Regional Anesthesia in Minimally Invasive Lumbar Spine Surgery

Study Overview
=================
Brief Summary
-----------------
Opioid overuse is a widespread public health crisis in the United States with increasing rates of addiction and overdose deaths from prescription opioids. Reducing the need for opiate analgesics in the post-operative setting has become a high priority in minimizing long-term opioid use in surgical patients. This study will serve to demonstrate the efficacy of the addition of regional analgesic techniques in reducing post-operative opioid requirements in patients undergoing common lumbar spinal surgical procedures.

Detailed Description
-----------------
Opioid abuse and misuse remain a public health crisis in the United States, notably in patients with chronic pain from degenerative spine disease. Perioperative pain management for patients undergoing spinal surgery remains largely reliant on opioid medications, with several known adverse effects including, but not limited to delirium, postoperative urinary retention (POUR), constipation and nausea. These side effects contribute to increased hospital length of stay (LOS) with increased incidence of overall in-hospital complications, perioperative costs, and increased rates of opioid habituation and addiction. Dependence on prescription opioids has been associated with wide-ranging social and economic consequences including increased opioid overdose resulting in death, growing opioid-related incarcerations, and spiraling opioid-related healthcare cost from treatment of addiction, opioid-related mental health issues, and debilitating chronic pain. Long-term requirements for opioid medications may be associated with the use of higher doses of opioids in the perioperative period for patients undergoing invasive surgery for spinal degenerative conditions. Studies have demonstrated that patients who consume fewer opioids for 30 days after surgery are less likely to progress to become chronic opioid users. Regional analgesic techniques have shown promise in decreasing post-operative pain and opioid requirements in thoracic and abdominal surgery but difficulties with post-operative neurological assessments have limited their use in spinal surgery. Inter-fascial plane blocks, however, have emerged as a safe and potentially useful regional analgesic technique to mitigate the pain-inducing effects of posterior spine surgery. Erector Spinae Plane Blocks (ESPBs), specifically, involve ultra-sound guided injection of local anesthetic (LA) posteriorly beneath the erector spinae muscles resulting in longitudinal and ventrolateral spread of the anesthetic into the paravertebral space where the ventral and dorsal rami of the spinal nerves are located thereby inducing a multi-level analgesic effect. Depending upon the LA used, this effect may last for 4 to 36 hours. The proposed study will examine the efficacy of preoperative ESPBs in reducing post-operative opioid utilization and its associated complications specifically after minimally invasive (MIS) lumbar spine surgery including both decompressive and instrumented fusion procedures. The guiding principle of MIS spine surgery is reduction of iatrogenic injury by utilizing muscle dilating approaches and tubular retractors rather than conventional open, subperiosteal muscle stripping techniques. The latter typically results in muscle denervation and devascularization as well as postoperative muscle atrophy and dead space creation that increase postoperative pain, muscle dysfunction, prolonged recovery times and complications. Since MIS spinal surgical procedures preserve normal paraspinal musculature compared to open surgery, the magnitude of effect of ESPBs may actually be more pronounced in this population. The investigators hypothesize that by conducting this investigation within the rigor of a double-blinded, randomized placebo-controlled clinical trial, the results will definitively demonstrate that the addition of regional analgesia in the form of ESPB during MIS lumbar spine surgery will 1) reduce post-operative opioid consumption and 2) reduce opioid-related complications and hospital LOS but 3) have no adverse effects on postoperative pain control.

Official Title
-----------------
Randomized, Placebo-controlled Trial of Erector Spinae Plane Blocks (ESPB) for Perioperative Pain Management for Minimally Invasive (MIS) Lumbar Spine Surgery

Conditions
-----------------
Lumbar Spinal Stenosis, Lumbar Disc Herniation, Lumbar Spondylolisthesis, Lumbar Spondylosis, Lumbar Radiculopathy, Lumbar Spine Instability, Synovial Cyst, Degenerative Disc Disease, Degenerative Spondylolisthesis, Degenerative Intervertebral Discs

Intervention / Treatment
-----------------
* Drug: Bupivacaine-Epinephrine 0.25%-1:200,000 Injectable Solution plus clonidine
* Drug: normal saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-80 Undergoing one of 3 procedure types: 1) 2 or more levels of MIS decompression (e.g., discectomy, foraminotomy, laminectomy); 2) 1-3 levels of MIS transforaminal lumbar interbody fusion (TLIF) (with or without additional levels of MIS decompression for no greater than 3 total operative levels); 3) 1-3 levels of anterior lumbar interbody fusion (ALIF) or MIS lateral lumbar interbody fusion (LLIF) accompanied by posterior percutaneous instrumentation at the same levels Willing and able to give consent Exclusion Criteria: Opioid tolerant at the time of the surgical procedure--defined as consuming greater than 30mg of morphine milligram equivalents (MME) daily (https://www.cdc.gov/drugoverdose/prescribing/guideline.html) Presence of an indwelling pain device (e.g., intrathecal opioid pump, spinal cord stimulator, dorsal root ganglion stimulator) Known allergy to bupivacaine, clonidine or similar local anesthetics Indication for surgery other than degenerative disease (e.g., neoplasm, infection, trauma) Chronic kidney disease (stage 3 or greater), or hepatic failure Active pregnancy Disease process or mental illness that would preclude accurate evaluation of pain in the perioperative period Active Worker's Compensation litigation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All patients will undergo surgery using an enhanced recovery after surgery (ERAS) multi-modal anesthesia protocol that is currently in standard use for MIS lumbar spine surgical procedures. Patients will be randomized in a 1:1 ratio to investigational and control arms.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational<br>Patients will undergo regional ESPB with bupivacaine plus clonidine in the holding area of the OR immediately prior to surgery. 30mL of 0.25% bupivacaine/1:200,000 epinephrine/50mcg clonidine will be administered bilaterally (total 60ml) to the lumbar paraspinal erector spine plane using ultrasound-guidance. | Drug: Bupivacaine-Epinephrine 0.25%-1:200,000 Injectable Solution plus clonidine<br>* Bupivacaine-Epinephrine 0.25%-1:200,000 plus clonidine 50 micrograms in 30cc syringes administered as ESPB<br>|
| Placebo Comparator: Control<br>Patients will receive a placebo injection of normal saline via the same ESPB technique. 30ml of normal saline will be administered bilaterally (total 60ml) to the lumbar paraspinal erector spine plane using ultrasound-guidance. | Drug: normal saline<br>* normal saline in 30cc syringes administered using ESPB technique<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inpatient opioid consumption | Mean per day inpatient opioid consumption in morphine milligram equivalents (MME) | Every 1 day during inpatient admission up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-discharge opioid consumption | Total and per day mean postoperative opioid consumption after hospital discharge in MME as recorded in medication diary by patients | 14 days (+/- 7days) ,56 days (+/- 14 days) and 90 days (+/- 19) postoperatively | 
| Postoperative opioid prescriptions filled | • Total MMEs of opioid prescriptions filled as found on the Illinois Prescription Monitoring Program website | From hospital discharge to 90 days postoperatively | 
| Length of hospital stay | Duration of hospital stay postoperatively measured in days as determined by the time at which each patient met discharge criteria | From time of surgery to time discharge criteria met in hours, up to 2160 hours | 
| Postoperative Urinary Retention (POUR) | Incidence of POUR measured as proportion of inpatient hospital days demonstrating the need for straight catheterization or foley placement | Immediately post-surgery to discharge, up to 90 days | 
| Post-operative delirium | Incidence of post-operative delirium as measured by the need for placement of physical restraints | Immediately post-surgery to discharge | 
| Post-operative delirium | Incidence of post-operative delirium as measured by the administration of new anti-psychotic medications | Immediately post-surgery to discharge, up to 90 days | 
| Postoperative pain scores | Mean daily VAS (visual analog scale) pain scores recorded in the electronic medical record (EMR) | Every 1 day during inpatient admission up to 30 days | 
| Patient-reported pain and functional outcomes | Change in Visual Analog Scale (VAS) for pain in the back and leg (0-10 with 10 being worst) | From baseline preoperative values to 6 week post-operative values | 
| Patient-reported pain and functional outcomes | Change in Oswestry Disability Index (ODI; 0 to 100 with 100 being worst) | From baseline preoperative values to 6 week post-operative values | 
| Patient-reported pain and functional outcomes | Change in Short Form 12/6D (SF-12/6D; 0 to 100 with 0 being worst) | From baseline preoperative values to 6 week post-operative values | 
| Peri-operative complications | Prospectively documented medical and surgical complications/adverse events (AEs) including rates of readmission or reoperation for AEs | Time of surgery to 6 weeks postoperative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
regional anesthesia, erector spinae plane block, minimally invasive spine surgery, randomized controlled trial