Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy (PE-POD)

Indiana University

Status and phase: Completed; Phase 4

Conditions: Post-traumatic Stress Disorder; Delirium; Cognitive Impairment; Depression; Anxiety

Treatments: Drug: Haloperidol; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02213900

VFR-398-Khan

Details and patient eligibility

About

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.

Full 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.

Enrollment: 135 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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135 participants in 2 patient groups, including a placebo group

Haloperidol

Experimental group

Description:

Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.

Treatment:

Drug: Haloperidol

Placebo

Placebo Comparator group

Description:

Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.

Treatment:

Drug: Placebo