Ancillary testing including barostat, SPECT, and satiety testing





Introduction


Gastroparesis presents with cardinal symptoms suggestive of delayed gastric emptying including nausea, vomiting, early satiety, postprandial fullness, bloating, visible distention, and upper abdominal pain. The diagnosis is made by documenting delays in gastric emptying on scintigraphy, breath testing, or wireless motility capsule testing. Depending on the methods used, delayed emptying is demonstrated in only 25–36% of patients with suspected gastroparesis . Those patients without gastric emptying delays are conferred related diagnoses including chronic unexplained nausea and vomiting (CUNV) or functional gastroduodenal disorders defined by the recent Rome IV publications including functional dyspepsia and chronic nausea vomiting syndrome (CNVS) .


Most studies show poor correlation of typical dyspeptic symptoms of gastroparesis and delayed gastric emptying . In the largest well-characterized National Institutes of Health (NIH) cohort of 425 patients with gastroparesis and related conditions, delays on gastric scintigraphy did not correlate with any gastroparesis symptom . Similar findings were observed in a 209 patient study using wireless motility capsules in which all individual symptoms consistent with gastroparesis showed no relation to delayed emptying . In a recent systematic review and meta-analysis which included only gastric emptying tests that spanned more than 3 hours in duration, gastric emptying did correlate with nausea, vomiting, abdominal pain, early satiety and fullness . However, this analysis excluded some of the best accepted studies relating gastric function to symptoms including the large 425 NIH-supported patient report.


It is standard clinical practice to prescribe prokinetic agents that stimulate gastric emptying to treat gastroparesis. However in one meta-analysis, acceleration of gastric emptying correlated poorly with improved symptoms in 34 prokinetic trials in gastroparesis . A more recent systematic review and meta-analysis reported closer associations of symptom reductions with improved gastric transit when only studies measuring emptying for more than 3 hours were included . However, this study included randomized trials of only 12 studies of the serotonin 5-HT 4 receptor agonist cisapride, the peripheral dopamine D 2 receptor antagonist domperidone, and with various ghrelin agonists none of which is FDA approved to treat gastroparesis in the United States. Importantly, this newer report excluded agents described in the earlier meta-analysis including erythromycin, metoclopramide, and pyloric injection of botulinum toxin raising questions about the clinical applicability of these updated findings.


It is evident that most patients with gastroparesis symptoms do not exhibit delayed gastric emptying and that emptying rates show imperfect correlation with presenting symptoms and with clinical responses to agents which improve gastric emptying delays. These observations suggest that other factors contribute to symptom genesis in those with suspected gastroparesis. Other pathophysiologic abnormalities of stomach function in patients with gastroparesis and functional dyspepsia include heightened perception of gastric stimulation and blunting of the reflex relaxation of the proximal stomach observed after meal ingestion. A number of testing methods have been devised to quantify these gastric functional parameters, but most have been restricted to research and are not broadly used in clinical practice. There is limited evidence to suggest these other markers are more relevant to symptom genesis or help more to inform treatment decisions in patients with gastroparesis symptoms than gastric emptying delays. The following sections describe technologies designed to measure gastric sensation and relaxation. Important features of each technology which are discussed include (i) performance characteristics that confirm reproducibility of test findings and modest intra- and interindividual coefficients of variation that permit discrimination of abnormal from normal values, (ii) definition of abnormal test findings that reliably distinguish relevant patient subsets with gastroparesis symptoms from healthy individuals and other patient groups with overlapping presentations, (iii) test responsiveness to pharmaceutical or other intervention in controls and patient populations to demonstrate the capability to detect improvements on treatment, and (iv) contrast with other related and unrelated tests of gut physiology to further examine potential mechanisms of dyspepsia symptom generation. When each of these features is considered, the potential clinical utilities and drawbacks of each test method are described.


Gastric physiology in gastroparesis and similar disorders unrelated to gastric emptying


Gastroduodenal hypersensitivity


Heightened visceral sensitivity as a potential pathogenic cause of symptom development has been most prominently described in generalized functional bowel disorders such as irritable bowel syndrome (IBS) . In these studies, perception of colorectal balloon inflation was increased in IBS patients with descriptions of both hyperalgesia (heightened symptoms compared to healthy controls for any given degree of distention) and allodynia (perception of distention at levels below the detection limits for healthy volunteers) . IBS patients also reported more generalized localization of pain with colon distention, reflective of altered patterns of pain referral. Similar methods have been adapted to gastric testing which have defined similar hypersensitivity to mechanical distention in patients with gastroparesis and functional dyspepsia. In general, perception of gastric distention requires activation of mechanoreceptor pathways . Different regions of the stomach exhibit distinct responses to distention in healthy subjects. Antral distention evokes nausea which can disrupt normal myoelectric findings including induction of gastric slow wave rhythm disturbances in normal human volunteers . Such findings are not observed with balloon inflation of the proximal stomach to similar pressures. Likewise, reports of bloating and upper abdominal pain are noted at lower pressures in association with lower compliance levels in the distal stomach compared to the gastric fundus. There is strong evidence for gastric hypersensitivity to distention in gastroparesis and functional dyspepsia as well as other manifestations of visceral hypersensitivity in these disorders including altered pain referral patterns . Furthermore, pain is more often reported during sham distention in functional dyspepsia patients compared to healthy controls indicating involvement of central nervous system pathways. In contrast, heightened perception of gastric distention is not noted with organic causes of dyspepsia.


Modulation of visceral sensation is a potentially important mechanism for treating functional gastroduodenal disorders including gastroparesis and functional dyspepsia. Medications with different receptor actions have been proposed as neuromodulators for these conditions. Tricyclic agents act by inhibiting norepinephrine reuptake with variable inhibition of serotonin and dopamine reuptake. Tricyclic drugs exhibit capabilities to reduce gut perception of distention and electrical stimulation in human and animal models . In an early, open-label study of refractory nausea and vomiting in diabetes, tricyclic prescription at median doses of 50 mg reduced symptoms in 88% and eliminated symptoms in nearly one-third of patients . Notably, 29% of these diabetic patients exhibited delayed gastric emptying consistent with gastroparesis. A follow-up randomized controlled trial (RCT) of tricyclic drugs in diabetic gastroparesis has not been conducted. However, a definitive RCT of the tricyclic agent nortriptyline was performed in 130 patients with idiopathic gastroparesis . In this study, 15 weeks of treatment with nortriptyline up to 75 mg daily dosing was not associated with greater decreases in overall or individual gastroparesis symptoms than placebo. Only anorexia significantly improved more on nortriptyline than on placebo. A different RCT comparing the tricyclic medication amitriptyline, the selective serotonin reuptake inhibitor escitalopram, and placebo showed selective improvements on amitriptyline compared to the other arms in a large cohort of functional dyspepsia patients . However in this dyspepsia study, symptom benefits with tricyclic therapy were prominent only in those with normal delayed gastric emptying and with epigastric pain. Taken together, these findings suggest that neuromodulatory tricyclic therapy may be most beneficial in patients with pain-predominant gastroparesis symptoms but only with normal emptying rates. Other antidepressants (e.g. mirtazapine, olanzapine) have antiemetic effects in individual cases and case reports of gastroparesis and functional dyspepsia. A small RCT has shown improvements with mirtazapine in functional dyspepsia, but no RCTs have been performed in gastroparesis and these agents do not have documented mechanisms to reduce gastric sensation . Likewise, other agents with pain modulating characteristics including gabapentin and pregabalin have not been rigorously investigated in gastroparesis.


Abnormal proximal gastric accommodation


Accommodation is the reduction in gastric tone and increase in gastric volume occurring after meal ingestion. These effects are most prominent in the proximal stomach but are also seen in the antrum to lesser degrees . These actions produce a reservoir for the stored food without increasing intragastric pressure. Accommodation is comprised of initial receptive relaxation of the stomach occurring within seconds of exposure to an oropharyngeal or gastric stimulus followed by adaptive gastric relaxation which peaks roughly 15 minutes after eating . Afterwards, proximal gastric tone slowly increases which is postulated to contribute to regulation of meal delivery to the distal stomach and small intestine . Large subsets of patients with gastroparesis and functional dyspepsia exhibit blunting of accommodation after meal ingestion. This leads to increased intragastric pressure with abnormal redistribution of food residue to the distal stomach, impairing the postprandial reservoir function of the proximal stomach .


Medications to reverse blunted meal-induced proximal gastric accommodation have been proposed as potential treatments for gastroparesis and functional dyspepsia. In dyspeptic patients, the 5-HT 1A receptor agonist buspirone improves meal-induced gastric relaxation and reduces postprandial fullness, early satiety, and bloating to greater degrees than placebo . Similarly, tandospirone, a different 5-HT 1A receptor agonist, elicited greater symptom improvements versus placebo in an RCT in functional dyspepsia . In contrast to other therapies of gastroparesis symptoms, 5-HT 1A agonists elicit little antiemetic effect. To date, no similar RCT of either 5-HT 1A receptor agonist has been conducted in gastroparesis.


Small intestinal factors


Although gastroparesis and related conditions are considered to result from gastric sensory or motor dysfunction, some findings suggest important roles for small intestinal factors (especially in the duodenum) in causing delayed gastric emptying and dyspepsia. Historical research has found jejunal contractile bursts that act as an intestinal brake to impair gastric emptying in diabetic patients . Physiologic studies have characterized duodenogastric feedback responses by which intestinal nutrient or acid perfusions blunt antral function, increase pyloric contractions, or delay stomach emptying . In functional dyspepsia, increases in duodenal eosinophils correlate with severity of early satiety, fullness, and abdominal pain . Duodenal eosinophilic infiltration also increases mucosal permeability which correlates with delayed solid food gastric emptying in preliminary studies . The methodologies described in the following sections are considered to quantify stomach function, but it is clear that some measures can be influenced by post-pyloric activities as well. In studies to measure liquid gastric emptying or assess meal tolerance with satiety testing, it is possible that early duodenal filling could elicit enterogastric reflexes to inhibit subsequent emptying or increase dyspeptic symptoms that would halt further meal ingestion. In both cases, these stomach tests would be abnormal primarily due to duodenal dysfunction emphasizing the importance of understanding their limitations.


Barostat testing to measure gastric sensitivity


Methods


Barostat methods are the best characterized techniques for quantifying perception of gut lumen distention. A typical gastric barostat study involves oral passage of a stiff plastic infusion catheter with a deflated polyethylene bag up to 1200 mL in capacity affixed to its tip ( Fig. 17.1 ) . The barostat bag is then unfolded by inflating with 250–300 mL air for 2 minutes followed by gentle traction to retract the bag into the gastric fundus . After deflating the bag and allowing a 15–30 minute interval of gastric adaptation, a series of isobaric distentions to maintain constant intrabag pressure are performed with concurrent measurement of symptom severity to assess gastric sensitivity. The minimum distending pressure is initially determined by increasing the intrabag pressure by 1 mmHg every 2–3 minutes until either a stable balloon volume ≥30 mL is achieved or visible respiratory variations in the barostat volume recordings are observed . Afterwards, incremental 2–3 minute isobaric distentions of the barostat bag are made in either staircase or random staircase fashion increasing the pressure 1–3 mmHg with each step until a predefined maximal pressure (usually ~20 mmHg) or volume (usually ~1000 mL) is achieved or when the patient reports maximal discomfort or pain. Pressures and volumes needed elicit first perception, threshold for discomfort, and maximal tolerated distention are recorded.




Figure 17.1


A typical gastric barostat study is shown. An infinitely compliant barostat bag is passed into the proximal stomach and maintained at a constant pressure via a strain gauge. When the stomach contracts, the strain gauge withdraws air from the bag to maintain pressure at constant level and when the stomach relaxes, the strain gauge injects air to maintain pressure at a constant level.

From Azpiroz F, Malagelada JR. Gastric tone measured by an electronic barostat in health and postsurgical gastroparesis. Gastroenterology 1987;92:934–43.


Variations on standard barostat methods have been developed by some investigators to glean addition information relating to gastric sensory function. In one study in 14 healthy humans, a double barostat bag technique was employed to characterize differences and similarities in sensitivity in separate gastric regions . Using this protocol, compliance was lower in the distal versus the proximal stomach but intrabag pressures needed to elicit first perception and discomfort were not different in the two regions. Furthermore, concurrent distention of barostat bags in one of the two regions did not influence sensitivity in the other segment. Another method involves use of a tensostat which measures wall tension by correcting for changes in gastric volume using Laplace’s law . In a study in healthy subjects, graded isobaric inflation of a barostat bag elicited increased sensation during glucagon infusion . Although both gastric volume and wall tension were increased, used of the tensostat determined that perception was more closely influenced by changes in tension rather than volume.


Performance characteristics


Performance characteristics of barostat testing of gastric sensitivity have been validated in small studies in healthy controls. In one report of 6 volunteers, isobaric proximal gastric distention produced threshold perception at first sensation at 12+4 mmHg, moderate sensation at 18+4 mmHg, and sensation of discomfort at 21+4 mmHg . These perceptions were not influenced by atropine, confirming the lack of impact of muscarinic pathways on this gastric response. It should be noted that proximal gastric distention elicited large amplitude antral contractions which diminished with onset of reports of discomfort, reinforcing that this testing does not measure baseline function of the stomach but rather is disruptive of normal gastric activity. When repeated testing is performed on separate days, threshold pressures for first sensation and for reports of discomfort are highly reproducible in both healthy controls and patients with dyspepsia . Pressure thresholds show lesser variabilities than volume thresholds for perception.


Findings in gastroparesis and similar disorders


Some studies have been conducted which characterize gastric hypersensitivity in patients with gastroparesis from different etiologies. In an early barostat study in patients with postsurgical gastroparesis, isobaric gastric distention reproduced the presenting symptoms of epigastric fullness, abdominal pain, and nausea . A subsequent article reported reductions in gastric volumes needed to induce discomfort in patients with prior truncal vagotomy compared to healthy individuals . Of 58 idiopathic gastroparesis patients with severely delayed emptying in another investigation, 29% exhibited hypersensitivity to isobaric distention with associated lower balloon volumes which related to increased prevalence of epigastric pain, early satiety, and weight loss . Symptom severity correlated with sensitivity to gastric distention (r=−0.39). In 18 patients with diabetic gastroparesis, perceptual thresholds for discomfort during isobaric distention were lower than for controls . Ten of 18 diabetics (55%) showed gastric hypersensitivity to distention during fasting (threshold <12 mmHg). Eight patients could not tolerate meal ingestion, but the other 10 patients reported lower thresholds for discomfort and increased perception scores with graded distention during the fed period.


Other studies in diabetic patients with unexplained upper gastrointestinal symptoms have reported similar findings. In 8 symptomatic type 1 diabetic patients, gastric compliance during progressive isobaric distention was higher than in healthy controls and was associated with increased distention-evoked nausea, bloating, and abdominal pain . Similar heightened sensitivity to gastric distention was observed in type 1 diabetics with dyspepsia during maintenance of euglycemia .


The largest volume of data on gastric barostat measures of sensitivity have been published on patients with functional dyspepsia. An older study reported that lower median gastric volumes were needed to elicit discomfort in functional dyspeptics than healthy controls (210 vs. 660 mL) . Several investigations have examined the role of organic factors as contributors to hypersensitivity in functional dyspepsia. One study found no relation of Helicobacter pylori infection to gastric sensation, while a second observed more frequent gastric hypersensitivity to isobaric distention in H. pylori positive versus negative patients with functional dyspepsia . A third report found increases in sensitivity in functional dyspepsia patients but not in those with organic causes of dyspepsia . Gastric sensation in functional dyspepsia subtypes has been examined with one study noting hypersensitivity to barostat testing in those with epigastric pain predominance, whereas another investigation related gastric sensitivity to the postprandial distress variant on confirmatory factor analyzes .


Analyzes have been performed to identify other variables which are associated with increased perception of isobaric distention on barostat testing in functional dyspepsia. In a large study of 160 functional dyspepsia patients, hypersensitivity to gastric distention was observed in 34% of patients including both lower pressure and volume for perception of discomfort and lower wall tension at levels producing discomfort which were associated with increased symptoms confirming worsening of sensory abnormalities after meals . On multivariate analyzes, weight loss was associated with hypersensitivity and pain and belching were associated with relevant or severe hypersensitivity while BMI inversely related to the risk of hypersensitivity. In another study, postprandial sensitivity to gastric distention was greater than fasting sensitivity in patients with dyspepsia ( Fig. 17.2 ) . Postprandial thresholds needed to elicit discomfort correlated with overall symptom severity with an r value of −0.43. On multivariate analyzes, postprandial discomfort threshold and postprandial compliance were determinants of postprandial symptom severity. In an evaluation of other motor parameters that contribute to gastric sensation, barostat bags were inflated to volumes just under the threshold for detection (208+14 mL) in 12 functional dyspepsia patients with prior barostat testing showing hypersensitivity as well as normal fundic accommodation and gastric emptying . Seventy-eight phasic contractions were recorded during barostat recording at these subthreshold volumes, of which 39 (50%) were perceived 6+0.4 s after their occurrence. Of 88 transient increases in symptom intensity, 39 (44%) were accompanied by phasic contractions. These findings suggest that both tonic and phasic motor activity correlate with symptoms in functional dyspepsia.




Figure 17.2


Individual meal-related symptoms are shown for functional dyspepsia patients who exhibited normal sensitivity (clear bars) vs. hypersensitivity (black bars) to fasting distention (A) and postprandial distention (B). There were no differences in meal-related symptoms with fasting distention, but dyspeptic patients who were hypersensitive to postprandial distention reported increased meal-related postprandial fullness, nausea, and epigastric pain compared to those who showed normal sensitivity to postprandial distention.

From Farre R, Vanheel H, Vanuytsel T, et al. In functional dyspepsia, hypersensitivity to postprandial distention correlates with meal-related symptom severity. Gastroenterology 2013;145:566–73.


Responsiveness to pharmaceutical and other intervention


Barostat quantification of gastric sensitivity has shown good responsiveness to a range of medication and non-medicinal stimuli in healthy cohorts. In one study of 18 normal volunteers, the 5-HT 4 receptor agonist prokinetic drug cisapride decreased pressures needed to elicit threshold perception and discomfort during isobaric gastric distention . In contrast, use of another agent with prokinetic properties—intravenous ghrelin—did not influence pressures needed to induce threshold or discomfort perception after meals in normal volunteers during gastric barostat testing . Examining agents with potential to modify gastric sensitivity, capsaicin administration in healthy subjects increased proximal gastric compliance but also increased perception scores across a range of distending pressures and reduced pressures needed to elicit discomfort showing involvement of vanilloid receptor 1 pathways in fundic sensation . In healthy volunteer studies in which experimental anxiety was evoked by exposure to disturbing facial expressions and audiotapes with anxious autobiographical reports reduced gastric volumes but not pressures required to elicit discomfort on isobaric gastric distention .


Limited investigation has been performed in functional dyspepsia to confirm pharmacologic responsiveness of gastric barostat methods. In one investigation of 20 patients with functional dyspepsia with known hypersensitivity, treatment with the 5-HT 1A receptor agonist sumatriptan reduced perception scores across a range of gastric pressures and increased the pressures need to induce threshold and discomfort perception .


Comparisons with other methods


The barostat remains the definitive means of measuring gastric sensation in patients with gastroparesis symptoms. Other small studies have examined other methods to assess perception of gastric stimulation. In a comparison study in functional dyspepsia, 30 patients exhibited hypersensitivity to distention of both the proximal and distal stomach compared to healthy controls using tensostats . Functional dyspeptics in a different report exhibited increased symptom scores compared to normal subjects after consuming 0.75 mg capsaicin, reflecting chemical hypersensitivity in affected patients .


Barostat measures of gastric perception have been contrasted with findings of other physiologic tests to relate hypersensitivity to other potential pathogenic factors of symptom generation. Several studies have related sensation to gastric emptying in functional dyspepsia. One study observed combined decreased thresholds to perception of isobaric and isovolumetric distention and prolonged gastric emptying half times in patients compared to healthy controls, however only volumes required to induce symptoms correlated with emptying rates . In two other studies, there was no correlation of gastric hypersensitivity with delayed gastric emptying in functional dyspepsia patients or volunteers . Using another methodology proposed to relate to nausea generation, isobaric antral distention induced greater symptoms and disrupted gastric slow wave rhythm more than with proximal gastric distention in healthy volunteers . Finally, gastric sensitivity has been related to central nervous system pathways in functional dyspepsia. In one study, thresholds for discomfort on isobaric testing were associated with lack of pregenual anterior cingulate activation and no dorsal pons and amygdala deactivation on H 2 15 O-PET testing during distention . In these dyspeptic individuals, degrees of anxiety showed negative correlation with pregenual anterior cingulate and midcingulate activation and positive correlation with dorsal pons activation suggesting involvement of emotional factors in pain modulation.


Clinical utility and drawbacks


Gastric barostat testing is the definitive means to distinguish abnormal gastric sensitivity in patients with unexplained dyspeptic symptoms suggesting gastroparesis. The method shows good reproducibility, relatively low variabilities of test results, excellent capability to define abnormalities in specific patient subsets, and responsiveness to gastric stimulation. However, this method is challenging for patients due to the requirement for uncomfortable oral intubation using a catheter with a large volume deflated barostat bag as well as the discomfort associated with isobaric gastric distention . Additionally, relatively few laboratories around the world are capable of conducting gastric barostat measures of gastric perception. However, an audit of 414 barostat studies performed at the referral center with the greatest experience with this method was conducted more than a decade ago which reported that 98.1% of tests were tolerated and 94.1% were technically adequate . Air leaks and low intrabag volumes precluded accurate interpretation in a small number of studies and testing was terminated in 7 sessions (1.7%) because of intolerance of the intubation or maintaining catheter position in the throat for the time needed to complete the study. When these factors are considered, this form of testing is mostly restricted to research and has only limited clinical relevance.


Barostat testing to measure gastric tone and accommodation


Methods


As part of comprehensive gastric barostat testing, measurement of accommodation testing after meal ingestion can be performed in healthy controls and patients with unexplained dyspeptic symptoms. The method was first reported in healthy dogs in which a highly compliant barostat bag was positioned in the stomach and inflated to 2 mmHg above intragastric pressure as described previously for sensation testing . This pressure was maintained with recording of gastric tone during fasting and after consuming test meals. These dogs exhibited initial receptive relaxations followed by more prolonged phases of accommodation that were not detected on gastric manometric testing. A standard barostat study in humans is performed similarly with setting initial intrabag pressures to 2 mmHg above minimum distending pressure after a 20–30 minute period of gastric adaption followed fasting recording and then by ingestion of a standardized 250–350 mL (~300–360 kcal) liquid nutrient meal . Postprandial gastric tone is measured for 20–60 minutes for optimal characterization of accommodation responses. In one variation of a typical study, a double barostat bag technique was employed in healthy controls and showed that both the proximal and distal stomach relaxed after meal consumption . Furthermore, antral distention reduced postprandial proximal gastric relaxation indicating the presence of intragastric reflex modulation of accommodation.


Performance characteristics


As with its use to assess sensation, studies have assessed reproducibility and variability of gastric barostat testing to quantify gastric accommodation responses to meals. In an evaluation in healthy volunteers, the accommodation response in healthy subjects began within 5 minutes after consuming a liquid meal and volumes remained increased over baseline for 115 minutes postprandially . Intrasubject differences in accommodation measurements in healthy volunteers and patients with dyspepsia between studies performed twice averaged 100 mL . In this same investigation, coefficients of variation were 19% in controls and 43% in dyspeptics. It has been suggested that this modest degree of reproducibility necessitates recruitment of relatively large sample sizes to be able to detect significant differences in accommodation volumes between subject groups .


Findings in gastroparesis and similar disorders


Barostat measures of tone and accommodation have defined abnormal findings in gastroparesis. Forty-three percent of 58 idiopathic gastroparesis patients with severely delayed emptying exhibited impaired accommodation which related to high prevalence rates of early satiety, abdominal pain, and weight loss . Only 10 of 18 patients with diabetic gastroparesis exhibited a gastric relaxation response to meal ingestion in another study ( Fig. 17.3 ) . Accommodation was blunted in 9 of these 10 individuals. However, accommodation responses correlated poorly with individual symptom scores with r values ranging from −0.01 to 0.4.




Figure 17.3


Patients with refractory diabetic gastroparesis exhibited blunted meal-induced gastric accommodation on barostat testing compared to healthy controls (A). Individual responses are shown (B). Horizontal lines represent the mean values and the error bars represent the standard error of the mean (SEM).

From Kumar A, Attaluri A, Hashmi S, et al. Visceral hypersensitivity and impaired accommodation in refractory diabetic gastroparesis. Neurogastroenterol Motil 2008;20:635–42.


Likewise, diabetic patients with dyspepsia also exhibit abnormal gastric accommodation on barostat testing. Meal-induced accommodation was blunted in 14 type 1 diabetics which was associated with wide antral areas on ultrasound and with reduced vagal tone measured by respiratory sinus arrhythmia on electrocardiography . Maximal accommodation volume increases after a liquid meal also were decreased in a second study in 8 type 1 diabetics during euglycemia .


Tone and accommodation measurements using barostat methods have shown abnormalities after gastroesophageal surgery. In an early barostat study, patients with postsurgical gastroparesis exhibited significantly higher intragastric volumes at low pressures compared to healthy controls suggestive of reduced tone . However in another study, gastric tone during distention was higher in patients who had undergone prior truncal vagotomy compared to healthy subjects and meal-evoked tone decreases were absent in the postvagotomy patients . Fasting tone was higher in 6 of 16 patients who underwent distal gastrectomy for malignancy who experienced dyspepsia after surgery than in 10 who were asymptomatic . Meals elicited accommodation responses in all 10 asymptomatic post-surgical patients but induced delayed responses in only 2 of 6 with dyspepsia. Accommodation measured by barostats were impaired in patients who reported dyspepsia but not dysphagia after undergoing Nissen fundoplication compared to pre-fundoplication patients which correlated with postprandial fullness .


Accommodation defects are found in subsets of patients with functional dyspepsia using barostat methods. Intragastric volume and accommodation responses in the first postprandial hour were blunted in 160 functional dyspeptics compared to 80 healthy controls . In this study, 40% of dyspeptics exhibited impaired accommodation using a cutoff of 64 mL. These findings mimic an older study which also showed blunted accommodation in 40% of 40 functional dyspepsia patients that also was associated with early satiety and weight loss as well as a different study in which fasting gastric tone was higher in dyspepsia patients than controls . However, another report focusing just on functional dyspepsia patients with predominant early satiety observed impaired accommodation in 79% of patients . In one investigation in dyspepsia patients, barostat measures of accommodation did not relate to H. pylori status . In another study of functional dyspepsia subgroups, those with postinfectious dyspepsia more often exhibited blunted accommodation to a liquid meal versus individuals with unspecified onset dyspepsia .


Responsiveness to pharmaceutical and other intervention


Barostat measurements of gastric accommodation detect responses to pharmacologic stimulation and to non-drug interventions in animal models and healthy humans. In canine studies, gastric accommodation on barostat testing is enhanced by gastric electrical stimulation . Effects of prokinetic agent administration on accommodation in normal controls show variable responses which depend on the medication choice. Meal-induced accommodation is enhanced by cisapride and intravenous ghrelin, but fasting gastric tone is increased and meal-induced gastric relaxation is reduced in duration by motilide treatments including intravenous erythromycin and motilin . As with its impact on gastric sensation, experimental anxiety induced by noxious images and audiotapes inhibits meal-induced gastric relaxation for 60 minutes on barostat testing .


Responsiveness also has been demonstrated for accommodation volumes on isobaric testing in functional dyspepsia. In separate studies, buspirone and sumatriptan enhanced blunted gastric accommodation responses to meal ingestion in dyspeptics . In a comparison of different functional dyspepsia subgroups, patients with unspecified-onset dyspepsia exhibited gastric relaxation to sumatriptan while individuals with postinfectious dyspepsia showed no response suggesting impaired gastric nitrergic function .


Comparisons with other methods


Barostat measures of gastric tone have been compared to those of other less invasive methodologies. Gastric volumes after both glucagon and erythromycin administration measured by barostat methods and magnetic resonance imaging show good correlation; both methods also detect dynamic volume waves in response to pharmaceutical stimulation as well .


As with gastric sensitivity measurements, the tensostat has also been employed to quantify fundic reflex responses to stimulation. Fundic relaxation in response to antral distention or intestinal nutrient delivery was blunted in patients with functional dyspepsia compared to normal volunteers .


Barostat accommodation responses have been related to other gastric physiologic parameters in healthy volunteers and patients with dyspeptic symptoms. In the report showing increased accommodation with buspirone, there was associated delay in liquid phase gastric emptying without slowing of solid food emptying . Blunting of accommodation to meal ingestion was associated with hypersensitivity to postprandial distention on barostat sensitivity testing in a study of controls and patients with functional dyspepsia . However in a different report, impaired accommodation was not associated with either hypersensitivity to barostat testing or to delayed gastric emptying in healthy volunteers and functional dyspepsia patients .


Clinical utility and drawbacks


The barostat has been deemed the reference method to measure gastric accommodation on the basis of multiple published studies demonstrating it use in varied subject populations ( Table 17.1 ) . However, its limited reliability and its invasive and uncomfortable nature have been proposed to contribute to biased gastric tone measurements. In the previously described audit of barostat tests performed at the main institution performing these studies, negative values for fundic accommodation (postprandial volumes less than fasting) were noted in 10% of tracings and thus were not considered interpretable. Others have raised concerns about this method including its non-physiologic nature, its artificial alteration of intragastric meal distribution, and its exaggeration of gastric contractions or induction of irregular contractions during measurements of accommodation . Because of these drawbacks, barostat testing to measure gastric accommodation is mostly a research technique with a restricted role in clinical testing.


Feb 4, 2021 | Posted by in GASTROENTEROLOGY | Comments Off on Ancillary testing including barostat, SPECT, and satiety testing
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