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

Not Applicable

Terminated

• Conditions: Inflammation; Spinal Stenosis
• Interventions: Drug: Placebo group; Drug: Dexmedetomidine group

• Registration Number: NCT01377623
• Lead Sponsor: NYU Langone Health

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.

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2011-01-03
• Study First Submitted QC: 2011-06-20
• Study First Posted: 2011-06-21
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Results First Submitted: 2016-03-14
• Results First Submitted QC: 2016-10-24
• Results First Posted: 2016-12-14
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-09
• Last Update Posted: 2017-07-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 66

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo group	Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).
Dexmedetomidine group	Dexmedetomidine group	Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Concentration of IL-6	Post-operative Day 1
Concentration of IL-1a	Post-operative Day 1
Concentration of TNF-alpha	Post-operative Day 1
Concentration of IL-8	Post-operative Day 1

Trial Locations

Locations (2)

Hospital for Special Surgery; 🇺🇸 New York, New York, United States

NYU Langone Medical Center, Department of Anesthesiology; 🇺🇸 New York, New York, United States