The effect of lactulose in the treatment of chronic functional constipation in children

Nội dung text: The effect of lactulose in the treatment of chronic functional constipation in children

1. JOURNAL OF MEDICAL RESEARCH THE EFFECT OF LACTULOSE IN THE TREATMENT OF CHRONIC FUNCTIONAL CONSTIPATION IN CHILDREN Do Thi Minh Phuong, Nguyen Thi Viet Ha Department of Pediatrics, Hanoi Medical University Constipation is a common gastrointestinal problem in children. The aim of the present study was to evaluate the beneficial effects of lactulose in the management of functional constipation in children. An open clinical trial was conducted in 140 children aged 1 – 5 years at the National Children Hospital, Hanoi, Vietnam with a diagnosis of functional constipation. The reslult suggest that frequency and consistency of defecation, as well as clinical symptoms were improved significantly when using lactulose with 2 ml/ kg/day. The mean weekly stool frequency improved from 1.9 ± 0.8 times to 4.9 ± 1.8 times after 1 month and to 5.9 ± 1.4 times after 3 months of treatment (p < 0.01). The rate of effective treatment (the weekly stool frequency ≥ 3 times and fecal incontinence ≤ 1 time every two weeks) was 68% after 1 month and increased to 72.8% after 2 and 3 months of treatment. In addition to using laxatives, fiber and fluid intake per day > 80% standard recommendation improve the effect in the treatment. In conclusion, lactulose is a safe, effective and well-tolerated long-term treatment for constipation. Regular supplement of fiber and fluid in children with constipation is important to improve the effect in the treatment of constipation. Keywords: chronic functional constipation, lactulose, children, Rome III I. INTRODUCTION Constipation is one of the mast common fecal retention and functional constipation. constipation digestive complaints in chil- The North American Society for Pediatric dren, and has recently grown into a dispro- Gastroenterology, Hepatology and Nutrition portionate public health problem. A recent define constipation as a delay or difficulty in systematic review of pediatric patents of defecation, present for 2 or more week [2]. the sample reported constipation in 0.7% to The occurrence of chronic functional consti- 29.6% of the sample [1]. Functional consti- pation in children can lead to significant ab- pation was recognized as a separate clinical dominal pain, anal fissure, loss of appetite, entity by combining features of functional faecal incontinence and social isolation. The aim of constipation management is to produce soft, painless stools and to pre- Corresponding author: Do Thi Minh Phuong, Depart- vent the re-accumulation of feces, which ment of Pediatrics, Hanoi Medical University can be achieved through dietary modifica- Email: dominhphuong@hmu.edu.vn tion, behavioral interventions, fecal disim- Received: 13 August 2017 paction and the use of laxatives, or a com- Accepted: 16 November 2017 bination thereof [6]. Lactulose is considered JMR 111 E2 (2) - 2018 61
2. JOURNAL OF MEDICAL RESEARCH to be safe and recommended for all ages in ria for at least 1 month, whereas those > 4 the management of constipation by NASP- years need to fulfill ≥ 2 of the criteria for at GHAN and ESPGHAN [3]. Many studies least 2 months and have insufficient criteria have demonstrated that lactulose improved for irritable bowel syndrome. A total of 140 frequency and consistency of defecation children from ages 1 - 5 years old present- and clinical symptoms [4; 5; 7; 8]. To our ing with constipation based on a modifica- knowledge, however, no large studies eval- tion of the Rome III criteria were eligible for uat the effect of lactulose in childhood con- the trial. stipation have been published in Vietnam. Evaluation of treatment outcome The primary objective of the present study All patients were examined, advised to was to evaluate the beneficial effects of lac- change dietary, adherence to daily toilet tulose in the treatment of chronic functional training, used lactulose with 2 ml/kg/day. If constipation in children. patients have diarrhea, the dose of lactulose will decrease 1 ml/kg/day. After 1 week of II. MATERIALS AND METHODS treatment, patients still defecate hard stool 1. Subjects < 3 times per week, lactulose will increase 140 children aged 1 - 5 years recruited 3 ml//kg/day. Parents received fiber chart from the sample consisted of the National of common foods; the Bristol stool chart; Children Hospital, Hanoi, Vietnam with a di- and a stool diary to record the frequency of agnosis of functional constipation daily bowel movements, fecal soiling, stool Study design consistency, as well as any symptoms they The treatment trial was performed in Ha- considered important. The children were noi, Vietnam from 1/10/2013 to 31/11/2014. evaluated clinically at study entry and at 4, The Rome III guideline was used to diag- 8 and 12 weeks after enrollment. Treatment nose patients with chronic functional con- responses were assessed by evaluation of stipation [9]. According to the guideline, in the daily stool diary. Treatment compliance the absence of organic pathology, patients was assessed by direct interview with the must meet two or more of the following cri- patient, checking the diary cards (on which teria: 1) Two or fewer defecations in the toi- the number of daily capsules taken was let per week. 2) At least one episode of fecal recorded), and counting the capsules re- incontinence per week after the acquisition turned by the patient at each visit. of toileting skills. 3) History of retentive pos- Statistical analysis turing or excessive volitional stool retention. Statistical analysis was performed us- 4) History of painful or hard bowel move- ing the computer software SPSS 16.0. Stu- ments. 5) Presence of a large fecal mass in dent’s t test was used to compare means the rectum. 6) The history of large diameter of continuous variables approximating a stools which may obstruct the toilet. Infants normal distribution. The x² test or Fisher’s up to 4 years have to fulfill ≥ 2 of the crite- exact test was used, as appropriate, to compare percentages. A p-value < 0.05 was 62 JMR 111 E2 (2) - 2018
3. JOURNAL OF MEDICAL RESEARCH considered statistically significant. III. RESULTS 2. Ethics Baseline characteristics of study This study was approved by the Sci- groups ence Council of Hanoi Medical University. From 1/10/2013 to 31/11/2014, 140 chil- A written informed consent was signed by dren presenting with constipation were en- children’s parents/ caretakers before partic- rolled in the study. ipating in the present study. Table 1. Baseline characteristics Age (months) 35,9 ± 17,4 Boys (%) 51.8 Gender Girls (%) 43.2 Disease duration (months) 11 ± 9.7 Mean weekly stool frequency 1,9 ± 0,8 Type 1 77.9 Stool consistency (%) Type 2 22.2 Patients with painful bowel movements (%) 80.7 Patients with anal fissure (%) 54.3 Patients with a fecal mass in the rectum (%) 66,4 The beneficial effects of lactulose with 2 ml/kg/day in the treatment of chronic func- tional constipationin children. Figure 1 shows the mean stool frequency increased from 1.9 ± 0.8 stools/ week at base- line to 4.9 ± 1.8 at weeks 4 and 5.9 ± 1.4 at the end of the study (p < 0.01). Fingure 1. Change in the weekly stool frequency JMR 111 E2 (2) - 2018 63
4. JOURNAL OF MEDICAL RESEARCH The successful treatment rate (defined as weekly stool frequency ≥ 3 times and fecal in- continence ≤ 1 time every 2 weeks) was 68% after 4 weeks and increased to 72.8% after 8 and 12 weeks of treatment. Table 2. Change in stool consistency during treatment Stool consistency (%) Type 1 Type 2 Type 3 Type 4 p-value Baseline 78.6 21.4 0 0 < 0.01 4 weeks 0 9.7 49.5 40.8 8 weeks 0 2.9 30.1 67 < 0.01 12 weeks 0 0 14.6 85.4 Stool consistency : Type 1 – Separate hard lumps, like nuts; Type 2 – Sausage – shaped, but lumpy; Type 3 – Like a sausage but with cracks on its surface; Type 4 – Like a sausage or snake, smooth and soft. The percentage of patients used 2ml of lactulose/ kg/ day after 4 weeks of treatment was 87.4%. This rate decreased to 80.6% (after 8 weeks) and 75.5% after 12 weeks (Table 2). Table 3. Change in dose of lactulose from baseline to after 12 weeks Time At 4 weeks At 8 weeks At 12 weeks Dose n % n % n % 1 ml/kg/day 11 10.7 14 13.6 17 16.5 2 ml/kg/day 90 87.4 83 80.6 78 75.7 3 ml/kg/day 2 1.9 6 5.8 7 6.8 Amount of water and fiber/ day affect to treatment Table 3 shows a difference in the mean weekly stool frequency between fiber intake per day > 80% and ≤ 80% standard recommended after 4 weeks, 8 weeks and 12 weeks of treatment with p value.Children with fiber intake per day ≤ 80% standard recommendation had increased risk for hard stools (type 2 - 3) compared to > 80% group at 4 weeks and 8 weeks (p < 0.05). Table 4: Amount of fiber/day affect to mean weekly stool frequency Time Amount of fiber n (%) X ± SD p value ≤ 80% 49 (47.6) 4.4 ± 1.8 At 4 weeks 0.03 > 80% 54 (52.4) 5.2 ± 1.8 64 JMR 111 E2 (2) - 2018
5. JOURNAL OF MEDICAL RESEARCH ≤ 80% 35 (34) 4.7 ± 1.7 At 8 weeks 0.02 > 80% 68 (66) 5.5 ± 1.5 ≤ 80% 11 (10.7) 5.5 ± 1.9 At 12 weeks 0.30 > 80% 92 (89.3) 6 ± 1.3 IV. DISCUSSION Based on recommendations from NASP- creased to from 2 to 5 times per week, and GHAN and ESPGHAN, we chose a daily following 2 weeks of treatment increased intake of mean dose of lactulose (2 ml/kg/ to 6 times per week. Prior to treatment, the day) in this study. The results showed that stool consistencies of all enrolled patients the frequency and consistency of defeca- ranged from type 1 to 3 on the Bristol Stool tion and other clinical symptoms as painful Scale. Lactulose treatment also improved bowel movements, anal fissure, fecal incon- the stool consistency to 3.64 ± 1.33 follow- tinence, blood in stool improved significant- ing 1 week of treatment and 3.63 ± 1.33 fol- ly (p < 0.05). lowing 2 weeks [7]. In this study, we used different doses of In our study, almost 70% of children with lactulose to evaluate the effects of lactulose constipation were successfully treated after in the treatment of functional constipation. 4 weeks of treatment. This rate increased The effective dose of lactulose was change- up to 72.8% after 8 weeks. The lactulose able based on factors such as diet, adher- dose of 2 ml/kg/day is appropriate for chil- ence to treatment, duration of constipation dren with constipation. After 4 weeks of and any previous used medications. Ban- treatment, almost all patients maintained aszkiewicz’ trial used lactulose with 1 ml/ the dose of 2 ml/kg/day; only 10.7% of kg/day, which showed that the mean weekly them reduced the dose (1 ml/kg/day) due stool frequency improved, as did our study to diarrhea, and a few had to be increased [4]. According to Sadeghzadeh's study, the due to unresponsive treatment (1.9%). The frequency of defecation per week increased success rate in our study was higher than from 0.8 ± 0.8 to 1.5 ± 0.98 times (in the Voskuijl’s study after 8 weeks of treatment lactulose group) and from 1.7 ± 0.8 to 2.1 (29%). In Voskuijl’s study, the mean lact- ± 0.7 times (in the lactulose plus protease ulose dose associated with improvement group) after 4 weeks of treatment [5]. The were 11.52 (4.56) g/day (1.9 sachets) and improvement of frequency of defecation in 13.86 (6.66) g/day (2.3 sachets) at 4 and this study was slower than our results. 8 weeks. The optimal dose of lactulose in In one study conducted by Wang, 111 clinically successful patients < 6 years and patients over 8 years of age received lac- ≥ 6 years was 0.96 (0.45) g/kg/day and 0.45 tulose with 15 ml/kg, the median stool fre- (0.27) g/kg/day, respectively [8]. According quency following 1 week of treatment in- to Wang, the effective rate of treatment was JMR 111 E2 (2) - 2018 65
6. JOURNAL OF MEDICAL RESEARCH 39.64% after 1 week and increased 41.44% the National Children Hospital in Hanoi, after 2 weeks of treatment [7]. Vietnam for their assistance. We also wish Limited water and fiber intake per day to thank all children and their parents who as risk factors for constipation have been participated in the study for their precious shown in many studies. The results of our collaborative spirit. study showed that fiber intake per day ≤ REFERENCES 80% standard recommendation affected the effect of lactulose in improving the frequen- 1. Van den Berg MM, Benninga MA, Di cy and consistency of defecation and clinical Lorenzo C (2006). Epidemiology of child- symptoms. Dietary fiber is good for treating hood constipation: a systematic review. constipation, but the role of additional fiber American Journal of Gastroenterology, 101, in improving the effect of constipation treat- 2401 - 2409. ment is not yet approved. In Kokke, and 2. Vandenplas Y, De Greef E, Devreker Loening-Baucke's clinical trials, there was T et al. (2013).Probiotics and prebiotics in no significant improvement in bowel move- infants and children. Current Infectious Dis- ments after fiber therapy compared with ease Reports, 15(3), 251 - 262. placebo and traditional treatments such as 3. Tabbers MM, DiLorenzo C, Berger lactulose (Duphalac) [10; 11]. MY, et al. (2014). Evaluation and treatment The strength of our study lies in the large of functional constipation in infants and chil- sample size for a pediatric trial, a compli- dren: evidence-based recommendations ance rate of 73,6%, and a follow-up. A from ESPGHAN and NASPGHAN. Journal weakness of the study was the difficulty of of Pediatric Gastroenterology and Nutrition, conducting a randomized double-blind trial 58, 258 - 274. over a wide weight range, as would be un- 4. Banaszkiewicz A, Szajewska H. ethical having control groups allowing more (2005). Ineffectiveness of Lactobacillus GG optimal dosing. as an adjunct to lactulose for the treatment of constipation in children: a double - blind, V. CONCLUSION placebo – controlled randomized trial. The Lactulose is a safe, effective and well-tol- Journal of Pediatrics, 146(3), 364 - 369. erated long-term treatment for constipation. 5. Sadeghzadeh M, Rabieefar A, Regular supplement of fiber and fluid over Khoshnevisasl P, et al. (2014). The effect 80%, according to standard recommenda- of probiotics on childhood constipation: ran- tion for constipated children is important to domized controlled double blind clinical tri- improve the effect in the treatment of con- al. International Journal Pediatric, 937212. stipation. 6. Rowan-Legg A. (2011). Managing functional constipation in children. Paediat- Acknowledgments ric Child Health, 16(10), 661 – 670. We would like to thank the doctors and 7. Wang Y, Wang B, Jiang X et al staff at the Gastrointestinal department at (2012). Polyethylene glycol 4000 treatment 66 JMR 111 E2 (2) - 2018
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