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Literature Review - February 2023

Feb 1, 2023, 08:19 AM by Harsha Shanthanna, MD, PhD, FRPCP, Yashar Eshraghi, MD, Bhavana Yalamuru, MBBS, Nathalie Lunden, MD, and Anthony Machi, MD

Cite as: Machi A. Literature review - February 2023. 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 Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients with Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial.

Hara S, Andresen H, Solheim O, et al. JAMA 2022;328(15):1506-14.

Summary by Harsha Shanthanna, MD, PhD, FRPCP

Introduction: Spinal cord stimulation (SCS) therapy involves modulation of afferent pain signals using epidural leads with electrodes that are connected to a subcutaneous implantable pulse generator. The most common clinical indication is for patients with persistent back and/or leg pain after previous spine surgery. Recent advances allow paresthesia free modalities such as burst stimulation, which is supposed to improve the efficacy and tolerability of SCS therapy.

Methods: This single center, study included 50 patients with chronic lumbar radicular pain (CLRP) after lumbar spine surgery. Included study participants were required to demonstrate a reduction of 2 points or more (NRS 0–10-point scale) during a 2-week SCS trial testing using tonic (with paresthesia) stimulation, after which patients underwent 2 periods of burst stimulation and 2 periods of placebo stimulation using multiple crossover randomization, with each period consisting of 3 months. Burst stimulation consisted of a 40-Hz burst mode of constant current stimuli with 4 spikes per burst. At the end of each period, outcomes were collected, impedance and coverage were tested using tonic stimulation, and patients were allocated to the next period. Patients were evaluated for self-reported change in Oswestry Disability Index (ODI) from baseline (primary outcome), along with pain scores and other secondary outcomes. 

Results: 47 (94%) patients provided at least one follow-up ODI outcome capture for final analysis. The mean changes in ODI were −10.6 points for burst stimulation and −9.3 points for placebo stimulation, resulting in a mean between-group difference of −1.3 points (95% Confidence Interval, −3.9 to 1.3 points; P = 0.32). There were no significant differences in any secondary outcomes, including pain scores or quality of life measures.

Key point: In patients with CLRP after lumbar spine surgery, burst SCS as compared to placebo stimulation did not result in any significant difference in back pain related disability.




Post-Acute Sensory Neurological Sequelae in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: The COVID-PN Observational Cohort Study

Odozor C, Kannampallil T, Abdallah A, et al. Pain 2022;163(12):2398-410.

Summary by Yashar Eshraghi, MD

Introduction: COVID-19 infection can cause neurological sequelae, but the occurrence of peripheral neuropathy symptoms and cranial nerve dysfunction is unknown. The goal of this study was to compare symptoms of pain and peripheral neuropathy (primary) and symptoms in cranial nerve distribution (secondary) within 90 days after testing in people with a positive SARS-CoV-2 test, to those with a negative test in the same timeframe.

Methods: Thirty to 90 days after the index SARS-CoV-2 test, patients completed a web-based questionnaire assessing pain, peripheral neuropathy-related sensory symptoms, and symptoms in the distribution of cranial nerves. Univariate analyses compared the outcomes between the groups. Multivariable analysis was used to determine the odds for neuropathy symptoms after adjusting for key baseline variables. 

Results: 1,556 participants were included: 542 CV+ patients and 1,014 control subjects. CV+ patients reported a higher occurrence of peripheral neuropathy symptoms in the extremities anytime within 90 days post infection (28.8% vs 12.9%, odds ratio [OR] [95% confidence interval] = 2.72 [2.10-3.54]), as well as such symptoms persisting up to 90 days after infection (6.1% vs 1.9%, OR = 3.39 [1.91-6.03]). The occurrence of pain in the extremities was higher in the CV+ group (24.2% vs 9.8%, OR = 2.95 [2.21-3.91]). SARS-CoV-2 infection was also associated with higher occurrence of peripheral neuropathy symptoms, after adjusting for the history of chronic pain and neuropathy (OR = 3.19 [2.37-4.29]).

Key Point: This study suggested that SARS-CoV-2 infection was independently associated with an increased risk of pain and peripheral neuropathy symptoms.



Ultrasound-Guided Cervical Retro-Laminar Block for Cervical Radicular Pain: A Comparative Analysis

Khashan M, de Santiago J, Pardo I, et al. Spine. 2022;47(19):1351-6.

Summary by Bhavana Yalamuru, MBBS

Introduction: Cervical epidural steroid injections are used to manage and treat cervical radicular pain. However, they are associated with several risks including catastrophic neurological damage. In 2021, a novel pilot study by the same team of authors demonstrated that ultrasound-guided retrolaminar cervical blocks (RLCBs) can treat cervical radicular pain, with a significantly improved safety profile. In this study, the team retrospectively evaluated the outcomes in patients with cervical radicular pain who underwent a retrolaminar ultrasound-guided cervical block between August 2019 and March 2021.

Methods: 138 patients with cervical radicular pain on clinical diagnosis and MRI imaging were assessed for eligibility, 103 were enrolled in the study, and 98 were analyzed. The data from this cohort were analyzed retrospectively, and, based on duration of pain, the patients were divided into three groups < 4 months, 4-12 months, and >12 months. Primary endpoints studied were improvement in pain scores using numeric rating scale (NRS) and function as assessed with the neck disability index. Pain scores were assessed a month later, patients with NRS scores < 4 were offered a 3-month follow up, those with NRS pain scores >4 were offered a repeat RLCB. A maximum of 3 RLCB were offered/ performed. The pain scores and neck disability index were collected at each visit.  If there was no improvement after 3 RLCBs, a surgical reevaluation was performed. To evaluate clinical significance, a change of 2.5 for NRS and 3.5 for NDI was considered minimal clinically important difference (MCID).

Results:  76.5% of subjects had a lower preprocedural NRS, and 73% had improved final NRS; 83% of subjects had lower post procedural NDI, and 80% had NDI reduction that surpassed the MCID. There  was a significant difference between the values of the mean final NRS and NDI for the three groups (P-value <0.03). The most difference was found between the group with symptoms less than 4 months and the group with more than 12 months of symptoms. Only 8 patients required surgery due to refractory pain.

Key Point:  The RLCB was used to treat cervical radicular pain effectively and should be studied with prospective randomized trials for evaluation as an alternative to cervical epidural steroid injections in future.



The Association of Postoperative Opioid Prescriptions with Patient Outcomes

Howard R, Brown C, Lai Y, et al. Ann Surg 2022; 276(6):e1076-e1082.

Summary by Nathalie Lunden, MD

Introduction: Opioids are potent analgesics that address the acute nociceptive pain of surgical procedures, and postoperative opioid prescribing is an overwhelmingly common practice in the United States. However, the practice carries significant risk. This article sought to understand outcomes associated with patients who were not prescribed an opioid after surgery compared with patients who were prescribed an opioid after surgery.

Methods: This was a retrospective study of patients who underwent surgery in a 10-month period in 2019. The authors used a clinical registry maintained by the Michigan Surgical Quality Collaborative made up of 70 hospitals. The cohort included patients > 18 years old who underwent common surgical procedures. The primary variable was whether the patient was prescribed an opioid after surgery. Other covariates were collected, including patient demographics, patient characteristics, and clinical characteristics. The primary outcome was the incidence of adverse events within 30 days of discharge. This was a composite measure of emergency department visit, readmission, or reoperation. Secondary outcomes were patient-reported outcomes: postoperative pain within 7 days of discharge, satisfaction with care, quality of life, and regret to undergo surgery.

Results: A total of 22,345 patients were included. 80.9% were white-non Hispanic, and 52.4% had private insurance. Of these patients, 14.2% were not prescribed an opioid. After adjusting for differences in patient severity, clinical differences, and hospital/surgeon variation, there was no significant difference in the composite adverse events between the two groups. However, individually, there was a slightly higher rate of readmission within the “no opioid prescription” group. After adjusting for patient and clinical characteristics for secondary outcomes, patients who were not prescribed opioids reported less pain and were just as likely to be highly satisfied, report high quality of life, and have no regrets of having surgery.

Key Point: This was a large observational study, which demonstrated no difference in the overall rate of adverse events after discharge between patients who were and were not prescribed an opioid after some common surgeries, while patient-reported outcomes were just as good – if not better – for patients who were not prescribed an opioid. This study adds data supporting the feasibility of minimizing or potentially omitting opioids from routine postoperative care in the United States.



Effect of a Postoperative Multimodal Opioid-Sparing Protocol vs Standard Opioid Prescribing on Postoperative Opioid Consumption After Knee or Shoulder Arthroscopy

NO Pain investigators. JAMA 2022;328(13):1326-35.

Summary by Anthony Machi, MD

Introduction: Shoulder and knee arthroscopy are common orthopedic surgeries. Opioids are potent analgesics and often are the primary analgesics for postoperative pain for these surgeries. Due to the adverse effects of opioids, alternatives supported by robust evidence are sought to treat postoperative pain and reduce opioid utilization. This study compared an opioid-sparing protocol consisting of patient education, nonsteroidal anti-inflammatory drugs, and acetaminophen with standard opioid-based care as related to opioid consumption at 6 weeks after surgery.

Methods: A pragmatic prospective randomized clinical trial was performed from March 2021 to March 2022. The primary outcome was total outpatient opioid consumption at 6 weeks postoperatively. Secondary outcomes included patient-reported pain, number of oral morphine equivalents (OMEs) prescribed at discharge, patient-reported satisfaction with pain control, opioid refill requests, and adverse events. The sample size was calculated from existing literature, and it was predicted that the intervention group would consume 20 OMEs on average while the standard care group would consume 30 OMEs. Assuming an a of .05 and a b of 80%, the sample size required 68 patients per group.

Results: 200 patients were randomized, with 100 patients assigned to each group and 193 patients completing the trial. For the primary outcome, patients receiving standard care consumed significantly more opioids with a median of 40.0 mg OME consumed (IQR 7.5-105 mg; z = -6.55; P < 0.001), while patients in the opioid-sparing group consumed a median 0 mg OME (IQR 0-8.0 mg). There were no differences in secondary endpoints except amount of opioids prescribed: 341.2 mg (95% CI, 310.2-372.2 mg) in the standard care group and 40.4 mg (95% CI, 39.6-41.2 mg) in the opioid-sparing group. There were no differences in adverse events, but more patients reported medication-related adverse effects in the standard care group (32% vs 19%, P = 0.048).

Key Point: Among patients receiving arthroscopic shoulder and knee surgery, an opioid-sparing multimodal analgesia protocol significantly reduced opioid consumption and medication-related adverse effects while preserving patient satisfaction with post-operative analgesia.

The Effect of Postdural Puncture Headache on Pre-existing and New-Onset Headaches after Cesarean Section: A Retrospective Study

Bakır M, Rumeli S, Özge A, Türkyılmaz G. Heliyon 2022;8(10):e11014

Summary by Anthony Machi, MD

Introduction: Postdural puncture headache (PDPH) occurs in approximately 0.7% of obstetric patients who undergo neuraxial procedures. The acute effects have been investigated extensively previously; however, the impact of PDPH arising from spinal anesthesia on the development of new-onset chronic headaches or worsening of preexisting chronic headaches in the parturient is unclear.

Methods: A retrospective case-control study was conducted. The authors enrolled patients in 3 groups: 40 patients who underwent spinal anesthesia for cesarean section who developed PDPH (group P), 80 patients who underwent spinal anesthesia for cesarean section who did not develop PDPH (group S), and 80 patients who received general anesthesia for cesarean section (group G). The  primary endpoint was the increased incidence of new-onset headaches in patients who developed PDPH. A secondary endpoint examined patients with preexisting headaches, with a clinical worsening defined as a 25% or greater increase in the number of headaches per month following cesarean section.

Results: 221 subjects were enrolled, and 220 were analyzed. Eight of the 40 patients in group P 2 of the 80 patients in group S, and none in group G had new onset chronic headaches (p =0.001). There was no difference in the rate of preexisting headache; however, worsening occurred for 53.7% of patients with preexisting headache in group P, 14.8% in group S, and for none in group G (p=0.02).

Key Point: Parturients who had PDPH after spinal anesthesia had a significantly increased rate of new-onset chronic headache and worsening of preexisting headache in this retrospective study. More research is warranted.



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