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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Spinal Stenosis, Inflammation

Intervention / Treatment
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* Drug: Dexmedetomidine group
* Drug: Placebo group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (> 18) male or female who will undergo surgery for spinal fusion with general anesthesia. 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. Subject is ASA physical status 1, 2, or 3. Exclusion Criteria: Cognitively impaired (by history) Subject requires chronic antipsychotic history Subject is anticipated to require an additional surgery within 90 days after the intended spinal fusion Subject known to be in liver failure Subject has received treatment with alpha-2-agonist or antagonist within 2 weeks of study entry Subject for whom opiates, benzodiazepines, DEX are contraindicated Chronic use of steroids/NSAIDs Patients with serious bradycardia related arrhythmias, i.e. 2nd degree block.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR). | Drug: Placebo group<br>* 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).<br>|
| Experimental: Dexmedetomidine group<br>Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR). | Drug: Dexmedetomidine group<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Recovery Score (QoR-40) | The QoR-40 is a 40 item questionnaire in which each question is answered with a score of 1-5. QoR-40 scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). | Post-operative Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of TNF-alpha |  | Post-operative Day 1 | 
| Concentration of IL-1a |  | Post-operative Day 1 | 
| Concentration of IL-6 |  | Post-operative Day 1 | 
| Concentration of IL-8 |  | Post-operative Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal fusion, Inflammatory response, Inflammatory markers, Dexmedetomidine