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

Spinal Stenosis Clinical Trial

— DEXREDLOS  

Official title:

Does Continuous Perioperative Dexmedetomidine Infusion Reduce Time to Discharge in Patients Undergoing Major Lumbar Fusion? A Double-Blind, Placebo-Controlled Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00808665
• Other study ID #: IRB-081331
• Status: Completed
• Phase: Phase 4
• Start date: June 2009
• Est. completion date: December 2012

Study information

• Verified date: May 2018
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 Coronary Artery Bypass Graft (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists (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

Related Conditions & MeSH terms

• Lesions of Lumbosacral Intervertebral Disc
• Spinal Diseases
• Spinal Fusion Acquired
• Spinal Stenosis

Intervention

Drug:
• Dexmedetomidine
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.
• 0.9% Saline
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.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (5)

Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology. 1996 Apr;84(4):873-81. — View Citation

Ma D, Hossain M, Rajakumaraswamy N, Arshad M, Sanders RD, Franks NP, Maze M. Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype. Eur J Pharmacol. 2004 Oct 11;502(1-2):87-97. — View Citation

Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36. — View Citation

Sanders RD, Maze M. Alpha2-adrenoceptor agonists. Curr Opin Investig Drugs. 2007 Jan;8(1):25-33. Review. — View Citation

Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth. 2008;22(3):221-8. doi: 10.1007/s00540-008-0611-9. Epub 2008 Aug 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time Required After Surgery to Reach Fitness for Discharge From Hospital		Start of study drug to time to reach fitness for discharge from hospital (about 3 to 5 days)