psychomotor Disorders; Delirium; Psychomotor Agitation; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antiemetics; Gastrointestinal Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Hypnotics and Sedatives; Anti-Dyskinesia Agents; Dexmedetomidine; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: H2004/02026