Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation (DahLIA)

Austin Health

Status and phase: Completed; Phase 3; Phase 2

Conditions: Delirium

Treatments: Drug: Saline placebo; Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01151865

H2010/03891

Details and patient eligibility

About

The primary aim of the DahLIA trial is to determine, in patients with ICU-associated delirium and agitation who are otherwise pathophysiologically stable (as defined), the number of ventilator-free hours in the incident ICU admission in the 7 days following commencement of trial medication, in patients randomised to receive dexmedetomidine or placebo while receiving all other aspects of standard care.

The null hypothesis assumes no difference in the median number of ventilator-free hours in this ICU admission in the following 7 days, between patients receiving dexmedetomidine and placebo for ICU-associated agitation and delirium.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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, AND in the opinion of their treating intensivist their agitation is so severe as to make lessening their sedation unsafe.

These criteria will be objectively quantified as follows:

• they have required either mechanical restraint and/or anti-delirium or sedative medication in the 4 hours prior to seeking consent AND
• their Confusion Assessment Method for the ICU (CAM-ICU) test is positive for delirium in the 4 hours prior to seeking consent AND
• their Motor Activity Assessment Scale (MAAS) score is 5 or more in the 4 hours prior to seeking consent, confirming psychomotor agitation AND
• their SOFA score is less than or equal to 5 in the 4 hours prior to seeking consent, predicting a mortality or around 5%.

Exclusion criteria

• Age less than 18 years old

• Pregnancy or breastfeeding

• Advanced dementia (in the premorbid state requiring professional nursing care)

• Open or closed head injury

• Death is deemed imminent and inevitable

• The patient has previously been enrolled in the DahLIA study

• Patients who could not be extubated, or who would be intubated within the following 48 hours, even if delirium or agitation were corrected. This will include:

  • Patients receiving high dose opioid for analgesia (not sedation) ( > 40 mg/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 alpha 2 agonists

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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96 participants in 2 patient groups, including a placebo group

Dexmedetomidine

Active Comparator group

Description:

Dexmedetomidine will be administered intravenously as a maintenance infusion of 0.2 to 1.5 mcg/kg/hour, commencing at 0.5 mcg/kg/hour and titrated according to effect, for as long as deemed necessary by the treating physician. Specifically, the study medication may be (as recommended by the manufacturer) continued after extubation, and if discontinued may be restarted at any time up until ICU discharge. The clinician will have the option of using a loading dose of 1.0 mcg/kg IV over 20 minutes, as recommended by the manufacturer. Bedside nursing staff will adjust drug infusion rates as necessary, in consultation with the treating physician, aiming to achieve a Riker Sedation-Agitation Scale 20 score of 4.

Treatment:

Drug: Dexmedetomidine

Saline placebo

Placebo Comparator group

Description:

An identical syringe to that in the intervention arm, but which does not contain dexmedetomidine, will be provided. The initial rate of infusion and subsequent adjustments will be the same as in the dexmedetomidine group.

Treatment:

Drug: Saline placebo