Clinical trial NCT00808665
Conditions: Spinal Fusion Acquired Spinal Stenosis Lesions of Lumbosacral Intervertebral Disc Spinal Diseases
Keywords: Lumbar Fusion Inflammation Dexmedetomidine Length of Hospital Stay General Anesthesia Anti-inflammatory GPCR Cytokine Immune Response
Sponsor: Vanderbilt University Medical Center
Start date: 2009-06-01; Completion date: 2012-12-01
Enrollment: 68 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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 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.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Dexmedetomidine intervention 2: 0.9% Saline
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents: