Limitations of indirect methods of estimating small bowel transit in man

Pressman, Jeffrey; Hofmann, Alan F.; Witztum, Kathryn F.; Gertler, Stanford L.; Steinbach, Joseph H.; Stokes, Kusum; Kelts, Drew; Stone, Diane; Jones, B.; Dharmsathaphorn, Kiertisin

doi:10.1007/bf01296133

Cited by 18 publications

(9 citation statements)

References 28 publications

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“…Under these conditions, OCTTs differed between 70 and 205 min (Heine, Mohr and Münch, 1996;Wutzke et al, 1996). Other conventional methods for evaluation of OCTTs are based on radiographic and scintigraphic methods using barium meals, 111 In-labelled plastic particles, [ 14 C]xylose, [ 14 C]lactulose and [ 99m Tc]DTPA (Barrow et al, 1992;Ghoos et al, 1993;Hirakawa et al, 1988;King and Toskes, 1986;Madsen et al, 1991;Pressman et al, 1987;Sciarretta et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Other conventional methods for the determination of OCTT are based on radiographic and scintigraphic methods using 111 In-labelled plastic particles, [ 14 Barrow et al, 1992;Hirakawa et al, 1988;Madsen et al, 1991;Pressman et al, 1987;Sciarretta et al, 1994). For ethical reasons, invasive or radioactive methods for OCTTmeasurements are not justificable, especially in childhood and pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of oro-coecal transit time: a comparison of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans

et al. 1997

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Objective:The lactulose H 2 -breath test is the most widely used non-invasive approach for evaluation of orocoecal transit time (OCTT). In the present study, doubly-labelled lactose-[ 13 C, 15 N]ureide (DLLU) was synthesized to investigate the OCTT in comparison to the conventional lactulose H 2 -breath test. Additionally, the bacterial breakdown rate (BBR) and rate of elimination and the metabolic pathways of the cleavage products of DLLU ( 13 CO 2 , [ 15 N]urea, and 15 NH 3 ) were investigated. Design and subjects: In a first study, DLLU was administered as a single oral-pulse-labelling (dosage: one gram) either without and after pretreatment of five grams of unlabelled lactoseureide (LU) on the day prior to the study to twelve healthy adult volunteers after breakfast. Breath and urine were collected in one and two hourintervals, respectively, over a one-day period. 13 C-enrichment in breath as well as 15 N-enrichment in urine fractions were measured by continuous flow-isotope ratio mass spectrometry (CF-IRMS). In a second study, lactulose was administered to the same subjects (dosage: ten grams). Breath was collected in quarter, half and one hour-intervals over a ten hour-period. Hydrogen concentration in breath was analysed using an electrochemical detector. Results:The comparison of the lactose-[ 13 C]ureide 13 CO 2 -breath test and the lactulose H 2 -breath test showed that the mean increase of the 13 C-enrichment in CO 2 occurred 1.18 h later than the mean increase of H 2 in breath. The resulting OCTTs derived from the two methods were 3.02 1.7 h (P < 0.01), respectively. The 15 N-enrichment of urinary urea and ammonia without and after pretreatment with LU started between two and three hours after DLLUadministration. The cumulative percentage urinary excretion of the 15 N-and 13 C-tracer was 29.9% and 13.6% respectively, and was slightly increased after LU-pretreatment to 32.1% and 14.6% of the dose administered. A total of 35.2% of the 13 C was found to be exhaled and remained approximately constant after LU-pretreatment (36.2%). Conclusions: The use of the lactulose H 2 -breath test for evaluation of the OCTT showed a statistically significant shortening of 1.18 h in comparison to the lactose-[ 13 C]ureide 13 CO 2 -breath test in healthy adults. The most important limitations of the lactulose H 2 -breath test are its low specificity and sensitivity due to dosedependent accelerations of OCTT, interfering H 2 -rise from malabsorbed dietary fibre and H 2 -non-producers. In contrast, our lactose-[ 13 C]ureide 13 CO 2 -breath test was confirmed to avoid these disadvantages and to yield reliable results. This test is recommended especially if higher sensitivity and specificity is required, if IRMStechnique is available and if lactulose H 2 -tests lead to insufficient results.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of oro-coecal transit time: a comparison of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans

et al. 1997

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“…To overcome such a drawback, a solid food has been substituted for a liquid meal with apparent excellent results, achieving coefficients of variation, below 10%, for repeated determinations [18,35,36] and improving the reproducibility obtained with lactulose diluted in water [10,18]. Other investigators, however, have not observed such improvement [28], and at least one study obtained a high coefficient of variation of 17% with a liquid meal substrate [37]. In the present study, when lactulose was administered in a liquid formula meal the reproducibility of the test was unchanged relative to lactulose in water as substrate.…”

Section: Discussionmentioning

confidence: 99%

Influence of the Substrate on the Reproducibility of the Hydrogen Breath Test to Measure the Orocecal Transit Time

Casellas¹,

Malagelada²

1998

Digestion

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Background: The H₂ breath test is widely used for the measurement of the orocecal transit time (OCTT). However, its clinical applicability is limited by its suboptimal reproducibility. Aim: To investigate whether changes in the substrate for the H₂ breath test improve its reliability for the measurement of the OCTT. Methods: 72 consecutive patients referred for measurement of the OCTT were studied. The breath test was performed twice, on consecutive days. One group of patients (‘lactulose + water’ group) received lactulose 13.3 g in water both days. Another group (‘lactulose + diet’) received lactulose 13.3 g in a liquid meal of 400 kcal. A third group (‘lactulose-lactitol’) received 13.2 g of lactulose the first day and 10 g lactitol the following day. The fourth group (‘lactitol + water’) received lactitol 10 g in water both days. Alveolar breath was sampled every 10 min for the next 3 h for H₂ chromatography. Results: OCTT in the first and second day test for the groups ‘lactulose + water’, ‘lactulose + diet’ and ‘lactitol + water’ were similar. In these three groups, the values obtained on the first and second day did not differ from 0 and were also significantly correlated. However, the correlation and the mean coefficient of variation were better in group ‘lactulose + water’ than in the groups ‘lactulose + diet’ and ‘lactitol + water’. In group ‘lactulose-lactitol’ the results on both days were significantly correlated although the delta between matched values was different from 0 (p = 0.03). Conclusion: The meal substrate influences the variability of the OCTT. However, reproducibility of the test does not improve with the addition of a liquid meal.

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“…The SMD indicated an increase in transit time, however this was nonsignificant (SMD = 0.31, 95% CI −0.17 to 0.79; I 2 = 53%; see Supplementary Figure 14). The WMD was also calculated: clonidine increased significantly orocaecal transit time by 0.52 hours (31.2 minutes; 95% CI 0.06−0.98 h; I 2 = 61%) [Baxter et al 1987;Pressman et al 1987;Baumer et al 1989;Rubinoff et al 1989;Morali et al 1991;Mann and Shinkle, 1998;Camilleri et al 2003] (Supplementary Figure 15). Furthermore, clonidine decreased rectal losses of sodium (SMD = −0.81, 95% CI −1.67 to 0.05; I 2 = 59%; see Supplementary Figure 16) [Schiller et al 1985;Rabbani et al 1989;Buchman et al 2006] and chloride (SMD = −0.75, 95% CI −1.34 to 0.16; I 2 = 0%) (Supplementary Figure 17) [Schiller et al 1985;Rabbani et al 1989], but did not affect bicarbonate (SMD = 0.29, 95% CI −0.63 to 1.21; I 2 = 53%; see Supplementary Figure 18) and potassium losses (SMD = 0.11, 95% CI −0.46 to 0.67; I 2 = 0%; see Supplementary Figure 19) [Schiller et al 1985;Rabbani et al 1989] while it did not affect absorption of sodium (SMD = 0.31, 95% CI −0.44 to 1.06; I 2 = 0%; see Supplementary Figure 20) and potassium (SMD = 0.20, 95% CI −0.55 to 0.94; I 2 = 0%; see Supplementary Figure 21) [Schiller et al 1985;Buchman et al 2006].…”

Section: Meta-analysis Of the Main Outcomementioning

confidence: 99%

“…The case reports [Mcarthur et al 1982;Sacerdote, 1986;Zimmermann et al 1986;Roof, 1987;Migliore et al 1988;Scholz et al 1991;Schworer et al 1995] are discussed narratively in a separate section below because of possible high placebo rates and are not included in the meta-analysis. The remaining 24 trials/case series included 10 studies with healthy volunteers (total sample size = 150 participants) [Schiller et al 1985;Baxter et al 1987;Pressman et al 1987;Baumer et al 1989;Gregersen et al 1989;Rubinoff et al 1989;Thollander et al 1997Thollander et al , 1999Mann and Shinkle, 1998;Viramontes et al 2001] and 14 studies (total sample size = 493 patients) with faecal incontinence, irritable bowel syndrome, diabetes, alcohol withdrawal, heroin withdrawal, ultra-rapid opioid detoxification, short bowel syndrome (high output ileostomy or high rectal output), intestinal transplant and cholera patients [Fedorak et al 1985;Bretzke, 1987;Gupta and Jha, 1988;Rabbani et al 1989;Baumgartner and Rowen, 1991;Morali et al 1991;Rovera et al 1997;Camilleri et al 2003Camilleri et al , 2009Mcdoniel et al 2004;Buchman et al 2006;Farzam and Najafi, 2009;Bharucha et al 2010Bharucha et al , 2014. Results regarding statistical analysis of these studies are described in the following.…”

Section: Systematic Review and Meta-analysis Of Trialsmentioning

confidence: 99%

What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans

Fragkos

Zárate-López

Frangos

2016

Therap Adv Gastroenterol

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Background: Clonidine is considered an alternative treatment for refractory diarrhoea. The evidence in the literature is scarce and not conclusive. The present paper's purpose is to gather available evidence and provide a systematic answer regarding the effectiveness of clonidine for diarrhoea. Method: We performed a systematic review of clonidine and its effect on diarrhoea. Metaanalysis was performed with a random effects model of the standardized mean difference (SMD) or the weighted mean difference and heterogeneity was quantified with I 2 and publication bias was assessed with Egger's and Begg's test. Subgroup analyses and metaregression were performed to investigate sources of heterogeneity. Any empirical study describing use of clonidine for diarrhoea in humans independent of age was included. For the meta-analysis, papers had to provide sufficient data to produce an effect measure, while case reports were not included in the meta-analysis and are discussed narratively only. Results: A total of 24 trials and seven case reports were identified. Clonidine (median dose 300 μg/day) has been used for treatment of diarrhoea in irritable bowel syndrome, faecal incontinence, diabetes, withdrawal-associated diarrhoea, intestinal failure, neuroendocrine tumours and cholera; studies were also performed on healthy volunteers. Results indicate a strong effect of clonidine on diarrhoea (SMD = −1.02, 95% confidence interval [CI] −1.46 to −0.58) with a decrease of stool volume by 0.97 l/day, stool frequency by 0.4 times/day and increase in transit time by 31 minutes. In a sensitivity analysis of studies with functional diarrhoea and sample size over 10 subjects, the effect was similar −0.99 (95% CI −1.54 to −0.43). There is however significant heterogeneity and publication bias. Heterogeneity decreased in subgroup analyses by condition but not with other factors examined. A limitation of the present study includes small study effects. Conclusion: Clonidine is effective for treatment of diarrhoea and should be considered as an alternative when all other medications have failed.

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Limitations of indirect methods of estimating small bowel transit in man

Cited by 18 publications

References 28 publications

Evaluation of oro-coecal transit time: a comparison of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans

Evaluation of oro-coecal transit time: a comparison of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans

Influence of the Substrate on the Reproducibility of the Hydrogen Breath Test to Measure the Orocecal Transit Time

What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans

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