Intraoperative Infusion of Precedex to Reduce Length of Stay After Lumbar Spine Fusion (DEXREDLOS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
James L. Blair, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00808665
First received: December 15, 2008
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

Major lumbar spine surgery causes inflammation, soreness and swelling that can delay discharge from the hospital. Dexmedetomidine (DEX) has been shown to have anti-inflammatory effects. This study will evaluate whether DEX can help get patients out of the hospital faster after major spine surgery by reducing the inflammation associated with the procedure itself. A separate part of the study will evaluate the blood levels of some specific indicators of inflammation called cytokines. Measuring cytokines before and after surgery will aid in determining if DEX has altered the inflammatory response.


Condition Intervention Phase
Spinal Fusion Acquired
Spinal Stenosis
Lesions of Lumbosacral Intervertebral Disc
Spinal Diseases
Drug: Intravenous infusion of Dexmedetomidine or 0.9% Saline
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Continuous Perioperative Dexmedetomidine Infusion Reduce Time to Discharge in Patients Undergoing Major Lumbar Fusion? A Double-Blind, Placebo-Controlled Study

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Time required after surgery to reach fitness for discharge from hospital [ Time Frame: Fitness for discharge as assessed by specific study criteria ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: June 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexmedetomidine
At the beginning of spinal surgery, patients will receive 1 hour dexmedetomidine intravenous bolus of 0.7 mcg/kg, followed by infusion of dexmedetomidine at a rate of 0.5 mcg/kg/hour for 2 hours, followed by an infusion of dexmedetomidine at a rate of 0.2 mcg/kg/hour for the duration of the procedure and for 4 hours after the procedure.
Drug: Intravenous infusion of Dexmedetomidine or 0.9% Saline
Patients will be given 0.7 mcg/kg/hr of dexmedetomidine over the first hour of surgery, followed by continuous infusion of 0.5 mcg/kg/hr of dexmedetomidine for the next 2 hours of surgery. Dexmedetomidine dose will be reduced to 0.2 mcg/kg/hr for the duration of the procedure and continued at that rate for four hours postoperatively. Patients in the placebo arm will receive an equal per-kg IV volume of 0.9% Sodium Chloride over the same periods. Drug administration will be controlled for both arms of the study using a continuous infusion pump.
Other Names:
  • Dexmedetomidine
  • Precedex
  • Saline
  • 0.9% NaCl
  • Sodium Chloride
Placebo Comparator: Saline
Since this is a blinded study, at the beginning of spinal surgery, patients will receive a 1 hour 0.9% saline intravenous bolus at a rate and volume commensurate with a 0.7 mcg/kg/hour bolus of dexmedetomidine. Similarly, this will be followed with a saline infusion at a rate of 0.5 mcg/kg/hour for 2 hours, followed by an infusion of saline at a rate of 0.2 mcg/kg/hour for the duration of the procedure and for 4 hours after the procedure.
Drug: Intravenous infusion of Dexmedetomidine or 0.9% Saline
Patients will be given 0.7 mcg/kg/hr of dexmedetomidine over the first hour of surgery, followed by continuous infusion of 0.5 mcg/kg/hr of dexmedetomidine for the next 2 hours of surgery. Dexmedetomidine dose will be reduced to 0.2 mcg/kg/hr for the duration of the procedure and continued at that rate for four hours postoperatively. Patients in the placebo arm will receive an equal per-kg IV volume of 0.9% Sodium Chloride over the same periods. Drug administration will be controlled for both arms of the study using a continuous infusion pump.
Other Names:
  • Dexmedetomidine
  • Precedex
  • Saline
  • 0.9% NaCl
  • Sodium Chloride

Detailed Description:

Inflammation is a two-edged sword, one edge essential for healing, the other potentially delaying recovery. There is evidence that modest attenuation of the initial course of the inflammatory response (IR) - essentially "banking the fire" of the early IR - may be of benefit in shortening overall hospital course. Several medications have been evaluated/utilized intra- and perioperatively to modulate different components of IR, including local anesthetics, steroids and non-steroidal drugs. Additionally, the pro-and anti-inflammatory properties of various alpha- and beta-adrenergic agonists and antagonists have been characterized. Of this last category, dexmedetomidine (DEX), a highly specific ligand for all the subtypes of the alpha-2 receptor throughout the body, has substantial potency for sedation, analgesia and a reduction in the stress response in a wide variety of surgical environments as well as contributing to cardiovascular stability during CABG and open craniotomy. Additionally, DEX has been shown to have quite powerful anti-inflammatory activity in a murine endotoxin model. DEX's anti-inflammatory activity is likely expressed at G protein-coupled receptors (GPCRs) - either conformationally similar to, or the actual "native" alpha-2 receptor - on polymorphonuclear leukocytes, tissue macrophages, mast cells and other immune system cells. Through these receptors, DEX may attenuate the early phase of IR by limiting immune signaling or release of inflammatory cytokines, potentially favorably limiting the body's IR to injury.

In this present study, our primary assumption is that an ordinarily exuberant IR would be invoked by major spine fusion surgery. Continuous administration of intravenous DEX during and immediately after surgery might sufficiently modulate the IR to shorten hospital stay. Therefore, in a prospective, randomized, placebo-controlled, double blinded fashion, we plan to evaluate the potential for a perioperative infusion of DEX to reduce "time-to-fitness-for-discharge" (generally easier to mark and a more accurate surrogate of time-to-discharge) in patients undergoing major 3+ level lumbar spinal fusion procedures. Additionally, cytokine markers, pain scores and additional pain medication requirements associated with surgery will be measured.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ASA Classification I - III
  • Scheduled for Open Posterior Lumbar Fusion over 3+ (bony) levels

Exclusion Criteria:

  • Allergy to dexmedetomidine
  • Cardiac disease with reduced ejection fraction < 30%
  • History of cirrhosis, active hepatitis or attenuated hepatic function
  • Chronic use of steroids, COX-2 inhibitors, alpha-2 agonists, or statins
  • Current anticoagulant therapy
  • Patients requiring motor evoked potential (MEP) monitoring
  • Positive pregnancy test
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808665

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: James L Blair, DO Vanderbilt University
  More Information

Publications:
Responsible Party: James L. Blair, Assistant Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00808665     History of Changes
Other Study ID Numbers: IRB-081331
Study First Received: December 15, 2008
Last Updated: January 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Lumbar Fusion
Inflammation
Dexmedetomidine
Length of Hospital Stay
General Anesthesia
Anti-inflammatory
GPCR
Cytokine
Immune Response

Additional relevant MeSH terms:
Spinal Diseases
Spinal Stenosis
Bone Diseases
Musculoskeletal Diseases
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014