Lesions of Lumbosacral Intervertebral Disc, Spinal Diseases, Spinal Fusion Acquired, Spinal Stenosis
Conditions
Keywords
Lumbar Fusion, Inflammation, Dexmedetomidine, Length of Hospital Stay, General Anesthesia, Anti-inflammatory, GPCR, Cytokine, Immune Response
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.
Interventions
DRUGDexmedetomidine
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.
DRUG0.9% 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.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) |
Countries
United States
Participant flow
Pre-assignment details
68 participants were assessed for eligibility but 5 failed Inclusion and Exclusion criteria and were not randomized
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 31 |
| 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.
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. | 32 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Medication stopped by resident | 0 | 1 |
| Overall Study | only required minimally invasive surgery | 1 | 0 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | required an additional procedure | 0 | 1 |
| Overall Study | surgery cancelled | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Dexmedetomidine | Saline | Total |
|---|---|---|---|
| Age, Continuous | 63 years | 58 years | 60 years |
| Region of Enrollment United States | 31 participants | 32 participants | 63 participants |
| Sex: Female, Male Female | 21 Participants | 24 Participants | 45 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 32 |
| other Total, other adverse events | 23 / 30 | 26 / 32 |
| serious Total, serious adverse events | 1 / 30 | 3 / 32 |
Outcome results
Primary
Time Required After Surgery to Reach Fitness for Discharge From Hospital
Time frame: Start of study drug to time to reach fitness for discharge from hospital (about 3 to 5 days)
Population: analysis done on the 54 participants that received the entire course of Dexmedetomidine or placebo.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine | Time Required After Surgery to Reach Fitness for Discharge From Hospital | 3.2 days |
| Saline | Time Required After Surgery to Reach Fitness for Discharge From Hospital | 3.2 days |
p-value: 0.36Wilcoxon (Mann-Whitney)