Literature Review - August 2022

Jul 29, 2022, 00:05 AM by Bhavana Yalamuru, MBBS, Monika Nanda, MBBS, MPH, Engy Said, MD, Harsha Shanthanna, MD, PhD, FRPCP, Nathalie Lunden, MD, and Vinita Singh, MD, MS

Cite as: Yalamuru B, Nanda M, Said E, et al. Literature review - August 2022. ASRA Pain Medicine News 2022;47.

Editor’s note: “Literature Review” is a feature designed to provide you with brief summaries of recent articles of interest, particularly from sources that our readers might not normally consume.



The MOTION study: A Randomized Controlled Trial with Objective Real-World Outcomes for Lumbar Spinal Stenosis Patients Treated with the mild® Procedure: One-Year Results

Deer TR, Costandi SJ, Washabaugh E, et al. Pain Med 2022;23(4):625-34.

Summary by Bhavana Yalamuru, MBBS

Introduction: Lumbar spinal stenosis (LSS) is a debilitating condition and is one of the most common reasons for elderly patients to require spine surgery. Minimally invasive lumbar decompression (MILD) was first developed in 2005, with FDA approval in 2006. Shortly thereafter, multiple studies demonstrated the efficacy of the procedure. The MOTION study attempts to provide Level 1 objective real-world data for MILD as a first-line therapy in conjunction with conventional medical management (CMM) versus CMM alone in patients with LSS over a one-year interval. 

Methods: This prospective, multicenter, randomized controlled trial was conducted across 19 interventional pain management centers throughout the United States. Patients between 50-80 years with neurogenic claudication symptoms of more than 3 months and radiologic evidence of LSS with ligamentum flavum > 2.5 mm in thickness confirmed by preoperative MRI or CT were included in the study. Patients were randomized into 1:1 ratio for two parallel interventions. The test group received MILD + CMM, and the control group received CMM alone. The appropriate CMM regimen for each patient was determined by the site investigator at each site. The CMM measures were reflective of real-world practice and included home exercise, walking aids, and physical therapy, as well as early interventional therapies like epidural steroid injections, medial branch injections, radiofrequency ablation, and facet joint injections. Baseline function was evaluated with the Oswestry Disability Index (ODI), numeric pain rating scale (NPRS), and Zurich Claudication Questionnaire (ZCQ) scores

Subjective and objective outcome measures were used to assess pain, level of function, and safety data. The primary efficacy endpoint was mean improvement in ODI score at 1 year follow-up compared to baseline, and secondary endpoints included ZCQ (for symptom severity and physical function specific to LSS) and NPRS (to measure back and leg pain). For each measure, a patient receiving a subsequent lumbar spine intervention (lumbar decompression, spacer, stimulator, or laminectomy) was considered a non-responder and study failure.

Results: A total of 155 patients were enrolled and randomized, with 78 allocated to CMM alone and 77 to CMM + MILD; 69 patients in each group were included in the analysis. In the MILD + CMM group, patients achieved a mean improvement of 258% in walking time to onset of severe pain versus CMM group alone (p<0.001). The MILD + CMM group also experienced a 16.1-point composite OSI mean improvement, compared to 2.0 mean improvement in the CMM alone arm (p<0.001). Mean improvement for all secondary outcome measures demonstrated statistical significance in favor of MILD + CMM as well. There were no device- or procedure-related complications in either group. 

Key Point: The MOTION study demonstrated the durability of the MILD procedure to 1 year in a patient population seen in a typical clinic setting and demonstrated that the outcomes for MILD + CMM were better and statistically significant than CMM alone in the lumbar spinal stenosis population.

Continuous Pecto-Intercostal Fascial Block Provides Effective Analgesia in Patients Undergoing Open Cardiac Surgery: A Randomized Controlled Trial

Zhang Y, Min J, Chen S. Pain Med 2022;23(3):440-7.

Summary by Monika Nanda, MBBS, MPH

Introduction: Open cardiac surgery is associated with significant acute post-sternotomy pain that has been traditionally managed with opioids. Newer blocks have been studied recently for improving analgesia including transversus-thoracis-plane and pecto-intercostal fascial blocks (PIFBs). This study was conducted to evaluate if continuous PIFB would provide long-lasting analgesia and shorten hospital length-of-stay.

Methods: This was a double-blind, randomized, controlled study. Patients presenting for open cardiac surgery were randomly divided into two groups: the PIF group received bilateral PIFB catheters with ropivacaine, and the SAL group received the same block with saline. The PIF group received 20 ml of 0.33% ropivacaine on each side followed by an infusion of 0.1% at 8-10 ml/hour. Postoperatively, patient care analgesia was delivered using IV sufentanil.

The primary endpoint was postoperative pain (resting and dynamic) at 4, 8, 16, 24, 48, and 72 hours after extubation. The secondary outcome measures included analgesia requirements, time to extubation, length-of-stay in ICU, incidence of postoperative nausea and vomiting, time until return of bowel function, time to mobilization, time to urinary catheter removal, and length-of-stay in the hospital.

Results: Of the total 116 patients enrolled, 55 patients were analyzed in each group. Resting and dynamic pains were significantly reduced in the PIF group at all time intervals (p<0.001). Intraoperative and postoperative opioid consumption, ICU, and hospital length-of-stay were significantly reduced in PIF group (p<0.01). All secondary outcomes favored PIF group significantly.

Key Point: Bilateral continuous PIFB provided effective pain relief for 3 days and reduced ICU and hospital length-of-stay after open cardiac surgery.

Postoperative Opioid Prescribing and New Persistent Opioid Use: The Risk of Excessive Prescribing

Howard R, Brown CS, Lai Y-L, et al. Ann Surg 2022 Jan 21. 

Summary by Engy Said, MD

Introduction: Persistent opioid use after surgery in opioid-naïve patients beyond expected period of acute pain contributes to opioid-related harm as well as the opioid epidemic in the United States. Although studies have demonstrated an association between filling prescription and persistent opioid use, there is little data regarding whether the practice of prescribing opioids increases that risk.

Methods: Opioid-naïve patients (18 years and older) who underwent surgical procedures between January 1, 2017, and October 31, 2019, were identified retrospectively from the Michigan Surgical Quality Collaborative (MSQC) clinical registry. The Michigan Automated Prescription System (MAPS) was used to collect data of all prescription fills from those patients identified in the MSQC clinical registry. The primary outcome was new persistent opioid use defined as filling at least one opioid prescription on post-discharge days 4-90 and then filling at least one additional opioid prescription between post-discharge days 91-180. Immediate postoperative prescription fill was defined between post-discharge days 0-3.

Results: A total of 37,654 patients were included with a mean age of 52.2 (SD 16.7) years and 20,923 (55.6%) were female. Of the total, 31,920 (84.8%) patients were prescribed opioids at discharge, and 622 of them (1.7%) developed new persistent opioid use after surgery. Of those who were NOT prescribed opioids at discharge, 2.1% (123 patients) developed new persistent opioid use. Being prescribed an opioid at discharge was not associated with new persistent opioid use (aOR 0.88 [95% CI 0.71-1.09]). However, among patients prescribed an opioid, patients prescribed the second largest (12 [IQR 3] pills) and largest (20 [IQR 7] pills) quartiles of prescription size had higher odds of new persistent opioid use compared to patients prescribed the smallest quartile (7 [IQR 1] pills) of prescription size (aOR 1.39 [95% CI 1.04-1.86]) and aOR 1.97 [95% CI 1.44-2.70], respectively).

Key Point: Although simply prescribing opioid prescription does not necessarily increase the risk of long-term use, providing a larger opioid prescription likely does.

Acute Inflammatory Response via Neutrophil Activation Protects Against the Development of Chronic Pain

Parisien M, Lima LV, Dagostino C, et al. Sci Transl Med 2022;14(644):eabj9954.

Summary by Harsha Shanthanna, MD, PhD, FRPCP

Introduction: The pathophysiological processes involved in the transition from acute to chronic pain are not well understood. Many pain conditions may be preceded by a phase of injury and inflammation, with complex interactions between inflammatory, nervous system, and immune pathways. It is commonly assumed that risks of active (untreated) inflammation outweigh any adaptive beneficial effects and that this has a direct positive correlation in causing chronic pain.

Methods: This report consisted of four different studies investigating the association of inflammatory pathways and their influence on recovery from pain or its surrogate. In one study, 98 patients from a larger human lower-back pain (LBP) cohort were selected to investigate the associations between genome-wide transcriptomics and the development of chronic LBP (CLBP) at 3 months. Patients with acute LBP of moderate intensity (>4 units in a 0-10 scale), who had standard treatment (including NSAIDS) were included. Patients were categorized as resolved (R) or persistent pain (P) at 3 months. Changes in relative cell-type fractions were explored using RNA sequencing and were matched to genes expressed by each cell type. Biological pathways correlating with the differentially expressed genes were explored. In a separate study, investigators tested this hypothesis in patients of temporomandibular (TMD) pain, including a comparison with control group. In preclinical assays of pain models, they tested the effects of different medications (including NSAIDS) on their influence on mechanical allodynia. Lastly, they examined the relationship between analgesic usage and CLBP in patients from the UK Biobank project, to assess whether anti-inflammatory drugs influenced recovery.

Results: In CLBP patients, there were no differences between R and P patients at baseline in their differentially expressed genes. However, at 3 months 1,700 genes were observed to be differentially expressed in R patients after controlling for blood cell-types. The largest and consistent contribution was observed from neutrophil-specific genes and pathways driven by neutrophil activation. Although there was a positive correlation in the transcriptional changes over time in both groups (indicating similar biological responses regardless of outcome), the response was 75% larger in the R group. Similar changes supporting the importance of inflammatory pathways medicated by neutrophils were observed in the TMD pain patients and preclinical assays. Retrospectively, patients reporting NSAID usage with acute back pain were at 1.76-fold greater risk of developing CLBP.

Key point: The magnitude of inflammatory process induced by neutrophil activation and its modulation can potentially influence recovery from pain in musculoskeletal conditions.

Topical Cannabidiol (CBD) After Total Knee Arthroplasty Does Not Decrease Pain or Opioid Use: A Prospective Randomized Double-Blinded Placebo-Controlled Trial

Haffar A, Khan IA, Abdelaal MS, et. al. J Arthroplasty 2022:S0883-5403(22)00383-7

Summary by Nathalie Lunden, MD

Introduction: Multimodal analgesia is increasingly important in pain management of post-surgical pain. With the use of cannabidiol (CBD) increasing in the United States, this study aimed to elucidate the benefits of topical CBD in the treatment of after total knee arthroplasty (TKA)

Methods: This was a prospective randomized double-blinded placebo-controlled study. The patients studied were those undergoing primary unilateral TKA and were naïve to THC/CBD products. Patients taking over 20 morphine mg equivalents (MME) for 30 consecutive days in the past 90 days were excluded. Patients who refused general anesthesia and a nerve block also were excluded. There were 80 patients that completed the study. All patients received spinal anesthesia and adductor canal block using 15 mL 0.5% ropivacaine without an intra-articular cocktail. Patients were randomized into 4 groups: CBD alone, essential oils (EO), CBD + EO, and placebo (no CBD or essential oils). All patients and providers were blinded. The concentration of CBD used was 120 mcg/ounce formulation. Patients applied the topical formulation from post-op day (POD) 0 and three times daily until POD 14. Patients were given meloxicam 15 mg, acetaminophen 975 mg, and gabapentin 300 mg preoperatively and continued post-op with the addition of oxycodone 10 mg every 4-6 hours as needed for severe pain. Outcomes included visual analog scale (VAS) pain scores, narcotic use, numeric rating scale sleep (NRS) scores, and cumulative post-op opioid use (42 days). These outcomes were collected preop, POD 0, 1, 2, 7, 14, and 42.

Results: The CBD group had a slightly higher mean VAS pain score on POD 2 compared to the EO. Cumulative opioid consumption (MME) was similar among all four groups during their hospital stay, and on POD 7, 14, and 42. Similarly, no significant differences were observed in NRS-sleep quality scores on POD 0, 1, 2, 7, 14, and 42. Mild complications were reported, which included erythematous reaction at the application site.

Key Point: When treating postoperative surgical pain after TKA, CBD appears to have no benefit in decreasing pain or opioid use at the dose and frequency given in this study.

A Prospective Long-Term Follow-Up of Dorsal Root Ganglion Stimulation for the Management of Chronic Intractable Pain

Eldabe S, Copley S, Gulve A, et al. Pain 2022;163(4):702-10.

Summary by Vinita Singh, MD, MS

Introduction: This was a single-center prospective study on long-term (5-7 years) follow-up of dorsal root ganglion stimulation (DRGS) for intractable chronic pain with a single device. DRGS has been shown to provide consistent, precise stimulation for distal anatomical regions that can be used to treat intractable focal neuropathic pain. However, data on long-term efficacy and safety is needed.

Methods: Subjects routinely scheduled to receive DRGS were eligible for the study. Patients entered study phase 1 (DRGS trial phase) following informed consent. Patients with clinically sufficient pain relief during the trial progressed to phase 2 (implantation phase). Outcomes were measured at baseline (during recruitment) and 1, 3, 6, 12, and 24 months (+/-2 weeks) as well as at a last follow-up (5-7 years) post-implant. The last follow-up was conducted via telephone. The primary outcome was pain intensity on the visual analogue scale (VAS).

Results: A total of 42 patients were recruited for the study. Of these, 32 received a full implant, and 24 patients completed the 24-month follow-up. The mean difference in VAS at 24 months was -1.7 (0.2-3.3), p=0.03. Fourteen patients needed revisions during the first 24 months. At the last follow-up, 50% of the patients (16/32) retained the DRGS and had an average 29% reduction in pain [mean difference in VAS= -2.1 (0.3-4), p=0.03]. Sixty-nine percent of the patients who received full implant (22/32) had 33 device-related or procedure-related complications, including infections (2), pain at the IPG site (6), lead fracture (5), lead migration (5), dural puncture (2), IPG moved (1), early battery depletion (2), patient switching device off (1), lack of paresthesia/pain relief (8), and IPG malfunction (1). Four patients had the device explanted for dissatisfaction (3) and change to SCS with rechargeable IPG (1).

Key Point: This small cohort, long-term follow-up study showed that DRGS provided pain relief for chronic intractable pain; however, the complication rate was high.



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