- Email: [email protected]
Anorectal Motility Abnormalities in Children with Encopresis and Chronic Constipation
Anorectal Motility Abnormalities in Children with Encopresis and Chronic Constipation Neeraj Raghunath, MD, Mark S. Glassman, MD, Michael S. Halata, MD, Stuart H. Berezin, MD, Julian M. Stewart, MD, PhD, and Marvin S. Medow, PhD Objective To evaluate the response to rectal distension in children with chronic constipation and children with chronic constipation and encopresis.
Study design We studied 27 children, aged 3 to 16 years, with chronic constipation; 12 had encopresis. Anorectal motility was measured with a solid state catheter. When the catheter was located in the internal sphincter, the balloon was inflated to 60 mL with air. Results There were no differences in age, sex distribution, and duration of constipation in the two groups. Comparing groups, anorectal manometry showed no differences in the resting sphincter pressure, recovery pressure, the lowest relaxation pressure, and percent relaxation. However, time to maximum relaxation, time to recovery to baseline pressure, and duration of relaxation were significantly higher in patients with constipation and encopresis, compared with patients who had constipation alone. Conclusions There may be an imbalance in neuromuscular control of defecation in constipated patients with encopresis that results in incontinence as a consequence of the increased time to recovery and duration of relaxation of the internal anal sphincter. (J Pediatr 2011;158:293-6).
D
efecation is a complex mechanism under the control of various reflexes.1-4 When stool enters the previously empty rectum, mechanical distension evokes the defecation reflex.5,6 This so-called rectoanal inhibitory reflex (RAIR), which elicits external sphincter contraction and internal sphincter relaxation, is intrinsic to the colon and is mediated through the enteric nervous plexus.6,7 Rectal distension also stimulates nerve endings in the submucosa, the signals of which are transmitted through pelvic splanchnic nerves to the second and third sacral nerves, representing extrinsic rectal innervation. The signal then travels reflexively back to the rectum and internal anal sphincter (IAS) by way of parasympathetic nerve fibers in the pelvic nerves.6 Alterations in appropriate function of these pathways have been associated with constipation and associated difficulties with complete bowel evacuation such as encopresis, also known as overflow incontinence.8 The common clinical history of children with chronic constipation and encopresis includes a prolonged period of infrequent and abnormal stools, often of several years’ duration. The frequency of soiling can range from several times a week to >10 times a day. At the time of diagnosis, most children have a dilated rectal ampulla that contains large amounts of stool.8,9 Earlier studies of anorectal manometry in these populations have reported that children with chronic constipation and encopresis have a decreased ability of the internal sphincter to relax during rectal distension,10,11 abnormalities in rectal and colonic sensitivity,10,12 and weak muscle contractions during defecation.11,13 Abnormal contractions of the external anal sphincter during defecation have also been reported.8,13 We compared the anorectal response to rectal distension in children with chronic constipation with that in children with chronic constipation and encopresis. We measured several variables of anorectal function to determine whether neuromuscular dysfunction is associated with encopresis.
Methods In this retrospective study, we examined the medical history and the results of anorectal motility testing in 15 children, aged 3 to 16 years, in whom chronic constipation was diagnosed with that of 12 children who had encopresis. Informed consent was not obtained, because this was a retrospective, chart review study that did not use patient identifiers; thus all results are anonymous. The Committee for the Protection of Human Subjects (internal review board) at New York Medical College considered informed consent unnecessary and thus granted a waiver for this study. All children had abnormal bowel function for >1 year, and all failed conventional therapies that included laxatives, fiber supplementation, or both. Subjects
COX-1 IAS RAIR
Cyclooxygenase-1 Internal anal sphincter Rectoanal inhibitory reflex
From the Department of Pediatrics, Division of Gastroenterology and Nutrition, New York Medical College, Valhalla, NY The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.07.063
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neither received ‘‘stimulant’’ type laxatives—senna (anthraquinone) or bisacodyl (diphenylmethane)—nor required manual disimpaction. All children were instructed to use bulk-producing agents (fiber), lubricants, or hydrating agents (osmotics) to treat their constipation. Children with chronic constipation were selected on the basis of the Rome III Criteria14 (Table I) and had onset of constipation at least 6 months before diagnosis. Encopresis was defined as repeated involuntary passage of feces somewhere other than in a toilet. No patient in the study had a history of delayed passage of meconium. Children with hypothyroidism, Hirschsprung disease, anal stenosis, genetic disorders, mental deficiency, chronic debilitating disease, or earlier colon surgery were excluded from the study. In addition, none of the patients had behavioral disorders, such as attentiondeficit/hyperactivity disorder. All the patients in the study underwent abdominal radiography, basic metabolic panel with calcium levels, thyroid function test, and celiac disease screening. Our patients did not undergo magnetic resonance imaging studies because none had overt signs of neurological impairment, urinary impairment, dermatologic signs of the lower back, or orthopedic signs, such as scoliosis and foot deformity. Anorectal manometric studies were performed while the patients were monitored during sedation with propofol. Our experience is that sedation enhances the accuracy of manometry while obviating the interference caused by movement of the subject. Earlier studies have shown that, with the exception of glycopyrolate, anesthetic agents do not influence the RAIR.15 Informed consent for the procedure was obtained in all cases before performance of these studies. Patient’s parents were instructed to administer enemas to their children the night before the testing. The catheter with side-facing pressure-sensing regions, fitted with a distal inflatable balloon, was initially inserted to 10 cm beyond the anal verge. The catheter was then withdrawn at 1-cm intervals until the IAS was identified as a zone of high-pressure. Although the pressure sensor was located within the internal sphincter, the balloon was rapidly inflated to 60 mL with air, thereby mimicking the presence of stool in the rectum. A volume of 60 mL was used in all subjects because this volume reliably elicits the RAIR in constipated children older than the age range studied. The balloon remained inflated for 5 seconds and was then deflated. Table I. Definition of chronic constipation according to the Rome III criteria14 $3 days per month in the past 3 months, with symptom onset at least 6 months before diagnosis with $2 of the following: Straining $25% of episodes of defecation Lumpy or hard stools $25% of episodes of defecation Sensation of incomplete evacuation $25% of episodes of defecation Sensation of anorectal obstruction/blockage $25% of episodes of defecation Manual maneuvers $25% of episodes of defecation <3 defecations per week
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Vol. 158, No. 2 In normal circumstances, this stimulus elicits the rectoanal inhibitory reflex, resulting in a measurable decrease in sphincter tone. The catheter was then withdrawn further until the proximal sensor was within the external sphincter and the distal sensor was in the internal anal sphincter. The normal manometric response to balloon distension in this position is an increase in the pressure of the external sphincter and a relaxation of the internal anal sphincter. After sufficient time was allowed for sphincter pressures to return to preinflation values, the maneuver was repeated at least 3 times at each location. Resting anal pressure, duration of relaxation, recovery anal pressure, lowest pressure, time to maximum relaxation, time to recovery, and percent of relaxation were then calculated. Manometric studies were preformed with the Medtronic Polygram Net v 4.0.525.45 recorder with a 2-channel solid state catheter with each sensor separated by 2 cm (model # P41-F2204 DD130; Medtronic Inc., Minneapolis, Minnesota). All data shown are reported as means plus or minus SEM, and differences in these values were compared with paired t tests. The study group population was evaluated with a Fisher exact test, and differences in the response curves to balloon insufflations were analyzed with multivariate analysis of variance with repeated measures, as were all determinations of multiple comparisons. Results were calculated with SPSS software version 11.0 (Statistical Package for the Social Sciences; SPSS Inc, Chicago, Illinois), and a P value <.05 was considered to be significant.
Results The group of 15 patients that had constipation alone consisted of patients aged 3 to 15 years of age. There were 12 patients with constipation and encopresis aged 5 to 13 years of age (Table II). There were no differences in the average age of the two study groups, and patients from each group reported being constipated for similar periods. There was also no difference in the proportion of female to male subjects in each group. The Figure shows tracings obtained from two representative patients during the performance of an anorectal manometric study, one patient with constipation and the other with constipation and encopresis. The temporal and manometric characteristics of anorectal muscle relaxation and recovery are dramatically different in these two subjects and when comparing the two groups. Quantitation of the variables that describe anorectal function are shown in Table III for patients in our study populations. There were no differences in the resting Table II. Patient demographics
Age (years) Years constipated Female/Male
Constipation
Constipation and encopresis
Significance
7.00 4.44 3.42 2.74 6 female/9 male
9.25 2.26 5.18 1.89 3 female/9 male
Not significant Not significant Not significant
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Figure. Elicitation of RAIR in two representative subjects, one with constipation (upper tracing) and one with constipation and encopresis (lower tracing). The time to maximum relaxation, the time to recovery, and the duration of relaxation were significantly higher in patients with constipation and encopresis compared with patients with constipation alone.
sphincter pressure, the recovery pressure, the lowest relaxation pressure, and the percent relaxation in the two groups. However, the time to maximum relaxation, the time to recovery, and the duration of relaxation were significantly prolonged in patients with constipation and encopresis, compared with patients with constipation alone.
Discussion Competent bowel control is achieved through the coordinated relaxation of the IAS, through the so-called RAIR, in the presence of adequate external sphincter tone. This study compared the RAIR response in children with constipation, with and without encopresis. Similar studies have been done.8-11,13,15 Our findings are that duration of relaxation, time to maximum relaxation, and time to recover adequate resting tone are significantly increased in children with constipation and encopresis, compared with children with constipation alone. A study of individuals without anorectal symptoms showed increased amplitude and duration of relaxation in the proximal anal canal compared with the distal anal Table III. Anorectal motility parameters Constipation n = 15 Time to max relax (seconds) 4.52 1.62 Time to recovery (seconds) 8.95 3.11 Resting sphincter pressure 45.35 13.52 (mm Hg) Duration of relax (seconds) 13.48 3.69 Recovery pressure (mm Hg) 43.65 13.28 Lowest pressure (mm Hg) 21.98 12.06 % relaxation 53.21 19.43
Constipation and encopresis n = 12
P value
5.56 1.92 <.02 18.36 5.50 <.001 51.33 17.45 Not significant 24.07 6.11 <.001 51.17 17.57 Not significant 25.50 15.24 Not significant 50.10 17.73 Not significant
canal.16,17 Similar regional differences have also been shown in the response to elicitation of the RAIR, in which anal sphincter relaxation in constipated patients was more accentuated proximally than distally in the anal canal.18 However, sphincter relaxation in constipated patients with obstructive defecation showed similar sphincter relaxation both in the proximal and distal segments.18 Anal canal motility amplitude and characteristics of relaxation did not differ significantly among healthy individuals, patients with incontinence, and patients with intestinal constipation.19 Although we noted an increased duration of relaxation and a delayed recovery in constipated, encopretic patients, resting pressures in all our constipated subjects is similar to that reported for healthy control subjects.20,21 The pathogenesis of fecal incontinence is unclear, but may result from a defect in the autonomic control of defecation. Altered manometric results are found in patients after spinal cord transection, sacral surgery, or nerve blockade.22-25 In animals, when parasympathetic nerves arising from the second to fourth sacral nerves were stimulated, contraction of the rectum and relaxation of the internal anal sphincter was observed.26 Case reports of abnormal RAIR in patients with spinal shock and or meningocele suggest that the RAIR is modulated by an extrinsic pathway.27 The cause of fecal incontinence in our patient population at this time remains unclear; it may be caused by a primary autonomic defect in constipated patients with encopresis or be a result of long-standing constipation, with fecal impaction that results in a sacral neuropathy. In either case, the result of inappropriate neuromuscular function may be encopresis. Thus, the autonomic nervous system may be a modulator of defecation. Nurko examined children with sacral agenesis, which is a model of parasympathetic denervation in the absence of surgery, trauma, and anesthesia.24 Similar to our findings, these patients had larger and longer IAS relaxations after balloon distention of the rectum, with a left shift of the volume/ relaxation curve of the RAIR. The mechanism by which fecal incontinence occurs in this setting is unknown, but likely involves modulation by the parasympathetic branch of the extrinsic autonomic nervous system. The RAIR is mediated by intramural reflexes and can be elicited independent of the spine22,28,29 as it is preserved after spinal cord transection,30 bilateral hypogastric nerve blockade,2 complete isolation of the rectum from its extrinsic nerve supply,29 bilateral resection of the sacral nerves,31 and after destruction of the sacral cord.2 Because the resting baseline pressures were not different in the two groups we studied, and other authors have reported similar pressures in control and constipated patients, it may be that parasympathetic input is not important for the regulation of the resting IAS pressure.22,30 Although studies in animals and humans have shown that IAS resting pressure is caused by myogenic activity of this sphincter,24,28,30 this may not be the only regulator of sphincter tone. The cyclooxygenase-1 (COX-1) pathway plays a significant role in the maintenance of basal tone in IAS smooth muscle in rats.32). Studies of the specific effects of COX-1
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products and their inhibitors therefore are suggested because they may have implications for the therapeutic rationale for COX-1-selective inhibitors in the hypertensive IAS associated with some anorectal motility disorders. The variables that we measured in the constipated children are similar to those previously reported for resting internal anal sphincter pressure and percent relaxation. The finding of a prolonged duration of relaxation in children with encopresis suggests that this abnormality in anorectal function may be, at least in part, responsible for this complication of constipation. We postulate that because of the increased length of time during IAS relaxation, larger amounts of stool are able to move into the rectal vault, making it more difficult to maintain continence. As suggested by other authors, this may be caused by inappropriate function of the sacral branch of the parasympathetic nervous system. Whether this is a result of an underlying neuropathy or a consequence of chronic constipation is unclear. Further investigations are warranted to determine the exact nature of this parasympathetic dysfunction. n Submitted for publication Mar 17, 2010; last revision received Jun 23, 2010; accepted Jul 27, 2010. Reprint requests: Marvin S. Medow, PhD, Associate Professor of Pediatrics and Physiology, New York Medical College, The Center for Pediatric Hypotension, 19 Bradhurst Ave, Suite 1600S, Hawthorne, NY 10532. E-mail: [email protected].
References 1. Burleigh DE, D’Mello A. Neural and pharmacologic factors affecting motility of the internal anal sphincter. Gastroenterology 1983;84:409-17. 2. Denny-Brown D, Robertson EG. ‘‘An investigation of the nervous control of defecation’’ by Denny-Brown and Robertson: a classic paper revisited. 1935. Colorectal Dis 2004;6:376-83. 3. Pedersen E, Harving H, Klemar B, Torring J. Human anal reflexes. J Neurol Neurosurg Psychiatry 1978;41:813-8. 4. Sarna SK. Colonic motor activity. Surg Clin North Am 1993;73:1201-23. 5. Shafik A, Ali YA, Afifi R. Is the rectum a conduit or storage organ? Int Surg 1997;82:194-7. 6. Shafik A, El-Sibai O, Ahmed I. Parasympathetic extrinsic reflex: role in defecation mechanism. World J Surg 2002;26:737-40. 7. O’Riordain MG, Molloy RG, Gillen P, Horgan A, Kirwan WO. Rectoanal inhibitory reflex following low stapled anterior resection of the rectum. Dis Colon Rectum 1992;35:874-8. 8. Loening-Baucke V. Factors determining outcome in children with chronic constipation and faecal soiling. Gut 1989;30:999-1006. 9. Loening-Baucke VA, Cruikshank BM. Abnormal defecation dynamics in chronically constipated children with encopresis. J Pediatr 1986;108:562-6. 10. Loening-Baucke VA. Sensitivity of the sigmoid colon and rectum in children treated for chronic constipation. J Pediatr Gastroenterol Nutr 1984; 3:454-9. 11. Loening-Baucke VA. Abnormal rectoanal function in children recovered from chronic constipation and encopresis. Gastroenterology 1984;87: 1299-304.
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Vol. 158, No. 2 12. Goligher JC, Hughes ES. Sensibility of the rectum and colon. Its role in the mechanism of anal continence. Lancet 1951;1:543-7. 13. Wald A, Chandra R, Chiponis D, Gabel S. Anorectal function and continence mechanisms in childhood encopresis. J Pediatr Gastroenterol Nutr 1986;5:346-51. 14. Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis 2006;15:237-41. 15. Pfefferkorn MD, Croffie JM, Corkins MR, Gupta SK, Fitzgerald JF. Impact of sedation and anesthesia on the rectoanal inhibitory reflex in children. J Pediatr Gastroenterol Nutr 2004;38:324-7. 16. Goes RN, Simons AJ, Masri L, Beart RW, Jr. Gradient of pressure and time between proximal anal canal and high-pressure zone during internal anal sphincter relaxation. Its role in the fecal continence mechanism. Dis Colon Rectum 1995;38:1043-6. 17. Williamson JL, Nelson RL, Orsay C, Pearl RK, Abcarian H. A comparison of simultaneous longitudinal and radial recordings of anal canal pressures. Dis Colon Rectum 1990;33:201-6. 18. Netinho JG, Ayrizono ML, Coy CS, Fagundes JJ, Goes JR. Amplitude and recovery velocity of relaxation induced by rectoanal inhibitory reflex and its importance for obstructive evacuation. Arq Gastroenterol 2005;42: 19-23. 19. Zbar AP, Aslam M, Gold DM, Gatzen C, Gosling A, Kmiot WA. Parameters of the rectoanal inhibitory reflex in patients with idiopathic fecal incontinence and chronic constipation. Dis Colon Rectum 1998;41: 200-8. 20. Lanfranchi GA, Bazzocchi G, Brignola C, Campieri M, Labo G. Different patterns of intestinal transit time and anorectal motility in painful and painless chronic constipation. Gut 1984;25:1352-7. 21. Molnar D, Taitz LS, Urwin OM, Wales JK. Anorectal manometry results in defecation disorders. Arch Dis Child 1983;58:257-61. 22. Beuret-Blanquart F, Weber J, Gouverneur JP, Demangeon S, Denis P. Colonic transit time and anorectal manometric anomalies in 19 patients with complete transection of the spinal cord. J Auton Nerv Syst 1990;30: 199-207. 23. Devroede G, Arhan P, Duguay C, Tetreault L, Akoury H, Perey B. Traumatic constipation. Gastroenterology 1979;77:1258-67. 24. Morera C, Nurko S. Rectal manometry in patients with isolated sacral agenesis. J Pediatr Gastroenterol Nutr 2003;37:47-52. 25. Rosen R, Buonomo C, Andrade R, Nurko S. Incidence of spinal cord lesions in patients with intractable constipation. J Pediatr 2004;145:40911. 26. Matsufuji H, Yokoyama J. Neural control of the internal anal sphincter motility. J Smooth Muscle Res 2003;39:11-20. 27. Li WC, Xiao CG. Anorectal functions in patients with lumbosacral spinal cord injury. Chin J Traumatol 2006;9:217-22. 28. Gonella J, Bouvier M, Blanquet F. Extrinsic nervous control of motility of small and large intestines and related sphincters. Physiol Rev 1987;67: 902-61. 29. Lubowski DZ, Nicholls RJ, Swash M, Jordan MJ. Neural control of internal anal sphincter function. Br J Surg 1987;74:668-70. 30. Frenckner B. Function of the anal sphincters in spinal man. Gut 1975;16: 638-44. 31. Gunterberg B, Kewenter J, Petersen I, Stener B. Anorectal function after major resections of the sacrum with bilateral or unilateral sacrifice of sacral nerves. Br J Surg 1976;63:546-54. 32. de Godoy MA, Rattan N, Rattan S. COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter. Am J Physiol Gastrointest Liver Physiol 2009;296:G219-25.
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Study design We studied 27 children, aged 3 to 16 years, with chronic constipation; 12 had encopresis. Anorectal motility was measured with a solid state catheter. When the catheter was located in the internal sphincter, the balloon was inflated to 60 mL with air. Results There were no differences in age, sex distribution, and duration of constipation in the two groups. Comparing groups, anorectal manometry showed no differences in the resting sphincter pressure, recovery pressure, the lowest relaxation pressure, and percent relaxation. However, time to maximum relaxation, time to recovery to baseline pressure, and duration of relaxation were significantly higher in patients with constipation and encopresis, compared with patients who had constipation alone. Conclusions There may be an imbalance in neuromuscular control of defecation in constipated patients with encopresis that results in incontinence as a consequence of the increased time to recovery and duration of relaxation of the internal anal sphincter. (J Pediatr 2011;158:293-6).
D
efecation is a complex mechanism under the control of various reflexes.1-4 When stool enters the previously empty rectum, mechanical distension evokes the defecation reflex.5,6 This so-called rectoanal inhibitory reflex (RAIR), which elicits external sphincter contraction and internal sphincter relaxation, is intrinsic to the colon and is mediated through the enteric nervous plexus.6,7 Rectal distension also stimulates nerve endings in the submucosa, the signals of which are transmitted through pelvic splanchnic nerves to the second and third sacral nerves, representing extrinsic rectal innervation. The signal then travels reflexively back to the rectum and internal anal sphincter (IAS) by way of parasympathetic nerve fibers in the pelvic nerves.6 Alterations in appropriate function of these pathways have been associated with constipation and associated difficulties with complete bowel evacuation such as encopresis, also known as overflow incontinence.8 The common clinical history of children with chronic constipation and encopresis includes a prolonged period of infrequent and abnormal stools, often of several years’ duration. The frequency of soiling can range from several times a week to >10 times a day. At the time of diagnosis, most children have a dilated rectal ampulla that contains large amounts of stool.8,9 Earlier studies of anorectal manometry in these populations have reported that children with chronic constipation and encopresis have a decreased ability of the internal sphincter to relax during rectal distension,10,11 abnormalities in rectal and colonic sensitivity,10,12 and weak muscle contractions during defecation.11,13 Abnormal contractions of the external anal sphincter during defecation have also been reported.8,13 We compared the anorectal response to rectal distension in children with chronic constipation with that in children with chronic constipation and encopresis. We measured several variables of anorectal function to determine whether neuromuscular dysfunction is associated with encopresis.
Methods In this retrospective study, we examined the medical history and the results of anorectal motility testing in 15 children, aged 3 to 16 years, in whom chronic constipation was diagnosed with that of 12 children who had encopresis. Informed consent was not obtained, because this was a retrospective, chart review study that did not use patient identifiers; thus all results are anonymous. The Committee for the Protection of Human Subjects (internal review board) at New York Medical College considered informed consent unnecessary and thus granted a waiver for this study. All children had abnormal bowel function for >1 year, and all failed conventional therapies that included laxatives, fiber supplementation, or both. Subjects
COX-1 IAS RAIR
Cyclooxygenase-1 Internal anal sphincter Rectoanal inhibitory reflex
From the Department of Pediatrics, Division of Gastroenterology and Nutrition, New York Medical College, Valhalla, NY The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.07.063
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neither received ‘‘stimulant’’ type laxatives—senna (anthraquinone) or bisacodyl (diphenylmethane)—nor required manual disimpaction. All children were instructed to use bulk-producing agents (fiber), lubricants, or hydrating agents (osmotics) to treat their constipation. Children with chronic constipation were selected on the basis of the Rome III Criteria14 (Table I) and had onset of constipation at least 6 months before diagnosis. Encopresis was defined as repeated involuntary passage of feces somewhere other than in a toilet. No patient in the study had a history of delayed passage of meconium. Children with hypothyroidism, Hirschsprung disease, anal stenosis, genetic disorders, mental deficiency, chronic debilitating disease, or earlier colon surgery were excluded from the study. In addition, none of the patients had behavioral disorders, such as attentiondeficit/hyperactivity disorder. All the patients in the study underwent abdominal radiography, basic metabolic panel with calcium levels, thyroid function test, and celiac disease screening. Our patients did not undergo magnetic resonance imaging studies because none had overt signs of neurological impairment, urinary impairment, dermatologic signs of the lower back, or orthopedic signs, such as scoliosis and foot deformity. Anorectal manometric studies were performed while the patients were monitored during sedation with propofol. Our experience is that sedation enhances the accuracy of manometry while obviating the interference caused by movement of the subject. Earlier studies have shown that, with the exception of glycopyrolate, anesthetic agents do not influence the RAIR.15 Informed consent for the procedure was obtained in all cases before performance of these studies. Patient’s parents were instructed to administer enemas to their children the night before the testing. The catheter with side-facing pressure-sensing regions, fitted with a distal inflatable balloon, was initially inserted to 10 cm beyond the anal verge. The catheter was then withdrawn at 1-cm intervals until the IAS was identified as a zone of high-pressure. Although the pressure sensor was located within the internal sphincter, the balloon was rapidly inflated to 60 mL with air, thereby mimicking the presence of stool in the rectum. A volume of 60 mL was used in all subjects because this volume reliably elicits the RAIR in constipated children older than the age range studied. The balloon remained inflated for 5 seconds and was then deflated. Table I. Definition of chronic constipation according to the Rome III criteria14 $3 days per month in the past 3 months, with symptom onset at least 6 months before diagnosis with $2 of the following: Straining $25% of episodes of defecation Lumpy or hard stools $25% of episodes of defecation Sensation of incomplete evacuation $25% of episodes of defecation Sensation of anorectal obstruction/blockage $25% of episodes of defecation Manual maneuvers $25% of episodes of defecation <3 defecations per week
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Vol. 158, No. 2 In normal circumstances, this stimulus elicits the rectoanal inhibitory reflex, resulting in a measurable decrease in sphincter tone. The catheter was then withdrawn further until the proximal sensor was within the external sphincter and the distal sensor was in the internal anal sphincter. The normal manometric response to balloon distension in this position is an increase in the pressure of the external sphincter and a relaxation of the internal anal sphincter. After sufficient time was allowed for sphincter pressures to return to preinflation values, the maneuver was repeated at least 3 times at each location. Resting anal pressure, duration of relaxation, recovery anal pressure, lowest pressure, time to maximum relaxation, time to recovery, and percent of relaxation were then calculated. Manometric studies were preformed with the Medtronic Polygram Net v 4.0.525.45 recorder with a 2-channel solid state catheter with each sensor separated by 2 cm (model # P41-F2204 DD130; Medtronic Inc., Minneapolis, Minnesota). All data shown are reported as means plus or minus SEM, and differences in these values were compared with paired t tests. The study group population was evaluated with a Fisher exact test, and differences in the response curves to balloon insufflations were analyzed with multivariate analysis of variance with repeated measures, as were all determinations of multiple comparisons. Results were calculated with SPSS software version 11.0 (Statistical Package for the Social Sciences; SPSS Inc, Chicago, Illinois), and a P value <.05 was considered to be significant.
Results The group of 15 patients that had constipation alone consisted of patients aged 3 to 15 years of age. There were 12 patients with constipation and encopresis aged 5 to 13 years of age (Table II). There were no differences in the average age of the two study groups, and patients from each group reported being constipated for similar periods. There was also no difference in the proportion of female to male subjects in each group. The Figure shows tracings obtained from two representative patients during the performance of an anorectal manometric study, one patient with constipation and the other with constipation and encopresis. The temporal and manometric characteristics of anorectal muscle relaxation and recovery are dramatically different in these two subjects and when comparing the two groups. Quantitation of the variables that describe anorectal function are shown in Table III for patients in our study populations. There were no differences in the resting Table II. Patient demographics
Age (years) Years constipated Female/Male
Constipation
Constipation and encopresis
Significance
7.00 4.44 3.42 2.74 6 female/9 male
9.25 2.26 5.18 1.89 3 female/9 male
Not significant Not significant Not significant
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ORIGINAL ARTICLES
February 2011
Figure. Elicitation of RAIR in two representative subjects, one with constipation (upper tracing) and one with constipation and encopresis (lower tracing). The time to maximum relaxation, the time to recovery, and the duration of relaxation were significantly higher in patients with constipation and encopresis compared with patients with constipation alone.
sphincter pressure, the recovery pressure, the lowest relaxation pressure, and the percent relaxation in the two groups. However, the time to maximum relaxation, the time to recovery, and the duration of relaxation were significantly prolonged in patients with constipation and encopresis, compared with patients with constipation alone.
Discussion Competent bowel control is achieved through the coordinated relaxation of the IAS, through the so-called RAIR, in the presence of adequate external sphincter tone. This study compared the RAIR response in children with constipation, with and without encopresis. Similar studies have been done.8-11,13,15 Our findings are that duration of relaxation, time to maximum relaxation, and time to recover adequate resting tone are significantly increased in children with constipation and encopresis, compared with children with constipation alone. A study of individuals without anorectal symptoms showed increased amplitude and duration of relaxation in the proximal anal canal compared with the distal anal Table III. Anorectal motility parameters Constipation n = 15 Time to max relax (seconds) 4.52 1.62 Time to recovery (seconds) 8.95 3.11 Resting sphincter pressure 45.35 13.52 (mm Hg) Duration of relax (seconds) 13.48 3.69 Recovery pressure (mm Hg) 43.65 13.28 Lowest pressure (mm Hg) 21.98 12.06 % relaxation 53.21 19.43
Constipation and encopresis n = 12
P value
5.56 1.92 <.02 18.36 5.50 <.001 51.33 17.45 Not significant 24.07 6.11 <.001 51.17 17.57 Not significant 25.50 15.24 Not significant 50.10 17.73 Not significant
canal.16,17 Similar regional differences have also been shown in the response to elicitation of the RAIR, in which anal sphincter relaxation in constipated patients was more accentuated proximally than distally in the anal canal.18 However, sphincter relaxation in constipated patients with obstructive defecation showed similar sphincter relaxation both in the proximal and distal segments.18 Anal canal motility amplitude and characteristics of relaxation did not differ significantly among healthy individuals, patients with incontinence, and patients with intestinal constipation.19 Although we noted an increased duration of relaxation and a delayed recovery in constipated, encopretic patients, resting pressures in all our constipated subjects is similar to that reported for healthy control subjects.20,21 The pathogenesis of fecal incontinence is unclear, but may result from a defect in the autonomic control of defecation. Altered manometric results are found in patients after spinal cord transection, sacral surgery, or nerve blockade.22-25 In animals, when parasympathetic nerves arising from the second to fourth sacral nerves were stimulated, contraction of the rectum and relaxation of the internal anal sphincter was observed.26 Case reports of abnormal RAIR in patients with spinal shock and or meningocele suggest that the RAIR is modulated by an extrinsic pathway.27 The cause of fecal incontinence in our patient population at this time remains unclear; it may be caused by a primary autonomic defect in constipated patients with encopresis or be a result of long-standing constipation, with fecal impaction that results in a sacral neuropathy. In either case, the result of inappropriate neuromuscular function may be encopresis. Thus, the autonomic nervous system may be a modulator of defecation. Nurko examined children with sacral agenesis, which is a model of parasympathetic denervation in the absence of surgery, trauma, and anesthesia.24 Similar to our findings, these patients had larger and longer IAS relaxations after balloon distention of the rectum, with a left shift of the volume/ relaxation curve of the RAIR. The mechanism by which fecal incontinence occurs in this setting is unknown, but likely involves modulation by the parasympathetic branch of the extrinsic autonomic nervous system. The RAIR is mediated by intramural reflexes and can be elicited independent of the spine22,28,29 as it is preserved after spinal cord transection,30 bilateral hypogastric nerve blockade,2 complete isolation of the rectum from its extrinsic nerve supply,29 bilateral resection of the sacral nerves,31 and after destruction of the sacral cord.2 Because the resting baseline pressures were not different in the two groups we studied, and other authors have reported similar pressures in control and constipated patients, it may be that parasympathetic input is not important for the regulation of the resting IAS pressure.22,30 Although studies in animals and humans have shown that IAS resting pressure is caused by myogenic activity of this sphincter,24,28,30 this may not be the only regulator of sphincter tone. The cyclooxygenase-1 (COX-1) pathway plays a significant role in the maintenance of basal tone in IAS smooth muscle in rats.32). Studies of the specific effects of COX-1
Anorectal Motility Abnormalities in Children with Encopresis and Chronic Constipation
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products and their inhibitors therefore are suggested because they may have implications for the therapeutic rationale for COX-1-selective inhibitors in the hypertensive IAS associated with some anorectal motility disorders. The variables that we measured in the constipated children are similar to those previously reported for resting internal anal sphincter pressure and percent relaxation. The finding of a prolonged duration of relaxation in children with encopresis suggests that this abnormality in anorectal function may be, at least in part, responsible for this complication of constipation. We postulate that because of the increased length of time during IAS relaxation, larger amounts of stool are able to move into the rectal vault, making it more difficult to maintain continence. As suggested by other authors, this may be caused by inappropriate function of the sacral branch of the parasympathetic nervous system. Whether this is a result of an underlying neuropathy or a consequence of chronic constipation is unclear. Further investigations are warranted to determine the exact nature of this parasympathetic dysfunction. n Submitted for publication Mar 17, 2010; last revision received Jun 23, 2010; accepted Jul 27, 2010. Reprint requests: Marvin S. Medow, PhD, Associate Professor of Pediatrics and Physiology, New York Medical College, The Center for Pediatric Hypotension, 19 Bradhurst Ave, Suite 1600S, Hawthorne, NY 10532. E-mail: [email protected].
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