NEWSLETTER

ABSTRACT

Peripheral nerve stimulation (PNS) is a relatively novel therapeutic intervention that has been gaining popularity in the management of various chronic pain conditions. The new intervention has shown promising results with a narrow risk margin for complication and has gained US Food and Drug Administration (FDA) approval. Stimulation targets one or two peripheral nerves supplying the target region. Duration of treatment varies from 60 days for temporary microelectrodes to permanent implants that are kept indefinitely. With the increasing number of patients with implanted peripheral nerve stimulators the situation is starting to arise when they present for a surgical procedure that warrants a regional anesthesia block. Basal electric stimulation for neuromodulation of chronic pain is usually not sufficient to ameliorate post-procedural pain. Patients therefore require supplemental peripheral nerve block (PNB) with an in-situ peripheral nerve stimulator sometimes to the same target. In this article, we discuss peripheral nerve stimulators and their implications in the peri-operative settings with emphasis on an adjunctive PNB for acute pain. ⁶

INTRODUCTION

PNS gradually emerged over the last two decades as a minimally invasive intervention for chronic extremity pain. Multiple studies have demonstrated the potential for clinically significant pain relief and improvements in quality of life, including reductions in disability, decreased analgesic usage, increases in daily activities, and improvements in sleep. This relatively new technique is continuously evolving and has shown success in treating many chronic pain conditions, including nerve injury, complex regional pain syndrome, occipital neuralgia, and post-surgical pain.¹ The advent came to build on the legacy of spinal cord stimulation (SCS) that evolved over the second half of the last century from the introduction of gate control theory of neuro-modulation in 1965 and the first commercially available SCS system in 1968 ending with FDA approval in 1977. SCS is now an established treatment in chronic pain practices in North America for intractable chronic pain. Building on the successful integration of SCS in clinical practice and further encouraged by the opioid pandemic, PNS has gained interest as a novel tool in pain management. The potential for PNS to reduce opioid analgesic usage was demonstrated in preclinical studies.^2-6 Theories on the analgesic mechanism of PNS all stem from the gate-control theories through which PNS exerts its effect through central neuromodulation of pain pathways or reduce peripheral mediators of pain. ^7-9 Despite evidence of its analgesic utility, earlier application of PNS via open neurosurgical placement limited its clinical adoption due to invasiveness and complications. Improvement of the PNS technology led to the modern systems that consist of one or two microelectrodes placed percutaneously under ultrasound guidance similar to regional nerve blocks. Ultrasound guided percutaneous PNS were first reported in 2009 by Huntoon and Burgher for chronic neuropathic pain.^10-11 In 2014, Rauck et al reported significant reduction in pain scores in nine out of fourteen patients with phantom limb pain. ¹² More interestingly, data from a multicenter, randomized, double-blind, placebo-controlled trial on phantom limb showed a significant reduction in average pain scores up to 12 months after a 60-day PNS treatment. ¹³ Temporary transcutaneous PNS, for a maximum of 60 days, was approved by the FDA in 2016 for symptomatic relief of chronic, intractable pain, post-surgical and post-traumatic acute pain. The FDA approval paved the way for wider use of PNS across various pathological entities and different clinical scenarios.

PNS For Chronic Pain Conditions

Currently the only FDA approved indication for PNS use is for chronic intractable pain after failure of other less invasive treatment modalities. These chronic pain conditions include post-amputation extremity pain, complex regional pain syndrome, neuropathies, osteoarthritis and chronic headaches. Complex regional pain syndrome (CRPS) and post amputation pain which include residual limb pain ⁷ (RLP) and phantom limb pain (PLP) are both chronic, extremity pain syndromes known for resilience to most first line pain management strategies hence represented a good target to test the utility of nerve stimulation after exhaustion of medical therapy. Electrical stimulation has been tried in many historical studies on PLP even preceding the currently available PNS systems. ^4,14,15 In one review of 117 patients receiving PNS who were followed up to 53 months, 65% reported an increase in their activities of daily living and more than 75% were satisfied with therapy. ¹⁶ More recently a multicenter, double blinded, randomized controlled trial investigated the efficacy of percutaneous PNS in PLP and found a significantly greater proportion of subjects receiving PNS (n=7/12, 58%, p=0.037) demonstrate ≥50% reductions in average postamputation pain during weeks 1-4 compared with subjects receiving placebo (n=2/14, 14%). ^[13] Many case reports on CRPS have been published illustrating the beneficial effect of PNS in patients with reflex sympathetic dystrophy. ¹⁷ In a large retrospective series by Chmeila et al, 165 patients had PNS systems implanted for a diagnosis of CRPS. Investigators reported decreased pain scores at 12-months follow up, reduced number of patients on chronic opioid therapy and 51% of patient reporting improvement in functional status over a median follow up of 74 months. ¹⁸ Chronic neuropathic pain especially post-traumatic has also been articulated as an indication of PNS by the FDA. Eisenberg et al, applied PNS in 46 suffering from intractable pain due to peripheral nerve injuries where the majority of patients (78%) had long term relief of >50%.¹⁹ In a small series by Huntoon et al, 75% of patients with extremity neuropathic pain refractory to other therapies achieved 50% or greater pain relief after a brief period (3-7 days) of stimulation. ¹¹ PNS also emerged as a useful tool in the treatment of intractable headaches and facial pain syndromes by targeting the terminal branches of the cervical plexus most commonly the greater occipital nerve but also supra-orbital and auriculo-temporal nerves. Schwedt et al reported significant improvement in severity and frequency of headaches across 15 patients with medically refractory headaches, an effect that was sustained on the long term with mean follow up 19 months. ²⁰ In a recent study, Zhou et al reported improvement in head pain intensity, duration and frequency in twenty four patient who had permanent PNS implanted after a successful trial. ²¹

Peri-Operative Considerations

Authors foresee the next arena for PNS will be in the peri-operative settings. Whether primarily as an acute pain management technique, perhaps an adjunct to conventional PNBs. PNS does possess some functional qualities that can support its utilization in the peri-operative settings. Theoretically, PNS does not induce proprioception, motor or sensory deficits as opposed to conventional local nerve blocks which can aid in post-operative ambulation and reduce risk of falls. It also spares the patient systemic effects of opioids and even fear of systemic toxicity with higher doses of local anesthetic 8 nerve catheters. Finally, PNS can be implanted for much longer duration so provide a more sustained analgesic effect. In contrast to regional block catheters, the increased duration of treatment of PNS is associated with extremely low infection rate (1 in 32000 indwelling days). ²³

Based on results from Ilfeld’s group, it appears that analgesia is not only possible but it is very effective for a number of ambulatory procedures. Current barriers include insurance coverage in the perioperative setting. Moreover, if designing an anesthetic plan that matches the intensity of a surgical stimulus, peripheral nerve blockade with local anesthetic may be more reliable and accessible. In the future, PNBs with local anesthetic could be combined with PNS for patients who are at risk for uncontrolled postoperative pain. When performing nerve block procedures, staying away from the PNS leads would prevent damage to the indwelling PNS device. The table below summarizes a list of potential indications for combined PNS and nerve block with local anesthetic. ^{(Table 1)}

YES: Regional Blocks Are Safe To Perform With PNS Implant In Place

Spinal anesthesia and epidural catheters have been used in select patients with SCS who present for surgical procedures and in laboring women. ²³ When considering spinal anesthesia, imaging of the spine gives an insight into the position of the SCS and the feasibility of lumbar puncture. Since there will be epidural fibrosis following SCS, epidural catheter placement for analgesia is usually not recommended and in most cases avoided.

Unlike SCS, PNS electrodes tend to be small (depending on the company of PNS) and percutaneously placed. Thicker, permanent electrodes can be identified by ultrasound imaging and radiological imaging. Thinner 60 day temporary electrodes on the other hand need radiological imaging to ascertain the location. Also, a part of the 60 day temporary electrode is outside the skin giving us an idea where the electrode most likely would be. Further, the amount of scarring with a percutaneous PNS implantation should be less than an open procedure.

Most PNS implants, at this time, are being placed for chronic pain. The acute exacerbation of the pain during and after a surgical procedure necessitates a regional block. This could be achieved through a single injection or a catheter for continuous infusion ^{(Figure 1)}. Regional anesthesia can be safely performed either distal or proximal to the implanted lead without any untoward effects to the PNS system. ^{(Table 1)} With better image quality of ultrasound machines and availability of echogenic needles, the theoretical chance of lead disruption or lead fracture is at the most minimal to none. Also, the electrodes are very malleable and tensile making them resistant to any damage from an accidental 9 needle to electrode contact. A clear communication between the pain physician, anesthesiologist, surgeon, regional team and the patient would ensure a safe and effective way of administering perioperative nerve blocks.

NO: Regional Blocks Are Not Necessary And Have Risk

In patients with existing peripheral nerve stimulators, the addition of PNBs may not be warranted in the perioperative setting. First, the safety profile of combining the two interventions has not been established. Many of these patients already have pre-existing neuropathy, which is a relative contraindication for offering PNBs in some institutions. ²⁴ Peripheral nerve catheters would add another indwelling object inside of the patient. The resulting infection risk is not known. Because the American College of Graduate Medical Education (ACGME) anesthesiology residency training curriculum does not specifically cover the management of peripheral nerve stimulators, anesthesiologists are not expected to know about lead placement or wire location. Without guidelines, anesthesiologists are guessing as to the minimum safe distance to place a PNB to avoid the wires of the indwelling device. Although the risk of error has not been studied in this specific scenario, it is known that increasing complexity of treatment can lead to iatrogenic complications.

Next, there have not been any studies determining the synergistic or antagonistic effect of PNBs when done in conjunction with PNS. The reasons for performing a PNB would include the following: decreased pain scores, decreased opioid-related side effects, decreased anesthetic-related complications, and increased patient satisfaction. It is not yet clear if the addition of a PNB would produce any of these outcomes, especially in cases where general anesthesia is necessary. Overall, PNBs can be done, but it may not be necessary in the current perioperative setting.