Background

This chapter will discuss the possible use and importance of antroduodenal manometry in the diagnosis and treatment of gastroparesis. As discussed in other chapters, gastroparesis is defined by symptoms of nausea, vomiting and abdominal pain. Generally there is a delay in the emptying of the stomach. There is a question as to whether these symptoms and signs are (1) due to an alteration in contractions of the stomach, pylorus, and duodenum or (2) incidental to the contractile pattern of these parts of the gastrointestinal tract. The presence of delayed gastric emptying with the presence of dyspepsia defines gastroparesis and differentiates the syndrome from chronic unexplained nausea and vomiting (CUNV) or gastroparesis-like syndrome .

The stomach and small intestine work as a coordinated unit to process and utilize ingested food by propelling the digested material out of the stomach and down the small intestine. Interest in the physiologic process controlling upper gut functional movement was stimulated by studies from dogs at the Mayo Clinic showing different motor patterns in the stomach and small intestine . The animal studies were expanded to humans using a water-perfused catheter to measure pressure changes in the small intestine . These studies suggested that aboral contractions through the stomach and small intestine contributed to normal flow of intraluminal contents and that these contractions differed during fasting from those in the postprandial period.

The alteration of the coordinated contractions of the stomach and the small bowel may contribute to symptoms of different clinical conditions such as gastroparesis, functional dyspepsia or intestinal pseudo-obstruction. Each of these conditions may or may not be associated with delayed gastric emptying. It is unclear if these different clinical syndromes are associated as part of a spectrum of disease.

Physiology of gastric emptying

There are several potential patterns that can be identified by recording motility from the stomach and small intestine. First is to determine the amplitude of intraluminal pressure resulting from contractions in each segment of the upper gastrointestinal tract. Second is to identify the pattern of contractions. The stomach, pylorus and upper small intestine work as a coordinated unit to grind food into small particles (<3 mm) and to propel the ingested food aborad into the intestine. This normal pattern allows digestion and absorption of the nutrients. In addition normally coordinated contractions prevent stasis of intestinal contents and potential reflux back into the stomach .

The stomach has multiple functions including accommodation to food, grinding of the food into small (2–3 mm) particles to allow passage through the pylorus, and coordinated contractions of the antrum, pylorus and duodenum to facilitate distal passage of the ingested food. A barostat measures tone of the fundus and analyzes gastric accommodation. This technique is discussed elsewhere. Antroduodenal manometry measures phasic contractions in the antrum, pylorus and duodenum. High-pressure or uncoordinated contractions in the duodenum can delay or decrease gastric emptying . Discrete ports of a manometry catheter best measure these abnormal phasic contractions of the small bowel. Pyloric contractions or tonal changes can be measured by a sleeve manometer or EndoFLIP .

Coordinated phasic contractions of the body and antrum of the stomach are initiated by interstitial cells of Cajal (ICC) concentrated in the pacemaker zone on proximal greater curvature. The ICC also are present throughout the stomach forming the conduction system. There are ICC which also pace intestinal motility, generating a plateau slow-wave frequency of approximately 11 cycles/min in the proximal intestine . There is a marked difference in the frequency of contractions between the stomach (3 cycles/min) and small intestine (11 cycles/min). In mice and rats ICC and slow waves are absent in the pylorus, although they appear present in humans . In healthy human controls, pyloric contractions are a mixture of antral-type and duodenal-type. Tonic and phasic pyloric contractions increase the resistance across the antroduodenal junction leading to gastric retention of ingesta .

In addition to measuring amplitude, frequency and coordination of antroduodenal contractions during fasting, the response to food is also important. During fasting a programmed motor pattern occurs . This interdigestive motor complex during fasting consists of a burst of continuous contraction followed by quiescent periods. This complex generally initiates in the stomach and migrates down the intestine approximately every 90 minutes. The migration out of the stomach moves larger indigestible materials (>3 mm in size) from the stomach and through the small bowel. This pattern functions as an “intestinal house keeper” sweeping sloughed cells and other debris toward the colon . Eating switches the pattern to a fed pattern consisting of an increased number of contractions with a less recognizable pattern.

Locally released neurotransmitters initiate different contractile patterns in the antrum and small bowel. In humans motilin stimulates a migrating complex only in the antrum and generally does not stimulate phasic contractions in the pylorus or duodenum . In the small intestine somatostatin agonists initiate the migrating complex .

Pathophysiology of antroduodenum causing gastroparesis

Different patterns of altered antroduodenal motility are associated with upper abdominal symptoms. Electrogastrography and antroduodenal motility are abnormal in many patients with functional dyspepsia . Antral hypomotility may delay gastric emptying and cause abdominal pain, nausea and vomiting . Antral hypomotility can be associated with a long lag phase of the gastric emptying cycle further contributing to delay in emptying a solid meal . The time period of the lag phase is used to grind a solid food into small particles for emptying. In addition to antral hypomotility, diabetic patients with recurrent nausea and vomiting may have a prolonged period of pyloric contractility after eating .

Pathophysiologic alterations of smooth muscle (myopathy) or neural function (neuropathy) will alter the manometric pattern of the antropyloroduodenal segment and disrupt movement of gastric contents out of the stomach and through the intestine . Myopathy is reflected by low-amplitude contractions that are coordinated under normal neural control. In neuropathy the contractions have normal or increased amplitude, but the contractions are uncoordinated because of disturbed neural control. Abnormal neural control of the antrum and small intestine is identified by the absence of a phase-3 of the migrating motor complex (MMC) or retrograde uncoordinated migration of the MMC. An abnormal pattern of the MMC disrupts emptying of indigestible materials from the stomach and the small intestine . Disruption of the complex in the stomach can lead to bezoars, or in the small intestine to small bowel bacterial overgrowth .

Abdominal pain can be severe and occurs in greater than 30% of patients with gastroparesis, associated either with diabetes or idiopathic . The pain can be a major component of the symptom complex, resulting in opiate use and altered mood. Gastroparesis symptoms correlate poorly with motility capsule transit, but lower abdominal symptoms are associated with altered intestinal transit in greater than 40% of patients .

Techniques for recording antroduodenal manometry

Antroduodenal motility can be measured with catheters with solid state or water-perfused pressure transducers passed through the oropharynx into the stomach and small intestine. Recent development of a wireless motility capsule (WMC) allows measurement of intraluminal pressure amplitude throughout the gastrointestinal tract and determines patterns of contraction . In addition the WMC allows measurement of transit . Magnetic resonance or ultrasonography has been used to record gastric and duodenal motility, although these techniques are less widely available .

Pyloric motor function can now be measured using a sleeve manometer that integrates the pressure over a linear distance of the sleeve. Pyloric distensibility can be measured using the endoscopic functional luminal imaging probe (EndoFLIP) . Using a sleeve allows pressure sampling over the linear region surrounding the sphincter .

Perfused catheters have side holes that measure intraluminal pressure as resistance to a constant flow of water. Water-perfused manometry requires a low compliance, pneumohydralic perfusion system linked to a multilumen catheter and external strain gauge transducers .

Solid-state manometers respond more quickly to a pressure event giving a higher fidelity response. The solid-state systems may record a higher percentage of pressure events and do not add intraluminal water into the stomach and small intestine .

Perfused catheters and solid-state manometry catheter allow the simultaneous recording of pressure events at multiple locations throughout the stomach and small bowel. Sensors can be placed 1–2 cm apart if localized segments or sphincters are being studied. Sphincter pressure can be accurately measured using an electronic or water perfused sleeve. Generally longer segments of stomach and small intestine are studied using placement of an unlimited number of sensors 5–15 cm apart. To evaluate propagation of the migrating motor complex the length of small bowel measured should be greater than 20 cm.

The duration of an antroduodenal motility test can vary depending on the information needed on the patients disease. Most studies use a 5-hour duration. The use of perfused catheters restricts the duration of the study to avoid a large water bolus into the intestine . Solid-state catheters can record for 24 hours and allow ambulatory studies. The longer studies allow evaluation of sleep and different meals on the antroduodenal motility. Solid-state catheters allow high-resolution manometry of the antrum and duodenum, allowing demonstration of multiple pacemakers and retrograde propagation . The shorter studies must be at least 3 hours to insure the observation of a phase-3 complex. Although often there is a migrating complex every 90 minutes, a 3–6 hour fasting period maybe necessary to define the complex. The fed response should be recorded at least one hour after eating. The contractions may not begin for up to 20 minutes after the meal. There may be a prolonged delay of the fed response if the gastric emptying is slowed. The majority of studies examine the effect of fasting and eating a meal on the stomach and small intestine .

Since opiates and prokinetic drugs can alter the antroduodenal motility pattern, these should be stopped at least 12 hours before the study. Hyperglycemia delays gastric emptying and decreases the antral contractions . Therefore, fasting glucose should be monitored and kept near a normal range.

Parental administration of pharmaceutical agents allows evaluation of the response of the stomach and small intestine . Drugs that specifically stimulate the stomach or the small intestine help define an abnormality of the antrum or duodenum. Erythromycin binds to the motilin receptor and initiates phasic gastric contractions that mimic the migrating complex in the stomach . Erythromycin usually does not stimulate contractions in the pylorus or duodenum . Octreotide stimulates a prolonged increase of small intestinal contractions with inhibition of gastric contractions .

Wireless Motility Capsules contain a pressure, pH and temperature sensor allowing simultaneous, sequential measurement of gastric emptying and pressure in the stomach and small intestine . The movement through different regions of the gastrointestinal tract can be measured by changes in pH (stomach-acidic, small bowel-alkaline, cecum-acidic). The emptying of the capsule from the stomach is associated with a burst of high amplitude gastric contractions. The emptying of the capsule from the stomach correlates with radionuclide gastric emptying , but was not identical . This is to be expected since the capsule functions as a non-digestible solid emptied by the MMC compared to a solid meal that is ground up into small particles and emptied as a regular meal . The catheter antroduodenal manometry and wireless motility capsule identified almost identical phase-3 activity in the stomach and the small intestine . Small intestinal transit and contractions also can be measured with the wireless motility capsule, however different segments of the gut only can be measured sequentially not simultaneously .

The wireless motility capsule is useful for measuring gastric and small intestinal contractions, as well as total gut transit, in children, similar to antroduodenal manometry evaluation with a tube . The wireless study has an additional benefit of increased comfort to the patient with the absence of motility catheter placement down the esophagus.

Evaluation of the pyloric mechanism has added to understanding of antroduodenal motor function. Early studies by the Malagelada laboratory suggested that abnormal pyloric pressures may be associated with gastroparesis. Pyloric pressure, relaxation and compliance are involved in the control of gastric emptying . Different tools provide different information about the pyloric function. Pyloric pressure can be measured using a perfused sleeve catheter which measures the radial force of the sphincter . The EndoFLIP additionally measures the distensibility of the sphincter . The volume of flow through a circular opening is proportional to the opening diameter of the lumen raised to the fourth power . Studies using the EndoFLIP in human subjects showed the pyloric compliance inversely correlates with gastric emptying, but there was absence of correlation between pyloric pressure and gastric emptying .

Interpretation of antroduodenal manometry

Antroduodenal manometric recordings are recorded during fasting, after a meal or pharmaceutical stimulation. The tracing is evaluated for the presence and pattern of the MMC. During fasting the MMC, with a well-coordinated phase −3, should be present. The contractile pattern and amplitude of contractions after stimulation with pharmaceuticals such as erythromycin, octreotide or neostigmine should be measured . Phasic contractile activity at 3 cycles/min occurs in the stomach after administration of intravenous erythromycin or azithromycin and in the small intestine at 11 cycles/min after subcutaneous octreotide . Unlike erythromycin, azithromycin initiates phase-3 contractions in the duodenum also . This information will identify alterations of neural control of the stomach and small intestine and the integrity of the smooth muscle response.

During fasting the phase-3 of the migrating complex in the antrum and duodenum is defined as contractile activity at the maximum frequency for 1 minute in the antrum (2–3 cycles/min) and 2 minutes in the duodenum (10–12 cycles/min). A phase-3 is abnormal when it is retrograde, simultaneous, or interrupted for more than 2 minutes on one of the intestinal segments. Eating abolishes the fasting pattern of the MMC and replaces it with a more irregular pattern of contractions. This is a neural response that is dependent on the caloric and fat content of the meal.

Antral hypomotility is defined as absence of gastric phase-3 low-amplitude gastric contractions (<30 mmHg) and no response to erythromycin. Findings in functional dyspepsia include retrograde or cluster contractions with a normal amplitude (>15 mmHg) in the small intestine . Neuropathic pseudo-obstruction is defined by disorganized high amplitude small intestinal contractions. Myopathic pseudo-obstruction has normally coordinated contractions with low amplitude antral (<30 mmHg) and duodenal (<15 mmHg) contractions. A stationary cluster contraction compatible with partial small-bowel obstruction is a prolonged (> 5 minutes) non-migrating burst of contractions .

Indications for antroduodenal manometry

Antroduodenal manometry can be used to evaluate gastric, pyloric and enteric motor function in patients with chronic symptoms of unexplained nausea, vomiting, and/or abdominal pain. Patients with undiagnosed symptoms and no anatomic disease may or may not have delayed gastric emptying. Antroduodenal manometry may help define conditions such as antral hypomotility, non-ulcer dyspepsia, chronic intestinal pseudo-obstruction or a partial mechanical obstruction. These conditions may present with symptoms of gastroparesis. Pyloric manometry should be performed if there is the suspicion of possible vagal denervation of the pylorus and the possible need for botulinum injection or G-POEM.

The presence of a normal antroduodenal manometry with normal contractile amplitude and contractile pattern, will focus therapy on visceral afferent dysfunction as the cause of symptoms. Thus, the results of antroduodenal manometry studies can minimize unnecessary surgeries in patients with dysmotility or redirect therapy in patients with normal studies . Antroduodenal manometry can identify a normal motility pattern or an abnormal pattern consistent with myopathy or neuropathy in the stomach or the small bowel. The response to the different stimulating drugs is a useful adjunct for targeted therapy.

Antroduodenal manometry can identify a partial small-bowel obstruction missed by small bowel X-ray or abdominal CT scan . Differentiation between pseudo-obstruction and mechanical obstruction can lead to an appropriate surgical procedure. Antroduodenal manometry can identify the presence or absence of generalized pseudo-obstruction involving the entire gut in patients being evaluated for colectomy to treat colonic inertia .

Use of antroduodenal manometry findings in treatment plans

Previous studies showed that greater than 70% of patients with nausea and vomiting had an abnormal antroduodenal motility, which resulted in a new diagnosis or treatment in 10–15% of these patients . Fasting and fed patterns of small intestinal motility over 24 hours showed abnormalities in 40% of patients and suggested a change in therapy in 20% . One third of the patients with functional symptoms have autonomic dysfunction which correlates with an altered upper bowel motility . Functional dyspepsia with symptoms of nausea, vomiting, and abdominal pain, may have disturbed neural control of the gastrointestinal tract much like the more severe condition neuropathic pseudo-obstruction .

Both adults and children can have severe nonulcer dyspepsia, which may mimic a surgical lesion . Antroduodenal manometry may make an important contribution to the patients’ care since 18% of children and 51% of adults with manometric evidence for nonulcer dyspepsia had no improvement in their symptoms after surgery .

Patients with symptoms related to partial bowel obstruction may have normal radiographic studies with no change in bowel caliber, but have a disturbance of upper intestinal motility . Imaging studies showing dilated bowel can cause confusion between ileus, pseudoobstruction or obstruction in this group of patients. Thus, antroduodenal manometry allows the characterization of the gastric and small intestinal contractions as either obstruction or pseudoobstruction. The definition of altered motility patterns can suggest specific pharmacologic treatment. Gastric contractions can be stimulated by erythromycin and small intestinal contraction can be stimulated by octreotide . The response of the stomach and the small intestine to the diagnostic administration of erythromycin and/or octreotide determines if these drugs will be therapeutically effective.

Erythromycin stimulates continuous contraction in the gastric antrum and body . Erythromycin can stimulate gastric contractions in patients with altered gastric MMC due to a previous antrectomy . This observation is in contrast to children who did not respond to erythromycin stimulation if the fasting gastric phase-3 was absent .

Octreotide can stimulate phase-3 like continuous small intestinal contractions in patients with an abnormal intestinal motility consistent with neuropathic pseudoobstruction. Regularizing intestinal contraction may decrease intestinal bacterial overgrowth . Octreotide stimulated phasic contractions in most patients, but some patients were unresponsive. Octreotide may be useful in patients with myopathic pseudoobstruction . Since patients with neuropathic pseudoobstruction may have a variable response , octreotide may be useful only in patients in whom stimulation was noted on antroduodenal motility. Octreotide increased the volume of enteral feeding in children with chronic intestinal pseudoobstruction in whom octreotide stimulated phase-3 activity and intestinal motility index . The wireless motility capsule can suggest abnormalities of myoneural function in the stomach and small bowel leading to similar treatment as noted above.

There has been increased use of the motility capsule because of the ease of placement. The motility capsule shows a decreased number of contractions and motility index in the stomach and duodenum of gastroparetics . The majority of patients with decreased motility had diabetic not idiopathic gastroparesis. Symptoms of gastroparesis, including nausea, vomiting, early satiety and abdominal pain did not correlate with motility capsule transit through the intestinal tract . However, the capsule can identify multiregional dysmotility resulting in delayed transit in diabetics, which can lead to changes in therapy . Furthermore, increased duodenal contractile activity did correlate with symptom severity in patients with gastroparesis . The motility capsule shows a lower ileocecal junction pressure along with slower small intestinal transit in patients with small intestinal bacterial overgrowth .

Decreased pyloric distensibility and/or increased pyloric pressure identify dysfunction of the pylorus which can contribute to altered gastric emptying . Intrapyloric botulinum injection, dilation or gastric peroral endoscopic pyloromyotomy (G-POEM) have been used to treat the pyloric dysfunction .

A normal study in patients presenting with nausea, vomiting and abdominal pain suggests a disturbance of the afferent sensory system rather than a defect efferent nerve conduction, altered smooth muscle contraction or bowel obstruction. Previous studies in patients with a normal manometry have not demonstrated an occult small bowel obstruction . Patients with a normal antroduodenal manometry were given a trial of a tricyclic antidepressant to decrease visceral hypersensitivity and patients with pseudo obstruction were treated with prokinetics . A meta-analysis showed effective reduction in functional abdominal pain following low dose tricyclic therapy . The data are against referring postsurgical patients with normal antroduodenal manometry for exploratory abdominal surgery. Low dose tricyclic therapy was less effective in relieving symptoms associated with gastroparesis .

Summary

The high association of delayed gastric emptying with altered antroduodenal manometry suggests that many of the patients have a more generalized disturbance in upper gut motility. Gastric emptying can be delayed by antral hypomotility or uncoordinated antral contractions. Uncoordinated duodenal contraction can delay gastric emptying in patients with normal antral contraction. The sequential use of erythromycin and octreotide may improve upper gut propulsion because of these drugs’ specific stimulation of stomach or small intestine . Gastric emptying, pyloric distensibility and antroduodenal manometry may be necessary to fully define the patient’s upper gastrointestinal motility function. Major advances in motility measurement with the wireless motility capsule and EndoFLIP have further improved management of gastroparesis.