Rino A Gani, A. Aziz Rani, Marcellus Simadibrata and Paulus Simadibrata - Orocecal Transit Time in Normal Adults at Cipto Mangunkusumo National Center General Hospital, Jakarta

ORIGINAL ARTICLE




ORIGINAL ARTICLE

Orocecal Transit Time in Normal Adults at Cipto Mangunkusumo National Center General Hospital, Jakarta Paulus Simadibrata*, Rino A. Gani**, Marcellus Simadibrata. K***, A. Aziz Rani*** * Department of Internal Medicine, Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta ** Division of Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta *** Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta ABSTRACT Background Orocecal transit time can be used to measure intestinal tract motility. Orocecal transit time measurement can be beneficial in various clinical conditions. This study aims at determining the orocecal transit time in healthy adults at the Cipto Mangunkusumo National Center General Hospital, Jakarta. Materials and method The 36 healthy adults in this study were taken from the Cipto Mangunkusumo National Center General Hospital community, Jakarta. Orocecal transit time was determined using the hydrogen breath test using 20 mL of lactulose (13.3 g). After fasting of at least 10 hours, subjects were asked to undergo the hydrogen breath test while fasting for 30 minutes for a total of 3 hours. Increased H2 concentration of equal to or over 10 parts per million from the basal (fasting value) was considered as the point when lactulose reached the caeccum, thus considered as the orocecal transit time. If no H2 increase was found during the evaluation, the subject was considered to have produced no H2. Results Out of the 36 study subjects, 31 people (86.1%) produced H2, thus available for orocecal transit time evaluation. The average orocecal transit time from the 31 subjects was 93.9 ± 31.7 minutes. The other five subjects did not have increased H 2 concentration in the 3 hours of hydrogen breath test, and thus were considered as non-H2 producers. Conclusion The average orocecal transit time from the 31 healthy adults from the Cipto Mangunkusumo National Center General Hospital community was 93.9 ± 31.7 minutes. The hydrogen breath test is an easy, safe, quick, and relatively low-cost method of evaluation that can be clinically applied, even though its specificity and sensitivity varies from one study to another in foreign countries. Key words: Orocecal transit time, hydrogen breath test, normal adults. BACKGROUND Gastrointestinal motility has gained attention from gastroenterologist all over the world for its important role in the pathogenesis of various bowel symptoms. Various studies on gastrointestinal motility have been conducted with various different methods. Meanwhile, even though there have been great development in the understanding 38 of the neuro-hormonal control mechanism on gastrointestinal motility, its clinical application is still limited. Thus, gastroenterologists greatly focus their attention on a non-invasive and easy method of evaluation of gastrointestinal transit time.1 Presently, several methods of evaluation have been utilized, including manometry; scintigraphy with standard The Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy

ORIGINAL ARTICLE

Orocecal Transit Time in Normal Adults at Cipto Mangunkusumo National Center General Hospital, Jakarta

radio-labeled fluid or solid substrates, radio-opaque markers, bio-magnetic method, and breath test evaluation.2,3,4 Evaluation of intestinal motility stated as the oro-cecal transit time (OCTT) have also been frequently used abroad, both using simple and complicated techniques. The technique of OCTT evaluation in humans includes the hydrogen breath test and gamma scintigraphy using radioactive markers. OCTT evaluation has been conducted frequently under various clinical conditions, including scleroderma and systemic sclerosis. Thus, it is beneficial in further management of the patient.5,6,7 However, the normal OCTT value varies greatly from different literatures, and there has been no report on OCTT evaluation results from Indonesia. This study aims to determine the normal value of OCTT in healthy adults. The benefit of this study is to determine a normal OCTT value to be used as a standard of comparison with OCTT values from patients with gastrointestinal dysmotility in Indonesia. MATERIALS AND METHOD Thirty-six healthy adults from the Cipto Mangunkusumo National Center General Hospital community, Jakarta, participated in this study. All study subjects did not demonstrate any gastrointestinal complaints, and did not suffer from any infectious disease in the preceding month. Subjects with history of diabetes mellitus were excluded from the study. Routine blood evaluation was conducted as baseline data. Subjects were required to fast at least 10 hours prior to the hydrogen breath test. Subjects were required to avoid smoking and exercise one day prior to the test. All subjects gave oral informed consent. The hydrogen breath test was conducted using 20 ml (13.3 g) of lactulose substrate (Lactulax®, PT. Ikapharmindo, Jakarta). The hydrogen breath test was performed once during fasting as a basal value, then every 30 minutes up to a total of 3 hours. The instrument used for the hydrogen breath test was a Lactomer manufactured by Hoek Loos, Netherlands, that is capable of detecting up to 0-200 ppm H2 with an accuracy rate of ± 2%. 8,9 The point when H2 was increased to 10 parts per million (ppm) or more from the basal value was considered as the time when lactulose entered the caecum, and was considered as the OCTT (in minutes).10 If there was no increase in H 2 concentration from the basal value, the subject was considered as a non-H2 producer. Volume 3, Number 2, August 2002 RESULTS Out of the 36 study subjects, the average age was 38.8 ± 12.1 years, with the greatest age group being from 30-39 years, consisting of 31 subjects (33.3%) The characteristics of study subjects can be found in Table 1 as follows. Table 1. Characteristics and Laboratory Data of 36 Subjects Sex (M/F) Age (year) Height (cm) Body weight 2 BMI (kg/m ) Hb (g/dL) Ureum (mg/dL) Creatinine (mg/dL) Blood sugar (g/dL) 13/23 38.8  12.1 160.6  8.5 61.0  11.7 23.6  3.8 13.4  1.1 27.9  7.1 0.8  0.2 89.2  7.9 All values are expressed as mean  standard deviation. M: male; F: female; BMI: body mass index; Hb: haemoglobin level. Out of the 36 subjects, only 31 subjects (86.1%) demonstrated an increased H2 concentration of over 10 ppm from the basal value, thus providing an OCTT value, while the remaining 5 (13.9%) did not produce an increase in H2 (Figure 1). The average OCTT value of the 31 subjects was 93.9 ± 31.7 minute with a median value of 90 minutes (minimum 60 minutes-maximum 150 minutes). Analysis using t test demonstrated no statistically significant association between OCTT and sex (p = 0.841). Because the variation coefficient is over 20%, wecontinued with the non-parametric test (MannWhitney test), which did not demonstrate a statistically significant relationship (p = 0.602) (Table 2). There was no statistically significant relationship between OCTT and age group. One-way analysis of variance (ANOVA) found a p value of p = 0.684 (Table 2). There was no statistically significant relationship between OCTT and body mass index (BMI). One-way analysis of variance (ANOVA) found a p value of p = 0.727 (Table 2). Table 2. Distribution and Significance of the Correlation Between OCTT and Sex Sex n OCTT Significance Significance test (minute) (p  0.05) Male 11 Mean 95.5  26.2 Median 90 (60-150) p = 0.602 Mann-Whitney Female 20 Mean (NS) 93.0  35.0 Median 90 (60-150) NS: non-significant 39

Orocecal Transit Time in Normal Adults at Cipto Mangunkusumo National Center General Hospital, Jakarta

Paulus Simadibrata, Rino A. Gani, Marcellus S. Kolopaking, A. Aziz Rani

Table 3. Distribution and Significance of the Correlation Between OCTT and Age Age (year) n OCTT (minute) Significance test 17–19 1 20-29 7 30-39 12 40-49 6 50-59 4 60-69 1 Mean 60.0 Median 60 (60-60) Mean 85.7  36.5 Median 60 (60-150) Mean 102.5  32.5 Median 90 (60-150) Mean 90.0  32.9 Median 90 (60-150) Mean 90.0  24.5 Median 90 (60-120) Mean 120.0 Median 120 (120-120) Significance (p  0.05) One-way ANOVA p = 0.684 (NS) NS: not significant Table 4. Distribution and Significance of the Correlation Between OCTT and BMI 2 BMI (kg/m ) n OCTT (minute)  18.5 4 18.5 - 25.0 20  25.0 7 Significance test Significance (p  0.05) Mean 82.5  28.7 Median 75 (60120) Mean 94.5  31.2 Median 90 (60150) Mean 98.6  37.6 Median 90 (60150) One-way ANOVA p = 0.727 (NS) NS: not significant 120 100 80 60 40 20 0 0 30 60 90 120 150 180 Time (minute) Figure 1. Result of The Hydrogen Breath Test of 31 Subjects DISCUSSION OCTT evaluation using the hydrogen breath test has frequently been performed in various studies abroad using various specificity and sensitivity.10 The hydrogen breath test has been compared to other methods in various studies, and demonstrated a close correlation between the point of hydrogen increase with isotop appearance in the caecum or ascending colon. 11 We chose the hydrogen breath test since it is a relatively low-cost, easy, quick, safe, and non-invasive method compared to evaluation methods using radioactive materials or manometry using electrodes that need to be inserted into the gastrointestinal tract. The hydrogen breath test was performed in the morning, not during other times, noting the clear circadian pattern in the hydrogen breath test, being higher in the morning and decreasing to the nadir point in the 40 afternoon.12 Smoking can increase the concentration of H2 in the expiration air, while exercise or hyperventilation can reduce H 2 concentration in the expiration air.15 Thus, subjects were asked not to smoke or exercise one day prior to the hydrogen breath test.13,14 In addition, it has been proven that smoking and nicotine increases the oro-cecal transit time.15 The lactulose we used as substrate for the hydrogen breath test was a carbohydrate that is not absorbed in the gastrointestinal tract. Thus, it is expected to reach the caecum for fermentation by bowel bacteria to produce H2 gas that can be measured.16 The finding that 13.9% subjects did not produce H2 gas was in accordance with data from studies abroad that 0-27% of all people are not H 2 producers. However, the incidence of non-H2 producers depend on the criteria used as a cutoff point for H2 production.17 Data from a large study demonstrated that 98% of the United States population secreted H2, while 33% secreted CH4.18 The possibility that the subjects of our study were CH4 producers cannot be eliminated, but to determine this fact, other methods for CH4 evaluation would need to be used. Our study found an average OCTT value of 93.9 ± 31.7 minutes, which was similar to that found in various studies abroad.19,20,21 Nevertheless, further study using larger samples is required to establish a more accurate and reliable normal value for the Indonesian population. From statistical analysis, OCTT and sex, age, and BMI did not demonstrate a statistically significant correlation. Previous studies also did not demonstrate a correlation between OCTT and sex or age. 22 A study by Madsen (1992) reported that sex, age, and BMI did not influence gastrointestinal transit time.23 However, a study by Wald et al (1981) demonstrated significant elongation of OCTT in the luteal phase is compared to the follicular phase of the female menstruation cycle.24 CONCLUSION We have conducted a study on intestinal motility established through the OCTT of 36 healthy adults from the Cipto Mangunkusumo National Central General Hospital, Jakarta. We found an average value of 93.9 ± 31.7 out of 31 subjects. There was no statistically significant correlation between OCTT and age, sex, and BMI. The use of the hydrogen breath test to determine OCTT in daily clinical application may be recommended, since it is non-invasive, easy, fast, safe, and costs relatively less than other methods of evaluation. The Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy

Paulus Simadibrata, Rino A. Gani, Marcellus S. Kolopaking, A. Aziz Rani

Orocecal Transit Time in Normal Adults at Cipto Mangunkusumo National Center General Hospital, Jakarta

ACKNOWLEDGMENTS The authors wish to thank Badriul Hegar, MD., from the Department of Pediatrics, Faculty of Medicine University of Indonesia, Jakarta, for his assistance in conducting the hydrogen breath test. REFERENCES 1. Gilmore IT. Orocaecal transit time in health and disease. Gut 1990; 31: 250-1. 2. Bonapace ES, Maurer AH, Davidoff S, Krevsky B, Fisher RS, Parkman HP. Whole gut transit scintigraphy in the clinical evaluation of patients with upper and lower gastrointestinal symptoms. Am J Gastroenterol 2000; 95: 2838-47. 3. Camilleri M, Zinsmeister AR, Greydanus MP, Brown ML, Proano M. Towards a less costly but accurate test of gastric emptying and small bowel transit. Dig Dis Sci 1991; 36: 609-15. 4. Basile MB, Neri M, Carriero A, Casciardi S, Comani S, Del Gratta C, et al. Measurement of segmental transit through the gut in man: a novel approach by the biomagnetic method. Dig Dis Sci 1992; 37: 1537-43. 5. Madsen JL, Hendel L. Gastrointestinal transit times of radiolabeled meal in progressive systemic sclerosis. Dig Dis Sci 1992; 37: 1404-8. 6. Wegener M, Adamek RJ, Wedmann B, Jergas M, Altmeyer P. Gastrointestinal transit through esophagus, stomach, small and large intestina in patients with progressive systemic sclerosis. Dig Dis Sci 1994; 39: 2209-15. 7. Matsumoto T, Lida M, Hirakawa M, Kuroki F, Lee S, et al. Breath hydrogen test using water-diluted lactose in patients with gastrointestinal amyloidosis. Dig Dis Sci 1991; 36: 1756-60. 8. Humbert P, López de Soria, Fernández-Bañares F, Juncá J, Planas R, Quer JC, et al. Magnesium hydrogen breath test using end expiratory sampling to assess achlorhydria in pernicious anaemia patients. Gut 1994; 35: 1205-8. 9. Hegar B, Buller HA. Breath hydrogen test in lactose malabsorption. Paediatr Indones 1995; 35: 161-71. 10. Spiller RC. Chemical detection of transit. In: Kumar D, Wingate D (editor). An illustrated guide to gastrointestinal motility. 2nd edition. London: Churchill Livingstone, 1993: 308-18. 11. Staniforth DH. Comparison of orocaecal transit times assessed by the lactulose/breath hydrogen and the sulphasalazine/ sulphapyridine methods. Gut 1989; 30: 978-82. Volume 3, Number 2, August 2002 12. Kagawa M, Iwata M, Toda Y, Nakae Y, Kondo T. Circadian rhythm of breath hydrogen in young women. J Gastroenterol 1998; 33: 472-6. 13. Thompson DG, O’Brien JD, Hardie JM. Influence of the oropharyngeal microflora on the measurement of exhaled breath hydrogen. Gastroenterology 1986; 91: 853-60. 14. Thompson DG, Binfield P, De Belder A, O’Brien J, Warren S, Wilson M. Extra intestinal influences on exhaled breath hydrogen measurements during the investigation of gastrointestinal disease. Gut 1985; 26: 1349-52. 15. Scott AM, Kellow JE, Eckersley GM, Nolan JM, Jones MP. Cigarette smoking and nicotine delay postprandial mouth-cecum transit time. Dig Dis Sci 1992; 37: 1544-7. 16. Lieberthal MM. The pharmacology of lactulose. In: Conn HO, Bircher J (editors). Hepatic encephalopathy: management with lactulose and related carbohydrates. 1st edition. Michigan: Medi-Ed Press, 1988: 145-76. 17. Levitt MD. Production and excretion of hydrogen gas in man. N Engl J Med 1969; 281: 122-7. 18. Perman JA. Modler S. Glycoproteins as substrates for production of hydrogen and methane by colonic bacterial flora. Gastroenterology 1982; 83: 388-93. 19. Camboni G, Basilisco G, Bozzani A, Bianchi PA. Repeatability of lactulose hydrogen breath test in subjects with normal or prolonged orocecal transit. Dig Dis Sci 1988; 33: 1525-7. 20. Corbett CL, Thomas S, Read NW, Hobson N, Bergman I, Holdsworth CD. Electrochemical detector for breath hydrogen determination: measurement of small bowel transit time in normal subjects and patients with the irritable bowel syndrome. Gut 1981; 22: 836-40. 21. Tobin MV, Fisken RA, Diggory RT, Morris AI, Gilmore IT. Orocaecal transit time in health and in thyroid disease. Gut 1989; 30: 26-9. 22. Kagaya M, Iwata N, Toda Y, Nakae Y, Kondo T. Small bowel transit time and colonic fermentation in young and elderly women. J Gastroenterol 1997; 32: 453-6. 23. Madsen JL. Effect of gender, age and body mass index on gastrointestinal transit times. Dig Dis Sci 1992; 37: 1548-53. 24. Wald A, Van Thiel DH, Hoechstetter L, Gavaler JS, Egler KM, Verm R, et al.Gastrointestinal transit: the effect of the menstrual cycle. Gastroenterology 1981; 80: 1497-1500. 41

Orocecal Transit Time in Normal Adults at Cipto Mangunkusumo National Center General Hospital, Jakarta



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