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Contribution of Ascites to Impaired Gastric Function and Nutritional Intake in Patients With Cirrhosis and Ascites
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2005;3:1095–1100
Contribution of Ascites to Impaired Gastric Function and Nutritional Intake in Patients With Cirrhosis and Ascites BASHAR A. AQEL,* JAMES S. SCOLAPIO,* ROLLAND C. DICKSON,* DUANE D. BURTON,‡ and ERNEST P. BOURAS* *Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida; and ‡Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
Background & Aims: Protein calorie malnutrition and weight loss are common among patients with cirrhosis and ascites. The cause of these symptoms is unclear, with several putative mechanisms proposed. The primary aims of this study were to compare gastric volumes and accommodation between patients with cirrhosis complicated by ascites and healthy controls, and to evaluate the effect of large-volume paracentesis in the patient group. Methods: Patients with cirrhosis and ascites underwent assessment of gastric volumes as measured by single-photon emission computed tomography, gastric sensation assessed by a validated nutrient drink test, and a 3-day assessment of caloric intake before and after large-volume paracentesis. Age- and sex-adjusted linear regression models were used to compare gastric volumes and accommodation ratios between patients and healthy volunteers. Paired Wilcoxon ranksum tests were used to compare gastric measures before and after paracentesis among the patient group. Results: Fifteen patients (median age, 54 y) were compared with 112 healthy (age- and sex-matched) controls. Median postprandial gastric volumes (627 mL patients vs 721 healthy controls) and gastric accommodation were reduced significantly in patients compared with healthy controls (P ⴝ .02 and .006, respectively). After paracentesis: (1) fasting gastric volumes were increased (median 312 mL post- vs 241 mL pre-, P ⴝ .04), (2) patients tolerated ingestion of larger maximum volumes (median 964 mL post- vs 738 mL pre-, P ⴝ .04), and (3) caloric intake was increased (median 34% kcal post- vs 3110 kcal pre-, P ⴝ .005). Conclusions: Postprandial gastric volumes and accommodation ratios are reduced in patients with cirrhosis and ascites compared with healthy controls. In addition, large-volume paracentesis increases fasting gastric volumes, volumes ingested until maximal satiation, and caloric intake.
atients with cirrhosis and ascites frequently complain of dyspeptic symptoms such as early satiety, nausea, and postprandial fullness.1 These symptoms have been associated with decreased oral intake and clinically significant weight loss. Although several putative mech-
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anisms have been proposed, the main cause of these symptoms in these patients is not known. One hypothesis is that delayed gastric emptying results in the sensation of satiety.2– 6 However, in a prospective Mayo Clinic study of patients with cirrhosis and ascites, no differences in gastric emptying between patients and healthy controls were identified.7 In addition, despite improvements in satiety and caloric intake after largevolume paracentesis, no changes in gastric emptying were identified. Gastric accommodation is a vagally mediated reflex that results in reduced gastric tone and increased gastric compliance, thereby facilitating the ingestion of large volumes of solids or liquids without inducing symptoms or the vomiting reflux. Impaired gastric accommodation has been associated with early satiety and other postprandial upper-gut symptoms in a variety of gastrointestinal disorders such as functional dyspepsia, rumination syndrome, postvagotomy/gastric surgery, and diabetes mellitus when associated with vagal neuropathy.8 –17 As a result of increased wall tension and stimulation of visceral afferents or alteration of cerebral perception, patients may develop gastric hypersensitivity while fasting or postprandially.15,18 –21 Recently, it was shown that fasting gastric volumes are associated with food intake and postprandial symptoms.22,23 Furthermore, pharmacologic manipulation leading to relaxation of the stomach has been shown to decrease sensitivity to gastric distention and meal-induced symptoms,14,15,20,24,25 with one study suggesting a direct effect on gastric tension mechanoreceptors.26 These findings suggest that the measurement of gastric volumes and their relationship with regard to accommodation after a meal may facilitate our understanding of Abbreviation used in this paper: SPECT, single-photon emission computed tomography. © 2005 by the American Gastroenterological Association 1542-3565/05/$30.00 PII: 10.1053/S1542-3565(05)00531-8
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upper-gastrointestinal symptoms in the postprandial period. Previously, the only reliable measurement of proximal gastric volumes and accommodation involved the placement of a polyethylene balloon into the stomach while linking it to a barostat device. More recently, a noninvasive method to measure fasting and postprandial volumes of the entire stomach using single-photon emission computed tomography (SPECT) was developed27 and validated.28 This novel approach, which requires no oral or nasogastric intubation, provides the opportunity to examine safely patients with cirrhosis and portal hypertension who may have esophageal or gastric varices. The primary aim of this prospective study was to evaluate gastric volumes and accommodation in patients with cirrhosis and ascites compared with healthy controls. We also wished to examine the impact of largevolume paracentesis in these patients while assessing satiety and nutritional intake.
Materials and Methods Study Participants The Mayo Clinic institutional review board approved all protocols, and all participants signed informed consent forms. Fifteen patients, aged 18 –70 years, with cirrhosis and ascites and symptoms of early satiety, nausea, and/or postprandial fullness who were presenting for large-volume paracentesis were included. Patients with a prior history of abdominal or gastric surgery, vagotomy, diabetes mellitus, confirmed diagnosis of autonomic neuropathy, or who were on medications that may alter gastrointestinal motility were excluded. Control data from 112 healthy age- and sex-matched controls previously studied using identical imaging techniques were used for comparison.28
Experimental Design After an initial screen, review of the study, and informed consent the participants completed a 3-day caloric assessment. Patients then presented to the study unit after an overnight fast where they underwent SPECT scanning of gastric volumes before and after a test meal. Subsequently patients completed a nutrient drink test and underwent large-volume paracentesis. Preparacentesis and postparacentesis weights and abdominal girth measurements were obtained. Within 24 – 48 hours after paracentesis the patients returned to the research unit after an overnight fast where they underwent repeat SPECT and nutrient drink tests. Measurements of weight and abdominal girth were obtained again. For 3 days after the paracentesis, patients underwent a repeat caloric assessment and review with a dietician.
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Measurement of Gastric Volumes and Accommodation A noninvasive method developed at the Mayo Clinic and validated against the standard gastric barostat was used to measure the fasting and postprandial gastric volumes after an intravenous injection of technetium-99m pertechnetate and imaging with SPECT.27,28 This technique has reproduced the gastric volumes reported in response to pharmacologic treatments and in patients with dyspepsia as measured by the barostat technique.14,29 –31 All tomographic studies were acquired on a large field of view, dual-head, gamma camera system (ADAC Phillips, Milpitse, CA) equipped with lowenergy, high-resolution collimators. Patients were positioned supine on the imaging table with the detectors over the upper and midabdomen to ensure imaging of the stomach and small bowel. Gastric volumes were measured using the SPECT-Analyze PC 2.5 (Biomedical Imaging Resource, Mayo Foundation, Rochester, MN) software system. The gastric mucosa is able to take up the administered technetium-99m pertechnetate from the circulating blood pool. Starting 10 minutes after the intravenous injection of 10 mCi technetium-99m pertechnetate, SPECT imaging was performed while fasting and for a total of 20 minutes after ingestion of 300 mL of Ensure (1 kcal/mL; Ross Nutrition, Abbott Laboratories, Columbus, OH). Gastric volumes were assessed during 2 postprandial periods: 0 –10 minutes and 10 –20 minutes after the meal. Transaxial images of the stomach were rendered with Analyze to reconstruct 3-dimensional images of the stomach and to measure gastric volumes during the fasting and postprandial periods. Extraneous structures such as the upper duodenum or a kidney in close proximity to the stomach, which had not been removed in the segmentation algorithm, were removed manually. The volume ratio between the postprandial and fasting volumes (gastric accommodation ratio ⫽ postprandial volume/fasting volume) was calculated.
Nutrient Drink Test All patients underwent 2 standardized nutrient drink tests,32,33 1 before large-volume paracentesis and another within 48 hours after paracentesis. Patients reported to the research unit on an empty stomach. Ensure (1 kcal/mL, 11% fat, 73% carbohydrate, 16% protein) was poured into a cup at a constant rate (30 mL/min), and patients were requested to maintain intake at the poured rate until a maximum tolerated volume was reached. Patients scored their satiation (feeling of fullness) at 5-minute intervals by using a graphic rating scale that combined verbal descriptors on a scale graded 0 –5 (0 ⫽ no symptoms, 5 ⫽ maximal satiety). Patients stopped meal intake when a score of 5 was reached. Total volume ingested was recorded.
Caloric Assessment All enrolled patients completed a written food diary for 3 consecutive days before and after paracentesis. Caloric
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Table 1. Patient Characteristics Total number ⫽ 15 Age (y)a Sex (male:female) Diagnosis Viral hepatitis Cryptogenic Alcoholic liver disease Non-alcoholic steatohepatitis Child–Pugh class A B C Fluid removed during paracentesis (L)a Decrease in body weight (kg)a Decrease in abdominal girth (cm)a aData
54 (51–65) 10:5 8/15 3/15 3/15 1/15 3/15 11/15 1/15 5.3 (4.0–6.8) 5.5 (3.6–6.6) 10 (8.3–12.5)
Figure 1. Gastric accommodation: healthy controls vs patients. Data are expressed as median (interquartile range). P ⫽ .006.
Gastric Volumes: Healthy Controls Versus Patients
are expressed as median (interquartile range).
assessment was completed with the assistance of a registered dietician.
Statistical Analysis By using a 25% overall coefficient of variation in our healthy population with the SPECT technique,20 our 15 patients provided 80% power to detect differences of 16%–23% between the test situations. Age- and sex-adjusted linear regression models were used to compare gastric volumes and accommodation ratios between patients and healthy volunteers, with these measures considered on the natural logarithm scale. Paired Wilcoxon rank-sum tests were used to compare gastric measures and nutritional assessment before and after paracentesis among the patient group. Demographic, physiologic, and clinical data are shown as medians and quartiles.
Results
Fasting gastric volumes among controls and patients did not differ. However, there was a smaller volume response to a meal in the patient group (P ⬍ .01), leading to reduced postprandial gastric volumes in patients compared with their healthy controls (P ⫽ .02) (Table 2). The decreased response to a standard meal was reflected in a decreased accommodation ratio in the patient group (P ⫽ .006, Figure 1). Gastric Volumes: Effect of Large-Volume Paracentesis Fasting gastric volumes increased significantly after large-volume paracentesis (P ⫽ .04) (Table 3). Although the postprandial gastric volumes tended to be greater after paracentesis vs before paracentesis, there was no significant difference in the median values. The significantly enlarged fasting gastric volumes relative to the modestly enhanced postprandial volumes yielded no significant change in the accommodation ratio. Nutrient Drink Test and Nutritional Intake
Study Population Fifteen patients (10 men, 5 women) with cirrhosis and ascites completed the trial (Table 1). The median age of the patients was 54 years. Large-volume paracentesis was completed in all patients, with a median of 5.3 L removed. Patients underwent a mean decrease in weight of 5.5 kg and a decrease in abdominal circumference of 10 cm after paracentesis.
The maximum tolerated volume and total caloric intake over the 3-day period were increased after largevolume paracentesis (P ⱕ .05) (Table 4).
Discussion We have shown that postprandial gastric volumes and associated accommodation ratios are reduced in pa-
Table 2. Gastric Volumes: Healthy Controls Versus Patients
Fasting gastric volume (mL) Postprandial volume (mL) Volume change (mL) Accommodation ratio
Healthy controls
Patients (before paracentesis)
P value
209 (177–258) 721 (651–813) 500 (447–563) 3.4 (2.8–4.0)
241 (182–328) 627 (551–709) 389 (345–422) 2.7 (2.1–2.9)
.14 .02 ⬍.01 .006
NOTE. Data are expressed as median (interquartile range).
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Table 3. Gastric Volumes: Effect of Large-Volume Paracentesis
Fasting gastric volume (mL) Postprandial volume (mL) Volume change (mL) Accommodation ratio
Before paracentesis
After paracentesis
P value
241 (182–328) 627 (551–709) 389 (345–422) 2.7 (2.1–2.9)
312 (230–361) 696 (612–808) 385 (323–502) 2.4 (1.8–2.9)
.04 .2 .4 .2
NOTE. Data are expressed as median (interquartile range).
tients with cirrhosis and ascites compared with healthy controls. Furthermore, large-volume paracentesis increases fasting gastric volumes, a finding associated with an increased tolerance to ingestion of a liquid nutrient drink as well as improved caloric intake over a 3-day period. SPECT assessment of gastric volumes was ideal in this clinical situation because oral or nasogastric placement of a barostat balloon is not a practical option in patients with cirrhosis and portal hypertension. This technology has identified similar changes in response to therapy in other clinical and research situations.28,31,34,35 By using ultrasound, Izbeki et al36 showed impaired gastric accommodation of the proximal stomach in patients with alcohol-induced liver cirrhosis. Similar results were found in patients with portal hypertension secondary to the hepatosplenic form of mansonic schistosomiasis.37 Taken with our current findings, it would appear that patients with cirrhosis and ascites have abnormalities of gastric accommodation or tone similar to those identified in a variety of other gastrointestinal disorders presenting with similar dyspeptic symptoms.11–14,21,38,39 However, although postprandial gastric volumes tended to increase after large-volume paracentesis, no improvement in the gastric accommodation ratio was seen secondary to the significant increase in fasting gastric volumes. This study identified a relationship between fasting gastric volumes, satiety, and caloric intake, with larger fasting gastric volumes associated with greater ingested volumes at maximum satiety and increased caloric intake over a 3-day period. This association between increased fasting gastric volumes and delayed satiation also has been identified elsewhere, with studies showing altered sensory or satiety testing in individuals with increased gastric volumes secondary to pharmacologic manipula-
tion.14,15,20,24 –26,30,34,35 This is considered to be secondary to a requirement of greater pressures (or volumes) to activate stretch or tension receptors when the stomach is relaxed. The pathophysiology of the abnormalities identified in patients with cirrhosis and portal hypertension is not understood fully and probably is multifactorial. Previous studies have shown that patients with cirrhosis and ascites have significantly higher variceal pressure and wall tension,40 and patients with portal hypertension also experience a significant increase in the portal pressure during the postprandial period.41 The increase in portal pressure may lead to increased gastric wall tension, thus reducing gastric relaxation. Because removal of ascitic fluid has been associated with improved pressures, largevolume paracentesis could enhance gastric relaxation, reflected in the increased fasting gastric volumes noted in this study. Octreotide, a long-acting somatostatin analog, results in splenic vasoconstriction, decreased portal flow, and blunting of the postprandial increase in portal pressure.41 Via this mechanism, it could contribute to the increased gastric volumes seen in healthy controls treated with octreotide.35 Other mechanisms that may impact gastric volumes and accommodation in our patient group include loss of gastric wall elasticity secondary to edema and vascular ectasia, autonomic dysfunction, altered levels of gastrointestinal hormones that influence gastric motility, and reduced levels of albumin.6,37,42– 46 Because albumin was infused during paracentesis in all patients, it is possible that changes in oncotic pressure could have contributed to the observed effects. Oncotic pressures and albumin measurements were not tracked in this investigation. A more straightforward explanation for the increased fasting gastric volumes is a simple mechanical one, with the
Table 4. Effect of Large-Volume Paracentesis on Nutrient Drink Test and Nutritional Intake
Maximum tolerated volume (mL) Caloric intake (kcal over 3 d)
Before paracentesis
After paracentesis
P value
738 (469–1078) 3110 (2160–3860)
964 (611–1276) 3470 (3048–5369)
.04 .005
NOTE. Data are expressed as median (interquartile range).
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removal of ascitic fluid reducing intraabdominal pressure or providing more room for the stomach to relax within the peritoneal cavity. Much like the pathophysiology underlying symptom generation in patients with functional dyspepsia, the cause of symptoms in patients with cirrhosis and portal hypertension undoubtedly is multifactorial and heterogeneous, and the relationships between different disturbances are unclear. Reduced food intake and subsequent malnutrition is a common problem in patients with cirrhosis in general, particularly those with ascites. Increasing ascites and associated symptoms of dyspepsia often are indications for paracentesis. Our data show a possible physiologic mechanism for improvement in patient symptoms after paracentesis. Other studies suggest that medications working on visceral sensation or gastric tone may be beneficial for patients with these physiologic abnormalities.20,24,26,34,47–50 Because several studies now suggest that fasting tone and gastric volumes appear to be significant in determining satiation, this deserves further investigation and may be a reasonable target for pharmacologic manipulation. In conclusion, postprandial gastric volumes and the accommodation ratio are reduced in patients with cirrhosis and ascites compared with healthy age- and sexmatched controls. Fasting gastric volumes increased after large-volume paracentesis, and this finding is associated with a significant increase in the maximum tolerated volumes during ingestion of a nutrient drink and caloric intake over a 3-day period.
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31. Delgado-Aros S, Kim DY, Burton DD, et al. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol 2002;282:G424 –G431. 32. Tack J, Caenepeel P, Piessevaux H, et al. Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia. Gut 2003;52:1271– 1277. 33. Chial HJ, Camilleri C, Delgado-Aros S, et al. A nutrient drink test to assess maximum tolerated volume and postprandial symptoms: effects of gender, body mass index and age in health. Neurogastroenterol Motil 2002;14:249 –253. 34. Delgado-Aros S, Chial HJ, Cremonini F, et al. Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health. Aliment Pharmacol Ther 2003;18:507–514. 35. Foxx-Orenstein A, Camilleri M, Stephens D, et al. Effect of a somatostatin analogue on gastric motor and sensory functions in healthy humans. Gut 2003;52:1555–1561. 36. Izbeki F, Kiss I, Wittmann T, et al. Impaired accommodation of proximal stomach in patients with alcoholic liver cirrhosis. Scand J Gastroenterol 2002;37:1403–1410. 37. Aprile LR, Meneghelli UG, Martinelli AL, et al. Gastric motility in patients with presinusoidal portal hypertension. Am J Gastroenterol 2002;97:3038 –3044. 38. Tack J, Caenepeel P, Fischler B, et al. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology 2001;121:526 –535. 39. Tack J, Demedts I, Dehondt G, et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology 2002;122:1738 –1747. 40. Kravetz D, Bildozola M, Argonz J, et al. Patients with ascites have higher variceal pressure and wall tension than patients without ascites. Am J Gastroenterol 2000;95:1770 –1775. 41. Vorobioff JD, Gamen M, Kravetz D, et al. Effects of long-term propranolol and octreotide on postprandial hemodynamics in
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Address requests for reprints to: Ernest P. Bouras, MD, Mayo Clinic, Davis E6A, 4500 San Pablo Road, Jacksonville, Florida 32224. Presented in part at Digestive Disease Week, New Orleans, Louisiana, May 17, 2004, and appears in abstract form in Gastroenterology 2004;126:A396.
Contribution of Ascites to Impaired Gastric Function and Nutritional Intake in Patients With Cirrhosis and Ascites BASHAR A. AQEL,* JAMES S. SCOLAPIO,* ROLLAND C. DICKSON,* DUANE D. BURTON,‡ and ERNEST P. BOURAS* *Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida; and ‡Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
Background & Aims: Protein calorie malnutrition and weight loss are common among patients with cirrhosis and ascites. The cause of these symptoms is unclear, with several putative mechanisms proposed. The primary aims of this study were to compare gastric volumes and accommodation between patients with cirrhosis complicated by ascites and healthy controls, and to evaluate the effect of large-volume paracentesis in the patient group. Methods: Patients with cirrhosis and ascites underwent assessment of gastric volumes as measured by single-photon emission computed tomography, gastric sensation assessed by a validated nutrient drink test, and a 3-day assessment of caloric intake before and after large-volume paracentesis. Age- and sex-adjusted linear regression models were used to compare gastric volumes and accommodation ratios between patients and healthy volunteers. Paired Wilcoxon ranksum tests were used to compare gastric measures before and after paracentesis among the patient group. Results: Fifteen patients (median age, 54 y) were compared with 112 healthy (age- and sex-matched) controls. Median postprandial gastric volumes (627 mL patients vs 721 healthy controls) and gastric accommodation were reduced significantly in patients compared with healthy controls (P ⴝ .02 and .006, respectively). After paracentesis: (1) fasting gastric volumes were increased (median 312 mL post- vs 241 mL pre-, P ⴝ .04), (2) patients tolerated ingestion of larger maximum volumes (median 964 mL post- vs 738 mL pre-, P ⴝ .04), and (3) caloric intake was increased (median 34% kcal post- vs 3110 kcal pre-, P ⴝ .005). Conclusions: Postprandial gastric volumes and accommodation ratios are reduced in patients with cirrhosis and ascites compared with healthy controls. In addition, large-volume paracentesis increases fasting gastric volumes, volumes ingested until maximal satiation, and caloric intake.
atients with cirrhosis and ascites frequently complain of dyspeptic symptoms such as early satiety, nausea, and postprandial fullness.1 These symptoms have been associated with decreased oral intake and clinically significant weight loss. Although several putative mech-
P
anisms have been proposed, the main cause of these symptoms in these patients is not known. One hypothesis is that delayed gastric emptying results in the sensation of satiety.2– 6 However, in a prospective Mayo Clinic study of patients with cirrhosis and ascites, no differences in gastric emptying between patients and healthy controls were identified.7 In addition, despite improvements in satiety and caloric intake after largevolume paracentesis, no changes in gastric emptying were identified. Gastric accommodation is a vagally mediated reflex that results in reduced gastric tone and increased gastric compliance, thereby facilitating the ingestion of large volumes of solids or liquids without inducing symptoms or the vomiting reflux. Impaired gastric accommodation has been associated with early satiety and other postprandial upper-gut symptoms in a variety of gastrointestinal disorders such as functional dyspepsia, rumination syndrome, postvagotomy/gastric surgery, and diabetes mellitus when associated with vagal neuropathy.8 –17 As a result of increased wall tension and stimulation of visceral afferents or alteration of cerebral perception, patients may develop gastric hypersensitivity while fasting or postprandially.15,18 –21 Recently, it was shown that fasting gastric volumes are associated with food intake and postprandial symptoms.22,23 Furthermore, pharmacologic manipulation leading to relaxation of the stomach has been shown to decrease sensitivity to gastric distention and meal-induced symptoms,14,15,20,24,25 with one study suggesting a direct effect on gastric tension mechanoreceptors.26 These findings suggest that the measurement of gastric volumes and their relationship with regard to accommodation after a meal may facilitate our understanding of Abbreviation used in this paper: SPECT, single-photon emission computed tomography. © 2005 by the American Gastroenterological Association 1542-3565/05/$30.00 PII: 10.1053/S1542-3565(05)00531-8
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upper-gastrointestinal symptoms in the postprandial period. Previously, the only reliable measurement of proximal gastric volumes and accommodation involved the placement of a polyethylene balloon into the stomach while linking it to a barostat device. More recently, a noninvasive method to measure fasting and postprandial volumes of the entire stomach using single-photon emission computed tomography (SPECT) was developed27 and validated.28 This novel approach, which requires no oral or nasogastric intubation, provides the opportunity to examine safely patients with cirrhosis and portal hypertension who may have esophageal or gastric varices. The primary aim of this prospective study was to evaluate gastric volumes and accommodation in patients with cirrhosis and ascites compared with healthy controls. We also wished to examine the impact of largevolume paracentesis in these patients while assessing satiety and nutritional intake.
Materials and Methods Study Participants The Mayo Clinic institutional review board approved all protocols, and all participants signed informed consent forms. Fifteen patients, aged 18 –70 years, with cirrhosis and ascites and symptoms of early satiety, nausea, and/or postprandial fullness who were presenting for large-volume paracentesis were included. Patients with a prior history of abdominal or gastric surgery, vagotomy, diabetes mellitus, confirmed diagnosis of autonomic neuropathy, or who were on medications that may alter gastrointestinal motility were excluded. Control data from 112 healthy age- and sex-matched controls previously studied using identical imaging techniques were used for comparison.28
Experimental Design After an initial screen, review of the study, and informed consent the participants completed a 3-day caloric assessment. Patients then presented to the study unit after an overnight fast where they underwent SPECT scanning of gastric volumes before and after a test meal. Subsequently patients completed a nutrient drink test and underwent large-volume paracentesis. Preparacentesis and postparacentesis weights and abdominal girth measurements were obtained. Within 24 – 48 hours after paracentesis the patients returned to the research unit after an overnight fast where they underwent repeat SPECT and nutrient drink tests. Measurements of weight and abdominal girth were obtained again. For 3 days after the paracentesis, patients underwent a repeat caloric assessment and review with a dietician.
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Measurement of Gastric Volumes and Accommodation A noninvasive method developed at the Mayo Clinic and validated against the standard gastric barostat was used to measure the fasting and postprandial gastric volumes after an intravenous injection of technetium-99m pertechnetate and imaging with SPECT.27,28 This technique has reproduced the gastric volumes reported in response to pharmacologic treatments and in patients with dyspepsia as measured by the barostat technique.14,29 –31 All tomographic studies were acquired on a large field of view, dual-head, gamma camera system (ADAC Phillips, Milpitse, CA) equipped with lowenergy, high-resolution collimators. Patients were positioned supine on the imaging table with the detectors over the upper and midabdomen to ensure imaging of the stomach and small bowel. Gastric volumes were measured using the SPECT-Analyze PC 2.5 (Biomedical Imaging Resource, Mayo Foundation, Rochester, MN) software system. The gastric mucosa is able to take up the administered technetium-99m pertechnetate from the circulating blood pool. Starting 10 minutes after the intravenous injection of 10 mCi technetium-99m pertechnetate, SPECT imaging was performed while fasting and for a total of 20 minutes after ingestion of 300 mL of Ensure (1 kcal/mL; Ross Nutrition, Abbott Laboratories, Columbus, OH). Gastric volumes were assessed during 2 postprandial periods: 0 –10 minutes and 10 –20 minutes after the meal. Transaxial images of the stomach were rendered with Analyze to reconstruct 3-dimensional images of the stomach and to measure gastric volumes during the fasting and postprandial periods. Extraneous structures such as the upper duodenum or a kidney in close proximity to the stomach, which had not been removed in the segmentation algorithm, were removed manually. The volume ratio between the postprandial and fasting volumes (gastric accommodation ratio ⫽ postprandial volume/fasting volume) was calculated.
Nutrient Drink Test All patients underwent 2 standardized nutrient drink tests,32,33 1 before large-volume paracentesis and another within 48 hours after paracentesis. Patients reported to the research unit on an empty stomach. Ensure (1 kcal/mL, 11% fat, 73% carbohydrate, 16% protein) was poured into a cup at a constant rate (30 mL/min), and patients were requested to maintain intake at the poured rate until a maximum tolerated volume was reached. Patients scored their satiation (feeling of fullness) at 5-minute intervals by using a graphic rating scale that combined verbal descriptors on a scale graded 0 –5 (0 ⫽ no symptoms, 5 ⫽ maximal satiety). Patients stopped meal intake when a score of 5 was reached. Total volume ingested was recorded.
Caloric Assessment All enrolled patients completed a written food diary for 3 consecutive days before and after paracentesis. Caloric
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Table 1. Patient Characteristics Total number ⫽ 15 Age (y)a Sex (male:female) Diagnosis Viral hepatitis Cryptogenic Alcoholic liver disease Non-alcoholic steatohepatitis Child–Pugh class A B C Fluid removed during paracentesis (L)a Decrease in body weight (kg)a Decrease in abdominal girth (cm)a aData
54 (51–65) 10:5 8/15 3/15 3/15 1/15 3/15 11/15 1/15 5.3 (4.0–6.8) 5.5 (3.6–6.6) 10 (8.3–12.5)
Figure 1. Gastric accommodation: healthy controls vs patients. Data are expressed as median (interquartile range). P ⫽ .006.
Gastric Volumes: Healthy Controls Versus Patients
are expressed as median (interquartile range).
assessment was completed with the assistance of a registered dietician.
Statistical Analysis By using a 25% overall coefficient of variation in our healthy population with the SPECT technique,20 our 15 patients provided 80% power to detect differences of 16%–23% between the test situations. Age- and sex-adjusted linear regression models were used to compare gastric volumes and accommodation ratios between patients and healthy volunteers, with these measures considered on the natural logarithm scale. Paired Wilcoxon rank-sum tests were used to compare gastric measures and nutritional assessment before and after paracentesis among the patient group. Demographic, physiologic, and clinical data are shown as medians and quartiles.
Results
Fasting gastric volumes among controls and patients did not differ. However, there was a smaller volume response to a meal in the patient group (P ⬍ .01), leading to reduced postprandial gastric volumes in patients compared with their healthy controls (P ⫽ .02) (Table 2). The decreased response to a standard meal was reflected in a decreased accommodation ratio in the patient group (P ⫽ .006, Figure 1). Gastric Volumes: Effect of Large-Volume Paracentesis Fasting gastric volumes increased significantly after large-volume paracentesis (P ⫽ .04) (Table 3). Although the postprandial gastric volumes tended to be greater after paracentesis vs before paracentesis, there was no significant difference in the median values. The significantly enlarged fasting gastric volumes relative to the modestly enhanced postprandial volumes yielded no significant change in the accommodation ratio. Nutrient Drink Test and Nutritional Intake
Study Population Fifteen patients (10 men, 5 women) with cirrhosis and ascites completed the trial (Table 1). The median age of the patients was 54 years. Large-volume paracentesis was completed in all patients, with a median of 5.3 L removed. Patients underwent a mean decrease in weight of 5.5 kg and a decrease in abdominal circumference of 10 cm after paracentesis.
The maximum tolerated volume and total caloric intake over the 3-day period were increased after largevolume paracentesis (P ⱕ .05) (Table 4).
Discussion We have shown that postprandial gastric volumes and associated accommodation ratios are reduced in pa-
Table 2. Gastric Volumes: Healthy Controls Versus Patients
Fasting gastric volume (mL) Postprandial volume (mL) Volume change (mL) Accommodation ratio
Healthy controls
Patients (before paracentesis)
P value
209 (177–258) 721 (651–813) 500 (447–563) 3.4 (2.8–4.0)
241 (182–328) 627 (551–709) 389 (345–422) 2.7 (2.1–2.9)
.14 .02 ⬍.01 .006
NOTE. Data are expressed as median (interquartile range).
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Table 3. Gastric Volumes: Effect of Large-Volume Paracentesis
Fasting gastric volume (mL) Postprandial volume (mL) Volume change (mL) Accommodation ratio
Before paracentesis
After paracentesis
P value
241 (182–328) 627 (551–709) 389 (345–422) 2.7 (2.1–2.9)
312 (230–361) 696 (612–808) 385 (323–502) 2.4 (1.8–2.9)
.04 .2 .4 .2
NOTE. Data are expressed as median (interquartile range).
tients with cirrhosis and ascites compared with healthy controls. Furthermore, large-volume paracentesis increases fasting gastric volumes, a finding associated with an increased tolerance to ingestion of a liquid nutrient drink as well as improved caloric intake over a 3-day period. SPECT assessment of gastric volumes was ideal in this clinical situation because oral or nasogastric placement of a barostat balloon is not a practical option in patients with cirrhosis and portal hypertension. This technology has identified similar changes in response to therapy in other clinical and research situations.28,31,34,35 By using ultrasound, Izbeki et al36 showed impaired gastric accommodation of the proximal stomach in patients with alcohol-induced liver cirrhosis. Similar results were found in patients with portal hypertension secondary to the hepatosplenic form of mansonic schistosomiasis.37 Taken with our current findings, it would appear that patients with cirrhosis and ascites have abnormalities of gastric accommodation or tone similar to those identified in a variety of other gastrointestinal disorders presenting with similar dyspeptic symptoms.11–14,21,38,39 However, although postprandial gastric volumes tended to increase after large-volume paracentesis, no improvement in the gastric accommodation ratio was seen secondary to the significant increase in fasting gastric volumes. This study identified a relationship between fasting gastric volumes, satiety, and caloric intake, with larger fasting gastric volumes associated with greater ingested volumes at maximum satiety and increased caloric intake over a 3-day period. This association between increased fasting gastric volumes and delayed satiation also has been identified elsewhere, with studies showing altered sensory or satiety testing in individuals with increased gastric volumes secondary to pharmacologic manipula-
tion.14,15,20,24 –26,30,34,35 This is considered to be secondary to a requirement of greater pressures (or volumes) to activate stretch or tension receptors when the stomach is relaxed. The pathophysiology of the abnormalities identified in patients with cirrhosis and portal hypertension is not understood fully and probably is multifactorial. Previous studies have shown that patients with cirrhosis and ascites have significantly higher variceal pressure and wall tension,40 and patients with portal hypertension also experience a significant increase in the portal pressure during the postprandial period.41 The increase in portal pressure may lead to increased gastric wall tension, thus reducing gastric relaxation. Because removal of ascitic fluid has been associated with improved pressures, largevolume paracentesis could enhance gastric relaxation, reflected in the increased fasting gastric volumes noted in this study. Octreotide, a long-acting somatostatin analog, results in splenic vasoconstriction, decreased portal flow, and blunting of the postprandial increase in portal pressure.41 Via this mechanism, it could contribute to the increased gastric volumes seen in healthy controls treated with octreotide.35 Other mechanisms that may impact gastric volumes and accommodation in our patient group include loss of gastric wall elasticity secondary to edema and vascular ectasia, autonomic dysfunction, altered levels of gastrointestinal hormones that influence gastric motility, and reduced levels of albumin.6,37,42– 46 Because albumin was infused during paracentesis in all patients, it is possible that changes in oncotic pressure could have contributed to the observed effects. Oncotic pressures and albumin measurements were not tracked in this investigation. A more straightforward explanation for the increased fasting gastric volumes is a simple mechanical one, with the
Table 4. Effect of Large-Volume Paracentesis on Nutrient Drink Test and Nutritional Intake
Maximum tolerated volume (mL) Caloric intake (kcal over 3 d)
Before paracentesis
After paracentesis
P value
738 (469–1078) 3110 (2160–3860)
964 (611–1276) 3470 (3048–5369)
.04 .005
NOTE. Data are expressed as median (interquartile range).
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removal of ascitic fluid reducing intraabdominal pressure or providing more room for the stomach to relax within the peritoneal cavity. Much like the pathophysiology underlying symptom generation in patients with functional dyspepsia, the cause of symptoms in patients with cirrhosis and portal hypertension undoubtedly is multifactorial and heterogeneous, and the relationships between different disturbances are unclear. Reduced food intake and subsequent malnutrition is a common problem in patients with cirrhosis in general, particularly those with ascites. Increasing ascites and associated symptoms of dyspepsia often are indications for paracentesis. Our data show a possible physiologic mechanism for improvement in patient symptoms after paracentesis. Other studies suggest that medications working on visceral sensation or gastric tone may be beneficial for patients with these physiologic abnormalities.20,24,26,34,47–50 Because several studies now suggest that fasting tone and gastric volumes appear to be significant in determining satiation, this deserves further investigation and may be a reasonable target for pharmacologic manipulation. In conclusion, postprandial gastric volumes and the accommodation ratio are reduced in patients with cirrhosis and ascites compared with healthy age- and sexmatched controls. Fasting gastric volumes increased after large-volume paracentesis, and this finding is associated with a significant increase in the maximum tolerated volumes during ingestion of a nutrient drink and caloric intake over a 3-day period.
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Address requests for reprints to: Ernest P. Bouras, MD, Mayo Clinic, Davis E6A, 4500 San Pablo Road, Jacksonville, Florida 32224. Presented in part at Digestive Disease Week, New Orleans, Louisiana, May 17, 2004, and appears in abstract form in Gastroenterology 2004;126:A396.