The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for the Mitigation of Complications of Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise and international representation to establish evidence-based guidance on the mitigation of neuromodulation complications. This Neurostimulation Appropriateness Consensus Committee (NACC)® project intends to update evidence-based guidance and offer expert opinion that will improve efficacy and safety. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to October 2023. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the mitigation of complications associated with neurostimulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for Spinal Cord Stimulation Long-term Outcome Optimization and Salvage Therapy.

INTRODUCTION: The International Neuromodulation Society (INS) has recognized a need to establish best practices for optimizing implantable devices and salvage when ideal outcomes are not realized. This group has established the Neurostimulation Appropriateness Consensus Committee (NACC)® to offer guidance on matters needed for both our members and the broader community of those affected by neuromodulation devices. MATERIALS AND METHODS: The executive committee of the INS nominated faculty for this NACC® publication on the basis of expertise, publications, and career work on the issue. In addition, the faculty was chosen in consideration of diversity and inclusion of different career paths and demographic categories. Once chosen, the faculty was asked to grade current evidence and along with expert opinion create consensus recommendations to address the lapses in information on this topic. RESULTS: The NACC® group established informative and authoritative recommendations on the salvage and optimization of care for those with indwelling devices. The recommendations are based on evidence and expert opinion and will be expected to evolve as new data are generated for each topic. CONCLUSIONS: NACC® guidance should be considered for any patient with less-than-optimal outcomes with a stimulation device implanted for treating chronic pain. Consideration should be given to these consensus points to salvage a potentially failed device before explant.

The Polyanalgesic Consensus Conference (PACC)®: Intrathecal Drug Delivery Guidance on Safety and Therapy Optimization When Treating Chronic Noncancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

A Definition of Neuromodulation and Classification of Implantable Electrical Modulation for Chronic Pain.

OBJECTIVES: Neuromodulation therapies use a variety of treatment modalities (eg, electrical stimulation) to treat chronic pain. These therapies have experienced rapid growth that has coincided with escalating confusion regarding the nomenclature surrounding these neuromodulation technologies. Furthermore, studies are often published without a complete description of the effective stimulation dose, making it impossible to replicate the findings. To improve clinical care and facilitate dissemination among the public, payors, research groups, and regulatory bodies, there is a clear need for a standardization of terms. APPROACH: We formed an international group of authors comprising basic scientists, anesthesiologists, neurosurgeons, and engineers with expertise in neuromodulation. Because the field of neuromodulation is extensive, we chose to focus on creating a taxonomy and standardized definitions for implantable electrical modulation of chronic pain. RESULTS: We first present a consensus definition of neuromodulation. We then describe a classification scheme based on the 1) intended use (the site of modulation and its indications) and 2) physical properties (waveforms and dose) of a neuromodulation therapy. CONCLUSIONS: This framework will help guide future high-quality studies of implantable neuromodulatory treatments and improve reporting of their findings. Standardization with this classification scheme and clear definitions will help physicians, researchers, payors, and patients better understand the applications of implantable electrical modulation for pain and guide informed treatment decisions.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Occipital Nerve Stimulation for the Treatment of Patients With Medically Refractory Occipital Neuralgia: Update.

BACKGROUND: The Guidelines Task Force conducted a systematic review of the relevant literature on occipital nerve stimulation (ONS) for occipital neuralgia (ON) to update the original 2015 guidelines to ensure timeliness and accuracy for clinical practice. OBJECTIVE: To conduct a systematic review of the literature and update the evidence-based guidelines on ONS for ON. METHODS: The Guidelines Task Force conducted another systematic review of the relevant literature, using the same search terms and strategies used to search PubMed and Embase for relevant literature. The updated search included studies published between 1966 and January 2023. The same inclusion/exclusion criteria as the original guideline were also applied. Abstracts were reviewed, and relevant full text articles were retrieved and graded. Of 307 articles, 18 were retrieved for full-text review and analysis. Recommendations were updated according to new evidence yielded by this update . RESULTS: Nine studies were included in the original guideline, reporting the use of ONS as an effective treatment option for patients with medically refractory ON. An additional 6 studies were included in this update. All studies in the original guideline and this current update provide Class III evidence. CONCLUSION: Based on the availability of new literature, the current article is a minor update only that does not result in modification of the prior recommendations: Clinicians may use ONS as a treatment option for patients with medically refractory ON.

Efficacy of Continuous Intrathecal Infusion Trialing with a Mixture of Fentanyl and Bupivacaine in Chronic Low Back Pain Patients.

Intrathecal trialing is used as a screening prognostic measure prior to intrathecal drug delivery system implant. The purpose of this study was to determine the efficacy of a continuous intrathecal infusion of an admixture of bupivacaine and fentanyl in patients with chronic low back pain. Patients with refractory chronic low back pain in the setting of previous lumbar spine surgery and/or chronic vertebral compression fracture(s) were enrolled in a randomized double blind cross-over study comparing saline infusion to infusion of a solution containing bupivacaine combined with low-dose fentanyl over a 14-18 hour period. The primary outcome measure was the change in pain intensity at the end of the screening trial. Patients who experienced significant pain reduction from either infusion relative to baseline pain were offered a permanent implant. In total, 36 patients were enrolled, with 31 patients trialed and 25 implanted. At the end of the screening trial, pain scores, at rest or with activity, decreased appreciably in both groups; however, significantly better improvements occurred in the fentanyl/bupivacaine group compared to saline both with activity and at rest (P = .016 and .006, respectively). Treatment order appeared to affect outcome with saline demonstrating a placebo response. At 12 months following implant, primary and secondary outcome measures continued to be significantly reduced from baseline. Continuous intrathecal delivery of a combination of zlow-dose fentanyl with bupivacaine is superior to saline in screening intrathecal trialing for back pain reduction. With longer term delivery, a sustained reduction of chronic low back pain was also observed.

Research design considerations for randomized controlled trials of spinal cord stimulation for pain: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials/Institute of Neuromodulation/International Neuromodulation Society recommendations.

ABSTRACT: Spinal cord stimulation (SCS) is an interventional nonpharmacologic treatment used for chronic pain and other indications. Methods for evaluating the safety and efficacy of SCS have evolved from uncontrolled and retrospective studies to prospective randomized controlled trials (RCTs). Although randomization overcomes certain types of bias, additional challenges to the validity of RCTs of SCS include blinding, choice of control groups, nonspecific effects of treatment variables (eg, paresthesia, device programming and recharging, psychological support, and rehabilitative techniques), and safety considerations. To address these challenges, 3 professional societies (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials, Institute of Neuromodulation, and International Neuromodulation Society) convened a meeting to develop consensus recommendations on the design, conduct, analysis, and interpretation of RCTs of SCS for chronic pain. This article summarizes the results of this meeting. Highlights of our recommendations include disclosing all funding source and potential conflicts; incorporating mechanistic objectives when possible; avoiding noninferiority designs without internal demonstration of assay sensitivity; achieving and documenting double-blinding whenever possible; documenting investigator and site experience; keeping all information provided to patients balanced with respect to expectation of benefit; disclosing all information provided to patients, including verbal scripts; using placebo/sham controls when possible; capturing a complete set of outcome assessments; accounting for ancillary pharmacologic and nonpharmacologic treatments in a clear manner; providing a complete description of intended and actual programming interactions; making a prospective ascertainment of SCS-specific safety outcomes; training patients and researchers on appropriate expectations, outcome assessments, and other key aspects of study performance; and providing transparent and complete reporting of results according to applicable reporting guidelines.

Effects of Bupivacaine on Opioid Patient-Controlled Intrathecal Analgesia in Chronic Pain Patients Implanted with Drug Delivery Systems.

BACKGROUND: Combining neuraxial opioids and local anesthetics in acute pain results in improved duration of analgesia and reduced dosages and adverse effects. Although commonly used in intrathecal drug delivery systems (IDDS) for chronic pain, the effectiveness of this admixture has not been examined specifically in relation to patient-controlled intrathecal analgesia (PCIA). METHODS: IDDS-implanted chronic noncancer pain patients receiving opioids with bupivacaine (O + B) were randomized to receive either opioids without bupivacaine (O) or O + B in a double-blind manner, at IDDS refills, for one week and then crossed over to the other solution for another week. Primary outcome measures included numeric rating scale (NRS) pain scores before and within 30 minutes after PCIA boluses. Secondary outcome measures included average NRS scores and functional outcome measures. RESULTS: Seventeen patients were enrolled, and 16 patients completed the study. There were no differences in NRS scores before and after PCIA boluses between the O and O + B conditions, though pain scores improved significantly (average decrease in NRS scores: O 1.81 ± 1.47 vs O + B 1.87 ± 1.40, P = 0.688). No differences were noted in speed of onset or duration of analgesia. Although more patients subjectively preferred the O + B treatment, the difference was not statistically significant. No differences were noted in secondary outcome measures, with the exception of global impression of change having higher scores in O compared with O + B. CONCLUSIONS: Acutely removing bupivacaine from a chronic intrathecal infusion of opioids and bupivacaine in patients with chronic noncancer pain did not adversely affect PCIA effectiveness, nor did it affect speed of onset or duration of effect. These findings are divergent from those in acute pain and may have to do with study conditions and pain phenotypes.

Systematic Review of Research Methods and Reporting Quality of Randomized Clinical Trials of Spinal Cord Stimulation for Pain.

This systematic review assessed design characteristics and reporting quality of published randomized clinical trials of spinal cord stimulation (SCS) for treatment of pain in adults and adolescents. The study protocol was registered with PROSPERO (CRD42018090412). Relevant articles were identified by searching the following databases through December 31, 2018: MEDLINE, Embase, WikiStim, The Cochrane Database of Systematic Reviews, and The Cochrane Central Register of Controlled Trials. Forty-six studies were included. Eighty-seven percent of articles identified a pain-related primary outcome. Secondary outcomes included physical functioning, health-related quality of life, and reductions in opioid use. Nineteen of the 46 studies prespecified adverse events as an outcome, with 4 assessing them as a primary outcome. Eleven studies stated that they blinded participants. Of these, only 5 were assessed as being adequately blinded. The number of participants enrolled was generally low (median 38) and study durations were short (median 12 weeks), particularly in studies of angina. Fifteen studies employed an intention-to-treat analysis, of which only seven specified a method to accommodate missing data. Review of these studies identified deficiencies in both reporting and methodology. The review's findings suggest areas for improving the design of future studies and increasing transparency of reporting. PERSPECTIVE: This article presents a systematic review of research methods and reporting quality of randomized clinical trials of SCS for the treatment of various pain complaints. The review identifies deficiencies in both methodology and reporting, which may inform the design of future studies and improve reporting standards.

Peripheral Nerve Stimulation for Facial Pain Using Wireless Devices.

Since its original introduction several decades ago, peripheral nerve stimulation (PNS) of the craniofacial region has been traditionally performed using devices intended for spinal cord stimulation applications with inevitably high rate of technical challenges and procedural complications. The lower invasiveness of recently developed wireless neurostimulation systems makes them much better suited for craniofacial applications. Here, we discuss the preliminary clinical data from several published reports and the ongoing multicenter prospective study of wireless PNS in the craniofacial region. Advances in wireless transmission of electrical signals may make wireless neurostimulation even more attractive in the future. Since most of the evidence supporting PNS for facial pain comes from small subsets of the population, case series and case reports, there will need to be larger, randomized controlled trials with cost efficacy analyses in order to validate the role of wireless PNS as the standard of care.

Comparative Effectiveness of Targeted Intrathecal Drug Delivery Using a Combination of Bupivacaine with Either Low-Dose Fentanyl or Hydromorphone in Chronic Back Pain Patients with Lumbar Postlaminectomy Syndrome.

OBJECTIVE: Targeted intrathecal drug delivery (TIDD) is an effective interventional pain management modality often used in postlaminectomy patients with refractory chronic low back pain. A combination of intrathecal bupivacaine with an opioid is often used. However, intrathecal catheter tip granulomas have occurred with use of morphine or hydromorphone but generally not with fentanyl. The objective of this study was to compare the efficacy of TIDD using bupivacaine/fentanyl vs bupivacaine/hydromorphone in patients with chronic intractable low back pain postlaminectomy. MATERIALS AND METHODS: A retrospective comparative analysis of consecutive patients with lumbar postlaminectomy syndrome who were trialed and later received TIDD with a combination of bupivacaine/hydromorphone or bupivacaine/fentanyl between June 2009 and May 2016 at a single tertiary medical center. RESULTS: We identified a cohort of 58 lumbar postlaminectomy patients receiving a TIDD admixture of either hydromorphone/bupivacaine (30 patients) or low-dose fentanyl/bupivacaine (28 patients) with at least two years of follow-up. The fentanyl group had significantly lower baseline opioid consumption and a lower rate of intrathecal opioid dose escalation. Both groups had similar and significant reductions in pain scores over the two-year follow-up period. No granulomas were observed. CONCLUSION: TIDD using a low-dose fentanyl admixture with bupivacaine in patients with postlaminectomy syndrome and refractory chronic low back pain results in similar pain relief to TIDD with hydromorphone and bupivacaine. Low-dose intrathecal fentanyl leads to a lower rate of opioid escalation and may be safer than hydromorphone.

Pain Management Best Practices from Multispecialty Organizations During the COVID-19 Pandemic and Public Health Crises.

BACKGROUND: It is nearly impossible to overestimate the burden of chronic pain, which is associated with enormous personal and socioeconomic costs. Chronic pain is the leading cause of disability in the world, is associated with multiple psychiatric comorbidities, and has been causally linked to the opioid crisis. Access to pain treatment has been called a fundamental human right by numerous organizations. The current COVID-19 pandemic has strained medical resources, creating a dilemma for physicians charged with the responsibility to limit spread of the contagion and to treat the patients they are entrusted to care for. METHODS: To address these issues, an expert panel was convened that included pain management experts from the military, Veterans Health Administration, and academia. Endorsement from stakeholder societies was sought upon completion of the document within a one-week period. RESULTS: In these guidelines, we provide a framework for pain practitioners and institutions to balance the often-conflicting goals of risk mitigation for health care providers, risk mitigation for patients, conservation of resources, and access to pain management services. Specific issues discussed include general and intervention-specific risk mitigation, patient flow issues and staffing plans, telemedicine options, triaging recommendations, strategies to reduce psychological sequelae in health care providers, and resource utilization. CONCLUSIONS: The COVID-19 public health crisis has strained health care systems, creating a conundrum for patients, pain medicine practitioners, hospital leaders, and regulatory officials. Although this document provides a framework for pain management services, systems-wide and individual decisions must take into account clinical considerations, regional health conditions, government and hospital directives, resource availability, and the welfare of health care providers.

Ocular pain response to treatment in dry eye patients.

PURPOSE: Pain is a frequently reported symptom in dry eye disease (DED). We examine the factors associated with ocular pain severity and patient-reported improvement in ocular pain to commonly used dry eye and pain treatments. METHODS: Cross-sectional study of patients presenting for dry eye management. Demographics, ocular and medical history, OSDI, numeric pain scale, pain descriptors, and subjective response to tried eye drop, systemic, and non-pharmacologic treatments were collected. Statistical analysis was performed to identify differential treatment response in patients with various pain levels using the non-parametric test for trend. RESULTS: 144 patients were categorized into 4 groups according to reported pain severity. Increasing pain was significantly associated with younger age, history of refractive surgery, higher OSDI score, and less likelihood of corneal staining. Patients with higher pain intensity were more likely to report a history of fibromyalgia, depression, anxiety, and migraine. Patients with greater pain severity were less responsive to treatment with artificial tears (p < 0.001), lubricating ointment (p = 0.002), steroid eye drops (p = 0.03), cyclosporine 0.05% (p = 0.03), 20% autologous serum tears (p = 0.01), hot compresses (p = 0.04), lid hygiene (p = 0.002) and punctal occlusion (p = 0.03). CONCLUSIONS: Dry eye patients with severe ocular pain often have associated psychological and systemic pain conditions. Treating the underlying DED is beneficial in reducing ocular pain, however the low rate of a satisfactory response highlights the need for further investigation of effective therapies. Cross-sectional studies can provide guidance in the treatment of patients with dry eye-related ocular pain and guide future prospective studies on potentially effective therapies.

Effect of Long-Term Intrathecal Bupivacaine Infusion on Blood Pressure.

OBJECTIVES: The local anesthetic bupivacaine is a common analgesic adjuvant medication used in combination with opioids in intrathecal drug delivery systems (IDDSs). While the acute effects of spinal bupivacaine injection on blood pressure (BP) have been studied, there is a dearth of data regarding long-term effects of continuous intrathecal bupivacaine infusion. MATERIALS AND METHODS: A retrospective review of all noncancer pain patients receiving bupivacaine through IDDSs from January 2013 to November 2017 was performed. Blood pressure values before implantation, and after implant at the 1-week, 3-month, 6-month and 1-year time points are recorded as well as corresponding bupivacaine and opioid doses in the IDDS. RESULTS: Eighty-two patients were included in the study; median patient age was 64 years and intrathecal catheter tips were located predominantly in the lower thoracic spine. Significant decreases in systolic blood pressure (SBP) and mean arterial pressure (MAP) relative to baseline occurred in patients receiving chronic lower thoracic intrathecal bupivacaine delivery at 3, 6, and 12 months post-implant (-12.96 ± 18.21; p < 0.001 and - 6.38 ± 12.04; p < 0.001, respectively). The only significant decrease in DBP was observed at 1 year post-implant (-3.09 ± 11.76; p < 0.05). Similar decreases in BP values occurred in patients with or without hypertension. CONCLUSIONS: Long-term thoracic intrathecal infusion of bupivacaine likely exerts a lowering effect on BP, primarily because of a significant decrease in SBP. This effect is likely due to efferent sympathetic blockade by bupivacaine.

Intrathecal Trialing of Continuous Infusion Combination Therapy With Hydromorphone and Bupivacaine in Failed Back Surgery Patients.

OBJECTIVES: Intrathecal (IT) trial is a prognostic interventional pain management procedure employed to determine the potential success of treating intractable pain with an implantable infusion device system. There is a dearth of data regarding trials with continuous infusion of combination therapy (e.g. opioid combined with local anesthetic). The objective of the this study was to determine the overall outcomes of continuous infusion IT trials and factors influencing long-term success of IT therapy in patients with chronic intractable pain post-laminectomy. MATERIALS AND METHODS: This is a retrospective analysis of all patients with lumbar failed back surgery syndrome (FBSS) who were trialed with a combination of hydromorphone and bupivacaine with a temporary externalized IT catheter from March 2007 to June 2014. RESULTS: From a cohort of 62 patients fulfilling the inclusion criteria, 54 (87.10%) patients had successful IT trials. No significant differences were found between successful and failed trial patients with regards to age, sex, pre-trial pain numeric rating scale scores, pre-trial morphine equivalent daily dose, or trial dosages. Significant positive correlations were found between pretrial oral opioid intake and end of trial hydromorphone dose and hydromorphone dose escalation at 12 months and 24 months. CONCLUSIONS: Patients with refractory low back pain due to FBSS who underwent successful combination IT trial with hydromorphone and bupivacaine infused through a temporary IT catheter had significantly improved pain intensity scores following permanent implant. Higher pre-trial MEDD was correlated with higher trial and post-implant opioid doses and higher rates of opioid dose escalation post-implant.