Geoff Davidson

Delayed gastric emptying in ventilated critically ill patients: Measurement by 13C-octanoic acid breath test

ObjectiveTo measure gastric emptying in ventilated critically ill patients with a new noninvasive breath test. DesignSingle-center, open study. SettingCombined medical and surgical intensive care unit of a university hospital. SubjectsThirty unselected mechanically ventilated critically ill patients receiving gastric feeding and 22 healthy volunteers. InterventionsNone. PatientsAfter 4 hrs without feeding, intragastric infusion of 100 mL of a liquid meal (Ensure) labeled with 100 &mgr;L 13C-octanoic acid. End-expiratory breath samples were collected into evacuated tubes from the respirator circuit every 5 mins for the first hour, then every 15 mins for 3 hrs. End-expiratory breath samples were also collected from volunteers studied supine after an overnight fast following an identical infusion via a nasogastric tube. Breath 13CO2 was measured with an isotope ratio mass spectrometer. Measurements and Main Results Performance of the breath test posed no difficulty or interference with patient care. The CO2 level was >1% in 1297/1300 breath samples, indicating satisfactory end-expiratory timing. Data are median and interquartile range. Gastric emptying was slower in patients compared with volunteers: gastric emptying coefficient 2.93 (2.17–3.39) vs. 3.58 (3.18–3.79), p < .001 and gastric half emptying time, derived from the area under the 13CO2 curve, 155 min (130–220) vs. 133 min (120–145), p < .008. Fourteen of the 30 patients had a gastric emptying coefficient <95% of all volunteers and 11 had a gastric half emptying time longer than 95% of all volunteers. The Acute Physiology and Chronic Health Evaluation (APACHE II) score (median 22, range 13–43) either at admission or on the day of the study did not correlate with gastric emptying coefficient. ConclusionGastric emptying of a calorie-dense liquid meal is slow in 40% to 45% of unselected mechanically ventilated patients in a combined medical and surgical intensive care unit. The 13C-octanoic acid breath test is a novel and useful bedside technique to measure gastric emptying in these patients.

Esophageal body and lower esophageal sphincter function in healthy premature infants

BACKGROUND & AIMS Gastroesophageal reflux is a common problem in premature infants. The aim of this study was to use a novel manometric technique to measure esophageal body and lower esophageal sphincter pressures in premature infants. METHODS Micromanometric feeding assemblies (OD, < or = 2 mm) incorporating 4-9 manometric channels were used in 49 studies of 27 premature neonates. Esophageal body motility was recorded at three sites for 20 minutes after feeding. Twenty attempts (one per minute) were made to stimulate swallowing via facial stimulation (Santmyer reflex). In 32 studies lower esophageal sphincter pressures were recorded (sleeve) for 15 minutes before and after feeding. RESULTS Peristaltic motor patterns were less common than non-peristaltic motor patterns (26.6% vs. 73.4%; P < 0.0001) that comprised 31.1% synchronous, 34.6% incomplete, and 6.3% retrograde pressure waves. Reflex swallowing was elicited more frequently in neonates older than 34 weeks postconceptional age than in younger infants (33.4% vs. 20.4%; P < 0.05). Mean lower esophageal sphincter pressure was 20.5 +/- 1.7 mm Hg before and 13.7 +/- 1.3 mm Hg after feeding (P < 0.0005). CONCLUSIONS Premature infants show nonperistaltic esophageal motility that may contribute to poor clearance of refluxed material. In contrast, the lower esophageal sphincter mechanisms seem well developed.

Autoimmune enteropathy with anti-goblet cell antibodies

A 9-year-old boy with a 5-year history of severe protracted diarrhea requiring home parenteral nutrition and a 1 year history of abnormal liver function tests was admitted for duodenal, rectal, and liver biopsy. Duodenal biopsy results showed mild villus blunting, a mild lymphocytic infiltrate, and absent goblet cells. Paneth cells and endocrine cells could not be identified. Review of several previous biopsies showed an almost total absence of goblet cells by light microscopy. Anti-goblet cell antibodies of the immunoglobulin (Ig)G class were shown by immunofluorescence with a titer of 1:512. Histological examination of rectal mucosa also showed a total lack of goblet cells, orderly surface epithelial cells, and infiltration of the colonic crypts by lymphocytes. Immunoperoxidase staining of rectal mucosa showed increased numbers of lymphocytes with an excess of CD3+, CD45RO+ T cells, and increased numbers of B cells labeling with B1 and L26. Increased numbers of CD25+ (activated) lymphocytes were also observed. HLA/DR expression was striking and observed in both the crypt and surface enterocytes, as well as in the lamina propria. Immunological assessment of the patient showed an inverted CD4/CD8 ratio and IgA/IgG4 deficiency. The liver biopsy and radiological investigation were in keeping with chronic sclerosing cholangitis. Although a slight and transient improvement in histological appearances was observed with prednisolone there was no significant improvement of diarrhea. Trials of azothiaprine and oral cyclosporin did not result in clinical or histological improvement.

Reproducibility of the 13C-octanoic acid breath test for assessment of gastric emptying in healthy preterm infants

BACKGROUND The 13C-octanoic acid breath test has been used to measure gastric emptying in preterm infants, but the reproducibility of the test has not been evaluated in this population. METHODS Fifty-six paired breath test analyses were performed on 28 healthy preterm infants 1 to 5 days apart using the same food type, volume, and energy content for each paired sample. Breath samples were taken before the feeding, at 5-minute intervals after feeding for 30 minutes, then each 15 minutes for 4 hours. Samples were analyzed using an isotope-ratio mass spectrometer, and 3C recovery was used to calculate values for gastric-emptying coefficient and gastric half-emptying time. RESULTS There was no significant difference between test results on different days in the paired samples studied. gastric-emptying coefficients for the first and subsequent samples were 2.6+/-0.1 (mean+/-SEM) and 2.7+/-0.1, respectively, and half-emptying times were 44.5+/-3.7 minutes and 41.4+/-3.2 minutes. CONCLUSION The 13C-octanoic acid breath test is a reliable, noninvasive, and reproducible measure of gastric emptying in preterm infants that should have wide application for use in this population.

Epithelial growth of the small intestine in human infants

BACKGROUND Findings in studies in rodents have suggested that epithelial growth of the small intestine is dependent on activation of the immune system. The purpose of this study was to compare changes of postnatal epithelial growth with immunologic activity in humans. METHODS Duodenal biopsies were obtained by endoscopy from 74 infants. Villus area, crypt length, and mitotic count were measured, using a microdissection technique. Enterocyte height, intraepithelial lymphocytes and mucosal mast cells were recorded in histologic sections, and soluble interleukin-2 receptor levels were measured in sera. These data were compared with those from 77 adult control subjects. RESULTS Mean +/- SD villus area was similar in infants compared with that in adults (0.364 +/- 0.108 mm2 vs. 0.339 +/- 0.1 mm2); but mean crypt length was 31% longer (270 +/- 56 microm vs. 206 +/- 29 microm; p < 0.0001), and mitotic count was 68% higher (4.2 +/- 2.8 vs. 2.5 +/- 1 per crypt; p < 0.0001) in infants. Enterocyte height was lower during infancy (27.0 +/- 3.4 microm vs. 30.9 +/- 4.6 microm; p < 0.0001). There was no evidence of a trophic effect on the small intestine of breast feeding compared with the effect of bottle feeding. Counts of intraepithelial lymphocytes but not mucosal mast cells were significantly less in infants. Mean soluble interleukin-2 receptor levels peaked during early infancy, compared with levels in adults (1,820 +/- 596 U/ml vs. 695 +/- 359 U/ml). CONCLUSION These results indicate that epithelial proliferation is increased during infancy at an age when immunologic activity is high.

Effect of Age on Fructose Malabsorption in Children Presenting With Gastrointestinal Symptoms

Objectives:Fructose malabsorption can produce symptoms such as chronic diarrhoea and abdominal pain. Here, we retrospectively review breath hydrogen test (BHT) results to determine whether age has an effect on the clinical application of the fructose BHT and compare this with the lactose BHT. Patients and Methods:Patients were referred to a gastroenterology breath-testing clinic (2003–2008) to investigate carbohydrate malabsorption as a cause of gastrointestinal symptoms. Patients received either 0.5 g/kg body weight of fructose (maximum of 10 g) or 2 g/kg of lactose (maximum of 20 g), in water, and were tested for 2.5 hours. Results:Patient age showed a significant effect on the fructose BHT results (P < 0.001, 0.1–79 years old, n = 1093). The odds of testing positive for fructose malabsorption in paediatric patients (15 years old or younger, n = 760) decreased by a factor of 0.82/year (95% confidence interval 0.79–0.86, P < 0.001). There were 88.2% positive in younger than 1-year-olds, 66.6% in 1- to 5-year-olds, 40.4% in 6- to 10-year-olds, and 27.1% in 10- to 15-year-olds. In contrast, 39.3% of lactose BHTs were positive, with no significant relation between patient age and test result (P = 0.115, 0.1–89 years old, n = 3073). Conclusions:The majority of infants with gastrointestinal symptoms exhibited fructose malabsorption, but the capacity to absorb fructose increased with patient age up to 10 years old. The low threshold for fructose absorption in younger children has significant implications for the performance and interpretation of the fructose BHT and for the dietary consumption of fructose in infants with gastrointestinal symptoms.

Evaluation of the 13C‐triolein breath test for fat malabsorption in adult patients with cystic fibrosis

Background and Aims: A simple non‐invasive test not requiring the use of radioactive isotopes is required to assess fat malabsorption in adult cystic fibrosis (CF) patients. Breath tests using substrates labeled with 13C meet these conditions. The 14C‐triolein breath test is sensitive and specific for measuring fat malabsorption, but involves radiation exposure. The aim of this study was to examine the utility of a test using a 13C label and to determine whether pancreatic replacement therapy would return the test to the values of a normal control group.

Intrasubject variability of gastric emptying in the critically ill using a stable isotope breath test.

BACKGROUND AND AIMS Isotope breath tests are increasingly used to evaluate the effects of prokinetic drugs on gastric emptying. The aim was to assess intrasubject variability in gastric emptying, when using an isotope breath test in the critically ill. METHODS A retrospective analysis of data was undertaken in 12 patients who had gastric emptying measurements on consecutive days using a (13)C-octanoic acid breath test. The gastric emptying coefficient--GEC (a global index for the gastric emptying rate), and the t(50) (calculated time for 50% of meal to empty) were calculated, together with the coefficient of variability for these parameters. Data are mean (SD). RESULTS Neither GEC (day 1: 3.3 (0.8) vs. day 2: 3.1 (0.6); P = 0.31) nor t(50) (day 1: 127 (43) min vs. day 2: 141 (48) min; P = 0.46) were significantly different between the two days. Intrasubject variability was less for GEC (15.6%) than for t(50) (31.8%). CONCLUSION There is only modest intrasubject variability in GEC measurements using the (13)C-octanoic acid breath test in critically ill patients. As such, it may be an acceptable measurement tool to assess the effects of prokinetic drugs in this group.

Sucrose malabsorption and impaired mucosal integrity in enterally fed critically ill patients: A prospective cohort observational study

Objective:Inadequate nutrition is common in critical illness due in part to gastric stasis. However, recent data suggest that altered small intestinal mucosal function may be a contributing factor. The aim of this study was to examine the effects of critical illness on sucrose absorption, permeability, and mucosal morphology. Design:Prospective, observational study. Setting:Tertiary critical care unit. Subjects:Twenty mechanically ventilated patients (19 men; 52.2 ± 20.5 yr; 9 feed intolerant; Acute Physiology and Chronic Health Evaluation II score 16.2 ± 6.0) and 20 healthy subjects (14 men; 51.6 ± 21.5 yr). Interventions:Following a 4-hr fast, a “meal” (100 kcal Ensure, 20-g enriched 13C-sucrose, 1.1 g rhamnose, 7.5 mL lactulose) was administered into the small intestine. Sucrose absorption was evaluated by analyzing 13CO2 concentration (cumulative percent of administered 13C dose recovered) in expiratory breath samples taken at timed intervals. At 90 minutes, a plasma lactulose/rhamnose concentration was also measured, with lactulose/rhamnose ratio, a marker of small intestinal mucosal permeability. When possible duodenal biopsies were taken in critically ill patients on insertion of the small intestinal feeding catheter and examined for disaccharidase levels and histology. Data are mean ± SD. Results:When compared with healthy subjects, critically ill patients had significantly reduced cumulative 13CO2 recovery (90 min: 1.78% ± 1.98% vs. 8.04% ± 2.55%; p < 0.001) and increased lactulose/rhamnose ratio (2.77 ± 4.24 vs.1.10 ± 0.98; p = 0.03). The lactulose/rhamnose ratio was greater in feed-intolerant patients (4.06 ± 5.38; p = 0.003). In five patients, duodenal mucosal biopsy showed mild to moderate epithelial injury. Sucrase levels were normal in all patients. Conclusions:Sucrose absorption is reduced and intestinal permeability increased in critically ill patients, possibly indicating an impairment of small intestinal mucosal function. These results, however, are discordant with duodenal mucosal histology and sucrase levels. This may reflect an inactivation of sucrase in vivo or inadequate nutrient exposure to the brush border due to small intestinal dysmotility.

Zinc homeostasis and gut function in children with celiac disease

BACKGROUND Celiac disease (CD) is an immunologic enteropathy triggered by the intake of gluten. It is thought that the enteropathy impairs gut function and absorption. OBJECTIVE We assessed the zinc-absorption capacity and small-bowel integrity in children with CD. DESIGN Children in whom a diagnosis of CD was considered clinically and either confirmed (n = 16; Marsh score ≥3) or not (n = 22; Marsh score of 0) with a small-bowel biopsy (SBB) were recruited. The fractional absorption of zinc (FAZ) was determined by the administration of an oral (67)Zn dose (2.5 mg) and an intravenous (70)Zn dose (0.2 mg) 2 h before and during the SBB, respectively. Spot urine samples were collected, and zinc isotopic ratios were determined by ion-coupled plasma mass spectrometry. Gut health was assessed by the ingestion of (13)C-sucrose (20 g) after an overnight fast, and breath samples were collected and analyzed by isotope ratio mass spectrometry. RESULTS There was no difference in FAZ between children with a Marsh score ≥3 (mean ± SEM: 0.68 ± 0.05) and children with a Marsh score of 0 (0.74 ± 0.05). The exchangeable zinc pool (EZP) was significantly (P < 0.05) lower in children with a Marsh score ≥3 (2.6 ± 0.8 mg/kg) than in children with a Marsh score of 0 (3.8 ± 1.4 mg/kg). Gut function in children with a Marsh score ≥3 (4.5 ± 0.7% cumulative dose recovered at 90 min) was lower than the lower cutoff of a normal gut-function breath test (5.06% cumulative dose recovered at 90 min) but not significantly different from that in children with a Marsh score of 0 (4.9 ± 0.4%). There was a significant (P < 0.01) correlation between zinc absorption and gut function in children with CD. CONCLUSIONS Zinc absorption did not appear below usual amounts in subjects with CD. Children with CD have impaired gut function that may affect their zinc nutritional status as shown by a smaller EZP. However, the EZP decrease in children with CD was not compared with that in healthy control subjects, and its biological meaning is uncertain.