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

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.