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Literature Review—May 2023

May 12, 2023, 16:28 PM by Monika Nanda, MBBS, MPH, Engy T. Said, MD, Yashar Eshraghi, MD, Nathalie Lunden, MD, Vinita Singh, MD, MS, Bhavana Yalamuru, MBBS, and Anthony Machi, MD

Cite as: Machi A. Literature review - May 2023. ASRA Pain Medicine News 2023;48.

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.

Reasons for Long-term Opioid Prescriptions After Guideline Directed Opioid Prescribing and Excess Opioid Pill Disposal

Barth RJ Jr, Porter ED, Kelly JL, et al. Ann Surg 2023;277(1):173-8.

Summary by Monika Nanda, MBBS, MPH

Introduction: Previous studies have demonstrated that 5%-10% of opioid-naïve patients receive long-term (3–12 months) opioid prescriptions after surgery. However, little is known about the reasons why long-term opioids are prescribed. The aim of this study was to determine the frequency and reasons for long-term opioid prescriptions after surgery in the setting of guideline-directed prescribing and interventions supporting excess opioid disposal.

Methods: Long-term postoperative opioid use was defined as an opioid prescription given 3 to 12 months after surgery. The authors studied long-term data from a previously reported prospective clinical trial that utilized a patient-centric discharge opioid prescribing guideline and opioid pill disposal and identified frequency and reasons for long-term opioid prescriptions. Adult opioid-naïve patients undergoing major elective surgical procedures were prospectively recruited at a tertiary care medical center. Long-term prescriptions were identified from the regional Prescription Drug Monitoring Program database. The electronic medical records of these patients were reviewed to identify the reasons for long-term prescriptions.

Results: Of the 229 patients enrolled, 221 were analyzed. Thirty-four patients (15.3%) filled a long-term opioid prescription. The most common reason for long-term opioid prescriptions was a newly diagnosed painful medical condition (18/35, 51%), such as cancer pain or metastases. The next common reason (15/35, 40%) was a new additional surgical procedure, different from the index surgery. Only 2 of 35 reasons (6%) were directly related to the index surgery.

Key Point: The use of patient-centric, guideline-directed opioid prescribing and interventions to maximize excess opioid disposal were very effective in reducing long-term opioid prescriptions. These approaches deserve further study.

Quadriceps Strain and TKA: Contribution of the Tourniquet and Intramedullary Rod to Postoperative Thigh Pain. A Randomized Controlled Trial

Stocks GW et al. J Bone Joint Surg Am 2023;105(6):455-461.

Summary by Engy T. Said, MD

Introduction: Thigh pain following total knee arthroplasty (TKA) is relatively common and can be significantly limiting for patients during recovery. While thigh pain is most commonly attributed to tourniquet use, thigh pain is still observed without tourniquet use. Other potential causes include intramedullary (IM) rod placement and quadriceps muscle strain. The authors hypothesized that thigh pain may result from the use of a tourniquet, from the mircrotrabecular fracture from an IM rod, or from both.

Methods: In this prospective randomized controlled trial, 97 patients scheduled for primary TKA were randomly assigned to one of four groups: a group of both tourniquet and IM rod, a group with IM rod, a group with tourniquet, and a group of neither tourniquet nor IM rod. On postoperative day 1 (POD1), magnetic resonance imaging (MRI) was used to determine quadriceps strain. Data collection preoperatively, intraoperatively, and up to 6 weeks postoperatively included pain at the knee and thigh, knee range of motion, thigh circumference, and presence of ecchymosis.

Results: The overall incidence of thigh pain on POD1 was 75% ( 73 of 97 patients). MRI results on POD1 showed quadriceps strain prevalence of 36% with no significant difference between the four groups. Incidence of thigh pain at the two-week clinical visit was 16% with 82% of patients who had a confirmed quadriceps strain on MRI on POD1 reporting continued thigh pain at the two-week visit. Tourniquet use increased the odds of quadriceps strain (53%) OR 2.7, 95% CI 1.1-6.7, P=0.028 vs IM rod (23%) OR 0.56, 95%CI 0.22-1.5, P=0.239.

Key Point: Thigh pain after TKA is in part due to quadriceps muscle strain, which in turn is more likely to occur with tourniquet use. Understanding potential etiologies and risk factors for thigh pain after TKA can help guide patients through recovery after TKA.

Spinal Versus General Anesthesia in Total Knee Arthroplasty: Are There Differences in Complication and Readmission Rates?

Heckmann N, De A, Porter K, Stambough J. J Arthroplasty 2023; 38(4):673-9.e1.

Summary by Nathalie Lunden, MD

Introduction: Spinal anesthesia is commonly used during primary TKA in the United States. Although the benefits of spinal anesthesia (SA) are well-described in the literature, little is understood regarding the short-term outcomes, namely length of stay (LOS), operative time, and readmission and revision rates between the two groups.

Methods: This is a retrospective study, which analyzed 270,251 patients from a nationwide joint replacement registry (AJRR) between 2017 and 2020. Forty-seven percent of patients received general anesthesia, and the remaining 53% underwent spinal anesthesia for their TKAs. Length of stay, operative time, 90-day readmission, and 90-day revisions were compared between the two groups.

Results: After adjusting for confounding factors, spinal anesthesia was associated with a lower risk of a LOS > 3 days (odds ratio [OR] 0.470, 95% CI 0.454-0.487, P <.0001), but slightly higher likelihood of having a longer operative time (OR 1.075, 95% CI 1.056-1.094, P <.0001). The spinal group also had lower rates of 90-day readmission (OR 0.845, 95% CI 0.790-0.904, P<.0001) and lower risk of 90-day all-cause revision (OR 0.506, 95% CI 0.462-0.555, P <.0001).

Key Points: Spinal anesthesia was associated with a decreased incidence of prolonged length of stay, slightly higher likelihood of having an operative time greater than the median operative time, lower readmission rates, and decreased early revision rates. This large retrospective study continues to support the use of spinal anesthesia for primary TKA. 

Capsaicin Treatment in Neuropathic Pain: Axon Reflex Vasodilatation After 4 Weeks Correlates with Pain Reduction

Sendel M, Dunst A, Forstenpointner J, et al. Pain 2023;164(3):534-542:

Summary by Yashar Eshraghi, MD

Introduction: Capsaicin, an agonist at the transient receptor potential vanilloid 1, is used for the topical treatment of peripheral neuropathic pain. The principal mechanism of action for capsaicin has been attributed to reversible receptor defunctionalization and degeneration and subsequent regeneration of cutaneous nociceptors. However, this process has been observed to be highly variable and at times poorly correlated with pain reduction. Following a series of other experiments, the authors hypothesized that accelerated regeneration and functional recovery of a subclass of nociceptive afferents, the peptidergic vasoactive nociceptors, was the potential cause of capsaicin induced analgesia.

Methods: In this noninterventional exploratory trial, 23 patients with different peripheral neuropathic pain etiologies (eg, painful polyneuropathy, peripheral nerve injury, or postherpetic neuralgia) were treated with one topical high-concentration, 179 mg capsaicin patch treatment. Baseline pain ratings, comorbidities, and quality of life metrics were assessed. Functional laser speckle contrast analysis (heat-evoked neurogenic vasodilatation to assess functional properties of peptidergic nociceptors) and quantitative sensory testing were performed in the affected skin. Four weeks after treatment, functional laser speckle contrast analysis and questionnaires were repeated. Telephone interviews were conducted at weeks 2, 10, and 12.

Results: Topical capsaicin treatment induced a significant reduction in pain intensity with a maximum at 4 weeks. At the same time, heat-evoked neurogenic vasodilatation was on average like pretreatment values. Half of the patients not only showed a functional recovery but also an improvement in vasodilatation, indicating regeneration of nerve fibers. Patients with improved heat-evoked neurogenic vasodilatation at week 4 showed a greater pain reduction than those with deterioration. The degree of vasodilatation significantly correlated with pain reduction.

Key Point: This study suggests that (1) regeneration of peptidergic nociceptors may be the mechanism behind capsaicin-induced analgesia and (2) a disease-modifying effect of capsaicin on these fibers already occurs 4 weeks after application.

Long-term Outcomes in Use of Opioids, Nonpharmacologic Pain Interventions, and Total Costs of Spinal Cord Stimulators Compared With Conventional Medical Therapy for Chronic Pain

Dhruva SS, Murillo J, Ameli O, et al. JAMA Neurol 2023;80(1):18-29.

Summary by Vinita Singh, MD, MS

Introduction: The spinal cord stimulator (SCS) is an important tool for pain relief using neuromodulation. However, the device is associated with higher cost at the initial implantation compared to conventional medical management (CMM).

Methods: The propensity-matched retrospective cohort study compared the long-term outcomes regarding frequency of other pain interventions (epidural and facet corticosteroid injection and radio frequency ablation), chronic opioid use, and other healthcare utilization between patients treated with SCS compared to patients treated with CMM using de-identified claims data from United States commercial and Medicare Advantage enrollees from 2015 to 2020. Patients with the diagnosis of failed back surgery syndrome, complex regional pain syndrome, chronic pain syndrome, and other postsurgical back and extremity pain were included. For the SCS group, the treatment initiation (index date) was the permanent SCS insertion date. Individuals in the CMM group were randomly imputed an index date matching the dates in the SCS group. Main outcomes measured were pharmacologic and non-pharmacologic pain interventions from 1 to 12 months and 13 to 24 months after the index date.

Results: A total of 1,260 patients in the SCS and 6,300 in the CMM groups were included in the final matched study cohort. During the first 12 months, patients in the SCS group had higher odds of chronic opioid use (adjusted odds ratio [aOR], 1.14; 95% CI, 1.01-1.29) compared with the CMM group, but lower odds of epidural and facet corticosteroid injections, radiofrequency ablation, and spine surgery. These differences dissipated in the second year.

Key Point: This is a large retrospective study showing no significant difference in healthcare utilization with SCS placement with respect to chronic opioid use or non-pharmacologic pain interventions at 2 years when compared to CMM in a cohort of patients with heterogeneous indications for SCS.

Capsaicin 8% Patch for Spinal Cord Injury Focal Neuropathic Pain, a Randomized Controlled Trial

Olusanya A, Yearsley A, Brown N, et al. Pain Med 2023;24(1):71-8.

Summary by Bhavana Yalamuru, MBBS

Introduction: The incidence of neuropathic pain after spinal cord injury ranges from 41% up to 70%. Pharmacologic management is the first line of management of neuropathic pain, however oral agents have shown only modest effect with significant adverse effects. Capsaicin 8% has been FDA approved to treat neuropathic pain secondary to diabetic peripheral neuropathy and post herpetic neuralgia. Capsaicin is a highly selective agonist of the TRPV1 receptors and at the concentration of 8% leads to destruction and desensitization of the nociceptor fibers lasting a few weeks to months. The authors sought to study the effectiveness of C8P (capsaicin 8% patch) to manage neuropathic pain due to SCI (spinal cord injury).

Methods: Thirty-four patients with refractory neuropathic pain due to SCI were screened to assess for eligibility, and 23 were excluded. Eleven patients were subsequently randomized into two groups (sequence 1 and sequence 2). The study design was a randomized, controlled, single blind crossover. The participants were blinded by placing a patch on the eye. Sequence 1(n=6), the low dose group, received 0.025% capsaicin patch (CON) for 12 weeks, and Sequence 2 (n= 5) were allocated to the Capsaicin 8% patch group (C8P). The two groups were crossed over at the end of 12 weeks. The total study period was 24 weeks. The outcome measures included pain (VAS- visual analogue scale; SCI version of multidimensional pain inventory MPI-SCI); function (spinal cord independence measure ( SCIM) and quality of life (WHOQOL-BREF- World health organization quality of life). The measures were recorded at the following intervals: VAS at 2,4,6,8, and12 weeks during each 12-week interval. MPI-SCI, SCIM, and WHO QOL BREF were all measured every 4 weeks. Each outcome was analyzed by a linear mixed model with treatment and time of measurement as fixed factors and baseline as covariate, followed by planned comparisons between treatments (ie, control, C8P) at each time of measurement.

Results: Eleven patients were enrolled and analyzed in a cross-over design. Changes were noted in VAS between CON and C8P at multiple time points. The statistically significant decrease in VAS was noted at week 2 (35% decrease in pain intensity, 1.91 points, 95% CI 0.59-3.22, P=0.029) and week 4 (29% decrease in pain intensity, 1.64 points, 95% CI 0.40-2.88, P=0.049). The pain severity subscale of MPI-SCI showed a statistically significant main effect of treatment, and the other subscales did not show any statistically significant treatment effects. C8P also demonstrated a main treatment effect over CON on the SCIM mobility subscale. WHO-QOL scores did not improve with C8P.

Key Point: Capsaicin 8% patch was successful in reducing neuropathic pain refractory to other treatments in this pilot study. C8P should be studied further in patients with neuropathic pain due to SCI to assess its efficacy since it shows promise as a treatment modality without the side effects seen with many other pharmacologic treatments in this population.

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