Cite as: Machi A. Literature review - November 2022. ASRA Pain Medicine News 2022;47. https://doi.org/10.52211/asra110122.053 

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.

Transforming Management of Opioid Use Disorder with Universal Treatment

Gupta R, et al. N Engl J Med 2022 Sep 21. Online ahead of print. https://doi.org/10.1056/nejmp2210121

Editors’ note: In a departure from the typical structure of the literature review, we highlight a critical perspective from a team of authors including representatives of the United States White House Office of National Drug Control Policy and the Department of Health and Human Services that addresses the widespread and profound problem of opioid use disorder (OUD) in the United States. Medication for opioid use disorder (MOUD) is lifesaving treatment for OUD that reduces the risk of death from overdose by 82%, while only an estimated 3%-10% of eligible individuals receive MOUD. MOUD can greatly reduce mortality and morbidity in this at-risk population. The authors ask clinicians, health care systems, and policymakers to radically transform access to treatment for opioid use disorder by addressing 6 fundamental actions tied to MOUD:

1. Expand addiction treatment and education infrastructure.
2. Increase access to prescription MOUD (methadone, buprenorphine, and naltrexone) in clinical and community-based programs.
3. Ease restrictions on telemedicine for MOUD.
4. Increase access to treatment with MOUD for people who are incarcerated.
5. Develop and support programs to address social determinants of health (eg, food insecurity, homelessness, discrimination).
6. Reduce stigma at the levels of language (“person with opioid use disorder”), societal structure (institutional policies), and community.
   

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A Prospective, Double-Blind, Pilot, Randomized, Controlled Trial of an “Embodied” Virtual Reality Intervention in Adults with Low Back Pain

Eccleston C, et al. Pain 2022 Sep 1;163(9):1700-15. https://doi.org/10.1097/j.pain.0000000000002617

Introduction: Fear of movement and reinjury plays an important role in the disability associated  with chronic low back pain. Cognitive behavioral therapy (CBT) is an effective intervention for fear whose reach is limited by challenges of scale for delivery. Virtual reality (VR) technologies offer the potential to deliver CBT at scale but have not been studied for treating this aspect of chronic pain. This study sought to test a VR intervention to address high fear of movement and reinjury compared to the existing standard of care.

Methods: The authors performed a pilot 3-arm, prospective, double-blind randomized controlled trial of adults with long-standing low back pain comparing a digital therapeutics software regimen (DTxP) with a sham placebo regimen and with an open standard care. The primary outcome was the reduction of fear of movement score as assessed by the Tampa Scale of Kinesiophobia (TSK). The regimen was performed for 6-8 weeks and then the standard care control arm was rerandomized to either (DTxP) or sham. Assessments including the TKS, Numeric Rating Scale (NRS) for pain, Oswestry Disability Index (ODI), PROMIS-6 item Pain Interference Score, and others were performed at baseline, posttreatment, 9 weeks, and 5 months. The bespoke DTxP was  delivered via off-the-shelf OCULUS Quest and Touch VR units and used an “embodied” model of psychology of pain that leveraged a safe virtual environment  to encourage exploration and repeated movement. The power calculation regarded the standard deviation for the TSK, and when n=10, precision reached in terms of 95% confidence interval was approximately +/- 5 units  for each group’s mean values.

Results: 34 subjects were enrolled: 11 to DTxP, 12 to placebo sham, and 11 to standard care. For the second randomization, 8 participants were allocated to DTxP or sham. Compared with baseline values, subjects in the DTxP arm reported lower ODI scores posttreatment (P=0.05) and at end of study (P=0.04), lower pain interference scores posttreatment (P<0.01), lower TSK score posttreatment (P<0.001) and at 5 months (P<0.01), and lower average pain NRS post- treatment (P=0.02) but not at 5 months (P=0.06). No serious adverse events were reported.

Key Point: The DTxP delivered by VR was superior to sham placebo and standard care for reducing fear of movement and reinjury. This study adds evidence for the efficacy of automated  VR-based psychological interventions for chronic pain management and rehabilitation. Further study is necessary for broader application.

Effect of Graded Sensorimotor Retraining on Pain Intensity in Patients with Chronic Low Back Pain

Bagg M, et al. JAMA 2022 Aug 2;328(5):430-9. https://doi.org/10.1001/jama.2022.9930

Introduction: Low back pain is exceedingly common in the United States and worldwide and is the most common cause of disability. Additional effective nonpharmaceutical noninterventional therapies with favorable safety profiles need to be validated to provide additional options for treatment.

Methods: The authors performed a parallel 2-group randomized clinical trial to investigate the effects of graded sensorimotor retraining in adult subjects with chronic nonspecific low back pain. The primary outcome was mean pain intensity over the prior week at 18 weeks after treatment measured by Numeric Rating Scale (NRS) 0-10 with a between-group minimum clinically important difference (MCID) of 1.0 and within group  MCID of 30% change from baseline. The sample size of 276 participants was calculated for an interaction effect between time and group randomization, using an estimated interobservation correlation of base 0.6 with decay rate of 0.1, with a significance level of .05, and power of 80% while accounting for a 15% loss to follow-up.  The two groups are:

• The intervention group underwent 12 weekly clinical sessions of 1 hour in person by a physiotherapist or exercise physiologist and home training 30-minute sessions 5 times weekly focused on education, movement, and physical activity
• The control group underwent 12 weekly clinical sessions by a physiotherapist and home training of similar duration addressing attention control without the education, while also receiving sham laser and shortwave diathermy and sham noninvasive brain stimulation.

Multiple secondary outcomes were collected from the Roland-Morris Disability (RMD), Euro-QoL-5 (EQ5) dimensions, and Back Beliefs questionnaires, as well as the Euro QoL-5 health thermometer, Depression Anxiety and Stress Scale, Tampa Scale of Kinesiophobia (TSK), and other indices.

Results: 276 subjects were enrolled, and 261 were analyzed. Subjects reported back pain for a median (IQR) of 5.0 (3.0-8.1) years. Baseline NRS mean (SD) in the intervention group was 5.6 (1.8) and in the control group 5.8 (1.8). The mean NRS in the intervention group was 3.1 at 18 weeks and 4.0 in the control group with an estimated between-group mean difference of -1.0 ([95% CI, -1.5 to -0.4]; P=.001) favoring the intervention group. Participants in the intervention group also had significantly improved disability on the RMD, quality of life on the EQ5, kinesiophobia on the TSK, and pain catastrophizing and pain self-efficacy. There were no serious adverse events.

Key Point: In patients with chronic low back pain, graded sensorimotor retraining modestly but meaningfully reduces pain intensity after 12 weeks of therapy.

Percutaneous Radiofrequency Ablation for Trigeminal Neuralgia Management: A Randomized, Double-blind, Sham-Controlled, Clinical Trial

Mansano A, et al. Pain Med 2022 Aug 27;pnac132 online ahead of print. https://doi.org/10.1093/pm/pnac132

Introduction: Trigeminal neuralgia results in severe pain that typically responds to anticonvulsants. However, up to 30% of patients suffer side effects of anticonvulsants that render them refractory to medication treatment. Multiple interventional treatments exist for refractory trigeminal neuralgia; however, one of the most common, percutaneous radiofrequency ablation (RFA), lacks high quality evidence despite its ubiquitous use. The primary aim of this study was to compare the effectiveness and safety of percutaneous radiofrequency ablation (RFA) with sham-controlled interventional care.

Methods: The authors performed a prospective, randomized double-blind sham-controlled clinical trial comparing percutaneous RFA with sham-controlled interventional care for adults with refractory trigeminal neuralgia of at least 6 months duration. The primary objective sought to compare mean reduction in Numerical Rating Scale (NRS) score at one month after RFA to mean reduction in NRS after sham treatment.  The minimum clinically important difference was defined as a reduction of 2 points from baseline. A sample size of 30 was determined based on a difference of at least 1.5 points on the NRS with a standard deviation of 2.0 with a significance level of .05 and power of 80% while accounting for a 20% loss to follow-up. The RFA group received a 75°C lesion for 60 seconds inside Meckel’s cave following confirmation of sensory and motor stimulation. The sham group had the same radiofrequency tip placed inside Meckel’s cave with location confirmation, but no lesion was performed. Subjects were evaluated at baseline, each week after the procedure in the first two months and then each month for 10 months with the NRS, 36-Item Short-Form Health Survey (SF-36) questionnaire and anticonvulsant dose. After one month participants, were allowed to switch to the other arm of the study.

Results: 30 patients were enrolled with 15 allocated to RFA and 15 allocated to sham. Both groups had similar baseline characteristics. One month following treatment, the mean NRS score decreased from 9.2 to 0.7 [standard deviation not provided] in the  RFA group and from 8.9 to 5.8 in the sham group. The RFA group had a greater improvement in all SF-36 scales, except general health perception and a markedly greater reduction in anticonvulsant dose: 84.75% vs 16.46%. Decreased sensation occurred in 40% of participants after RFA at 3 months with a decline in incidence thereafter. One patient in the RFA group developed masseter muscle weakness.

Opioid Versus Opioid-Free Analgesia After Surgical Discharge: A Systematic Review and Meta-Analysis of Randomized Trials

Fiore J, et al. Lancet 2022 Jun 18;399(10343):2280-93.  https://doi.org/10.1016/s0140-6736(22)00582-7

Introduction: Excess opioid prescribing for post-surgical pain after discharge contributes to the opioid addiction and overdose crisis, and yet opioid analgesia is commonplace for post-surgical pain after discharge in North America. The value of continuing to prescribe opioids within this context remains unclear. It is also unclear how opioid-free analgesic regimens compare to opioid-based regimens for reduction of pain intensity after discharge. This study sought to compare opioid regimens with opioid-free regimens for self-reported pain intensity on day 1 after discharge and vomiting up to 30 days after discharge.

Methods: The authors performed a systematic review and meta-analysis following the PRISMA Statement of MEDLINE, Embase, the Cochrane Library, Scopus, AMED, Biosis, and CINAHL from January 1, 1990 to July 8, 2021, and included multidose parallel design randomized controlled trials comparing opioid versus opioid-free analgesia in subjects age 15 years or older discharged after a surgical procedure. The primary outcome was pain intensity 1 day after discharge standardized to a visual analog scale of 0-10 and vomiting up to 30 days after discharge. Risk of bias assessment was performed using the Cochrane Risk of Bias Tool 2.0. Certainty of evidence was evaluated using the GRADE approach.

Results: 23,977 trials were identified and 567 underwent full review. 520 trials were excluded, with the most common reasons being inclusion of inpatient data and analgesia regimen not being opioid free. 47 trials with 6,607 patients undergoing elective day surgery were included. 30 trials studied minor surgical procedures, of which 63% were dental procedures, while 17 trials studied moderate complexity surgical procedures, of which 47% were orthopedic and 29% were general surgery. Compared with opioid-free analgesia, opioid-based regimens did not reduce pain intensity 1 day after discharge (weighted mean difference 0.01 cm, 95% CI -0.26 to 0.27; moderate certainty) or at other timepoints but was associated with an increased risk of vomiting (relative risk 4.50, 95% CI 1.93 to 10.51; high certainty) and other adverse events such as nausea, constipation, dizziness, and drowsiness (high-to-moderate certainty).

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Efficacy of Liposomal Bupivacaine and Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Periarticular Anesthetic for Patients Undergoing Knee Replacement: A Randomized Clinical Trial

Hamilton T, et al. JAMA Surg 2022 Jun 1;157(6):481-9. https://doi.org/10.1001/jamasurg.2022.0713

Introduction: Most patients who receive a knee replacement report moderate-to-severe acute post-surgical pain. Periarticular infiltration with liposomal bupivacaine in the setting of multimodal analgesia has been promoted as a potentially more effective treatment relative to periarticular infiltration with bupivacaine, but high quality clinical trials are lacking due to the small size of prior studies and the use of nonstandard comparators.

Methods: The authors conducted a multicenter, patient-blinded pragmatic randomized clinical superiority trial in 533 adults undergoing primary unilateral knee replacement at 11 institutions in the National Health Service in England. 266 mg liposomal bupivacaine admixed with 100 mg bupivacaine was compared with 100 mg bupivacaine alone when infiltrated periarticular at the end of surgery for the coprimary outcomes of Quality-of-Recovery 40 (QoR-40) score at 72 hours and visual analog scale (VAS) score area under the curve (AUC) from 6 to 72 hours. Secondary outcomes included QoR-40 and VAS scores at other time points, opioid consumption, functional outcomes, cost effectiveness, and adverse effects. A sample size of 500 (240 patients per arm) was required to detect a 5-point difference in the QoR-40 scores at P=.025 with 90% power, assuming a standard deviation of 15.5 and a 4% loss to follow-up.

Results: 533 participants were enrolled and analyzed. There were no differences in baseline characteristics. 89.7% of subjects received a total knee replacement, while 10.3% received a unicompartment knee replacement. There was no difference in QoR-40 score at 72 hours (adjusted mean difference 0.54 [97.5% CI, -2.05 to 3.13], P=.64) or the VAS score AUC from 6 to 72 hours (-21.5 [97.5% CI, -46.8 to 3.8]; P =.06). No difference was found in any secondary outcome including any functional outcome or opioid consumption except a statistically significant difference in VAS score the evening of surgery (-0.54 [97.5% CI, -1.07 to -0.02]; P=.02.

Key Point: Periarticular liposomal bupivacaine did not improve outcomes or reduce pain after knee replacement in this large, well-designed, pragmatic clinical trial.

Evaluation of the Impact of Assistive Artificial Intelligence on Ultrasound Scanning for Regional Anesthesia

Bowness J, et al. Br J Anaesth 2022 Sep 7;S007-0912(22)0043-8.  https://doi.org/10.1016/j.bja.2022.07.049

Introduction: Ultrasound-guided regional anesthesia (USGRA) involves identification of important anatomy including neural, vascular, and organ structures that are necessary to properly identify a target and perform procedures safely. This process can be challenging for inexperienced providers. Artificial intelligence (AI) may aid with interpretation of ultrasound imaging. Its application to assist USGRA is novel, and a comparison of employing AI for performance of USGRA versus standard USGRA techniques by inexperienced providers has not been previously investigated.

Methods: The authors performed a prospective randomized exploratory study involving 21 anesthesiologists inexperienced with USGRA. The subjects underwent standardized instruction for 6 different blocks by 3 experts and then performed 6 different scans on healthy volunteers utilizing SonoSite ultrasound machines, with half the scans assisted by AI provided by ScanNav™ and half the scans with standard USGRA technique. Subjects alternated using the AI such that each performed half of their scans with AI and half without AI in a randomized manner. 3 different experts assessed correct block view acquisition and correct structure visualization, rated subjects with a global rating score of scan performance and timed scans. Subjects reported scan confidence. There was no priori study to inform the design of this study, so the study authors planned to include 20 subjects as a pragmatic sample.

Results: 126 scans were performed by 21 subjects who were inexperienced with USGRA. 7 subjects were consultant/career grade anesthesiologists, and 14 were trainees. The correct view was obtained in 56/62 (90.3%) with AI assistance, while only 47/62 (75.1%) without AI (P=0.031). The correct structure was identified in 188/212 (88.8%) with AI, while only in 161/208 (77.4%) without AI (P=0.002). There was no difference in the other outcomes.

Key Point: AI assistance may be useful to improve USGRA performance by non-experts. More research is warranted.