Continuing Education Activity

Sacral neuromodulation (SNM) is performed because millions of people are affected by overactive bladder and are refractory to behavioral modifications or pharmacotherapy. Indications for SNM include urinary retention, urgency frequency, urge incontinence, and fecal incontinence. This activity describes sacral neuromodulation and reviews the interprofessional team's role in evaluating and treating patients who undergo this procedure.

Objectives:

• Identify the indications for sacral neuromodulation therapy.
• Describe the proposed mechanism of action for the various indications of sacral neuromodulation.
• Summarize the proper lead placement and neurostimulator implantation technique.
• Review some interprofessional team strategies that can create an environment leading to better patient outcomes.

Introduction

Sacral neuromodulation (SNM) is a safe, efficacious and minimally invasive advanced therapy indicated to treat urinary incontinence, urinary retention, urgency, frequency, and fecal incontinence in the United States for patients refractory to behavioral and pharmacologic treatment. In Canada and Europe, it is also indicated for chronic constipation.[1]

Sacral neuromodulation therapy was developed in 1982 by Tanagho and Schmidt, gaining FDA approval in 1997.[2][3] To date, there have been more than 300,000 patients treated with sacral neuromodulation implants worldwide.[4] Reviews suggest that between 16% to 29% of the population, with a few estimating up to 75%, experience some level of overactive bladder, including symptoms of urinary incontinence, urgency, or frequency.[5][6] Additionally, an estimated 25% to 40% of patients experiencing overactive bladder fail to achieve satisfactory results after first and second-line therapy (behavioral modifications and pharmacotherapy, respectively).[7] These patients have a refractory overactive bladder and may be eligible for SNM therapy.

SNM has been proven to produce good clinical results in otherwise intractable cases. One study conducted by Siegel et al. evaluated the therapeutic success rate in 340 patients using SNM at 36 months. The success rate for overactive bladder was 83% for patients who underwent SNM implantation (95% CI). Additionally, 80% of patients reported improvement in all urinary symptoms.[8][9]

The mechanism of action of sacral neuromodulation is not completely understood. However, the therapy seems to modulate spinal cord reflexes and brain involvement via afferent signaling rather than direct motor stimulation of the detrusor or urethral sphincter.[10] The most widely accepted theory suggests that SNM blocks or otherwise interferes with the afferent input to the sacral spinal cord, inhibiting detrusor overactivity resulting in clinical relief of urinary frequency and urgency.[11]

Anatomy and Physiology

Lower Urinary Tract

The lower urinary tract has two primary functions: to store and void urine. Regulation of these two functions requires precise but complex neuronal control. Any disruption to this neuronal control system can result in a "neurogenic bladder" (voiding dysfunction). Significant voiding dysfunction can also appear in the absence of any identifiable neurologic lesions.[11] Lower urinary tract disturbance symptoms include difficult voiding issues, post-void problems, and bladder storage symptoms such as frequency, urgency, urge incontinence, difficult urination, and incomplete emptying.[12]

Efferent Pathways of Lower Urinary Tract

Parasympathetic preganglionic fibers originate from the sacral spinal cord, S2-S4. Stimulation of the parasympathetic pathways initiates micturition by causing the bladder detrusor muscle to contract while inhibiting the urethral sphincter. Postganglionic fibers release acetylcholine and synapse with the M2 and M3 receptors in the bladder. M2 receptors are far more abundant in the detrusor, although the contraction of the bladder's smooth muscle is mainly attributed to stimulation of the M3 receptors. Parasympathetic innervation to the urethral smooth muscle that controls the internal urinary sphincter is inhibitory and is mediated by nitrous oxide.[11] Thus, anticholinergics that inhibit the M2/M3 receptor, such as oxybutynin and tolterodine, can be used as pharmacotherapy for overactive bladder, urgency, frequency, and urge incontinence.[5] Conversely, cholinergic agonists, such as bethanechol, can be used for nonobstructive urinary retention due to detrusor hypoactivity.[13]

Sympathetic preganglionic fibers originate from intermediolateral nuclei in the thoracolumbar region of the spinal cord. Axons will course through the hypogastric nerve and synapse in the inferior mesenteric ganglion, or they will travel through the paravertebral chain and join the pelvic nerves. Sympathetic pathways activation inhibit micturition, causing the detrusor to relax and the urethral sphincter to constrict.[11] Postganglionic sympathetic axons will synapse with β2 and β3 receptors in the detrusor wall and with α1 receptors of the urethral sphincter.[14] Medical therapy using β3 sympathetic agonists (such as mirabegron and vibegron, which are currently the only commercially available drugs with this mode of action) can effectively treat symptoms of urinary urgency, urinary frequency, overactivity, and urge incontinence without anticholinergic side effects.[5][15][16]

Somatic efferent fibers originate from Onuf's nucleus at S2-S4 and travel as the pudendal nerve to the external urinary sphincter, where they release acetylcholine when activated. The sphincter is composed of skeletal muscle and has cholinergic receptors. When stimulated by acetylcholine, a contraction is elicited, which will inhibit micturition both mechanically and reflexively. The pudendal nerve, together with the hypogastric nerve, also relays sensory input from the bladder neck, urethra, and perineum to the brain and spinal cord.[11]

The guarding reflex protects against accidental leakage from a sudden or involuntary increase in bladder pressure (stress incontinence). During episodes of suddenly increased bladder pressure (coughing, sneezing, standing, or laughing), excitatory afferent fibers signal Onuf's nucleus to activate somatic efferent fibers to contract the external urinary sphincter.[11]

Afferent Pathways of Lower Urinary Tract

Sensory information from the bladder travels to the dorsal horn of the spinal cord via the pelvic and hypogastric nerves. Afferent fibers transmit electrical impulses from tension receptors and nociceptors in the bladder wall. Bladder distension is normally mediated by myelinated (Aδ type fibers). However, unmyelinated C fibers can become overactive during inflammation and various neurogenic conditions.[11]

Sensory information from the urethra travels to the spinal cord via the pelvic and pudendal nerves. Urethral afferent nerves are activated by the passage of urine through the urethra, enhancing the parasympathetic input to the bladder. This causes a positive feedback mechanism to ensure complete bladder emptying.[11]

Sensory input from the lower urinary tract reaches the pontine micturition center in the brainstem, communicating with the frontal micturition inhibiting center in the cerebrum. This inhibits micturition until voluntary voiding is initiated in the cerebrum by inhibiting the micturition center.[17]

Rectum and Anal Sphincters

As the connection between the gastrointestinal tract (GI) and the anus, the rectum acts as both storage and a conduit for stool. The motor component of defecation involves both voluntary and involuntary muscles, while the sensory component is conducted through the pelvic nerves.[18] Neurogenic disturbances to the lower GI tract include diarrhea, constipation, and in particular, fecal incontinence. Obstetric anal trauma is one of the most common and well-recognized etiological factors for fecal incontinence.[19] A recent multi-institutional study involving 221 patients with fecal incontinence reported that 80% of the implanted patients had at least a 50% lasting improvement of their leakage problem.[20]

Defecation Reflexes

Rectoanal sampling, also known as the rectoanal inhibitory reflex, is a temporal reflexive process that occurs every eight to ten minutes when rectal contents are presented to the anal sensory mucosa.[21] The extent of relaxation of the internal anal sphincter depends on the degree of distension.[22] The descent of rectal contents into the upper anal canal allows for sensory discrimination of solid from liquid or gaseous contents.[23]

Defecation begins when rectal distension increases to a critical threshold, and this sensory information is relayed to the cerebral cortex.[24] The sensory stimulation and distension within the rectum cause a parasympathetic mediated reflex relaxation of the anal sphincters and pelvic floor, allowing stool to enter the lower rectum and the anal canal.[25] As the last bolus of stool passes the anal canal, the external sphincter initiates the closing reflex due to the release of the rectal distension.[26]

The external anal sphincter (EAS) is under somatic control from the pudendal nerve.[27] Deferment of defecation is achieved by contraction of the external anal sphincter opposing the rise in rectal pressure long enough to allow for muscle adaptation where rectal pressure declines and the feeling of urgency lessens.[28]

Mechanism of Sacral Neuromodulation

A complete understanding of sacral neuromodulation is yet to be determined as it is likely to have multiple mechanisms of action. The following section provides current theories regarding proposed mechanisms of action of SNM.

In neurogenic bladder conditions such as multiple sclerosis, meningomyelocele, and spinal cord injury, afferent C fibers can become more active due to neurologic and inflammatory disorders. In these conditions, C fibers can respond to bladder distension and activate voiding reflexes.[29] It is thought SNM blocks C fiber activity, inhibiting irregular voiding responses.[30] 

As previously described, the urethral guarding reflex protects against stress urinary incontinence. SNM is thought to inhibit the guarding reflex and induce voiding for patients with urinary retention.[31]

Sacral neuromodulation appears to stimulate relaxation of pelvic floor muscles and the urethra, which helps initiate micturition in patients with impaired bladder pressure, retention, and incomplete emptying.[11][32]

A possible central mechanism has also been suggested. Refractory overactive bladder patients successfully treated with sacral neuromodulation have shown significant activation of Brodmann's area 9 (left dorsolateral prefrontal cortex) after SNM treatment.[33]

Additional proposed mechanisms exist for urinary urgency and frequency. It has been suggested that SNM inhibits bladder afferent pathways by stimulating the afferent portion of the pudendal nerve. Incontinence may also be reduced by inhibiting preganglionic neurons of efferent bladder pathways. It is widely accepted that inhibition of the micturition reflex is part of the SNM mechanism because voluntary voiding is maintained throughout therapy.[11]

Precise mechanisms explaining how sacral neuromodulation helps control fecal incontinence are poorly understood. Most research suggests that placement of the SNM lead in the S3 region will cause stimulation of afferent fibers from the anal sphincter, rectum, and pelvic floor. Stimulation of these afferents reduces activation of C fibers during rectal filling, blocking inputs from the rectum to the pontine center.[34] It is also suggested that SNM can activate somatic afferent fibers to inhibit colonic activity and promote internal anal sphincter tone in a somato-visceral reflex mechanism.[35][36]

Indications

Sacral neuromodulation is indicated for refractory urinary tract dysfunction, including symptoms of nonobstructive urinary retention, urgency, frequency, and urge incontinence. It has also been shown to be effective even in Parkinson's patients with neurogenic bladder symptoms who are often refractory to treatment. In a recent study, 82% of patients with neurogenic bladders from Parkinson disease responded well to sacral neuromodulation therapy, and most were able to stop their overactive bladder oral medications.[37] Additionally, sacral neuromodulation is indicated for chronic fecal incontinence.[38][39][40]

Patient Selection

Patients eligible for sacral neuromodulation therapy for urinary incontinence must have refractory nonobstructive urinary retention, urgency, urge incontinence, or severe frequency that have failed to respond to behavioral modifications and pharmacotherapy with more than one medical therapy for >8 to 12 weeks.[41]

Patients are instructed to keep a voiding diary to establish a baseline level of urinary and fecal symptoms. This diary should be continued at least during the clinical trial period to determine if there is an improvement of 50% or greater, which would be considered a successful trial.[42]

Sacral neuromodulation is not recommended by the Amerian Urological Association Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction (2021) for spina bifida or spinal cord injured patients due to the high level of variability in bladder function and progression.[43] However, sacral neuromodulation may be offered to patients with other types of neurogenic bladder causing urgency, frequency, or urge incontinence not easily managed with more conservative measures.[43]

Contraindications

Patients must also not have contraindications to using SNM. They must not have any urinary obstruction or current pelvic infection. Patients with a severe or rapidly progressive neurologic disease are also relatively contraindicated for SNM therapy.[44]

Contraindications of SNM include shortwave diathermy, microwave diathermy or therapeutic ultrasound, mechanical obstruction, and inability to operate the patient programmer.[45] In earlier versions of sacral neuromodulation systems, all devices were not completely MRI compatible. As of 2020, all new implants are compatible with full-body MRIs. However, some implants before the Fall of 2019 do not have full MRI compatibility, so MRI evaluations and imaging must be limited for these patients to just the head and neck. A comprehensive listing of MRI-compatible sacral neuromodulation devices has recently been published.[4][46]

While age and comorbidities are not contraindications, there is some evidence to suggest that patients over 55 years old with three or more chronic comorbid conditions exhibit diminished success rates for improving their voiding symptoms with sacral neuromodulation.[47]

Equipment

Proper equipment includes a sacral neuromodulation kit, including the tined lead, foramen needle, and internal pulse generator (IPG). Additionally, sterile surgical drapes and a basic surgical instrument tray are required for surgery. Finally, a C-arm fluoroscopic unit is needed for the lead placement.

Personnel

During the peripheral nerve evaluation stage (step 1), a surgeon, a nurse, and an X-Ray technician are needed. During the implant stage (step 2), a surgeon, a nurse, a scrub technician, and an anesthesiologist or nurse anesthetist are necessary for the procedure. Optionally, a representative from the SNM manufacturer is available during the procedure to prepare and test the product for implantation, interrogation of the IPG, and checking the leads for motor response.

Technique

Evaluation

The evaluation stage allows for a trial of therapy before committing to the full implant. The evaluation procedure is done under local anesthesia because sensory innervation is an important indicator of lead placement. The patient is placed prone, and C-arm fluoroscopy is positioned. General landmarks of the sacrum are then identified, including:[45]

1. The base of the sacrum, which is found by following the iliac crest medially
2. The apex of the sacrum is found at the sacrococcygeal articulation
3. The median sacral crest is found on the sacrum midline in between the sacral foramina

A foramen needle is inserted into the S3 foramen at an angle of 60 degrees. The motor response should include great toe dorsiflexion and visualization of contraction in the perineum and anus called the bellows reflex. The sensory response should include fluttering/vibration or pulling the scrotum, vagina, perineum, or inner gluteal fold. It is important to be aware of responses of stimulation from the S2 and the S4 nerve roots, as these will not provide optimal therapy. Stimulation of the S2 root will result in pinching of the anal sphincter with plantar flexion and lateral rotation of the foot with sensation in the leg and buttock area. Stimulation of the S4 root will result in a bellows reflex with no lower extremity movement and a pulling sensation around the perineum.[48]

The stylet of the foramen needle is removed and is replaced with a directional guide. Keeping the directional guide in place, the foramen needle is then removed. A small transverse skin incision is then made at the skin entry point to facilitate passage of the introducer, which is advanced into the S3 foramen. The directional guide is removed, leaving the introducer sheath. The tined lead is advanced, so electrodes 2 and 3 (3 being the most proximal) straddle the sacral foramen, and electrodes 0 and 1 (0 being the most distal) are placed anterior to the bony sacrum.[49]

Recent literature suggests inserting the tined lead such that the lead occupies the most superior and medial space in the foramen.[50] This would cause electrode 3 to be pushed just past the foramen instead of straddling it. The lead stylet and introducer sheath are removed, allowing the tines to deploy and anchor the lead. All electrodes are tested, and ideally, motor and sensory responses are elicited at 2 mA or less. The lead is then tunneled through a small gluteal incision over the iliac crest (the future pocket site for the internal neurostimulator) and connected to a percutaneous extension cable, which is subsequently passed subcutaneously to the contralateral side just below the hip where it perforates the skin through a small incision. The percutaneous extension is plugged into the external neurostimulator for the trial period.[45]

Good prognostic indicators that suggest maximal success with sacral neuromodulation include optimal lead placement, ideal motor threshold levels, and the use of curved stylets.[51]

The most critical part of the procedure is the tined lead placement. It is essential that the lead tracks along the S3 root as this position is proven to provide optimal results. Care must be taken to correctly identify the sacral landmarks during lead placement. Video instructional guides are available to assist with learning lead placement and troubleshooting.[52]

The trial period lasts 7 to 14 days for the tined lead evaluation. Stage 2, involving full implantation or removal of the leads, must be scheduled separately and will be dependent on the trial results.[45]

CT guidance can also be used for electrode placement in selected cases as an alternative to C-arm fluoroscopy.[53]

Computer-assisted lead placement for sacral neuromodulation has recently been reported. This was done using a surgical navigation system with electromagnetic tracking to guide the lead placement to the S3 nerve roots. Such advances can make it easier to optimize lead placement in otherwise technically difficult clinical situations.[54]

Monopolar configurations are generally more effective and stimulate more motor nerve fibers at lower sensory thresholds resulting in greater therapeutic efficacy. In addition to reprogramming, changing the polarity or the position of the cathode lead can significantly change the sensory and motor responses.[55]

Implant

Implantation of the internal pulse generator (IPG) follows a successful trial, meaning at least a 50% clinical improvement of symptoms.[42] The former gluteal incision site is opened and widened to implant the IPG. The lead inserts directly into the IPG at the neurostimulator head. The IPG is typically not sutured in the pocket as this dislocation of the IPG is rare and to avoid the sensation of pulling or tugging.[45] An antimicrobial mesh pouch for IPG can optionally be sutured into the pocket for device stabilization and infection prevention.

Adverse events associated with sacral neuromodulation that lead to revision commonly include pain at the neurostimulator site (11.8% of patients with implants) and lead migration (7.9% of patients with implants).[56]

Neurostimulators come with preprogrammed factory settings for lower urinary tract disorders and fecal incontinence. Each program has a specified pulse width, frequency, active electrodes, and cycling pattern. Patients can only switch between preset programs and modify amplitude settings on the device. In the office, the provider can adjust all settings using a physician programmer to tailor programs to individual patient needs. After implantation, patients should have yearly follow-up visits to confirm continued symptom management. 

The duration of treatment is directly related to the longevity of the implantable battery. Non-rechargeable implants last on average of about five years.[57] With lower settings, battery longevity can be lengthened. Newer devices have higher capacity batteries that can be recharged wirelessly and last up to 15 years.[58] Other new developments in neuromodulation technology include improved programming. single-stage outpatient implantation, which is less invasive, and new lower-cost implantable devices.[39]

Complications

Most severe complications of sacral neuromodulation are associated with lead migration, implant site pain, or infection.[59]

The most common concern is that the patient no longer receives a benefit from the therapy. The neurostimulator should be interrogated to confirm it is turned ON. Resistances of the electrodes should be checked to rule out an open or short circuit. Assuming the device is on and there is no short, the programs should be adjusted. The program encodes which electrodes are active, including the frequency, amplitude, and pulse width of stimulation.[59] Adjustment of pulse width, in addition to standard programming changes, can aid in pain relief and problems with efficacy.[60]

Lead migration or improper placement is possible and can be identified with an X-ray. Lead revision surgery may be required but should be used only as a last resort.[52] This determination should be made after review with the manufacturing representative of the device troubleshooting flow process.

Sacral bilateral electrical pudendal nerve stimulation has been used successfully in patients who, after initial success, eventually fail standard sacral neuromodulation.[61][62][63]

Clinical Significance

Combination Therapy

Tang et al. studied a group of women with overactive bladder treated with sacral neuromodulation and tolterodine (an M2 and M3 antimuscarinic agent). After three months, the combination therapy was significantly superior to treatment by tolterodine alone for daily average single voided volume, a daily maximum single volume of urination, first desire to void, and maximum cystometric capacity (the volume that the bladder musculature can tolerate before the patient experiences a strong, uncontrollable desire to urinate).[64]

Alternate Treatment: Percutaneous Tibial Nerve Stimulation (PTNS/PTNM)

Percutaneous tibial nerve stimulation (PTNS) is another form of neuromodulation targeting the tibial nerve. It is performed by placing a needle connected to a low voltage stimulator cephalad to the medial malleolus in the foot to gently stimulate the tibial nerve. A portion of the electrical stimulation reaches the sacral nerves, which control bladder function. Patients often describe the treatment as a "tingling" or "pulsing" of the foot or ankle and are typically painless. Treatment sessions last for 30 minutes weekly. While symptomatic improvement can begin as early as the second session, many patients require multiple treatments before they experience a benefit. This requires that the patient commit to complete the full, initial twelve-weekly treatment regimen, at which point the clinical results are evaluated. Subsequent treatments may be needed intermittently to sustain the symptomatic benefit. 

PTNS can significantly improve urinary frequency, urgency, urge incontinence, and nocturia, with studies showing a benefit in 60% to 80% of the patients who try it.[65] Unlike anticholinergics or sacral neuromodulation, PTNS provides a carryover effect of continued symptom improvement even when the nerve is not actively stimulated.[66] One limitation of PTNS is the need for the patient to be present in a clinical office to receive therapy and the need to commit to a full, 12-week therapeutic trial. Both PTNS and SNM are well-tolerated, but PTNS may have fewer adverse effects and is significantly less invasive. However, PTNS has not been tested in the long term as SNM has.[67] Therefore, a choice between SNM and PTNS is primarily made by equipment availability and patient preference regarding proximity to a clinic and tolerance of surgery.[68] PTNS appears to be effective in helping fecal incontinence in other countries, but it has not been FDA approved for that indication in the US.[20] 

Alternate Treatment: Chemical Denervation of the Detrusor Using the Onabotulinum A Toxin

The FDA has approved botulinum toxin for therapeutic use.[69] Botulinum toxin injections can be effective for treating overactive bladder and urinary urge incontinence. Treatment efficacy lasts for around 6 to 12 months, after which further injections can be administered.[70] Disadvantages of this treatment modality include possible urinary tract infection and urinary retention (5% to 15% of patients may experience this).[71] 

A cost-effectiveness comparison of sacral neuromodulation compared to onabotulinum A toxin in managing refractory overactive bladder problems was recently published. It looks across multiple healthcare systems in five different countries over five and ten-year periods. Unfortunately, many of the available studies are sponsored by industry, which might impact the results. While the overall costs are roughly similar, botulinum toxin appeared to be more cost-effective in the short term, while the longer-term studies tended to favor sacral neuromodulation.[72] 

Pelvic Pain

Several studies suggest symptom improvement of pelvic pain, such as interstitial cystitis with SNM. In a study by Siegel et al., it was found that SNM reduced pain in 9 out of 10 patients with interstitial cystitis at 19 months of follow-up. The average pain on a scale of 0 to 10 was reduced from 9.7 at baseline to 4.4 at the end of the study, with a decreasing trend in hours of pain.[73] However, only grade C evidence currently exists for the use of sacral neuromodulation for interstitial cystitis, which is not currently an FDA-approved indication.[74]

While the precise mechanisms of action of sacral neuromodulation for pelvic pain still need to be elucidated, most research supports the theory of afferent signaling modulation to achieve symptomatic improvement. There seem to be several distinct mechanisms for symptom relief, and therapy likely functions differently for each clinical indication.

Future Use

Some spinal cord injured patients appear to have benefitted from the early use of sacral neuromodulation in preventing bladder functional deterioration. Detrusor overactivity and incontinence were prevented while bowel function, erectile activity, and a normal bladder capacity were maintained.[75][76][77]

Despite these encouraging results, the early use of sacral neuromodulation to change the course of a spinal cord injury and help preserve bladder function is still considered investigational.[78] 

Summary 

Ultimately, sacral neuromodulation provides a reasonable, safe, efficacious, and reversible alternative to other therapies for refractory overactive bladder, nonobstructive urinary retention, and fecal incontinence.[51]

Enhancing Healthcare Team Outcomes

Patient management is an essential component of sacral neuromodulation, and providers must closely monitor patients to receive optimal therapy. Symptom diaries can be an effective and objective method for providers to determine if therapeutic efficacy decreases. Additionally, patient expectations must be managed as it is likely patients will not experience 100% improvement of all symptoms. When therapy effectiveness has been reduced, providers must investigate the cause and troubleshoot the device. Many different variables can be used to program the patient’s IPG, and the patient must work with the medical team to modify program parameters to optimize therapy. This can be performed by physicians, advanced practice providers, and nursing staff in an outpatient setting. 

An interprofessional healthcare team including specialists, other clinicians (MDs, DOs, NPs, PAs), nursing staff, and pharmacists will best drive patient care to optimal outcomes. [Level 5]