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 Overview

• Status: Terminated
• Conditions: Inflammation; Spinal Stenosis
• Intervention / Treatment: Drug: Placebo group; Drug: Dexmedetomidine group

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 Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital For Special Surgery
    • New York, New York, United States, 10016
      • NYU Langone Medical Center, Department of Anesthesiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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).	Drug: Placebo 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).
Experimental: 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).	Drug: Dexmedetomidine 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).

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Michael Urban, MD, Hospital for Special Surgery, New York

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: January 3, 2011
• First Submitted That Met QC Criteria: June 20, 2011
• First Posted (Estimate): June 21, 2011

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Inflammatory markers; Dexmedetomidine; Inflammatory response; Spinal fusion
• Additional Relevant MeSH Terms: Pathologic Processes; Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Inflammation; Spinal Stenosis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 10-02185

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES