Examples of conventional (a) and spatiotemporal plot (b) of normal migrating motor complex (MMC) recorded in a child with recurrent vomiting. All three phases (phase I, phase II, and phase III) are well represented. Phase III is seen starting in the duodenum and migrating aborally toward the proximal jejunum. A period of quiescence (phase I) follows phase III; the latter is preceded by intermittent phasic activity (phase II). Phase III is readily recognized by using spatiotemporal plots. The recording has been performed with a 20-channel manometric catheter (side holes 2.5 cm apart)
Following the ingestion of food, the MMC cycle is interrupted and replaced by a pattern of regular antral contractions associated with apparently uncoordinated contractions of variable amplitude in the small intestine, termed “postprandial” or “fed” pattern (Fig. 8.2) [5, 16, 24]. These phasic contractions also show variable frequency and propagation. Typical postprandial contractions usually propagate over a shorter distance than those of phase III, and almost 80 % of them propagate less than 2 cm . This minute movement of postprandial contractions is devoted to mixing and grinding of the nutrient chyme, stirring, spreading and exposing the intestinal contents to a larger surface, and thus promoting its optimal absorption. Moreover, minute aboral transport is also sufficient in preventing bacterial colonization. Thus, normal postprandial motor activity is a compromise between optimal absorption and adequate clearance. The postprandial period lasts from the time of the evident increase in frequency and/or amplitude of contractions occurring after the introduction of a meal to the onset of the following phase III and is affected by the amount of calories as well as by the composition of the meal . For instance, fats induce a more prolonged fed pattern than protein and carbohydrates. Extrinsic neural control is a prerequisite for a normal postprandial pattern, since persisting MMC activity after meal intake has been reported after vagal cooling [26, 27]. Neural reflex, endocrine, and paracrine mechanisms also play a key role . In small infants aged less than 32 weeks post-conceptional age, who usually receive only small volumes of enteral feeding, the fasting pattern is not disrupted by either the bolus or continuous feeding. Between 31 and 35 weeks post-conceptional age, the larger volumes of enteral feeding induce a degree of postprandial activity, but it is only over 35 weeks post-conceptional age that a disruption of cyclical activity can be seen with feeds .
Examples of spatiotemporal plot of normal postprandial activity characterized by irregular but persistent phasic activity. Temporal and pressure resolution easily recognize the increase in motility index. The recording has been performed with a 20-channel manometric catheter (side holes 2.5 cm apart)
The presence of other distinct motility patterns has been identified in both healthy individual and patients. Discrete clustered contractions (DCCs ) or cluster of contractions (CCs) are defined as the presence of 3–10 pressure waves of slow frequency, each having a significantly higher amplitude and duration compared to isolated individual contractions [15, 28]. They propagate aborally for less than 30 cm at rate of 1–2 cm s−1 and usually show a rhythmic pattern with regular intervals of quiescence lasting at least 30 s (Fig. 8.3) . DCC are usually recorded during phase II, although they are occasionally seen during the postprandial period (phase III-like activity) [3, 14, 28, 29]. Postprandially, clusters of contractions seem to occur in association with mechanical obstruction or intestinal pseudo-obstruction, and they are characteristically nonpropagated . Bursts of contractions are defined as sequences of intense irregular pressure waves, which do not correspond to the definition for phase III or for DCC. They can be clearly distinguished from background pressure wave activity during both phase II and the postprandial period. Short bursts of propagating contractions have been described in healthy individuals, whereas sustained bursts of contractions confined to one limited segment (nonpropagated) lasting for a period of >30 min and associated with tonic intermittent baseline pressure elevation are considered an abnormal neuropathic pattern [21, 31, 32]. Giant migrating contractions or prolonged intestinal contractions are pressure waves of prolonged duration (>20 s) and high amplitude more than 30 mmHg. In healthy individuals, they occur primarily in the distal ileum and propagate uninterruptedly and rapidly with highly propulsive force over long distance in aboral direction in the small intestine and colon [33, 34].
Examples of conventional (a) and spatiotemporal plot (b) of short burst of contractions (arrow) recorded in the duodenum during phase II lasting more than 2 min. They can be clearly distinguished from background pressure wave activity during phase II. The 3rd channel is localized in the antrum. The recording has been performed with a 20-channel manometric catheter (side holes 2.5 cm apart)
Manometry is by nature a highly technical evaluation. When knowledgeably used, manometric examination provides an accurate description of intestinal neuromuscular function, but only if physical principles and equipment characteristics are respected. In general, manometric data are reliable only if the methodology used to acquire them is accurate.
A manometric apparatus setup consists of a pressure sensor and transducer combination that detects the gastric and small intestine pressure complex and transduces it into an electrical signal and a recording device to amplify, record, and store that electrical signal. The pressure sensor/transducer components of a manometric assembly function as a matched pair and are available in two general designs: either water-perfused catheters connected to a pneumohydraulic perfusion pump and to volume displacement transducers or strain gauge transducers with solid-state circuitry .
Low-Compliance Perfused Manometric System
The water infusion system includes a catheter composed of small capillary tubes, a low-compliance hydraulic capillary infusion pump, and external transducers. In adults, the small capillary tubes usually have an internal diameter of approximately 0.4–0.8 mm and an opening or port at a known point along the length of the catheter. In adults, the most commonly used catheters have an overall diameter of 4.5 mm . In children, in order to reduce the diameter of the catheter, smaller capillary tubes (with internal diameters of 0.35 mm) are utilized; moreover the study is performed at lower infusion rates . The manometric probes are usually tailored to the child’s size, and the distance between the recording ports should be decided based on the purpose of the investigation . Since one antral recording site is insufficient to provide an accurate recording of antral motor activity due to its continuous forward and backward movement, the manometric catheter should have at least five recording ports with the two most proximal side holes spaced 0.5–1.5 cm apart positioned 1 cm proximal to the pylorus to provide measurements of antral activity, while the remaining side holes are positioned in the small intestine and spaced 2.5–5 cm apart in infants and toddlers and 5–10 cm apart in children and adolescents [35, 36]. Each capillary tube is connected to an external transducer. The infusion pump, a simple and essential device for stationary manometry, perfuses the capillary tubes, providing a constant flow rate without increasing the compliance of the manometric system. When a catheter port is occluded (e.g., by a muscular contraction), there is a pressure rise in the water-filled tubes that is transmitted to the external transducers. High-fidelity recordings of intraluminal pressure are achieved by infusion rates from 0.1 to 0.4 mL min−1, even if they may provide an unacceptable amount of water to small babies or premature infants. In order to overcome this problem, perfusion rates as low as 0.02 mL min−1 have been successfully used . Furthermore, for prolonged studies, the use of a balanced saline solution should be considered.
A device activating the pressure transducers, storing their signals, and displaying the latter in such a way to allow immediate interpretation and analysis is needed. The personal computer has become the heart of any manometry system. It interfaces with purpose-designed electronic modules that activate and receive signals from pressure transducers, while commercially available software programs are essential for acquiring, displaying, and storing pressure recording data. Actually, the technical adequacy of different commercially available device recording systems is quite comparable. Probably the dominant consideration that should determine the choice of a system is the level of technical assistance and the training available locally to support the user.
The required characteristics of the manometric recording apparatus are defined by the magnitude of the pressure to be recorded and the frequency content and waveform of foregut contractile waves. It has been shown that the frequency response of manometric systems required to reproduce foregut pressure waves with 98 % accuracy is of 0–4 Hz (maximal recordable dP/dt: 300 mmHg/s). Most of commercially available manometric systems can provide a pressure rise rate of 300–400 mmHg/s, which is adequate for faithful recordings in the gastric antrum and small intestine.
Solid-State Manometric System
The main alternative to the water-perfused manometric system is a manometric assembly incorporating strain gauge sensors and solid-state electronic elements . In this system, the manometric probe contains miniature strain gauge pressure transducers built into the catheter at a fixed location along its length, so that pressure changes directly influence the transducers to generate electrical output signals. The probe can be plugged into a small box containing the electronics, which is then connected to the recording device and to a personal computer. In the ambulatory system, the recording devices are blind and need to be connected to a personal computer with the appropriate software to display and analyze the recording. The main advantage of using solid-state catheters is that the pressures are recorded directly from the area and are unrelated to the relative position of the subject; therefore, manometric studies may also be performed with the subjects in the upright position. This, and the fact that it does not require water perfusion, makes solid-state catheters suitable for long-term ambulatory monitoring of the intraluminal pressure . It has been calculated that for a given number of pressure recording points on a recording assembly, solid-state catheters are 20 times more expensive than a perfused manometric assembly. In the last years, the improvement in miniaturizing transducers has allowed the production of solid-state catheter with up to 36 recording channels with an external diameter comparable to that of the water-perfused manometric catheter used in small infants and children. However, there is still a very little experience in pediatric patients.
Manometric techniques have improved in a stepwise fashion from few pressure recording channels to the development of high-resolution manometry (HRM ), which is a relatively recent technique that enables more detailed definition, both in terms of space and time, of pressure profiles along segments of the gut . This has been achieved by a combination of new manometric assemblies, allowing intraluminal pressure to be recorded from up to 72 pressure sensors spaced less than 2 cm. At the same time, advances in computer processing allow pressure data to be presented in real time as a compact, visually intuitive “spatiotemporal plot” of gastric and small intestine pressure activity. HRM recordings may reveal the complex functional anatomy of the foregut, and recent studies suggest that spatiotemporal plots may provide objective measurements of the intraluminal pressure profile in the small intestine and improve the sensitivity and specificity of manometric recording by removing much of the ambiguity usually encountered using line plot analysis . However, further efforts to define the role of HRM in the diagnosis and management of neuromuscular disorders are needed.
Preparation of the Patient
Before starting the ADM manometric recording, it is important to assess patient information with regard to medical history, symptoms, medication, and allergies. Any drug with a known effect on gastrointestinal motility should be discontinued at least 72 h before the study.
It is important to emphasize that ADM manometry in children is performed in a different fashion to that in adults due to differences in size, cooperation, and neurological and developmental maturation. Performing manometric studies in children require great patience from the operator. The parents should be present during the testing in order to settle the child and to provide the child with a model of cooperative behavior with the physician. The cooperation can also be improved by the use of age-appropriate relaxation techniques. For example, infants may relax with swaddling and the use of a pacifier. Having a favorite toy can comfort toddlers. School age and older children benefit when equipment is shown and explained prior to the procedure. ADM manometry is best performed without sedation . However, in many children, sedation is necessary, and midazolam has been shown to be effective with no or minimal influence on pressure measurement . It is advisable to wait for complete child recovery from any drug effect before starting the motility tests. Finally, before starting the procedure, it is important to obtain and verify a signed informed consent, and it is also necessary to check that the fasting period has been of adequate duration. In healthy children, an overnight fast is enough, whereas in infants at least 4 h are necessary to eliminate nausea, vomiting, and aspiration. In children on parenteral nutrition, it should be stopped 12 h prior to the study, because of the effect of nutrients on hormones, which may affect the intestinal motility . Similarly, blood glucose levels should be carefully assessed, since hyperglycemia inhibits gastric emptying and reduces the occurrence of phase III [43, 44].
The manometric catheter can be placed either nasally or orally, but there is broad consensus that studies are better tolerated when the catheter is introduced through the nose. The catheter can also be placed through an existing gastrostomy or jejunostomy. The manometric probe should be positioned deep enough in the small intestine in order to prevent its falling back into the stomach as a consequence of postprandial gastric distension or duodenal contraction (Fig. 8.4). The tube placement can be performed either fluoroscopically or endoscopically . Under fluoroscopy, the probe placement usually requires high skill to pass the pyloric region, which may be easier with a firm probe rather than a soft, flexible one. The former, however, is more difficult to advance beyond the duodenal bulb due to its acute angle. Moreover, a hard probe may cause greater discomfort during the recording time especially in young children. The addition of a weighted probe tip may facilitate the placement as it utilizes the advantage of gravity. The probe can be also advanced through the pylorus using an endoscope and biopsy forceps, taking care to use as little air as possible to insufflate the bowel, given that overinflation may affect gastrointestinal motility and provoke a backward movement of the manometric probe. In some centers, the manometric recording is performed the day after the tube placement with additional radiology confirmation to ascertain appropriate catheter position, allowing for correction if necessary.
Fluoroscopic placement of ADM catheter . Note the position of the tip is in the distal duodenum at level of the ligament of Treitz
During the manometric recording using a water-perfused system, the patients usually maintain the same position (supine), whereas when using portable solid-state equipment, the patients are encouraged to perform daily activities when possible . Ambulatory manometry is usually performed for 24 h, whereas for stationary manometry, recording must be carried out until a phase III and/or clear-cut abnormalities are recorded. However, it is generally advisable to perform a fasting recording for at least 6 h (or two MMCs) and postprandial recording for at least 90 min . The type and the size of meal should be adjusted according to patient’s age and preference. In older children, the test meal should be of at least 400 kcal, in order to ensure an adequate postprandial response in the small intestine lasting for at least 90–120 min [25, 36]. In younger children, the test meal should provide at least 10 kcal kg−1. The meal should be balanced with at least 30 % of calories provided as fat content. However, in some cases, it is impossible to provide a predetermined volume to a patient, e.g., one with severe gastrointestinal dysmotility and inability to tolerate oral or enteral feeding. Finally, if no phase III is recorded during fasting, a drug stimulation test should be performed using iv erythromycin (1 mg kg−1 over a period of 30 min), which is able to induce a gastric phase III and allows assessment of its migration in the small intestine [46, 47]. Other agents such as azithromycin, octreotide, amoxicillin/clavulanate, ghrelin, and neostigmine were also found to induce phase III activity; however, there is still a lack of adequate clinical experience in the use of these agents to allow for a general recommendation [48–53].
Analysis of Manometric Recording
Both qualitative and quantitative analysis of the ADM tracings should be performed. Qualitative analysis includes the recognition of specific motor patterns as well as the overall characteristics of the fasting period (typical cyclical pattern of the MMC, characteristics of phase III activity including the total number of phase III occurrences, migration pattern, mean amplitude, mean peak velocity, and intervals) and fed period (presence of change in motility after test meal). Quantitative analysis includes the calculation of distal antral and duodenal motility indices (MI), expressing the contractile activity as the natural logarithm of the area under the manometric pressure peaks above a threshold pressure. Computerized data evaluation, including wave identification algorithms, artifact removal, and algorithms for detection of propagated activity, offers an improved degree of objectivity in the analysis of pressure tracing and can facilitate the quantitative analysis of relevant parameters .
A normal motility pattern is defined as the presence of at least one MMC per 24 h of recording (it has been shown that almost 95 % of normal children have phase III within 4-h fasting study), conversion to the fed pattern without return of MMC for at least 2 h after a 400-kcal meal, distal postprandial contractility (MI per 2 h > 13.67), small intestinal contraction >20 mmHg, and absence of abnormal findings described in Table 8.1 . Therefore, the presence and characteristics of the MMC and its response to nutrients are used as a marker of enteric neuromuscular function.
Manometric features associated with gastrointestinal motility disorders
Interdigestive or fasting period
• Absence of phase III
• Short intervals between phase III
• Abnormal phase III
• Non-migrating burst of contraction
• Sustained simultaneous cluster of contractions
• Low-amplitude contraction
Postprandial or fed period
• Failure to switch to postprandial period
• Postprandial hypomotility
– Low frequency of contraction
– Low-amplitude contraction
• Non-migrating cluster of contraction
Based on the findings of abnormal manometric features, various clinical/pathophysiological categories of abnormalities can be recognized [35, 55]. In patients with enteric neuropathy , the motor activity is typically disorganized and/or uncoordinated. The most compelling finding is represented by the absence of an MMC during a sufficient recording time (ideally 24 h); however, this scenario is a rare event in patients with enteric neuropathy. More common findings include the presence of retrograde or uncoordinated phase III activity (Fig. 8.5), increased frequency of phase III (in adults and older children >1 MMC cycle per hour) (Fig. 8.6), presence of nonpropagated bursts and sustained uncoordinated phasic activity, antral hypomotility, inability to establish a fed pattern after a test meal, and presence of phase III-like activity in the fed period. In patients with enteric myopathy, the normal manometric patterns are usually preserved, but the amplitude of contractions in both preprandial and postprandial periods does not exceed 20 mmHg (Fig. 8.7); however, low-amplitude contractions may also represent a consequence of gut dilatation proximal to an obstructive segment. For this reason, the absence of dilated loops is a prerequisite for a diagnosis of enteric myopathy. In patients with mechanical obstruction , multiple simultaneous giant contractions as well as the presence of simultaneous DCCs in the postprandial period are frequently reported. In neonates, the presence of high-amplitude retropropagated contractions should raise the suspicion of mechanical obstruction. In children with CNS abnormalities, an abnormal frequency and propagation of phase III, increased proportion of nonpropagated DCCs, antral hypomotility, abnormal proportion between periods of phase I and II activity, and altered postprandial pattern duration with the presence of phase III-like activity have been shown . Finally, in adult patients with postvagotomy syndrome, the most common manometric findings are an increased frequency of MMC, the absence of antral phase III and the presence of antral hypomotility after test meal, and altered postprandial pattern duration with a rapid return of MMC activity. An example of the different parameters that should be included in a manometric report is shown in Table 8.2.
Examples of conventional (a) and spatiotemporal plot (b) of an abnormal propagation of phase III in a child with neuropathic pediatric chronic intestinal pseudo-obstruction (PIPO). The 5th channel is localized in the antrum. The recording has been performed with a 20-channel manometric catheter (side holes 2.5 cm apart)
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