Inflammation, Spinal Stenosis
Conditions
Keywords
Spinal fusion, Inflammatory response, Inflammatory markers, Dexmedetomidine
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.
Interventions
DRUGDexmedetomidine group
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).
DRUGPlacebo group
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).
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Recovery Score (QoR-40) | Post-operative Day 3 | 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). |
Secondary
| Measure | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group 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). | 28 |
| Dexmedetomidine Group 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). | 26 |
| Total | 54 |
Baseline characteristics
| Characteristic | Placebo Group | Dexmedetomidine Group | Total |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 11.1 | 55.3 years STANDARD_DEVIATION 12.3 | 56.18 years STANDARD_DEVIATION 11.69 |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 15 Participants | 21 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 28 |
| serious Total, serious adverse events | 0 / 26 | 0 / 28 |
Outcome results
Primary
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).
Time frame: Post-operative Day 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine Group (PFD) | Quality of Recovery Score (QoR-40) | 183.04 units on a scale | Standard Deviation 2.76 |
| Placebo Group (PFS) | Quality of Recovery Score (QoR-40) | 169.3 units on a scale | Standard Deviation 3.87 |
Secondary
Concentration of IL-1a
Time frame: Post-operative Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine Group (PFD) | Concentration of IL-1a | 2.52 pg/ml |
| Placebo Group (PFS) | Concentration of IL-1a | 2.58 pg/ml |
Secondary
Concentration of IL-6
Time frame: Post-operative Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine Group (PFD) | Concentration of IL-6 | 60.8 pg/ml |
| Placebo Group (PFS) | Concentration of IL-6 | 50.0 pg/ml |
Secondary
Concentration of IL-8
Time frame: Post-operative Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine Group (PFD) | Concentration of IL-8 | 20.9 pg/ml |
| Placebo Group (PFS) | Concentration of IL-8 | 16.4 pg/ml |
Secondary
Concentration of TNF-alpha
Time frame: Post-operative Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine Group (PFD) | Concentration of TNF-alpha | 10.1 pg/ml |
| Placebo Group (PFS) | Concentration of TNF-alpha | 7.9 pg/ml |