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Investigation of small bowel motility
Chapter 21
Investigation of small bowel motility Edy E. Soffer Keck School of Medicine at The University of Southern California, Los Angeles, CA, United States
Key Points ● ● ● ●
Normal small bowel motility depends on the integrity of the neuromuscular apparatus of the bowel. Abnormal motility results from neuropathic or myopathic changes, or both. Intestinal manometry is the gold standard for assessing small bowel contractile patterns, but has limited availability. Transit tests serve as a surrogate measure of small bowel motility, are non-invasive, and are more widely available.
Introduction Normal small bowel motility is critical for ensuring the proper function of digestion and absorption of nutrients. Chyme entering the small bowel is propelled by peristaltic activity that allows adequate mixing with bile and enzymes, as well as contact time with small bowel mucosa. Between meals, the small bowel has a stereotypic cyclical motor pattern called the migrating motor complex (MMC) that facilitates the emptying of small bowel residue and helps prevent intestinal bacterial overgrowth. The organization and propagation of small bowel contractions is controlled primarily by the enteric nervous system and modulated by the autonomic nervous system, while the strength of contractions is dependent on the integrity of intestinal smooth muscle. Neuromuscular dysfunction can involve primarily the small bowel, as in primary visceral myopathy, or secondary to a systemic disease such as scleroderma. Neuromuscular dysfunction impairs small bowel transit and as a result the normal process of digestion and absorption. This results in a variety of symptoms such as abdominal pain, nausea, vomiting, bloating, diarrhea or constipation or weight loss. When small bowel motility is severely impaired, patients may present with a picture of intestinal pseudo-obstruction, with intestinal dilation but without a mechanical obstruction. However, this clinical presentation is rare, and most patients with dysmotility present with the symptoms described above, without obvious evidence of radiologic abnormalities [1]. It is in this clinical scenario of unexplained symptoms, and particularly in the absence of motor impairment of other segments of the gut, that tests of small bowel motility are performed to assess phasic events and contractile patterns, or small bowel transit.
Assessment of small bowel contractile activity Small bowel manometry Small bowel manometry detects intestinal phasic pressure events and their temporal and spatial relationships, and is the standard for recognizing intestinal motor patterns in health and disease. Current techniques in clinical use consist of stationary or ambulatory recording, using intraluminal perfused tubes or probes incorporating solid state pressure transducers. Daytime recording, during fasting and after the administration of a meal, and nighttime recording, provide data on patterns of motor activity of the small bowel that serve as an index of the integrity of the enteric neuromuscular apparatus. Indications: The main purpose of performing the test is to determine if abnormalities of enteric neuromuscular function are responsible for unexplained GI symptoms, when structural abnormalities have been excluded and known causes of dysmotility are not present. In the pediatric population, results of manometry have been proposed to predict the readiness for feeding in neonates [2], tolerance to jejunal feeding [3], response to prokinetic agents [4] and clinical outcome in children with pseudo-obstruction [5]. A normal manometry helps to exclude a neuromuscular disorder in children with suspected chronic intestinal pseudo-obstruction [6]. In adults, the primary indication is the evaluation of nausea and vomiting, and symptoms suggestive of dysmotility when clinical assessment and imaging study do not provide a clear diagnosis [7]. Clinical and Basic Neurogastroenterology and Motility. https://doi.org/10.1016/B978-0-12-813037-7.00021-2 © 2020 Elsevier Inc. All rights reserved.
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TABLE 1 Indications for gastroduodenojejunal manometry. 1. Clarify the diagnosis in patients with unexplained nausea, vomiting or symptoms suggestive of upper GI dysmotility 2. Confirm diagnosis in suspected chronic intestinal pseudo-obstruction syndromes when the diagnosis is unclear from clinical or radiological evaluations 3. Identify generalized dysmotility in patients with colonic dysmotility (e.g., chronic constipation), particularly prior to subtotal colectomy 4. Differentiate between neuropathic vs. myopathic gastric or small bowel dysfunction 5. Assess for possible mechanical obstruction when clinical features suggest, but radiological studies do not reveal, obstruction 6. Determine which organs need to be transplanted (isolated vs. multi-visceral transplantation) in patients with chronic intestinal pseudoobstruction being considered for intestinal transplantation
Manometry is used to determine whether generalized dysmotility exists in a patient with defined localized dysmotility (e.g., slow transit constipation), in particular, if surgery is being considered, since patients with evidence of generalized dysmotility do not respond as well to colectomy [8]. Manometry can suggest the presence of mechanical obstruction in patients with unexplained abdominal pain [9]. Finally, an unequivocally normal manometric study is perhaps the most clinically useful, investigation as it will exclude neuromuscular malfunction, and determine that the enteric nerves and muscles are functioning normally [7]. A list of indications is outlined in Table 1 [10]. Equipment: Recording is done by stationary (the most common method used in clinical practice) or ambulatory systems. Stationary systems make use of either a perfused system or a solid state assembly, connected to a stationary recording device. In perfused systems, the catheter assembly incorporates several lumens with side openings at desired levels (Fig. 1) [11]. Ambulatory recording requires a catheter that incorporates miniature strain-gauge transducers, connected to a portable solid-state recording device. Although a minimum of two sensors is recommended for the detection of motility patterns and their propagation [7], perfused systems can easily accommodate multiple sites, and the new high resolution catheters incorporate a large number of sensors that are closely spaced (Fig. 1B) [11]. Catheters are introduced trans-nasally, guided by fluoroscopy or endoscopy, after an overnight fast. Intubation assisted by endoscopy requires sedation provided by short acting agents, such as midazolam or propofol. A minimum interval of 1 h between intubation and the start of data acquisition is recommended.
FIG. 1 (A) Water-perfused manometry catheters like the one pictured are a bundle of thin polyvinyl tubes, with an outward facing opening (side hole) in each tube. The side holes function as point pressure sensors. They are typically configured at 3–5 cm intervals along the catheter. A low-compliance, pneumohydraulic pump slowly perfuses each of the tubes, and the pressure in each is converted to an electrical signal by a volume–displacement transducer. Pressure recorded by the system increases when water flowing through the side hole is impeded by radial contraction of the gut wall at the side hole. Information about gastrointestinal motor function may be lost with this technique because the side holes are widely spaced and sense in only one direction around the catheter circumference. (B) High-resolution manometry catheter pictured here is 4.2 mm in diameter and consists of 36 circumferential, solidstate, pressure sensors (copper colored bands, arrowhead). Sensors are spaced at 1-cm intervals, from center to center. This gives the catheter a recording segment of 35 cm. Each individual sensor (magnified at center) detects pressure from 12 loci (arrow) around its circumference. Computer processing of the signals coming from pressure sensing elements allows average circumferential pressures over the entire 35-cm recording segment to be displayed in real time and recorded for subsequent analysis. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
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Conduct of the study: Regardless of the system used, studies are performed after an overnight fast (including tube feeding). Medications that can affect GI motility (narcotics, anticholinergics, calcium channel blockers, erythromycin, and motility modulating drugs such as metoclopramide or domperidone) should be avoided for at least 48 h prior to the test. It is recommended that patients with diabetes mellitus should take 50% of their usual morning dose of insulin; blood glucose should be monitored during the study and insulin or glucose administered to maintain the blood sugar in a reasonable range [7]. Recording confined to daytime should start with a fasting period, to capture the MMC. The duration of recording during fasting varies among laboratories, ranging from 3 to 6 h. Fasting is followed by meal administration and further recording, for at least 2 h, in the postprandial state [7]. While average MMC cycle length is <2 h, the range is wide, from 0 to 6 in the course of 6 h of fasting, with at least one phase III in 6 h of recording in healthy subjects [12]. Ambulatory recording provides the most information about the MMC, because of the high likelihood of observing one during sleep [12]. However, extended recording during fasting to 6 h, followed by postprandial recording, provides comparable accuracy to ambulatory recording in most subjects, since a longer period of recording is unlikely to miss a phase III, in spite of the normal variability in MMC frequency [13].
Normal patterns of small bowel motility Fasting period: This period is characterized by a cyclical pattern of stereotypical motor activity termed the migrating motor complex cycle (MMC), composed of three phases. The most recognizable one is phase III, a burst of regular phasic pressure events occurring at a rate of 10–12 per min in the proximal small bowel that migrates aborally in health (Fig. 2). Duration varies but should be at least 2 min, and does not exceed 30 min [12]. The length of migration varies greatly, depending in part on the distance occupied by the sensors. Phase II precedes phase III and is the longest component of the cycle, characterized by irregular phasic activity. Phase I is a period of quiescence that follows phase III, that may or may not be present during the daytime, but should be present during sleep, in which case it normally may account for most of the cycle duration (Fig. 3). High resolution manometry has been extensively used in the study of esophageal motility in health and disease, and has greatly improved our understanding of esophageal physiology and pathology. Figs. 4–6 show a high resolution manometry recording of the gastroduodenal region. As in the esophagus, the pressure topography plots provide a much better appreciation of propagation pattern of individual phasic events and intuitive pattern recognition, as compared to the traditional line mode. However, catheters are expensive, drift hampers long recording in some systems, and while it has a promising potential for better understanding of small bowel motor physiology, it remains to be seen if the use of this technology in clinical practice would provide a higher diagnostic yield. A newer method, using fiber optics for high resolution recording, may provide further versatility [14].
FIG. 2 The pattern of small bowel motility during fasting in health. Tracing was obtained during an ambulatory recording. The five sensors are spaced 15 cm apart, two are placed in the duodenum (D), and three in the Jejunum (J). The tracing shows intermittent activity during phase II, the migrating band of contractions during phase III, followed by a short period of motor quiescence, termed phase I. During the day, phase I may be absent with intermittent activity starting right after the end of phase III.
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Duodenum
50 mm Hg Jejunum I
10 min
Jejunum II
FIG. 3 The migrating motor complex during sleep. Ambulatory recording during sleep from a healthy subject. The three sensors in the duodenum (D) or jejunum (J) are spaced 15 cm apart. Frequent phase IIIs are observed with hardly any activity during phase II. In comparison with the fasting during awake, the MMC during sleep is characterized by more frequent phase IIIs, shorter phase II and longer phase I. Sometimes phase II is absent altogether.
FIG. 4 High-resolution antroduodenal manometry. This is a fluoroscopic image showing placement of the high resolution manometry catheter for antroduodenal manometry. The dark rectangles are individual pressure sensors. The recording segment of the catheter is composed of 36 closely spaced, circumferential, pressure sensors spaced at a distance of 1 cm from center to center, providing a sensing length of 35 cm. It spans from the stomach to the level of the ligament of Treitz. Because a number of closely spaced sensors straddle the pylorus, appreciation of this transition zone (arrowhead) does not require special devices (such as a sleeve). Similarly, movement of the catheter does not affect recording from the antrum, which can happen, for example, after a meal. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
The fed pattern: The normal response to food ingestion is characterized by an irregular contractile activity, at a higher frequency than in the preceding fasting recording (excluding phase III), without return of MMC for at least 2 h after consumption of a 400-kcal meal [15], (Fig. 7).
Abnormal patterns of small bowel motility Patterns associated with neuropathic disorders: These recordings are characterized by an abnormal propagation of the MMC, failure of conversion to fed pattern or increased uncoordinated phasic contractile activity [16]. Figs. 8–10 show examples of such patterns, obtained from patients with unexplained gastrointestinal symptoms.
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FIG. 5 Phase III of the migrating motor complex (MMC) in the antrum and duodenum. (A) An antroduodenal manometry displayed in line mode was recorded from the catheter positioned in Fig. 4. It demonstrates a phase III of the MMC. Pressures are displayed from sensors spaced at 5-cm intervals to approximate the look of a conventional antroduodenal manometry. The top three channels display antral motor activity: high-amplitude peristaltic contractions at 3 cycles per min (cpm). The bottom three channels display duodenal motor activity: peristaltic contractions at 12 cpm. It is relatively easy to appreciate the direction the phase III complex and gastric pressure waves propagate, but very difficult to evaluate propagation of duodenal pressure waves. (B) The high- resolution manometry (HRM) color contour of the same data. The location of the pylorus, as estimated from the fluoroscopic image, is in the neighborhood of sensors 16 and 17. The HRM contour provides a more detailed depiction of antroduodenal motor function. The propagation of individual contractions can be discerned, even in this condensed tracing. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
FIG. 6 Duodenal phase III in a healthy subject. (A) This antroduodenal manometry is displayed in line mode to simulate a traditional tracing of phase III in the duodenum. The propagation pattern of contractile sequences is difficult to reliably determine. (B) The HRM color contour of the same tracing makes it easy to discern the complex pattern of propagation. Very low amplitude pressure waves are seen in the stomach (arrowhead). There are two pacemaker foci in the duodenum (*) from which pressure waves propagate antegrade and retrograde (arrows). Also notice that individual duodenal pressure waves propagate at varying velocities over different duodenal segments. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
Patterns associated with myopathic disorders: Are characterized by low amplitude contractions, of <20 mm Hg, in a non-dilated bowel [10]. Given the control mechanisms of small bowel motor function, it is intuitive that manometric abnormalities presenting with abnormal pattern of contractions are caused by neuropathic disorders, while the myopathic pattern is caused by intestinal myopathy. However, recent studies matching intestinal manometry with intestinal histopathology specimens show an overlap between the two diagnostic tests [17, 18]. Rather, the terms reflect the presence of such patterns in disease entities associated with neuropathy or myopathy, such as diabetes or scleroderma.
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FIG. 7 The postprandial period. Increased motor activity in the duodenum and jejunum following a 400 kcal meal. It may take 10–20 min for increased activity to occur. Ambulatory recording in a healthy subject. Sensors configuration same as in Fig. 2.
FIG. 8 Abnormal migration of phase III from duodenum to jejunum, with skipping of a segment of jejunum. Ambulatory manometry from a patient with severe dyspepetic symptoms. Sensors configuration same as in Fig. 2.
FIG. 9 Repetitive, long bursts of phase III like activity occurring simultaneously at different recording sites. Ambulatory manometry, sensors configuration same as in Fig. 2.
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Duodenum
50 mm Hg Jejunum I
10 min Jejunum II
FIG. 10 Sustained, uncoordinated contractile activity during sleep, in a TPN dependent patient with symptoms of abdominal pain, nausea and vomiting. Similar pattern was observed in the awake state. Ambulatory manometry, sensors spaced 15 cm apart.
Analysis: A qualitative evaluation of the manometry tracing provides most of the information obtained from the study. Here, the recording is inspected both for the presence of the normal motility patterns, as well as the absence of abnormal ones as described above. The quantitative assessment involves measuring the number of MMCs, the amplitude of contractions and the postprandial motility index, evaluated and validated primarily in the antrum. A normal pattern has the following features [10]: 1. At least one migrating motor complex (MMC) per 24 h. 2. Conversion to the fed pattern without return of MMC for at least 2 h after a 400-kcal meal. 3. Antral contractions >40 mm Hg and small intestinal contractions >20 mm Hg. 4. Absence of abnormal patterns as described above. Clinical utility of small bowel manometry: Manometry is useful when the reason for the patient's symptoms is not explained by an existing disease or other, less invasive tests. However, a number of factors impact the clinical usefulness of manometry. The test is time consuming, performed primarily in tertiary referral centers that have the necessary expertise, and performance is not standardized. As with manometric recording from other segments of the GI tract, the range of abnormal patterns is limited, they can be observed in various unrelated conditions, and their presence does not necessarily implicate intestinal dysmotility as the cause of symptoms. Retrospective studies have shown that manometry impacted management in up to a third of patients with suspected dysmotility, regarding decisions concerning choice of prokinetic agents, mode of feeding (enteral vs. parenteral), or colectomy for slow transit constipation [19, 20], though a therapeutic trial can also be helpful in the decision making. An unequivocally normal study is likely the most useful, excluding dysmotility as the cause of symptoms [10].
Wireless motility capsule The capsule has a single pressure sensor as well as pH and temperature sensors, and transmits data wirelessly to an outside data recorder. While it provides data on phasic contractions, its location along the small bowel cannot be determined and the single sensor precludes assessment of the propagation of contractile events and motor patterns. It can detect low amplitude contractions consistent with myopathic pattern. Currently, its main use is in the assessment of small bowel transit.
Use of imaging studies for assessment of small bowel motility Recently, analysis of imaging data has been used to distinguish between normal and abnormal small bowel motility. Endoluminal image analysis: In this method, images obtained from capsule endoscopy are subjected to computer analysis that evaluates features such as luminal occlusion to quantify contractions, pattern of luminal opening and bowel wall and type of luminal contents as observed in healthy subjects [21]. In a study of large number of patients with functional bowel
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disorder, the dynamic function of motor sequences was correlated with luminal closure and transit, using computerized algorithms. The results showed a divergence between patients and healthy controls [22]. The utility of this innovative but complex technology in clinical practice requires further studies. Dynamic magnetic resonance imaging (MRI): This modality consists of taking successive images over a period of time and subjecting the data to automated software programs that provide quantification of segmental or global small bowel motility. Applying this technology in a study of healthy subjects and patients with chronic intestinal pseudo-obstruction (CIPO), researchers showed that patients with CIPO had a decreased global motility of the bowel at rest, and after administration of a prokinetic agent, when compared to control [23].
Small bowel transit studies Normal small bowel motility ensures a normal transit of chyme throughout the small bowel that allows for the vital processes of digestion and absorption of nutrients along the gut. Impaired transit, caused by abnormal patterns of motility, can result in debilitating symptoms and malnutrition. Manometry and the newer tests described in the previous section are limited by a lack of widespread availability or, in the case of manometry, the associated discomfort. Transit tests that can serve as a surrogate to motility tests are an attractive alternative, given their wider availability, simplicity and better tolerance. The transit tests that are available in clinical practice are breath tests, scintigraphy and the wireless motility capsule.
Breath tests These tests make use of the metabolism of an ingested substrate by intestinal bacteria, that in turn results in release of gases (such as hydrogen, methane) which are absorbed from the intestinal lumen into the systemic circulation, allowing for measurement of the concentration of the gas in the breath. They are used in the clinical evaluation of carbohydrate malabsorption, small intestinal bacterial overgrowth and orocecal transit time (OCTT). Method: For breath test methodology please refer to Chapter 25 “Investigations for dietary carbohydrate malabsorption and gut microbiota.” Strength and limitations: Breath tests are safe, simple to perform, well tolerated and inexpensive, relative to alternative tests. However, they have quite a few limitations; the normal range is wide and reproducibility is poor [24], and lactulose can accelerate OCTT [25]. The test measures gastric and small bowel transit, and results in patients with delayed gastric emptying may not accurately reflect OCTT. Importantly, intestinal dysmotility causing intestinal stasis can be associated with small intestinal bacterial overgrowth, and an early hydrogen peak can preclude assessment of orocecal transit time. As a consequence of these limitations, a recent consensus statement recommended that breath testing should not be used to assess OCTT [26].
Scintigraphy This method is more reliable than breath test since it has less confounding issues. It is usually performed when assessment of whole gut transit is required. Following ingestion of liquid (water) or solid (meal or resin beads) labeled with radioisotope (111In or 99mTc), sequential scans are obtained for several hours. Regions of interest are constructed over the stomach and ascending colon. Transit time in the small bowel is calculated as a percentage of isotope (10, or 50%) arriving in the colon at a set time, usually 6 h, after correction for gastric emptying [27]. Delayed SBTT has variably been defined as colonic filling of <11% or <40% at 6 h, with substantial inter-(30%) and intra-subject (19%) variability [28]. Strengths and limitations: The test is well tolerated; utilizing existing technology performed under physiologic conditions and provides quantitative results. However, the normal range is wide; hence only extreme results are of diagnostic value. The test is costly, particularly given the need for prolonged scanning time required for data acquisition, and involves radiation exposure. As a result, scintigraphy has a very limited availability in clinical practice.
Wireless motility capsule (WMC) The WMC is a small (11.7 mm × 26.8 mm), non-digestible capsule that incorporates pH, pressure and temperature sensors. It records these values as it travels the length of the gut, and transmits the data to an outside recorder worn by the patient. The data receiver is returned after 3–5 days for data analysis. Thus, both regional transit time (stomach, small bowel or colon) and whole gut transit time can be obtained in ambulatory setting, with recording of meals, sleep and other events. Method: The WMC is swallowed right after a standard meal consisting of a bar of 255 kcal, and 50 mL of water. Medications that can reduce gastric acid secretion and affect gastric pH, such as proton pump inhibitors or histamine receptor antagonists need to be discontinued prior to the test. Likewise, medications that affect gut motility (as described in
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FIG. 11 A record of a whole gut transit of a wireless motility capsule in a healthy person. Time on the X axis, pH in white and pressure in red on the Y axis. Gastric emptying is indicated by a sharp rise in pH as the capsule passes into the alkaline environment of the duodenum. Passage into the cecum is indicated by a drop in pH. The drop in temperature (blue line) at the end of the study indicates the exit of the WMC. GET, gastric emptying time; SBTT, small bowel transit time; CBTT, colonic transit time. (From Rao SSC, Kuo B, McCallum RW, Chey WD, Dibaise JK, Hasler B, Koch KL, Lackner JM, Miller C, Saad R, Semler JR, Sitrin MD, Wilding GE, Parkman HP. Investigation of colonic and whole-gut transit with wireless motility. Capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol 2009;7:537–44.)
“Small bowel manometry” section under “Assessment of small bowel contractile activity” section) should be discontinued as well. Subjects are asked to remain fasted for 6 h, to allow for assessment of gastric emptying. Segmental transit time is determined by changes in pH profile along the gut. Gastric emptying time is defined as the time from ingestion of the WMC to an abrupt rise in pH of 2 or more units, signifying the passage of the capsule from the acidic environment of the stomach to the more alkaline one in the duodenum. Passage from the small bowel to the cecum is defined as a pH drop of >1 unit, sustained for >10 min, occurring ≥30 min after gastric emptying [29]. The time difference between gastric emptying and arrival to the cecum represents SBTT (Fig. 11). Normative data reported a median SBTT in health of 4.6 h (4.0–5.9 h, IQR) [30]. Clinical utility of WMC: Studies with WMC have shown that assessment of symptomatic patients can detect transit abnormalities in more than one segment [31], and when the test was performed in the evaluation of patients with suspected gastro paresis it detected extra-gastric transit delays in more than 40% of subjects [32]. The added data provided by the WMC was reported to influence patient management [33]. The test has a number of advantages over existing transit tests; it is non-invasive, well tolerated, and safe and provides information on transit in other segments of the gut. However, in patients with reduced gastric acidity or achlorhydria it might be difficult to assess gastric emptying. There are limited validation data in the small bowel compared to other gut segments. Passage of the capsule from ileum to cecum, based on a drop in pH, could not be clearly identified in >10% of healthy individuals, and the agreement between automated software analysis and manual reading was much lower for small bowel transit time compared to other segments or whole-gut transit time. Table 2 provides the strengths and limitations of the tests discussed above.
TABLE 2 Pros and cons of tests for the assessment of small bowel transit. Factor
Breath tests
Scintigraphy
Wireless motility capsule
Validated
++
++
+
Provides accurate and quantitative results
++
++
+++
Availability
++
+
+
Test performance and need
++
++
++
For specialized personnel patient inconvenience
++
++
++
Patient tolerance
++
+++
+++
Radiation exposure
−
++
− or +a
Expense
+
++
++
a
Depends on whether capsule retention is suspected.
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Conclusions Tests of small bowel motility are helpful in detecting neuromuscular dysfunction of the small bowel. Intraluminal recording remains the gold standard for detecting abnormal contractile patterns particularly myopathy and neuropathy. Transit studies, by virtue of their non-invasive nature and greater availability in clinical practice, can serve as a surrogate test for intestinal dysmotility. The wireless motility capsule offers simplicity, ambulatory recording and the assessment of segmental transit. Newer methods offer a promise for better understanding of small bowel motor physiology and pathophysiology.
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Comparative quantitative assessment of global small bowel motility using magnetic resonance imaging in chronic intestinal pseudo-obstruction and healthy controls. Neurogastroenterol Motil 2016;28(3):376–83. [24] Gasbarrini A, Corazza GR, Gasbarrini G, Montalto M, Di Stefano M, Basilisco G, Parodi A, Usai-Satta P, Vernia P, Anania C, Astegiano M, Barbara G, Benini L, Bonazzi P, Capurso G, Certo M, Colecchia A, Cuoco L, Di Sario A, Festi D, Lauritano C, Miceli E, Nardone G, Perri F, Portincasa P, Risicato R, Sorge M, Tursi A. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment Pharmacol Ther 2009;29(Suppl 1):1–49.
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[25] Miller MA, Parkman HP, Urbain JL, Brown KL, Donahue DJ, Knight LC, Maurer AH, Fisher RS, et al. Comparison of scintigraphy and lactulose breath hydrogen test for assessment of orocecal transit: lactulose accelerates small bowel transit. Dig Dis Sci 1997;42:10–8. [26] Rezaie A, Buresi M, Lembo A, Lin H, McCallum R, Rao S, Schmulson M, Valdovinos M, Zakko S, Pimentel M. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American Consensus. Am J Gastroenterol 2017;112:775–84. A detailed, up to date assessment of the indications, preparation, performance and, interpretation of results on breath tests. [27] Maurer AH, Krevsky B. Whole-gut transit scintigraphy in the evaluation of small-bowel and colonic transit disorders. Semin Nucl Med 1995;25:326–38. [28] Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, Scott MS, Simren M, Soffer E, Szarka L. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil 2011;23(1):8–23. A detailed assessment of the various methods of assessing segmental gut transit. [29] Rao SSC, Kuo B, McCallum RW, Chey WD, Dibaise JK, Hasler B, Koch KL, Lackner JM, Miller C, Saad R, Semler JR, Sitrin MD, Wilding GE, Parkman HP. Investigation of colonic and whole-gut transit with wireless motility. Capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol 2009;7:537–44. [30] Sarosiek I, Sarosiek J, Rao S, et al. Comparisons of alimentary tract transit times among normal subjects from two multicentre trials using SmartPill wireless pH/pressure recording capsule: its clinical implications. Am J Gastroenterol 2007;102(Suppl 2):S170. [31] Kuo B, Maneerattanasporn M, Lee AA, et al. Generalized transit delay on wireless motility capsule testing in patients with clinical suspicion of gastroparesis, small intestinal dysmotility, or slow transit constipation. Dig Dis Sci 2011;56:2928–38. [32] Hasler WL, May KP, Wilson LA, Van Natta M, Parkman HP, Pasricha PJ, Koch KL, Abell TL, McCallum RW, Nguyen LA, Snape WJ, Sarosiek I, Clarke JO, Farrugia G, Calles-Escandon J, Grover M, Tonascia J, Lee LA, Miriel L, Hamilton FA. Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis. Neurogastroentrol Motil 2018;30(2):13196. [33] Rao SS, Mysore KR, Attaluri A, Valestin J. Diagnostic utility of wireless motility capsule in gastrointestinal dysmotility. J Clin Gastroenterol 2011;45:684–90.
Further reading [34] Wang YT, Mohammed SD, Farmer AD, Wang D, Zarate N, Hobson AR, Hellström PM, Semler JR, Kuo B, Rao SS, Hasler WL, Camilleri M, Scott SM. Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol. Aliment Pharmacol Ther 2015;42:761–72. Assessment of the effect of testing protocol, gender and age on regional GI transit times in a large group of healthy subjects.
Investigation of small bowel motility Edy E. Soffer Keck School of Medicine at The University of Southern California, Los Angeles, CA, United States
Key Points ● ● ● ●
Normal small bowel motility depends on the integrity of the neuromuscular apparatus of the bowel. Abnormal motility results from neuropathic or myopathic changes, or both. Intestinal manometry is the gold standard for assessing small bowel contractile patterns, but has limited availability. Transit tests serve as a surrogate measure of small bowel motility, are non-invasive, and are more widely available.
Introduction Normal small bowel motility is critical for ensuring the proper function of digestion and absorption of nutrients. Chyme entering the small bowel is propelled by peristaltic activity that allows adequate mixing with bile and enzymes, as well as contact time with small bowel mucosa. Between meals, the small bowel has a stereotypic cyclical motor pattern called the migrating motor complex (MMC) that facilitates the emptying of small bowel residue and helps prevent intestinal bacterial overgrowth. The organization and propagation of small bowel contractions is controlled primarily by the enteric nervous system and modulated by the autonomic nervous system, while the strength of contractions is dependent on the integrity of intestinal smooth muscle. Neuromuscular dysfunction can involve primarily the small bowel, as in primary visceral myopathy, or secondary to a systemic disease such as scleroderma. Neuromuscular dysfunction impairs small bowel transit and as a result the normal process of digestion and absorption. This results in a variety of symptoms such as abdominal pain, nausea, vomiting, bloating, diarrhea or constipation or weight loss. When small bowel motility is severely impaired, patients may present with a picture of intestinal pseudo-obstruction, with intestinal dilation but without a mechanical obstruction. However, this clinical presentation is rare, and most patients with dysmotility present with the symptoms described above, without obvious evidence of radiologic abnormalities [1]. It is in this clinical scenario of unexplained symptoms, and particularly in the absence of motor impairment of other segments of the gut, that tests of small bowel motility are performed to assess phasic events and contractile patterns, or small bowel transit.
Assessment of small bowel contractile activity Small bowel manometry Small bowel manometry detects intestinal phasic pressure events and their temporal and spatial relationships, and is the standard for recognizing intestinal motor patterns in health and disease. Current techniques in clinical use consist of stationary or ambulatory recording, using intraluminal perfused tubes or probes incorporating solid state pressure transducers. Daytime recording, during fasting and after the administration of a meal, and nighttime recording, provide data on patterns of motor activity of the small bowel that serve as an index of the integrity of the enteric neuromuscular apparatus. Indications: The main purpose of performing the test is to determine if abnormalities of enteric neuromuscular function are responsible for unexplained GI symptoms, when structural abnormalities have been excluded and known causes of dysmotility are not present. In the pediatric population, results of manometry have been proposed to predict the readiness for feeding in neonates [2], tolerance to jejunal feeding [3], response to prokinetic agents [4] and clinical outcome in children with pseudo-obstruction [5]. A normal manometry helps to exclude a neuromuscular disorder in children with suspected chronic intestinal pseudo-obstruction [6]. In adults, the primary indication is the evaluation of nausea and vomiting, and symptoms suggestive of dysmotility when clinical assessment and imaging study do not provide a clear diagnosis [7]. Clinical and Basic Neurogastroenterology and Motility. https://doi.org/10.1016/B978-0-12-813037-7.00021-2 © 2020 Elsevier Inc. All rights reserved.
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TABLE 1 Indications for gastroduodenojejunal manometry. 1. Clarify the diagnosis in patients with unexplained nausea, vomiting or symptoms suggestive of upper GI dysmotility 2. Confirm diagnosis in suspected chronic intestinal pseudo-obstruction syndromes when the diagnosis is unclear from clinical or radiological evaluations 3. Identify generalized dysmotility in patients with colonic dysmotility (e.g., chronic constipation), particularly prior to subtotal colectomy 4. Differentiate between neuropathic vs. myopathic gastric or small bowel dysfunction 5. Assess for possible mechanical obstruction when clinical features suggest, but radiological studies do not reveal, obstruction 6. Determine which organs need to be transplanted (isolated vs. multi-visceral transplantation) in patients with chronic intestinal pseudoobstruction being considered for intestinal transplantation
Manometry is used to determine whether generalized dysmotility exists in a patient with defined localized dysmotility (e.g., slow transit constipation), in particular, if surgery is being considered, since patients with evidence of generalized dysmotility do not respond as well to colectomy [8]. Manometry can suggest the presence of mechanical obstruction in patients with unexplained abdominal pain [9]. Finally, an unequivocally normal manometric study is perhaps the most clinically useful, investigation as it will exclude neuromuscular malfunction, and determine that the enteric nerves and muscles are functioning normally [7]. A list of indications is outlined in Table 1 [10]. Equipment: Recording is done by stationary (the most common method used in clinical practice) or ambulatory systems. Stationary systems make use of either a perfused system or a solid state assembly, connected to a stationary recording device. In perfused systems, the catheter assembly incorporates several lumens with side openings at desired levels (Fig. 1) [11]. Ambulatory recording requires a catheter that incorporates miniature strain-gauge transducers, connected to a portable solid-state recording device. Although a minimum of two sensors is recommended for the detection of motility patterns and their propagation [7], perfused systems can easily accommodate multiple sites, and the new high resolution catheters incorporate a large number of sensors that are closely spaced (Fig. 1B) [11]. Catheters are introduced trans-nasally, guided by fluoroscopy or endoscopy, after an overnight fast. Intubation assisted by endoscopy requires sedation provided by short acting agents, such as midazolam or propofol. A minimum interval of 1 h between intubation and the start of data acquisition is recommended.
FIG. 1 (A) Water-perfused manometry catheters like the one pictured are a bundle of thin polyvinyl tubes, with an outward facing opening (side hole) in each tube. The side holes function as point pressure sensors. They are typically configured at 3–5 cm intervals along the catheter. A low-compliance, pneumohydraulic pump slowly perfuses each of the tubes, and the pressure in each is converted to an electrical signal by a volume–displacement transducer. Pressure recorded by the system increases when water flowing through the side hole is impeded by radial contraction of the gut wall at the side hole. Information about gastrointestinal motor function may be lost with this technique because the side holes are widely spaced and sense in only one direction around the catheter circumference. (B) High-resolution manometry catheter pictured here is 4.2 mm in diameter and consists of 36 circumferential, solidstate, pressure sensors (copper colored bands, arrowhead). Sensors are spaced at 1-cm intervals, from center to center. This gives the catheter a recording segment of 35 cm. Each individual sensor (magnified at center) detects pressure from 12 loci (arrow) around its circumference. Computer processing of the signals coming from pressure sensing elements allows average circumferential pressures over the entire 35-cm recording segment to be displayed in real time and recorded for subsequent analysis. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
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Conduct of the study: Regardless of the system used, studies are performed after an overnight fast (including tube feeding). Medications that can affect GI motility (narcotics, anticholinergics, calcium channel blockers, erythromycin, and motility modulating drugs such as metoclopramide or domperidone) should be avoided for at least 48 h prior to the test. It is recommended that patients with diabetes mellitus should take 50% of their usual morning dose of insulin; blood glucose should be monitored during the study and insulin or glucose administered to maintain the blood sugar in a reasonable range [7]. Recording confined to daytime should start with a fasting period, to capture the MMC. The duration of recording during fasting varies among laboratories, ranging from 3 to 6 h. Fasting is followed by meal administration and further recording, for at least 2 h, in the postprandial state [7]. While average MMC cycle length is <2 h, the range is wide, from 0 to 6 in the course of 6 h of fasting, with at least one phase III in 6 h of recording in healthy subjects [12]. Ambulatory recording provides the most information about the MMC, because of the high likelihood of observing one during sleep [12]. However, extended recording during fasting to 6 h, followed by postprandial recording, provides comparable accuracy to ambulatory recording in most subjects, since a longer period of recording is unlikely to miss a phase III, in spite of the normal variability in MMC frequency [13].
Normal patterns of small bowel motility Fasting period: This period is characterized by a cyclical pattern of stereotypical motor activity termed the migrating motor complex cycle (MMC), composed of three phases. The most recognizable one is phase III, a burst of regular phasic pressure events occurring at a rate of 10–12 per min in the proximal small bowel that migrates aborally in health (Fig. 2). Duration varies but should be at least 2 min, and does not exceed 30 min [12]. The length of migration varies greatly, depending in part on the distance occupied by the sensors. Phase II precedes phase III and is the longest component of the cycle, characterized by irregular phasic activity. Phase I is a period of quiescence that follows phase III, that may or may not be present during the daytime, but should be present during sleep, in which case it normally may account for most of the cycle duration (Fig. 3). High resolution manometry has been extensively used in the study of esophageal motility in health and disease, and has greatly improved our understanding of esophageal physiology and pathology. Figs. 4–6 show a high resolution manometry recording of the gastroduodenal region. As in the esophagus, the pressure topography plots provide a much better appreciation of propagation pattern of individual phasic events and intuitive pattern recognition, as compared to the traditional line mode. However, catheters are expensive, drift hampers long recording in some systems, and while it has a promising potential for better understanding of small bowel motor physiology, it remains to be seen if the use of this technology in clinical practice would provide a higher diagnostic yield. A newer method, using fiber optics for high resolution recording, may provide further versatility [14].
FIG. 2 The pattern of small bowel motility during fasting in health. Tracing was obtained during an ambulatory recording. The five sensors are spaced 15 cm apart, two are placed in the duodenum (D), and three in the Jejunum (J). The tracing shows intermittent activity during phase II, the migrating band of contractions during phase III, followed by a short period of motor quiescence, termed phase I. During the day, phase I may be absent with intermittent activity starting right after the end of phase III.
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Duodenum
50 mm Hg Jejunum I
10 min
Jejunum II
FIG. 3 The migrating motor complex during sleep. Ambulatory recording during sleep from a healthy subject. The three sensors in the duodenum (D) or jejunum (J) are spaced 15 cm apart. Frequent phase IIIs are observed with hardly any activity during phase II. In comparison with the fasting during awake, the MMC during sleep is characterized by more frequent phase IIIs, shorter phase II and longer phase I. Sometimes phase II is absent altogether.
FIG. 4 High-resolution antroduodenal manometry. This is a fluoroscopic image showing placement of the high resolution manometry catheter for antroduodenal manometry. The dark rectangles are individual pressure sensors. The recording segment of the catheter is composed of 36 closely spaced, circumferential, pressure sensors spaced at a distance of 1 cm from center to center, providing a sensing length of 35 cm. It spans from the stomach to the level of the ligament of Treitz. Because a number of closely spaced sensors straddle the pylorus, appreciation of this transition zone (arrowhead) does not require special devices (such as a sleeve). Similarly, movement of the catheter does not affect recording from the antrum, which can happen, for example, after a meal. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
The fed pattern: The normal response to food ingestion is characterized by an irregular contractile activity, at a higher frequency than in the preceding fasting recording (excluding phase III), without return of MMC for at least 2 h after consumption of a 400-kcal meal [15], (Fig. 7).
Abnormal patterns of small bowel motility Patterns associated with neuropathic disorders: These recordings are characterized by an abnormal propagation of the MMC, failure of conversion to fed pattern or increased uncoordinated phasic contractile activity [16]. Figs. 8–10 show examples of such patterns, obtained from patients with unexplained gastrointestinal symptoms.
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FIG. 5 Phase III of the migrating motor complex (MMC) in the antrum and duodenum. (A) An antroduodenal manometry displayed in line mode was recorded from the catheter positioned in Fig. 4. It demonstrates a phase III of the MMC. Pressures are displayed from sensors spaced at 5-cm intervals to approximate the look of a conventional antroduodenal manometry. The top three channels display antral motor activity: high-amplitude peristaltic contractions at 3 cycles per min (cpm). The bottom three channels display duodenal motor activity: peristaltic contractions at 12 cpm. It is relatively easy to appreciate the direction the phase III complex and gastric pressure waves propagate, but very difficult to evaluate propagation of duodenal pressure waves. (B) The high- resolution manometry (HRM) color contour of the same data. The location of the pylorus, as estimated from the fluoroscopic image, is in the neighborhood of sensors 16 and 17. The HRM contour provides a more detailed depiction of antroduodenal motor function. The propagation of individual contractions can be discerned, even in this condensed tracing. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
FIG. 6 Duodenal phase III in a healthy subject. (A) This antroduodenal manometry is displayed in line mode to simulate a traditional tracing of phase III in the duodenum. The propagation pattern of contractile sequences is difficult to reliably determine. (B) The HRM color contour of the same tracing makes it easy to discern the complex pattern of propagation. Very low amplitude pressure waves are seen in the stomach (arrowhead). There are two pacemaker foci in the duodenum (*) from which pressure waves propagate antegrade and retrograde (arrows). Also notice that individual duodenal pressure waves propagate at varying velocities over different duodenal segments. (From Conklin C, Pimentel M, Soffer E. Color atlas of high resolution manometry. New York: Springer Science, NYC; 2009, with permission.)
Patterns associated with myopathic disorders: Are characterized by low amplitude contractions, of <20 mm Hg, in a non-dilated bowel [10]. Given the control mechanisms of small bowel motor function, it is intuitive that manometric abnormalities presenting with abnormal pattern of contractions are caused by neuropathic disorders, while the myopathic pattern is caused by intestinal myopathy. However, recent studies matching intestinal manometry with intestinal histopathology specimens show an overlap between the two diagnostic tests [17, 18]. Rather, the terms reflect the presence of such patterns in disease entities associated with neuropathy or myopathy, such as diabetes or scleroderma.
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FIG. 7 The postprandial period. Increased motor activity in the duodenum and jejunum following a 400 kcal meal. It may take 10–20 min for increased activity to occur. Ambulatory recording in a healthy subject. Sensors configuration same as in Fig. 2.
FIG. 8 Abnormal migration of phase III from duodenum to jejunum, with skipping of a segment of jejunum. Ambulatory manometry from a patient with severe dyspepetic symptoms. Sensors configuration same as in Fig. 2.
FIG. 9 Repetitive, long bursts of phase III like activity occurring simultaneously at different recording sites. Ambulatory manometry, sensors configuration same as in Fig. 2.
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Duodenum
50 mm Hg Jejunum I
10 min Jejunum II
FIG. 10 Sustained, uncoordinated contractile activity during sleep, in a TPN dependent patient with symptoms of abdominal pain, nausea and vomiting. Similar pattern was observed in the awake state. Ambulatory manometry, sensors spaced 15 cm apart.
Analysis: A qualitative evaluation of the manometry tracing provides most of the information obtained from the study. Here, the recording is inspected both for the presence of the normal motility patterns, as well as the absence of abnormal ones as described above. The quantitative assessment involves measuring the number of MMCs, the amplitude of contractions and the postprandial motility index, evaluated and validated primarily in the antrum. A normal pattern has the following features [10]: 1. At least one migrating motor complex (MMC) per 24 h. 2. Conversion to the fed pattern without return of MMC for at least 2 h after a 400-kcal meal. 3. Antral contractions >40 mm Hg and small intestinal contractions >20 mm Hg. 4. Absence of abnormal patterns as described above. Clinical utility of small bowel manometry: Manometry is useful when the reason for the patient's symptoms is not explained by an existing disease or other, less invasive tests. However, a number of factors impact the clinical usefulness of manometry. The test is time consuming, performed primarily in tertiary referral centers that have the necessary expertise, and performance is not standardized. As with manometric recording from other segments of the GI tract, the range of abnormal patterns is limited, they can be observed in various unrelated conditions, and their presence does not necessarily implicate intestinal dysmotility as the cause of symptoms. Retrospective studies have shown that manometry impacted management in up to a third of patients with suspected dysmotility, regarding decisions concerning choice of prokinetic agents, mode of feeding (enteral vs. parenteral), or colectomy for slow transit constipation [19, 20], though a therapeutic trial can also be helpful in the decision making. An unequivocally normal study is likely the most useful, excluding dysmotility as the cause of symptoms [10].
Wireless motility capsule The capsule has a single pressure sensor as well as pH and temperature sensors, and transmits data wirelessly to an outside data recorder. While it provides data on phasic contractions, its location along the small bowel cannot be determined and the single sensor precludes assessment of the propagation of contractile events and motor patterns. It can detect low amplitude contractions consistent with myopathic pattern. Currently, its main use is in the assessment of small bowel transit.
Use of imaging studies for assessment of small bowel motility Recently, analysis of imaging data has been used to distinguish between normal and abnormal small bowel motility. Endoluminal image analysis: In this method, images obtained from capsule endoscopy are subjected to computer analysis that evaluates features such as luminal occlusion to quantify contractions, pattern of luminal opening and bowel wall and type of luminal contents as observed in healthy subjects [21]. In a study of large number of patients with functional bowel
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disorder, the dynamic function of motor sequences was correlated with luminal closure and transit, using computerized algorithms. The results showed a divergence between patients and healthy controls [22]. The utility of this innovative but complex technology in clinical practice requires further studies. Dynamic magnetic resonance imaging (MRI): This modality consists of taking successive images over a period of time and subjecting the data to automated software programs that provide quantification of segmental or global small bowel motility. Applying this technology in a study of healthy subjects and patients with chronic intestinal pseudo-obstruction (CIPO), researchers showed that patients with CIPO had a decreased global motility of the bowel at rest, and after administration of a prokinetic agent, when compared to control [23].
Small bowel transit studies Normal small bowel motility ensures a normal transit of chyme throughout the small bowel that allows for the vital processes of digestion and absorption of nutrients along the gut. Impaired transit, caused by abnormal patterns of motility, can result in debilitating symptoms and malnutrition. Manometry and the newer tests described in the previous section are limited by a lack of widespread availability or, in the case of manometry, the associated discomfort. Transit tests that can serve as a surrogate to motility tests are an attractive alternative, given their wider availability, simplicity and better tolerance. The transit tests that are available in clinical practice are breath tests, scintigraphy and the wireless motility capsule.
Breath tests These tests make use of the metabolism of an ingested substrate by intestinal bacteria, that in turn results in release of gases (such as hydrogen, methane) which are absorbed from the intestinal lumen into the systemic circulation, allowing for measurement of the concentration of the gas in the breath. They are used in the clinical evaluation of carbohydrate malabsorption, small intestinal bacterial overgrowth and orocecal transit time (OCTT). Method: For breath test methodology please refer to Chapter 25 “Investigations for dietary carbohydrate malabsorption and gut microbiota.” Strength and limitations: Breath tests are safe, simple to perform, well tolerated and inexpensive, relative to alternative tests. However, they have quite a few limitations; the normal range is wide and reproducibility is poor [24], and lactulose can accelerate OCTT [25]. The test measures gastric and small bowel transit, and results in patients with delayed gastric emptying may not accurately reflect OCTT. Importantly, intestinal dysmotility causing intestinal stasis can be associated with small intestinal bacterial overgrowth, and an early hydrogen peak can preclude assessment of orocecal transit time. As a consequence of these limitations, a recent consensus statement recommended that breath testing should not be used to assess OCTT [26].
Scintigraphy This method is more reliable than breath test since it has less confounding issues. It is usually performed when assessment of whole gut transit is required. Following ingestion of liquid (water) or solid (meal or resin beads) labeled with radioisotope (111In or 99mTc), sequential scans are obtained for several hours. Regions of interest are constructed over the stomach and ascending colon. Transit time in the small bowel is calculated as a percentage of isotope (10, or 50%) arriving in the colon at a set time, usually 6 h, after correction for gastric emptying [27]. Delayed SBTT has variably been defined as colonic filling of <11% or <40% at 6 h, with substantial inter-(30%) and intra-subject (19%) variability [28]. Strengths and limitations: The test is well tolerated; utilizing existing technology performed under physiologic conditions and provides quantitative results. However, the normal range is wide; hence only extreme results are of diagnostic value. The test is costly, particularly given the need for prolonged scanning time required for data acquisition, and involves radiation exposure. As a result, scintigraphy has a very limited availability in clinical practice.
Wireless motility capsule (WMC) The WMC is a small (11.7 mm × 26.8 mm), non-digestible capsule that incorporates pH, pressure and temperature sensors. It records these values as it travels the length of the gut, and transmits the data to an outside recorder worn by the patient. The data receiver is returned after 3–5 days for data analysis. Thus, both regional transit time (stomach, small bowel or colon) and whole gut transit time can be obtained in ambulatory setting, with recording of meals, sleep and other events. Method: The WMC is swallowed right after a standard meal consisting of a bar of 255 kcal, and 50 mL of water. Medications that can reduce gastric acid secretion and affect gastric pH, such as proton pump inhibitors or histamine receptor antagonists need to be discontinued prior to the test. Likewise, medications that affect gut motility (as described in
Investigation of small bowel motility Chapter | 21 315
FIG. 11 A record of a whole gut transit of a wireless motility capsule in a healthy person. Time on the X axis, pH in white and pressure in red on the Y axis. Gastric emptying is indicated by a sharp rise in pH as the capsule passes into the alkaline environment of the duodenum. Passage into the cecum is indicated by a drop in pH. The drop in temperature (blue line) at the end of the study indicates the exit of the WMC. GET, gastric emptying time; SBTT, small bowel transit time; CBTT, colonic transit time. (From Rao SSC, Kuo B, McCallum RW, Chey WD, Dibaise JK, Hasler B, Koch KL, Lackner JM, Miller C, Saad R, Semler JR, Sitrin MD, Wilding GE, Parkman HP. Investigation of colonic and whole-gut transit with wireless motility. Capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol 2009;7:537–44.)
“Small bowel manometry” section under “Assessment of small bowel contractile activity” section) should be discontinued as well. Subjects are asked to remain fasted for 6 h, to allow for assessment of gastric emptying. Segmental transit time is determined by changes in pH profile along the gut. Gastric emptying time is defined as the time from ingestion of the WMC to an abrupt rise in pH of 2 or more units, signifying the passage of the capsule from the acidic environment of the stomach to the more alkaline one in the duodenum. Passage from the small bowel to the cecum is defined as a pH drop of >1 unit, sustained for >10 min, occurring ≥30 min after gastric emptying [29]. The time difference between gastric emptying and arrival to the cecum represents SBTT (Fig. 11). Normative data reported a median SBTT in health of 4.6 h (4.0–5.9 h, IQR) [30]. Clinical utility of WMC: Studies with WMC have shown that assessment of symptomatic patients can detect transit abnormalities in more than one segment [31], and when the test was performed in the evaluation of patients with suspected gastro paresis it detected extra-gastric transit delays in more than 40% of subjects [32]. The added data provided by the WMC was reported to influence patient management [33]. The test has a number of advantages over existing transit tests; it is non-invasive, well tolerated, and safe and provides information on transit in other segments of the gut. However, in patients with reduced gastric acidity or achlorhydria it might be difficult to assess gastric emptying. There are limited validation data in the small bowel compared to other gut segments. Passage of the capsule from ileum to cecum, based on a drop in pH, could not be clearly identified in >10% of healthy individuals, and the agreement between automated software analysis and manual reading was much lower for small bowel transit time compared to other segments or whole-gut transit time. Table 2 provides the strengths and limitations of the tests discussed above.
TABLE 2 Pros and cons of tests for the assessment of small bowel transit. Factor
Breath tests
Scintigraphy
Wireless motility capsule
Validated
++
++
+
Provides accurate and quantitative results
++
++
+++
Availability
++
+
+
Test performance and need
++
++
++
For specialized personnel patient inconvenience
++
++
++
Patient tolerance
++
+++
+++
Radiation exposure
−
++
− or +a
Expense
+
++
++
a
Depends on whether capsule retention is suspected.
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Conclusions Tests of small bowel motility are helpful in detecting neuromuscular dysfunction of the small bowel. Intraluminal recording remains the gold standard for detecting abnormal contractile patterns particularly myopathy and neuropathy. Transit studies, by virtue of their non-invasive nature and greater availability in clinical practice, can serve as a surrogate test for intestinal dysmotility. The wireless motility capsule offers simplicity, ambulatory recording and the assessment of segmental transit. Newer methods offer a promise for better understanding of small bowel motor physiology and pathophysiology.
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[25] Miller MA, Parkman HP, Urbain JL, Brown KL, Donahue DJ, Knight LC, Maurer AH, Fisher RS, et al. Comparison of scintigraphy and lactulose breath hydrogen test for assessment of orocecal transit: lactulose accelerates small bowel transit. Dig Dis Sci 1997;42:10–8. [26] Rezaie A, Buresi M, Lembo A, Lin H, McCallum R, Rao S, Schmulson M, Valdovinos M, Zakko S, Pimentel M. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American Consensus. Am J Gastroenterol 2017;112:775–84. A detailed, up to date assessment of the indications, preparation, performance and, interpretation of results on breath tests. [27] Maurer AH, Krevsky B. Whole-gut transit scintigraphy in the evaluation of small-bowel and colonic transit disorders. Semin Nucl Med 1995;25:326–38. [28] Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, Scott MS, Simren M, Soffer E, Szarka L. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil 2011;23(1):8–23. A detailed assessment of the various methods of assessing segmental gut transit. [29] Rao SSC, Kuo B, McCallum RW, Chey WD, Dibaise JK, Hasler B, Koch KL, Lackner JM, Miller C, Saad R, Semler JR, Sitrin MD, Wilding GE, Parkman HP. Investigation of colonic and whole-gut transit with wireless motility. Capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol 2009;7:537–44. [30] Sarosiek I, Sarosiek J, Rao S, et al. Comparisons of alimentary tract transit times among normal subjects from two multicentre trials using SmartPill wireless pH/pressure recording capsule: its clinical implications. Am J Gastroenterol 2007;102(Suppl 2):S170. [31] Kuo B, Maneerattanasporn M, Lee AA, et al. Generalized transit delay on wireless motility capsule testing in patients with clinical suspicion of gastroparesis, small intestinal dysmotility, or slow transit constipation. Dig Dis Sci 2011;56:2928–38. [32] Hasler WL, May KP, Wilson LA, Van Natta M, Parkman HP, Pasricha PJ, Koch KL, Abell TL, McCallum RW, Nguyen LA, Snape WJ, Sarosiek I, Clarke JO, Farrugia G, Calles-Escandon J, Grover M, Tonascia J, Lee LA, Miriel L, Hamilton FA. Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis. Neurogastroentrol Motil 2018;30(2):13196. [33] Rao SS, Mysore KR, Attaluri A, Valestin J. Diagnostic utility of wireless motility capsule in gastrointestinal dysmotility. J Clin Gastroenterol 2011;45:684–90.
Further reading [34] Wang YT, Mohammed SD, Farmer AD, Wang D, Zarate N, Hobson AR, Hellström PM, Semler JR, Kuo B, Rao SS, Hasler WL, Camilleri M, Scott SM. Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol. Aliment Pharmacol Ther 2015;42:761–72. Assessment of the effect of testing protocol, gender and age on regional GI transit times in a large group of healthy subjects.