Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy

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.

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