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

Delirium Clinical Trial

— Dex  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00505804
• Other study ID #: H2004/02026
• Status: Completed
• Phase: Phase 2
• First received: July 23, 2007
• Last updated: January 22, 2013
• Start date: January 2005
• Est. completion date: November 2008

Study information

• Verified date: January 2013
• Source: Austin Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Agitation
• Delirium
• Intensive Care
• Psychomotor Agitation
• Respiration, Artificial
• Ventilator Weaning

Intervention

Drug:
• dexmedetomidine
Dexmedetomidine IV infusion of 0.0 to 0.7 mg/kg/min for as long a deemed necessary by the treating clinician.
• 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Austin Health	The Alfred

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from the commencement of treatment to extubation	the tiem taken to extubate the patient	days	No
Secondary	Time taken to achieve a satisfactory sedation score (score 3 or 4 on the Riker scale)	time to sedation score	hours	No
Secondary	The need for supplemental sedative and analgesic medication (morphine, midazolam or propofol, as clinically indicated)		During delivery of trial medication	No
Secondary	Average Riker score for agitation		During delivery of trial medication	No
Secondary	Average RASS score for agitation		During delivery of trial medication	Yes
Secondary	Need for re-intubation		During the same ICU admission	Yes
Secondary	Average Bergeron ICDSC score for delirium		During delivery of trial medication	No
Secondary	Duration of ICU stay		days	Yes