Pharmacological Management of Delirium

Official Title: “Pharmacological Management of Delirium”

The purpose of this study is to develop and test the feasibility of using a specific pharmacological protocol to reduce delirium burden among older adults in the Intensive Care Unit (ICU). The study will test the efficacy of a pharmacological intervention in reducing delirium severity and duration as well as length of stay and mortality compared to usual care.

In 2005, approximately 2.7 million Americans aged 65 and older spent at least one day in the intensive care unit (ICU), costing Medicare an estimated $27.5 billion. It is estimated that while hospitalized, up to 80% of these older ICU patients had delirium, an acute brain failure that is an independent predictor of morbidity and mortality which often goes unrecognized. Older adults with delirium are more prone to falls, injuries, pressure ulcers and restraints, complications which may also contribute to prolonged ICU and hospital length of stay, higher mortality rates, poorer functional status, limited rehabilitation, increased institutionalization, and higher health care costs. The literature supports treatment with a combination of a reduction in the use of benzodiazepines and anticholinergics and the use of low-dose neuroleptics such as haloperidol. However, there have been no randomized controlled trials evaluating the efficacy of this approach on reducing delirium severity, duration, and complications.

Building upon the e-CHAMP study, ("Enhancing Care for Hospitalized Older Adults With Memory Problems;" see NCT00182832), a recently completed quality improvement project tested the effectiveness of cognitive screening coupled with computerized decision support in reducing delirium and other hospital-related complications among 424 older adults hospitalized on the medical wards, which found that many of the older adults entering the study had already experienced delirium in the ICU prior to their transfer to the wards. This study will test a pharmacologic intervention that allows a more targeted approach to the care of older adults with delirium while still recognizing the clinicians' role in controlling symptoms and providing intensive care.

The hypothesis is that patients in the intervention arm as compared to usual care will have: - reduced delirium severity, as measured by the Delirium Rating Scale (DRS-R-98), at one week following randomization or hospital discharge - fewer hospital days with delirium or coma as determined by the Confusion Assessment Method in the ICU (CAM-ICU) - shorter hospital lengths of stay - lower ICU, hospital, and 30-day mortality

Intervention(s) in this Clinical Trial

• Behavioral: Reduced exposure to anticholinergics
  • Using the computerized support, physicians will be notified if they attempt to prescribe a patient a medication with anticholinergic properties and will be given a safe alternative to the drug. Patients who are in the non-haldol arm will have their medical records manually reviewed by the study pharmacist as the computerized support is not set to differentiate between patients who can & cannot receive Haldol
• Procedure: Reduced exposure to benzodiazepines
  • Tapering exposure to benzodiazepines by 50% over the first 48 hours after mechanical ventilation, complete stop by discharge; no benzodiazepine orders for patients not requiring mechanical ventilation
• Drug: Haloperidol
  • 0.5 to 1 mg haloperidol every 8 hours via oral or parenteral route for a total of seven days or until discharge from the hospital
• Procedure: Usual care
  • May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Pharmacological interventions
• Active Comparator: 2
  • Usual care
• Experimental: Arm 3
  • Non-Haldol arm for patients with prolonged QT or history of seizures. Patients are randomized and will still receive benzo & anticholinergic drug reduction in intervention arm, but will not receive Haldol.

Primary Measures

• Delirium severity, days free of delirium and coma, measured by DRS-R-98, CAM-ICU, and RASS
  • Time Frame: Daily
    Safety Issue?: No

Secondary Measures

• Length of stay
  • Time Frame: end of ICU stay and hospital stay
    Safety Issue?: No
• Mortality
  • Time Frame: ICU, in-hospital, 30-days post hospitalization
    Safety Issue?: No
• Hospital-acquired complications related to delirium or delirium management
  • Time Frame: Daily
    Safety Issue?: No

Inclusion Criteria:

• 18 years of age or older
• Hospitalized on an ICU ward
• Delirium based on the RASS and the CAM-ICU assessments at any day during ICU stay
• English speaking

Exclusion Criteria:

• Admitted directly to a regular non-ICU ward
• Previously enrolled in the study
• Not eligible for delirium assessment as determined by RASS scores
• Contraindications for use of haloperidol such as history of torsades-de-pointes
• History of allergic reaction to haloperidol
• Prior history of severe mental illness
• Alcohol-related delirium
• Pregnant or nursing
• Have had an aphasic stroke

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Regenstrief Institute, IU Center for Aging Research Other

Overall Clinical Trial Officials and Contacts

Malaz Boustani, MD Principal Investigator Indiana University School of Medicine  

Overall Contact: Tiffany L Campbell, BS 317-423-5605 tiffcamp@iupui.edu

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00842608

Study ID Number: IA0145

ClinicalTrials.gov Identifier: NCT00842608

Health Authority: United States: Federal Government