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

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 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

constipation digestive complaints in

chil-dren, and has recently grown into a

dispro-portionate public health problem A recent

systematic review of pediatric patents of

the sample reported constipation in 0.7% to

29.6% of the sample [1] Functional

consti-pation was recognized as a separate clinical

entity by combining features of functional

fecal retention and functional constipation The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition define constipation as a delay or difficulty in defecation, present for 2 or more week [2] The occurrence of chronic functional consti-pation in children can lead to significant ab-dominal pain, anal fissure, loss of appetite, faecal incontinence and social isolation The aim of constipation management is

to produce soft, painless stools and to pre-vent the re-accumulation of feces, which can be achieved through dietary modifica-tion, behavioral interventions, fecal disim-paction and the use of laxatives, or a com-bination thereof [6] Lactulose is considered

Corresponding author: Do Thi Minh Phuong,

Depart-ment of Pediatrics, Hanoi Medical University

Email: dominhphuong@hmu.edu.vn

Received: 13 August 2017

Accepted: 16 November 2017

to be safe and recommended for all ages in

the management of constipation by

NASP-GHAN and ESPNASP-GHAN [3] Many studies

have demonstrated that lactulose improved

frequency and consistency of defecation

and clinical symptoms [4; 5; 7; 8] To our

knowledge, however, no large studies

eval-uat the effect of lactulose in childhood

con-stipation have been published in Vietnam

The primary objective of the present study

was to evaluate the beneficial effects of

lac-tulose in the treatment of chronic functional

constipation in children

II MATERIALS AND METHODS

1 Subjects

140 children aged 1 - 5 years recruited

from the sample consisted of the National

Children Hospital, Hanoi, Vietnam with a

di-agnosis of functional constipation

Study design

The treatment trial was performed in

Ha-noi, Vietnam from 1/10/2013 to 31/11/2014

The Rome III guideline was used to

diag-nose patients with chronic functional

con-stipation [9] According to the guideline, in

the absence of organic pathology, patients

must meet two or more of the following

cri-teria: 1) Two or fewer defecations in the

toi-let per week 2) At least one episode of fecal

incontinence per week after the acquisition

of toileting skills 3) History of retentive

pos-turing or excessive volitional stool retention

4) History of painful or hard bowel

move-ments 5) Presence of a large fecal mass in

the rectum 6) The history of large diameter

stools which may obstruct the toilet Infants

up to 4 years have to fulfill ≥ 2 of the

crite-ria for at least 1 month, whereas those > 4 years need to fulfill ≥ 2 of the criteria for at least 2 months and have insufficient criteria for irritable bowel syndrome A total of 140 children from ages 1 - 5 years old present-ing with constipation based on a modifica-tion of the Rome III criteria were eligible for the trial

Evaluation of treatment outcome

All patients were examined, advised to change dietary, adherence to daily toilet training, used lactulose with 2 ml/kg/day If patients have diarrhea, the dose of lactulose will decrease 1 ml/kg/day After 1 week of treatment, patients still defecate hard stool

< 3 times per week, lactulose will increase

3 ml//kg/day Parents received fiber chart

of common foods; the Bristol stool chart; and a stool diary to record the frequency of daily bowel movements, fecal soiling, stool consistency, as well as any symptoms they considered important The children were evaluated clinically at study entry and at 4,

8 and 12 weeks after enrollment Treatment responses were assessed by evaluation of the daily stool diary Treatment compliance was assessed by direct interview with the patient, checking the diary cards (on which the number of daily capsules taken was recorded), and counting the capsules re-turned by the patient at each visit

Statistical analysis

Statistical analysis was performed us-ing the computer software SPSS 16.0 Stu-dent’s t test was used to compare means

of continuous variables approximating a normal distribution The x² test or Fisher’s exact test was used, as appropriate, to compare percentages A p-value < 0.05 was

considered statistically significant.

2 Ethics

This study was approved by the

Sci-ence Council of Hanoi Medical University

A written informed consent was signed by

children’s parents/ caretakers before

partic-ipating in the present study

III RESULTS

Baseline characteristics of study groups

From 1/10/2013 to 31/11/2014, 140 chil-dren presenting with constipation were en-rolled in the study

Table 1 Baseline characteristics

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

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

< 0.01

< 0.01

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

Dose

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

> 80% 54 (52.4) 5.2 ± 1.8

At 8 weeks ≤ 80% 35 (34) 4.7 ± 1.7 0.02

IV DISCUSSION

Based on recommendations from

NASP-GHAN and ESPNASP-GHAN, we chose a daily

intake of mean dose of lactulose (2 ml/kg/

day) in this study The results showed that

the frequency and consistency of

defeca-tion and other clinical symptoms as painful

bowel movements, anal fissure, fecal

incon-tinence, blood in stool improved

significant-ly (p < 0.05)

In this study, we used different doses of

lactulose to evaluate the effects of lactulose

in the treatment of functional constipation

The effective dose of lactulose was

change-able based on factors such as diet,

adher-ence to treatment, duration of constipation

and any previous used medications

Ban-aszkiewicz’ trial used lactulose with 1 ml/

kg/day, which showed that the mean weekly

stool frequency improved, as did our study

[4] According to Sadeghzadeh's study, the

frequency of defecation per week increased

from 0.8 ± 0.8 to 1.5 ± 0.98 times (in the

lactulose group) and from 1.7 ± 0.8 to 2.1

± 0.7 times (in the lactulose plus protease

group) after 4 weeks of treatment [5] The

improvement of frequency of defecation in

this study was slower than our results

In one study conducted by Wang, 111

patients over 8 years of age received

lac-tulose with 15 ml/kg, the median stool

fre-quency following 1 week of treatment

in-creased to from 2 to 5 times per week, and following 2 weeks of treatment increased

to 6 times per week Prior to treatment, the stool consistencies of all enrolled patients ranged from type 1 to 3 on the Bristol Stool Scale Lactulose treatment also improved the stool consistency to 3.64 ± 1.33 follow-ing 1 week of treatment and 3.63 ± 1.33 fol-lowing 2 weeks [7]

In our study, almost 70% of children with constipation were successfully treated after

4 weeks of treatment This rate increased

up to 72.8% after 8 weeks The lactulose dose of 2 ml/kg/day is appropriate for chil-dren with constipation After 4 weeks of treatment, almost all patients maintained the dose of 2 ml/kg/day; only 10.7% of them reduced the dose (1 ml/kg/day) due

to diarrhea, and a few had to be increased due to unresponsive treatment (1.9%) The success rate in our study was higher than Voskuijl’s study after 8 weeks of treatment (29%) In Voskuijl’s study, the mean lact-ulose dose associated with improvement were 11.52 (4.56) g/day (1.9 sachets) and 13.86 (6.66) g/day (2.3 sachets) at 4 and

8 weeks The optimal dose of lactulose in clinically successful patients < 6 years and

≥ 6 years was 0.96 (0.45) g/kg/day and 0.45 (0.27) g/kg/day, respectively [8] According

to Wang, the effective rate of treatment was

39.64% after 1 week and increased 41.44%

after 2 weeks of treatment [7]

Limited water and fiber intake per day

as risk factors for constipation have been

shown in many studies The results of our

study showed that fiber intake per day ≤

80% standard recommendation affected the

effect of lactulose in improving the

frequen-cy and consistenfrequen-cy of defecation and clinical

symptoms Dietary fiber is good for treating

constipation, but the role of additional fiber

in improving the effect of constipation

treat-ment is not yet approved In Kokke, and

Loening-Baucke's clinical trials, there was

no significant improvement in bowel

move-ments after fiber therapy compared with

placebo and traditional treatments such as

lactulose (Duphalac) [10; 11]

The strength of our study lies in the large

sample size for a pediatric trial, a

compli-ance rate of 73,6%, and a follow-up A

weakness of the study was the difficulty of

conducting a randomized double-blind trial

over a wide weight range, as would be

un-ethical having control groups allowing more

optimal dosing

V CONCLUSION

Lactulose is a safe, effective and

well-tol-erated long-term treatment for constipation

Regular supplement of fiber and fluid over

80%, according to standard

recommenda-tion for constipated children is important to

improve the effect in the treatment of

con-stipation

Acknowledgments

We would like to thank the doctors and

staff at the Gastrointestinal department at

the National Children Hospital in Hanoi, Vietnam for their assistance We also wish

to thank all children and their parents who participated in the study for their precious collaborative spirit

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