Colonic manometry and sacral nerve stimulation in patients with severe constipation
Philip G. Dinning
Department of Medicine University of New South Wales, St George Hospital, Kogarah, NSW 2217, Australia
CONSTIPATION, EPIDEMIOLOGY AND HEALTH CARE BURDENConstipation, a common cause of morbidity, is estimated to affect between 15 and 27% of the western world.1 The prevalence increases to 30-40% of people aged over 65.2 Direct and indirect costs and resource utilisation are substantial. Chronic constipation in the US accounts for 13.7 million days of restricted activity and 3.4 million days of bed disability.3 The diagnosis and management of constipation leads to 5.7 million physician visits and 0.6 million hospitalisations per year, accounting for total costs of $US235M (2006 value).4 Drug costs are high with $US368M per yr (1985 value) being spent on over the counter remedies 5 and an additional $US22M per year spent on prescription drugs.6
For many constipated patients laxative use will sufficiently alleviate their symptoms. However, for patients in whom laxatives do not restore normal bowel habit increased abdominal pain and bloating can result. Some patients, particularly those with obstructed defaecation can undergo a trial of biofeedback therapy, which can demonstrate significant improvement in quality of life and stool frequency.7,8 However, the long-term efficacy (>1yr) in patients with severe slow transit constipation is poor.9,10 Overall at least 36% of those presenting to the clinic subsequently fail non-surgical therapies (diet, bulking agents, laxatives, biofeedback).11 These patients can be extremely debilitated with physiological functioning, mental health, general health and bodily pain all scoring poorly on quality of life questionnaires in comparison to health.12 For such cases subtotal colectomy becomes an option. However as this is a major abdominal procedure it comes with all of the normal associated risks. In addition patients can develop post-operative small and large bowel complications such as intractable diarrhoea, small bowel obstruction, faecal incontinence and recurrent constipation.13,14
COLONIC PROPULSIVE MOTOR PATTERNS IN HEALTH AND PATIENTS WITH CONSTIPATIONThe cause of severe constipation remains undetermined; however abnormal colonic motor patterns are implicated. In health studies utilising combined colonic manometry and scintigraphy have shown that colonic propagating sequences (PS) and high amplitude propagating sequences (HAPS) are temporally associated with discrete movement of colonic content.15-17
Studies in health also demonstrate that defaecation is preceded by a series of PSs and HAPSs in which the site of origin of each PS approaching stool expulsion moves in an orad direction (Fig. 1).18
These data indicate that defaecation is a complex process incorporating the entire colon. Indeed in health motor activity in the proximal colon is an essential component of defaecation. Our own studies have also demonstrated that this pre-defecatory colonic response is absent in patients with obstructed defaecation.19
It is recognised that both HAPSs and long-extent PSs are deficient or absent in severe slow transit constipation 20-22 although the neural apparatus necessary for the generation of these motor patterns appears to be intact because intraluminal irritant laxatives can trigger them.16,23
This observation suggests that extrinsic or intrinsic factors capable of modulating the propulsive characteristics of PSs are likely to contribute to the pathogenesis of constipation. The actual mechanisms involved in the induction of these propulsive pressure waves are only partially understood.
The enteric nervous system provides the direct neuronal control of colonic motility, modulated through the sympathetic, parasympathetic and extrinsic afferent pathways. The vagal nerves provide parasympathetic innervation to the caecum, ascending colon and most of the transverse colon, whilst parasympathetic fibres from the second to the fourth sacral sections of the spinal cord innervate the distal part of the transverse colon, the descending colon and the rectosigmoid colon.
Therefore intuitively, stimulation of pelvic nerves would be expected to have a motor response confined to the distal colon and ano-rectum. Yet evidence exists to suggest that stimulation of pelvic nerves is capable of inducing pan-colonic motor patterns. For example rectal chemical stimulation in the healthy human colon induces proximal colonic PSs presumably through long recto-colonic afferent pathways.24 This pathway appears to be blocked in at least one form of constipation.25
It is possible that this attenuated pathway can be re-established through electrical stimulation of pelvic nerves. Indirect evidence supporting this hypothesis can be extrapolated from a case study in which a young female with severe constipation, received direct electrical stimulation to the anal canal and demonstrated significantly increased stool frequency.26
As defaecation in health is preceded by proximal colonic pressure waves and that patient demonstrated improved stool frequency, we could make the reasonable assumption that the electrical stimulation of the anal canal helped to re-establish pre-defecatory, pan-colonic pressure waves. Similar results were also obtained in patients with severe constipation and spinal cord injury. Here direct high voltage stimulation to the sacrum induced spontane ous stool evacuation.27-30
While high voltage stimulation can not be applied to patients with an intact spinal cord, applying direct low-voltage stimulation to the sacral nerves can achieve comparable results. For example a high proportion of patients undergoing sacral nerve stimulation treatment for urinary or faecal incontinence reported an incidental increase in stool frequency.31,32
Finally data recorded in vivo from a canine colon suggested that electrical stimulation of sacral nerves can generated a similar colonic pre-defecatory PS response to that observed during spontaneous defaecation.33 Taken collectively we can form the hypothesis that electrical stimulation of the pelvic floor nerves may be capable of inducing proximal colonic propulsive pressure waves in severe constipation, which in turn may improve constipation symptoms. This hypothesis prompted our lab to examine both the symptomatic and colonic response of the novel therapy sacral nerve stimulation (SNS) in a severely constipated cohort of patients.
SACRAL NERVE STIMULATION IN CONSTIPATIONThe techniques of sacral nerve stimulation (SNS) and its use in patient’s with urinary and fecal incontinence has been documented in several recent reviews.34-37 Briefly, SNS is a minimally invasive surgical technique that allows for direct electrical stimulation of the sacral nerves S2-S4 via an electrode placed through the sacral foramen. Of the three sacral roots used S3, which contains afferent sensory, efferent autonomic motor nerves and voluntary somatic nerves, provides the most satisfactory clinical response.37 The SNS technique involves two stages. The first, commonly termed
the peripheral nerve evaluation (PNE), is conducted over two to three weeks and involves a temporary wire, with a single electrode, being introduced to the sacral root and connected to an external stimulator. Patients that respond favorably to the PNE move on to the second stage where a pulse generator (Interstim®) connected to a tined lead with 4 electrodes, is implanted permanently.37
In comparison to SNS use in urinary and faecal incontinence, investigation of the effects of SNS in patients with constipation is still in its infancy. Only 4 previous studies had been published each with a small sample size (≥ 12).38-41 (Table 1).
The patients chosen to participate in these studies were carefully selected with all having long standing symptoms of constipation (unrelated to pelvic surgery) that had failed to respond to non-surgical therapy.38-41 In such patients the data suggests that SNS can improve stool frequency and reduce the percentage of time patients suffer from bloating and pain. Importantly these studies also report very few adverse events. However, it should be stressed that the majority of these data are derived from the short-term PNE phase (Table 1).
While SNS appears to influence stool frequency in constipated subjects the in vivo effects of SNS upon colonic motor function remained unknown. The only available data in humans had come from previous studies of patients with faecal incontinence, from which SNS had been shown to alter ano-rectal motor function.32, 42-45 In our own study of SNS in severe constipation we used our validated technique of pan-colonic manometry to simultaneously record colonic motor patterns during periods of SNS.46
The data obtained from this study indicates that SNS appears to induce both proximal and distal colonic motor patterns. Furthermore we observed an increase in the frequency of long extent PSs and the frequency of HAPSs (Fig. 2).
As mentioned above these particular motor patterns are linked to both colonic transit and defaecation in health. During the 3-week PNE phase 75% of the patients reported improvement in stool frequency (Table 1).
The mechanism of action of SNS in relation to initiating pan-colonic motor patterns remains unknown. It is likely that efferent neural pathways are activated but it is almost certain that afferent pathways are also activated. The rapidity of the colonic response to SNS 46 is certainly compatible with a neural pathway.
THE FUTURE OF SACRAL NERVE STIMULATION IN PATIENTS WITH SEVERE CONSTIPATION.The reported positive outcome in carefully selected patients, coupled with minimal adverse side effects suggests that SNS is a reasonable option for patients who are faced with surgical procedures such as a colectomy in order to relieve their constipation symptoms. In addition SNS, at least in treating faecal incontinence, has been shown to be highly cost effective in comparison to other surgical intervention.47
However, further work is still required. As yet only one randomized control trial has assessed the effects of SNS in costipated patients and that study had a sample size of two.40 Cleary data derived from adequately powered radomised control trials and long-term follow-up in patients with permanent implantation are still required. As is data determining which patients may benefit form SNS treatment.
In addition while a colonic response to SNS in constipation has been shown, the stimulation parameters necessary to optimise this colonic response remain unclear. Assessing the merits of various combinations of parameters (i.e. alteration to pulse width, frequency and amplitude) can be time consuming if the yardstick is a clinical response which can take weeks or even months to develop.41
Measurement of the immediate colonic contractile responses in the laboratory setting may prove to be a direct and powerful means of evaluating a wide range of stimulus parameters in order to help define the optimal ones.
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Supported by: NHMRC & Medtronic Australia.
Correspondence: Dr. Phil Dinning PhD Department of Gastroenterology St George Hospital, Kogarah, NSW, 2217 - Australia Tel +61 2 91132208 - Fax +61 2 91133993