Pilot Study on the Effect of Dexmedetomidine on Inflammatory Responses in Patients Undergoing Lumbar Spinal Fusion
The aim of the proposed study is to examine the effect of DEX on the inflammatory response in major surgery. More importantly, the investigators will correlate changes in the concentration of inflammatory mediators with meaningful clinical outcomes.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Pilot Study on the Effect of Dexmedetomidine on Inflammatory Responses in Patients Undergoing Lumbar Spinal Fusion|
- Concentration of cytokines (TNF-alpha, IL-1Beta, IL-2, IL-6, IL-10, IFN-gamma) at different time points will be our primary outcome. [ Time Frame: Change from baseline cytokin levels ] [ Designated as safety issue: No ]
- The secondary outcome parameters would be the quality of recovery score (QoR-40) to measure quality of recovery from surgery and a simple fatigue scale. [ Time Frame: Up to 2 weeks before the day of the surgery. On post-operative day 1, 2, 3. And phone follow-ups on day 30 and day 90 after the surgery. ] [ Designated as safety issue: No ]
|Study Start Date:||September 2010|
|Study Completion Date:||June 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Subjects undergoing one or two level spinal fusion surgery will be screened for eligibility to participate in the study. Subject will be screened, recruited and randomized during the preadmission visit or the day of surgery. Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).
Fifty six subjects (28 in each arm) will be enrolled. Subjects undergoing one or two level spinal fusion surgery will be screened for eligibility to participate in the study. Subject will be screened, recruited and randomized during the preadmission visit or the day of surgery. Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01377623
|United States, New York|
|Hospital for Special Surgery|
|New York, New York, United States, 10021|
|NYU Langone Medical Center, Department of Anesthesiology|
|New York City, New York, United States, 10016|
|Principal Investigator:||Alex Bekker, MD, PhD||NYU School of Medicine|
|Principal Investigator:||Michael Urban, MD||Hospital for Special Surgery, New York|