Cognitive Impairment, Delirium
Conditions
Keywords
confusion, dementia
Brief summary
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.
Detailed description
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
Interventions
BEHAVIORALReduced 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
PROCEDUREReduced 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
DRUGHaloperidol
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
PROCEDUREUsual care
May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
Sponsors
National Institute on Aging (NIA)
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
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 * Prior history of severe mental illness * Alcohol-related delirium * Pregnant or nursing * Have had an aphasic stroke
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Days Free of Delirium and Coma | Admission through day 8 of stay |
Secondary
| Measure | Time frame |
|---|---|
| Hospital Length of Stay Post Randomization | Participants were followed for the duration of hospital stay, an average of 11 days |
| Mortality | ICU, in-hospital, 30-days post hospitalization |
Countries
United States
Participant flow
Pre-assignment details
551 patients were consented into the study. After completing the consent and randomization, 6 patients withdrew from the study and were included in intention-to-treat analysis. 545 patients completed the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Haloperidol Eligible Intervention 0.5-1mg Haloperidol Q8h for 7 days, reduced exposure to anticholinergics, reduced exposure to benzodiazepines
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
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
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 | 174 |
| Haloperidol Eligible Usual Care Usual care
Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium | 177 |
| Haldol-Ineligible Arm Haldol-Ineligible arm for patients with contraindications for Haldol, unresolvable prolonged QTc, history of torsades de pointes, or history of seizures.
Patients are randomized and will still receive:
reduced exposure to anticholinergics, reduced exposure to benzodiazepines
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
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 | 99 |
| Haldol Ineligible Usual Care Usual Care
Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium | 101 |
| Total | 551 |
Baseline characteristics
| Characteristic | Haloperidol Eligible Intervention | Haloperidol Eligible Usual Care | Haldol-Ineligible Arm | Haldol Ineligible Usual Care | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 62 Participants | 63 Participants | 42 Participants | 42 Participants | 209 Participants |
| Age, Categorical Between 18 and 65 years | 112 Participants | 114 Participants | 57 Participants | 59 Participants | 342 Participants |
| Region of Enrollment United States | 174 participants | 177 participants | 99 participants | 101 participants | 551 participants |
| Sex: Female, Male Female | 98 Participants | 86 Participants | 65 Participants | 53 Participants | 302 Participants |
| Sex: Female, Male Male | 76 Participants | 91 Participants | 34 Participants | 48 Participants | 249 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 87 / 174 | 82 / 177 | 63 / 99 | 59 / 101 |
| serious Total, serious adverse events | 45 / 174 | 57 / 177 | 27 / 99 | 22 / 101 |
Outcome results
Primary
Days Free of Delirium and Coma
Time frame: Admission through day 8 of stay
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Haloperidol Eligible Intervention | Days Free of Delirium and Coma | 4 days |
| Haloperidol Eligible Usual Care | Days Free of Delirium and Coma | 5 days |
| Haldol-Ineligible Arm | Days Free of Delirium and Coma | 4 days |
| Haldol Ineligible Usual Care | Days Free of Delirium and Coma | 5 days |
Secondary
Hospital Length of Stay Post Randomization
Time frame: Participants were followed for the duration of hospital stay, an average of 11 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Haloperidol Eligible Intervention | Hospital Length of Stay Post Randomization | 20.2 days | Standard Deviation 33.5 |
| Haloperidol Eligible Usual Care | Hospital Length of Stay Post Randomization | 18.6 days | Standard Deviation 31.6 |
| Haldol-Ineligible Arm | Hospital Length of Stay Post Randomization | 18.8 days | Standard Deviation 17.1 |
| Haldol Ineligible Usual Care | Hospital Length of Stay Post Randomization | 14.9 days | Standard Deviation 11.8 |
Secondary
Mortality
Time frame: ICU, in-hospital, 30-days post hospitalization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Haloperidol Eligible Intervention | Mortality | 20 Participants |
| Haloperidol Eligible Usual Care | Mortality | 32 Participants |
| Haldol-Ineligible Arm | Mortality | 11 Participants |
| Haldol Ineligible Usual Care | Mortality | 8 Participants |