Literature Review - May 2022

May 1, 2022, 00:06 AM by Jerry Jones, MD; Anthony Machi, MD; Sudheer Potru, DO; Nathalie Lunden, MD

Cite as: Jones J, Machi A, Potru S, Lunden N. Literature review - May 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. 

Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty. A Triple Blinded Randomized Controlled Trial

YaDeau JT, Brummett, C, Mayman DJ. J of Arthroplasty 2022;S0883-5403(22)00133-4.

Summary by Jerry Jones, MD

Introduction: Excessive pain after total knee arthroplasty (TKA) is common and is linked to substantial negative outcome differences. Duloxetine, a serotonin and norepinephrine dual reuptake inhibitor, has been shown to improve analgesia for chronic pain conditions. Despite reducing opioid consumption after TKA in previous studies, duloxetine has not been shown to reduce pain with ambulation. These prior studies did not utilize current multimodal analgesia practices.

Methods: The authors performed a triple-blinded randomized controlled trial in patients who received either 60 mg of duloxetine on the day of surgery and for the next 14 days or placebo. All patients also received an anesthetic with a combined spinal epidural and a comprehensive multimodal analgesia regimen including adductor canal block, iPACK block, surgical periarticular injection, IV ketamine, intraoperative and postoperative NSAIDS, IV and oral acetaminophen, and as-needed oral oxycodone. Primary outcomes were numeric rating scale (NRS) scores with movement on postoperative days 1, 2, and 14, and cumulative opioid consumption surgery through postoperative day 14. Secondary outcomes included pain interference, satisfaction, performance on the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) inventory and other metrics.

Results: The authors enrolled 160 patients. Duloxetine was noninferior to placebo for NRS pain scores at rest and with movement, and it was superior to placebo for opioid consumption. Oral morphine equivalents through 14 days with duloxetine were 288 ± 226 and 432.5 ± 374 with placebo (p = .0039). No difference in side effects were noted. Patient satisfaction was improved, pain interference was decreased, and patients performed better on the KOOS JR in the duloxetine group.

Key Point: In the context of a comprehensive multimodal analgesia regimen after TKA, adding duloxetine for 2 weeks resulted in a 29% opioid reduction, greater patient satisfaction, less pain interference, and no side-effect differences but similar pain scores to patients who didn’t receive duloxetine.

Effects of Hypnosis vs Mindfulness Meditation vs Education on Chronic Pain Intensity and Secondary Outcomes in Veterans: A Randomized Clinical Trial

Williams RM, Day MA, Ehde DM, et al. Pain 2022.

Summary by Anthony Machi, MD

Introduction: Chronic pain is common in adults in the United States and even more common in veterans of the U.S. Armed Forces. Hypnosis and mindfulness meditation are two complementary and integrative health treatments that have shown benefit in the treatment of certain types of pain but lack evidence in the treatment of chronic pain. The authors sought to compare hypnosis and mindfulness meditation interventions against pain education as an active control for the treatment of chronic pain.

Methods: The authors conducted a prospective randomized controlled trial comparing hypnosis, mindfulness meditation, and education. Participants were veterans experiencing any type of chronic pain. Each intervention consisted of 8 sessions for 90 minutes over 8-10 weeks in cohorts of 3-12 participants following published protocols. The primary outcome was the average difference of the Average Pain Intensity (API) scores on a 0-10 numeric rating scale. Secondary outcomes included change in API scores at 3 and 6 months after treatment, various Patient Reported Outcomes Measurement Information System measures, and other measurements related to pain, mental health, and patient satisfaction. Analysis was performed with an intention-to-treat approach.

Results: The authors enrolled 328 subjects with 90% retention after treatment, 81% at 3 months, and 80% at 6 months. Participants in all 3 groups reported improvement in API after treatment; however, the changes were small and not statistically significant across each of the groups. There also were no significant differences in secondary outcomes apart from pain interference, which saw greater improvement in the hypnosis and meditation groups than the education group.

Key Point: Hypnosis, mindfulness meditation, and education all resulted in modest, nonsignificant improvement of chronic pain in veterans with a nonsignificant trend toward slightly greater improvement following hypnosis and mindfulness meditation at later time points.

Post-discharge Opioid Consumption After Minimally Invasive and Open Colectomy: Does Operative Approach Matter?

Vu J, Cleary RK, Englesbe MJ, et al. Ann Surg 2022;275(4)753-8.

Summary by Anthony Machi, MD

Introduction: Many factors contribute to opioid consumption after discharge from the hospital following surgery. Understanding and addressing these factors is necessary to mitigate behaviors that contribute to a worsening of the opioid crisis. Minimally invasive surgical approaches have been partly justified by a reported reduction in opioid use and hastening of postsurgical recovery; however, these approaches have not been examined for opioid consumption after colectomy.

Methods: The authors conducted a retrospective observational study of adult patients undergoing colectomy utilizing the Michigan Surgical Quality Collaborative (MSQC) database from January 2017 to May 2018. Current Procedural Terminology (CPT) codes were utilized to identify patients for each group from the MSQC from 43 hospitals. In addition to clinical outcomes, the MSQC began collecting patient-reported outcomes (PRO) including opioid consumption in January 2017. The primary study outcome was post-discharge opioid consumption in the 30 days after surgery as reported by the PRO surveys. Secondary outcomes addressed complications such as acute kidney injury, surgical site infection, anastomotic leak, and deep vein thrombosis. The authors used zero-inflated negative binomial regression analysis to test for an association between opioid consumption and surgical approach. Patients who did not report opioid consumption were excluded from the study, and data on postoperative analgesic modality were not reported.

Results: 562 patients completed the PRO survey during the study period. 279 had minimally invasive colectomy while 283 had open colectomy. The median (interquartile range) postoperative opioid prescription size was similar: 30(21) vs 30(25). After multivariable adjustment, no significant difference was shown for opioid consumption (p = 0.54) or the likelihood of using no opioids in patients undergoing minimally invasive vs open colectomy (p = 0.39). Larger prescriptions were associated with more opioid use, while age greater than 65 and a cancer diagnosis were associated with less opioid use.

Key Point: Opioid consumption is similar by patients after open and minimally invasive colectomy, but consumption was influenced by the size of the postoperative prescription, patient age, and diagnosis.

Passive Recharge Burst Spinal Cord Stimulation Provides Sustainable Improvements in Pain and Psychosocial Function: 2-Year Results from the TRIUMPH Study

Deer TR, Falowski SM, Moore GA, et al. Spine 2022; 47(7)548–56.

Summary by Sudheer Potru, DO

Introduction: Passive recharge burst (hereafter, burst) offers many patients viable options for chronic pain and is often used as salvage therapy for those who have failed traditional tonic stimulation. The previous TRIUMPH study was a prospective, single-arm study that studied a total of 269 patients who underwent a 3-to-31 day trial of burst stimulation and subsequent implantation; this article reviewed the 24-month data related to pain and functional outcomes.

Methods: Data was obtained from questionnaires and inventories assessing pain, mental health, sleep, physical function, and pain medication consumption at baseline, 6 months, 12 months, 18 months, and 24 months following permanent implantation. Most patients had radiculopathy or a persistent spinal pain syndrome (59% and 50%, respectively). Intervertebral disc disorders made up about 8% of participants, and about 2% had complex regional pain syndrome. 244 participants were trialed, 43 withdrew (including 19 unsuccessful trials), and 201 were implanted. Of these 201, 27 patients were withdrawn (including 10 explants) in the first six months, and in the subsequent months that followed, eight more explants and 37 more patients withdrew. In total, 128 patients were available for study follow-up at 24 months.

Results: Pain reduction (numeric rating scale) was significant at all timepoints and, on average, more than 60% at all intervals. Activity level demonstrated improvement with the percentage of those being moderately or very active escalating from 32% at baseline to 53% at 24 months. All evaluated psychosocial domains demonstrated statistically significant improvement. There was particular improvement in catastrophizing on the Pain Catastrophizing Scale, with nearly 80% with prior catastrophizing no longer doing so. Also, 61% of patients with depression were no longer clinically depressed. Health-related quality of life improved across all domains, and participant satisfaction was extremely high. More than 90% of study participants at 24 months would recommend this treatment to a family member with a similar condition.

Key Point: Burst stimulation represents an excellent option for patients with persistent spinal pain or radiculopathy as well as some other pain conditions; most results related to pain relief and quality of life appear to be sustained up to the 24-month mark.

Effects of a Low-Carbohydrate Ketogenic Diet on Reported Pain, Blood Biomarkers and Quality of Life in Patients with Chronic Pain: A Pilot Randomized Clinical Trial

Field R, Pourkazemi F, Rooney KB. Pain Med 2022;23(2)326-38.

Summary by Sudheer Potru, DO

Introduction: There is significant popularity in the mainstream media and among certain practitioners of integrative medicine related to the low-carbohydrate “ketogenic” diet, which has been reported to improve chronic pain by reducing inflammation and sensitivity within the nervous system. This study aimed to determine the effect of the ketogenic diet on pain scores, certain biomarkers, and quality of life.

Methods: The authors performed a pilot-randomized clinical trial in patients with chronic musculoskeletal pain. Participants underwent a 12-week dietary intervention including a 3-week removal of ultra-processed foods followed by randomization to either a whole-food (WF) or well-formulated ketogenic diet (WFKD). Outcomes included visual analogue scale scores, biomarkers (including high-sensitivity C-reactive protein and others), adherence, sleep, quality of life (QOL) measures, and psychological effects.

Results: Average weekly pain improved for both the WF and WFKD groups, with a greater reduction for the WFKD group. There was also a slightly greater improvement in quality of life for the WFKD group compared to WF, but both improved QOL. However, only the WFKD resulted in statistically significant improvements in pain interference (p = 0.013), weight, (p < 0.005), depression (p = 0.015), anxiety (p = 0.013), and levels of inflammation as measured by hSCRP (p = 0.009). Importantly, significant average pain reduction remained at three-month follow-up for both groups (WFKD p = 0.031, WF p = 0.011).

Key Point: Change in diet to a whole-food or ketogenic diet has the potential to assist with chronic pain, but there may be greater benefits to the ketogenic diet for the chronic pain patient in terms of greater pain reduction as well as weight loss and QOL measures.

A Multidisciplinary Transitional Pain Management Program Is Associated with Reduced Opioid Dependence After Total Joint Arthroplasty

Featherall J, Anderson JT, Anderson LA, et al. J Arthroplasty 2022; S0883-5403(22)00183-8.

Summary by Nathalie Lunden, MD

Introduction: Chronic opioid use is associated with addiction, overdose, and opioid-related death. Perioperative pain control in total hip arthroplasty (THA) and total knee arthroplasty (TKA) contributes to opioid overprescribing and subsequent chronic opioid dependence. In addition, chronic opioid use contributes to increased surgical-related complications such as venous thromboembolism, implant-related complications, readmission, prosthetic joint infection, early revision, and increased cost. The authors hypothesized that implementation of a multidisciplinary perioperative pain management program known as Transitional Pain Service (TPS) would reduce overall opioid use in the Veterans Affairs (VA) population as well as reduce the proportion of patients becoming chronic opioid users 90 days after recovery from THA or TJA.

Methods: The investigators conducted a historical control interventional study at the Veterans Affairs Medical Center. They enrolled opioid-naïve patients undergoing primary TJA, excluding patients who had active chronic opioid use, revision TJA, were discharged to an extended care facility, or were undergoing an additional surgery within the 90-day follow-up period. During the pre-TPS retrospective phase, no standardized pain control protocols were in place. Peripheral nerve blocks for TKA and periarticular injections of local anesthetic were routine in both TKA and THA. No central monitoring for opioid dosing and consumption was established. The TPS program intervention was studied prospectively and consisted of a preoperative assessment conducted by a TPS nurse. This determined baseline mental health and opioid use assessments. In addition, investigators collected baseline Patient Reported Outcome Measure Instrument Scale (PROMIS) scores for pain intensity and pain interference. Standardized education regarding expectations for pain, recovery, nonopioid analgesic use, coping strategies, and appropriate opioid use were provided. During the hospitalization, the pain management plan included non-opioid analgesics (NSAID, acetaminophen, and gabapentinoid), intraoperative local anesthetic, regional anesthesia as appropriate, and opioid medications for breakthrough pain. The TPS team provided daily recommendations to the surgical team and a discharge medication plan including an opioid taper plan. Follow-up by the TPS nurse was provided at several points in the 90-day follow-up period including referrals to outpatient psychology and long-term mental health as appropriate.

Results: The pre-TPS group consisted of 71 TJAs compared to 137 in the TPS group. Most of these surgeries were TKAs (69.3% TPS and 60.6% pre-TPS). The only major demographic difference was a greater incidence of anxiety disorder in the TPS group. Fewer patients in the TPS group demonstrated persistent opioid use at 90 days post-discharge (0.7% vs 9.9%; p = 0.004). In addition, the mean number of opioid tablets prescribed at discharge were fewer in the TPS group (39 tablets, standard deviation [SD] 24 vs 85 tablets, SD 29; p < .001). The mean number of tablets prescribed within the 90-day post-discharge interval was also fewer in the TPS group (49 tablets, SD 36 vs 119 tablets, SD 64; P < .001).

Key Points: The implementation of a multidisciplinary Transitional Pain Management program using multimodal pain control strategies significantly reduced the incidence of chronic opioid use after TJA in this patient population. It also significantly resulted in fewer opioid tablet prescriptions at discharge and within the 90-day post-discharge interval.

Machi_Anthony LR

Anthony Machi, MD, is an assistant professor in the department of Anesthesiology and Pain Management at the University of Texas (UT) Southwestern Medical Center in Dallas. Dr. Machi is also the program director for the fellowship in regional anesthesiology and acute pain medicine.
Dr. Jerry Jones
Jerry Jones, MD, is an assistant professor in the department of Anesthesiology in the College of Medicine at the University of Tennessee Health Sciences Center in Nashville, TN.

Sudheer Potru, DO, is is an assistant professor at the Emory University School of Medicine in Atlanta, GA.

Dr. Nathalie Lunden

Nathalie Lunden, MD, is an assistant professor of Anesthesiology at Oregon Health & Science University in Portland.
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