Literature Review - November 2022
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:
- Expand addiction treatment and education infrastructure.
- Increase access to prescription MOUD (methadone, buprenorphine, and naltrexone) in clinical and community-based programs.
- Ease restrictions on telemedicine for MOUD.
- Increase access to treatment with MOUD for people who are incarcerated.
- Develop and support programs to address social determinants of health (eg, food insecurity, homelessness, discrimination).
- Reduce stigma at the levels of language (“person with opioid use disorder”), societal structure (institutional policies), and community.
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
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.
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
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.
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
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.
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.
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).
Efficacy of Liposomal Bupivacaine and
Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Periarticular
Anesthetic for Patients Undergoing Knee Replacement: A Randomized Clinical
Hamilton T, et al. JAMA Surg 2022 Jun 1;157(6):481-9. https://doi.org/10.1001/jamasurg.2022.0713
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.
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
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
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
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
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.
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.