Anxiety, Cognitive Impairment, Delirium, Depression, Post-traumatic Stress Disorder
Conditions
Keywords
delirium, confusion, surgery, cognitive Impairment, post-traumatic Stress disorder, depression, anxiety
Brief summary
The purpose of this study is to investigate the effectiveness of a preventative low-dose of Haloperidol to prevent delirium in patients undergoing a esophagectomy, pneumonectomy or thoracotomy. Delirium is state of severe confusion and some symptoms include: * Cannot think clearly * Have trouble paying attention * Have a hard time understanding what is going on around them * May see or hear things that are not there. These things seem very real to them.
Detailed description
50% of patients who undergo esophageal and/or lung resection suffer from acute brain dysfunction or delirium postoperatively. Delirium is a state of brain failure characterized by disturbance of consciousness with reduced ability to focus, sustain, or shift attention that occurs over a short period of time and tends to fluctuate over the course of the day. Presence of delirium in the post-operative phase is associated with a longer length of both intensive care unit and hospital stay, increased health-care costs, long-term functional and cognitive decline, and an increased risk of in-hospital and post-discharge mortality. Haloperidol primarily acts by blocking dopamine (D2) receptors. This dopamine blockade in the cerebral cortex improves cognition and reduces delirium. Along with the dopamine blockade, haloperidol has anti-inflammatory properties. It inhibits production of lipopolysaccharide induced pro-inflammatory cytokines, interleukin (IL-1) and tumor necrosis factor alpha (TNF-α). Haloperidol also increases levels of Interleukin -1 receptor antagonist (IL-1RA), an anti-inflammatory cytokine that blocks the action of other pro-inflammatory cytokines. If unchecked, the inflammatory cytokines cause impaired concentration, sleep disturbances, and agitation the cardinal symptoms of delirium; and induce a reduction in cholinergic activity. Given the inhibitory effect of acetylcholine on certain cytokines such as interleukin-6, a repetitive cycle of inadequate regulation of inflammation due to cholinergic depletion ensues. Haloperidol with its anti-inflammatory properties seeks to mitigate this repetitive vicious cycle.
Interventions
DRUGHaloperidol
0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days
DRUGPlacebo
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least ≥ 18 years of age and older 2. Undergoing a possible or scheduled thoracotomy 3. English speaking
Exclusion criteria
1. History of Schizophrenia and Parkinson's disease 2. History of Severe Dementia 3. History of Alcohol Abuse 4. On Cholinesterase Inhibitors or Levodopa 5. Pregnant or Nursing 6. Corrected QT interval \> 550 milliseconds at the time of randomization 7. History of Neuroleptic Malignant Syndrome or Haloperidol Allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence | Up to 30 days | Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Low-dose Haloperidol in Reducing Days With Delirium | Up to 30 days | Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. |
| Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay | Date of hospital admission through date of hospital discharge, up to 3 weeks on average. | Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo. |
| Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up | Up to 3 months after hospital discharge on average. | Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Haloperidol Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days | 68 |
| Placebo Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.
Placebo | 67 |
| Total | 135 |
Baseline characteristics
| Characteristic | Haloperidol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 12.4 | 59.6 years STANDARD_DEVIATION 14 | 59.6 years STANDARD_DEVIATION 13.2 |
| Sex: Female, Male Female | 22 Participants | 13 Participants | 35 Participants |
| Sex: Female, Male Male | 46 Participants | 54 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 68 | 0 / 67 |
| serious Total, serious adverse events | 3 / 68 | 2 / 67 |
Outcome results
Primary
Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence
Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.
Time frame: Up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Haloperidol | Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence | 15 Participants |
| Placebo | Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence | 19 Participants |
Secondary
Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up
Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment.
Time frame: Up to 3 months after hospital discharge on average.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Haloperidol | Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up | Baseline RBANS Total Score | 31.7 Units on a scale | Standard Deviation 27.6 |
| Haloperidol | Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up | 3 Month RBANS Total Score | 31.8 Units on a scale | Standard Deviation 30.1 |
| Placebo | Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up | Baseline RBANS Total Score | 30.1 Units on a scale | Standard Deviation 22.8 |
| Placebo | Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up | 3 Month RBANS Total Score | 22.7 Units on a scale | Standard Deviation 23.2 |
Secondary
Efficacy of Low-dose Haloperidol in Reducing Days With Delirium
Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.
Time frame: Up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Haloperidol | Efficacy of Low-dose Haloperidol in Reducing Days With Delirium | 0.3 Days with Delirium | Standard Deviation 0.7 |
| Placebo | Efficacy of Low-dose Haloperidol in Reducing Days With Delirium | 0.5 Days with Delirium | Standard Deviation 0.9 |
Secondary
Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay
Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo.
Time frame: Date of hospital admission through date of hospital discharge, up to 3 weeks on average.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Haloperidol | Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay | ICU Length of Stay | 2.5 Days | Standard Deviation 2.2 |
| Haloperidol | Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay | Overall Length of Stay | 9.3 Days | Standard Deviation 3.5 |
| Placebo | Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay | ICU Length of Stay | 2.8 Days | Standard Deviation 10.2 |
| Placebo | Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay | Overall Length of Stay | 10.2 Days | Standard Deviation 4.6 |