Effectiveness, safety and cost-effectiveness of sacral neuromodulation for idiopathic slow-transit constipation: a systematic review.

AIM: Sacral neuromodulation (SNM) is a minimally invasive treatment option for functional constipation. Evidence regarding its effectiveness is contradictory, driven by heterogeneous study populations and designs. The aim of this study was to assess the effectiveness, safety and cost-effectiveness of SNM in children and adults with refractory idiopathic slow-transit constipation (STC). METHOD: OVID Medline, OVID Embase, Cochrane Library, the KSR Evidence Database, the NHS Economic Evaluation Database and the International HTA Database were searched up to 25 May 2023. For effectiveness outcomes, randomized controlled trials (RCTs) were selected. For safety outcomes, all study designs were selected. For cost-effectiveness outcomes, trial- and model-based economic evaluations were selected for review. Study selection, risk of bias and quality assessment, and data extraction were independently performed by two reviewers. For the intervention 'sacral neuromodulation' effectiveness outcomes included defaecation frequency and constipation severity. Safety and cost-effectiveness outcomes were, respectively, adverse events and incremental cost-effectiveness ratios. RESULTS: Of 1390 records reviewed, 67 studies were selected for full-text screening. For effectiveness, one cross-over and one parallel-group RCT was included, showing contradictory results. Eleven studies on safety were included (four RCTs, three prospective cohort studies and four retrospective cohort studies). Overall infection rates varied between 0% and 22%, whereas reoperation rates varied between 0% and 29%. One trial-based economic evaluation was included, which concluded that SNM was not cost-effective compared with personalized conservative treatment at a time horizon of 6 months. The review findings are limited by the small number of available studies and the heterogeneity in terms of study populations, definitions of refractory idiopathic STC and study designs. CONCLUSION: Evidence for the (cost-)effectiveness of SNM in children and adults with refractory idiopathic STC is inconclusive. Reoperation rates of up to 29% were reported.

Replacement Adaptor 09106 for patients with a dynamic graciloplasty or patients with sacral neuromodulation and abdominal implantable pulse generators: a retrospective, single centre, Stage 2a/2b development IDEAL case series.

AIM: Due to the introduction of a new implantable pulse generator (IPG), the Interstim II, patients with either a dynamic graciloplasty or an abdominally placed IPG for sacral neuromodulation could not undergo surgery to replace their IPG in the case of end of battery life. For these patients, the Medtronic Replacement Adaptor 09106 was created. This retrospective case series aims to study safety and feasibility of the Medtronic Replacement Adaptor 09106 in patients with abdominally placed IPGs. METHODS: Seventeen patients (11 women, six men) received a replacement adaptor with a follow-up of 6 months. Outcome measures consisted of a bowel habit diary. Adverse events were classified using the Clavien-Dindo classification. RESULTS: Outcome measures in the bowel habit diaries after replacement (feasibility) did not differ significantly from outcome measures before replacement. Adverse events occurred in four out of 17 patients (24%): two patients initially showed pocket site pain (Clavien-Dindo Grade I), which resolved without intervention. One patient suffered from poor wound closure (Clavien-Dindo Grade II) and one patient had persisting pocket pain (Clavien-Dindo Grade IIIa) for which a pocket revision was performed. Statistical analyses were performed making paired comparisons using a Wilcoxon signed rank test. CONCLUSION: The Medtronic Replacement Adaptor 09106 is a valuable option for patients with dynamic graciloplasty or sacral neuromodulation and abdominal IPG and has complication rates similar to replacement of the Interstim without Replacement Adaptor 09106.

Sacral Neuromodulation for Lower Urinary Tract and Bowel Dysfunction in Animal Models: A Systematic Review With Focus on Stimulation Parameter Selection.

OBJECTIVE: Conventional sacral neuromodulation (SNM) has shown to be an effective treatment for lower urinary tract and bowel dysfunction, but improvements of clinical outcome are still feasible. Currently, in preclinical research, new stimulation parameters are being investigated to achieve better and longer effects. This systematic review summarizes the status of SNM stimulation parameters and its effect on urinary tract and bowel dysfunction in preclinical research. MATERIALS AND METHODS: The literature search was conducted using three databases: Ovid (Medline, Embase) and PubMed. Articles were included if they reported on stimulation parameters in animal studies for lower urinary tract or bowel dysfunction as a primary outcome. Methodological quality assessment was performed using the SYRCLE Risk of Bias (RoB) tool for animal studies. RESULTS: Twenty-two articles were eligible for this systematic review and various aspects of stimulation parameters were included: frequency, intensity, pulse width, stimulation signal, timing of stimulation, and unilateral vs. bilateral stimulation. In general, all experimental studies reported an acute effect of SNM on urinary tract or bowel dysfunction, whereas at the same time, various stimulation settings were used. CONCLUSIONS: The results of this systematic review indicate that SNM has a positive therapeutic effect on lower urinary tract and bowel dysfunction. Using low-frequency-SNM, high-frequency-SNM, bilateral SNM, and higher pulse widths showed beneficial effects on storage and evacuation dysfunction in animal studies. An increased variability of stimulation parameters may serve as a basis for future improvement of the effect of SNM in patients suffering from urinary tract or bowel dysfunction.

Stimulation Parameters for Sacral Neuromodulation on Lower Urinary Tract and Bowel Dysfunction-Related Clinical Outcome: A Systematic Review.

OBJECTIVE: Sacral neuromodulation (SNM) has been used to treat patients with lower urinary tract dysfunction and bowel dysfunction for many years. Success rates vary between 50% and 80%, indicating that there is much room for improvement. Altering stimulation parameters may result in improved outcome. This paper reports a systematic review of the clinical efficacy of nonconventional stimulation parameters on urinary tract and bowel dysfunction. MATERIALS AND METHODS: Three databases were used for the literature search: Ovid (Medline, Embase) and PubMed. Papers were screened by two independent reviewers, who also extracted data from these papers. Clinical papers studying SNM stimulation parameters, that is, intermittent stimulation, frequency, pulse width, and amplitude, in urinary tract and bowel dysfunction were included. Quality of included papers was assessed using standardized guidelines. RESULTS: Out of 5659 screened papers, 17 papers, studying various stimulation parameters, were included. Overall quality of these papers differed greatly, as some showed no risk of bias, whereas others showed high risk of bias. Stimulation parameters included intermittent stimulation, frequency, pulse width, amplitude, and unilateral vs. bilateral stimulation. Especially high frequency SNM and either a narrow or wide pulse width seem to improve efficacy in patients with bowel dysfunction. Additionally, implementation of short cycling intervals is promising to improve quality of life for patients with urinary tract or bowel dysfunction. CONCLUSION: The results of our systematic review indicate that stimulation parameters may improve efficacy of SNM in treatment of both urinary tract dysfunction and bowel dysfunction.

Clinical efficacy of lead revisions during the test phase in sacral neuromodulation for fecal incontinence.

BACKGROUND: Success rates of up to 80% have been reported for the SNM screening period in the treatment of fecal incontinence (FI). Some patients who have an unsuccessful index implantation are successfully treated with SNM after a lead revision. There is a lack of studies comparing the outcomes of successful index implantations and successful lead revision. Therefore, the results of index implantations were compared with lead revisions in a single-center cohort. METHODS: Patients treated with SNM for FI between 2008 and 2016 were retrospectively reviewed. Patients with a successful index implantation were compared with patients who underwent lead revision after SNM screening. Primary outcome was a decrease in episodes of fecal incontinence of ≥ 50% documented by a 3-week bowel habit diary. RESULTS: Two hundred sixty-one patients (232 index group, 29 revision group) were eligible for SNM. Two hundred thirty-one patients (208 index group, 23 revision group) received permanent SNM. Follow-up was 68.8 months for the index group and 62.2 months for the revision group. The number of episodes of FI decreased from 20.6 (SD 19.3) to 3.4 (SD 4.2) in the index group and from 12.6 (SD 5.8) to 2.0 (SD 2.3) in the revision group. This effect was maintained up to 5 and 2 years in the index and revision group, respectively. Adverse events such as loss of efficacy which required surgical intervention did not differ between the two groups. CONCLUSION: Lead revision during the test phase is a valid option in patients with FI treated by SNM who suffer from loss of efficacy of the index electrode.

Sacral Neuromodulation for Fecal Incontinence: A Review of the Central Mechanisms of Action.

OBJECTIVE: Fecal incontinence (FI) has a devastating effect on the quality of life and results in social isolation. Sacral neuromodulation (SNM) is proven to be an effective, minimal invasive treatment modality for FI. Despite the increasing application of SNM, the exact mechanisms of action remain unclear. The initial assumption of peripheral motor neurostimulation is not supported by increasing evidence, which report effects of SNM outside the pelvic floor. A new hypothesis states that afferent signals to the brain are essential for a successful therapy. This study aimed to review relevant studies on the central mechanism of SNM in FI. METHODS: Clinical and experimental studies on the central mechanisms, both brain and spinal cord, of SNM for FI up to December 2015 were evaluated. RESULTS: In total, 8 studies were found describing original data on the central mechanism of SNM for FI. Four studies evaluated the central effects of SNM in a clinical setting and 4 studies evaluated the central effects of SNM in an experimental animal model. Results demonstrated a variety of (sub)cortical and spinal changes after induction of SNM. CONCLUSION: Review of literature demonstrated evidence for a central mechanism of action of SNM for FI. The corticoanal pathways, brainstem, and specific parts of the spinal cord are involved.

Fecal incontinence treated by sacral neuromodulation: Long-term follow-up of 325 patients.

BACKGROUND: Long-term results of large patient cohorts with fecal incontinence treated by sacral neuromodulation are limited. This study shows the long-term results after a mean follow-up of 7.1 years in 325 patients with fecal incontinence treated by continuous sacral neuromodulation. METHODS: All patients with fecal incontinence and eligible for sacral neuromodulation between 2000 and 2015 were evaluated retrospectively. Primary outcome was a decrease in episodes of fecal incontinence, which was defined as involuntary fecal loss at least once per week and documented by a 3 week bowel habit diary. Quality of life was assessed using the Short-Form 36 and the Fecal Incontinence Quality of Life Score. RESULTS: In the study, 374 patients were included for sacral neuromodulation screening and 325 patients (32 male, 9.7%) received permanent, continuous sacral neuromodulation. Mean age was 56.5 years (17-82 years) and mean follow-up was 7.1 years (3.0-183.4 months). In the 325 patients with permanent sacral neuromodulation, fecal incontinence episodes decreased from a mean of 16.1 ± 14.5 to 3.0 ± 3.7 per 3-week period after sacral neuromodulation (P < .001) according to the bowel habit diary. Sacral neuromodulation was removed due to unsatisfactory results in 81 patients. Quality of life (both Short-Form 36 and Fecal Incontinence Quality of Life Score) showed no significant difference compared with the Dutch population during follow-up. CONCLUSION: Long-term efficacy of sacral neuromodulation can be maintained in about half (52.7%) of all patients screened with sacral neuromodulation for fecal incontinence after a mean follow-up of 7.1 years. Importantly, the quality of life of patients with sacral neuromodulation for fecal incontinence did not differ from the general population.

Sacral neuromodulation in children and adolescents with chronic constipation refractory to conservative treatment.

PURPOSE: Functional constipation in children and adolescents is a common and invalidating condition. In a minority of patients, symptoms persist despite optimal conservative therapy. The aim of this study was to evaluate whether the short-term effects of sacral neuromodulation (SNM) in children and adolescents with constipation are sustained over prolonged period of time. METHODS: Patients aged 10-20 years, with refractory constipation, fulfilling the Rome III criteria, were included in our study. If SNM test treatment showed >50 % improvement in defecation frequency, a permanent stimulator was implanted. Primary outcome measure was defecation frequency during 3 weeks. Secondary endpoints were abdominal pain and Wexner score. To assess sustainability of treatment effect, a survival analysis was performed. Cross-sectional quality of life was assessed using the EQ-5D VAS score. RESULTS: Thirty girls, mean age 16 (range 10-20), were included. The mean defecation frequency increased from 5.9 (SD 6.5) in 21 days at baseline to 17.4 (SD 11.6) after 3 weeks of test treatment (p < 0.001). During test treatment, abdominal pain and Wexner score decreased from 3.6 to 1.5 and 18.6 to 8.5 (p < 0.001), respectively. Improvement of symptoms sustained during a median follow-up of 22.1 months (12.2-36.8) in 42.9 % of patients. On a scale from 0 to 100, quality of life was 7 points lower than the norm score (mean 70 vs. 77). CONCLUSION: SNM is a therapeutic option for children with chronic constipation not responding to intensive oral and/or laxative therapy, providing benefits that appear to be sustained over prolonged period of time.

Sacral nerve stimulation for intractable constipation.

OBJECTIVE: Traditional surgical procedures for intractable idiopathic constipation are associated with a variable outcome and substantial morbidity. The symptomatic response, physiological effect and effect on quality of life of sacral nerve stimulation (SNS) were evaluated in patients with constipation (slow transit and normal transit with impaired evacuation). METHODS: In a prospective study at five European sites patients who failed conservative treatment underwent 21 days test stimulation. Patients with >50% improvement in symptoms underwent permanent neurostimulator implantation. Primary end points were increased defecation frequency, decreased straining and decreased sensation of incomplete evacuation. RESULTS: 62 patients (55 female, median age 40 years) underwent test stimulation, of whom 45 (73%) proceeded to chronic stimulation. 39 (87%) of these 45 patients achieved treatment success. After a median 28 (range 1-55) months follow-up, defecation frequency increased from 2.3 to 6.6 evacuations per week (p<0.001). Days per week with evacuation increased from 2.3 to 4.8 (p<0.001). There was a decrease in time spent toileting (10.5 to 5.7 min, p=0.001), straining (75-46% of successful evacuations, p<0.001), perception of incomplete evacuation (71.5-46% of successful evacuations, p<0.001) and subjective rating of abdominal pain and bloating (p<0.001). Cleveland Clinic constipation score (0=no to 30=severe constipation) decreased from 18 to 10 (p<0.001). Visual analogue scale (VAS) score (0=severe to 100=no symptoms) increased from 8 to 66 (p<0.001). Patients with slow and normal transit benefited. Quality of life significantly improved. Colonic transit normalised in half of those with baseline slow transit (p=0.014). CONCLUSION: SNS is effective in the treatment of idiopathic slow and normal transit constipation resistant to conservative treatment. Clinical Trial Number NCT00200005.

Sacral neuromodulation for the treatment of chronic functional anorectal pain: a single center experience.

INTRODUCTION: Treatment of functional anorectal pain disorders remains a challenge. The purpose of this study is to describe a single center experience with sacral neuromodulation for the treatment of chronic functional anorectal pain. METHODS: This is a retrospective study based on prospectively collected data of patients treated with sacral neuromodulation for functional anorectal pain from April 2005 to August 2008. Symptoms were analyzed using a visual analog scale pain score (0 to 10). A 7-point Likert scale was used to rate global perceived effect. All patients had a percutaneous nerve evaluation and subsequent test stimulation to assess sacral neuromodulation outcome prior to permanent implantation. Patients were eligible for permanent sacral neuromodulation in case of a pain score <3 during test stimulation and/or >50% decrease in the pain score compared to baseline. RESULTS: Nine patients (2 males) were included in this study. Mean age was 53.8 years (27.6 to 74.0). Four patients (1 male) had successful test stimulation and were eligible for permanent implantation. Median pain score decreased from 8.0 (6.0 to 9.0) to 1.0 (0 to 2.0). All patients experienced a lasting improvement during the follow-up till 24 months. Global perceived effect in successful patient was 1 (completely recovered) in one patient and 2 (much improved) in three patients. CONCLUSION: This study showed that sacral neuromodulation can be a successful treatment for functional anorectal pain not responding to other treatments. Improvement obtained during test stimulation is a good predictor (diagnostic) for sustained success of permanent sacral neuromodulation.

A randomized physiotherapy trial in patients with fecal incontinence: design of the PhysioFIT-study.

BACKGROUND: Fecal incontinence (FI) is defined as the recurrent involuntary excretion of feces in inappropriate places or at inappropriate times. It is a major and highly embarrassing health care problem which affects about 2 to 24% of the adult population. The prevalence increases with age in both men and women. Physiotherapy interventions are often considered a first-line approach due to its safe and non-invasive nature when dietary and pharmaceutical treatment fails or in addition to this treatment regime. Two physiotherapy interventions, rectal balloon training (RBT) and pelvic floor muscle training (PFMT) are widely used in the management of FI. However, their effectiveness remains uncertain since well-designed trials on the effectiveness of RBT and PFMT versus PFMT alone in FI have never been published. METHODS/DESIGN: A two-armed randomized controlled clinical trial will be conducted. One hundred and six patients are randomized to receive either PFMT combined with RBT or PFMT alone. Physicians in the University Hospital Maastricht include eligible participants. Inclusion criteria are (1) adults (aged > or = 18 years), (2) with fecal incontinence complaints due to different etiologies persisting for at least six months, (3) having a Vaizey incontinence score of at least 12, (4) and failure of conservative treatment (including dietary adaptations and pharmacological agents). Baseline measurements consist of the Vaizey incontinence score, medical history, physical examination, medication use, anorectal manometry, rectal capacity measurement, anorectal sensation, anal endosonography, defecography, symptom diary, Fecal Incontinence Quality of Life scale (FIQL) and the PREFAB-score. Follow-up measurements are scheduled at three, six and 12 months after inclusion. Skilled and registered physiotherapists experienced in women's health perform physiotherapy treatment. Twelve sessions are administered during three months according to a standardized protocol. DISCUSSION: This section discusses the decision to publish a trial protocol, the actions taken to minimize bias and confounding in the design, explains the choice for two treatment groups, discusses the secondary goals of this study and indicates the impact of this trial on clinical practice. TRIAL REGISTRATION: The Netherlands Trial Register ISRCTN78640169.