Clinical trial NCT02213900: Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy
Official title: Preventing Post-Operative Delirium in Pneumonectomy, Esophagectomy and Thoracotomy Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Delirium
Cognitive Impairment
Post-traumatic Stress Disorder
Depression
Anxiety
Keywords: delirium
confusion
surgery
cognitive Impairment
post-traumatic Stress disorder
depression
anxiety
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2014-08-12
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence
timeFrame: Up to 30 days
Secondary outcomes:
measure: Efficacy of Low-dose Haloperidol in Reducing Days With Delirium
timeFrame: Up to 30 days
measure: Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay
timeFrame: Date of hospital admission through date of hospital discharge, up to 3 weeks on average.
measure: Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up
timeFrame: Up to 3 months after hospital discharge on average.
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: University Hospital
state: Indiana
Study officials:
affiliation: Regenstrief Institute, Inc.
name: Babar A Khan, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: IU School of Medicine
name: Kenneth A Kesler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khan BA, Perkins AJ, Campbell NL, Gao S, Khan SH, Wang S, Fuchita M, Weber DJ, Zarzaur BL, Boustani MA, Kesler K. Preventing Postoperative Delirium After Major Noncardiac Thoracic Surgery-A Randomized Clinical Trial. J Am Geriatr Soc. 2018 Dec;66(12):2289-2297. doi: 10.1111/jgs.15640. Epub 2018 Nov 21.