Clinical trial NCT01377623: Pilot Study on the Effect of Dexmedetomidine on Inflammatory Responses in Patients Undergoing Lumbar Spinal Fusion
Official title: Pilot Study on the Effect of Dexmedetomidine on Inflammatory Responses in Patients Undergoing Lumbar Spinal Fusion
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Spinal Stenosis
Inflammation
Keywords: Spinal fusion
Inflammatory response
Inflammatory markers
Dexmedetomidine
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2011-06-21
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Quality of Recovery Score (QoR-40)
timeFrame: Post-operative Day 3
Secondary outcomes:
measure: Concentration of TNF-alpha
timeFrame: Post-operative Day 1
measure: Concentration of IL-1a
timeFrame: Post-operative Day 1
measure: Concentration of IL-6
timeFrame: Post-operative Day 1
measure: Concentration of IL-8
timeFrame: Post-operative Day 1
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Medical Center, Department of Anesthesiology
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
Study officials:
affiliation: NYU School of Medicine
name: Alex Bekker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital for Special Surgery, New York
name: Michael Urban, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bekker A, Haile M, Kline R, Didehvar S, Babu R, Martiniuk F, Urban M. The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery. J Neurosurg Anesthesiol. 2013 Jan;25(1):16-24. doi: 10.1097/ANA.0b013e31826318af.