Pilot Study on the Effect of Dexmedetomidine on Inflammatory Responses in Patients Undergoing Lumbar Spinal Fusion

Surgical injury to tissue causes a variety of profound physiologic reactions which are
essential for the restoration of an organisms' homeostasis. The inflammatory response
involves a surge of stress hormones (i.e. ACTH, cortisol, catecholamines), activation of the
complement system, migration of leukocytes to the site of injury, the release of cytokines
(i.e. interleukins, tumor necrosis factor), as well as other cellular products (i.e.
superoxide radicals, proteases, growth factors) (1-3). An appropriate inflammatory cascade
is essential for tissue reconstitution and infection control. The associated impairment of
multiple organ function is generally mild, because of the physiological reserve of the
biological systems. However, a systemic inflammatory response may also lead to postoperative
complications in the elderly, neonates, and patients with significant co-morbidity (4, 5).
Indeed, mediators of inflammation may induce fatigue and prolong convalescence in healthy
patients. On the other hand, dysregulation or suppression of the inflammatory process may
lead to improper wound healing, infection and, as demonstrated recently, even an increase in
cancer recurrence due to reduction in natural killer cell activity (6, 7).

Anesthetic management may affect both immunostimulatory and immunosuppressive mechanisms
either directly by modulating functions of immune cells or indirectly by attenuating the
stress response. For example, inhalational anesthetics inhibit neutrophil function and
depress lymphocyte proliferation while increasing pro-inflammatory cytokine levels (8, 9)).
Propofol also inhibits neutrophil and monocyte function, and has strong anti-inflammatory
and anti-oxidative effects (10). Opioids attenuate the direct cell immune response, but have
only minimal effects on systemic inflammatory responses (11). It is expected that the choice
of anesthetic technique may disturb the balance between pro- and anti-inflammatory responses
thus affecting clinical outcomes. A most advantageous anesthetic choice would enhance or
have a neutral effect on cellular immunity while minimizing contribution to the systemic
inflammatory response.

Inclusion Criteria:

1. Adult (> 18) male or female who will undergo surgery for spinal fusion with general
anesthesia.

2. If female, subject is non-lactating and is either:

- Not of childbearing potential

- Of childbearing potential but is not pregnant at time of baseline as determined
by pre-surgical pregnancy testing.

3. Subject is ASA physical status 1, 2, or 3.

Exclusion Criteria:

1. Cognitively impaired (by history)

2. Subject requires chronic antipsychotic history

3. Subject is anticipated to require an additional surgery within 90 days after the
intended spinal fusion

4. Subject known to be in liver failure

5. Subject has received treatment with alpha-2-agonist or antagonist within 2 weeks of
study entry

6. Subject for whom opiates, benzodiazepines, DEX are contraindicated

7. Chronic use of steroids/NSAIDs

8. Patients with serious bradycardia related arrhythmias, i.e. 2nd degree block.