Long Term Treatment of children with chronic functional constipation with PEG 4000: Study
Constipation is a common problem in pediatric patients characterized by infrequent bowel movements or painful bowel movements.
The Paris Consensus on Childhood Constipation Terminology (PACCT) defines constipation as "a period of 8 weeks with at least 2 of the following symptoms: defecation frequency less than 3 times per week, faecal incontinence frequency greater than once per week, passage of large stools that clog the toilet, palpable abdominal or rectal faecal mass, stool withholding behavior, or painful defecation." (11)
While in general constipation in children is a temporary phenomenon, in many cases it can convert to a chronic problem. Children with chronic constipation are treated with a variety of medications, where pediatricians are always keeping an eye on the long-run impact of various medications on the health of the children.
Many previous studies have affirmed that lactulose /sorbitol, mineral oil, and magnesium hydroxide to be safe for long-term use in children. (1, 2)
Recently, polyethylene glycol (PEG) products have emerged as a new alternative to other laxatives for children with constipation. Compared to the traditional methods, Polyethylene glycol 3350 (PEG 3350), where 3350 defines the molecular weight was a relatively new osmotic laxative which was introduced in the 1990s for colonoscopic preparation, and disimpaction in children with chronic constipation(3,4).
From the beginning, the use of PEG 3350 solution has been by mixing it with electrolytes. However, concerns related to bad taste as well as its potential risk for causing electrolyte imbalance in children, PEG products saw very limited use in the initial days.
To overcome this problem, PEG products without electrolytes were introduced for children with constipation. (5, 6,7). Polyethylene glycol 3350 without electrolytes is supplied as a powder that is palatable when dissolved in a beverage such as water or juice.
With time PEG in another molecular weight of 4000, that is, PEG 4000 was introduced.
Being relatively new to the market compared to other products there were very few studies on the long-term safety of PEG products without electrolytes in children with chronic constipation that address both clinical and biochemical aspects. Moreover, studies of PEG 4000 are even rarer and the duration of the studies is not long (8, 9).
Keeping this background in mind, in 2010, Dr. Sun Hwan Bae and colleagues (10) at the Department of Pediatrics, Konkuk University Medical Center, Seoul, Korea undertook a study with the purpose to evaluate the long-term safety of polyethylene glycol (PEG) 4000 in children with constipation, particularly the biochemical aspects of safety.
The findings of the study were published in the Korean Journal of Pediatrics.
Materials and methods
After evaluating medical records of 350 children including 153 boys and 197 girls with a mean age of 8.43±4.56 yr (2-19), one hundred children (50 boys, 50 girls) were enrolled in this study. The enrolled children had been taking PEG 4000 for more than 6 months, under the diagnosis of chronic constipation of ROME III criteria15), between July 2007 and March 2010 at Konkuk University Hospital, and who had been under clinical and biochemical monitoring. The initial maintenance dose of PEG was 0.72±0.21 g/kg/d (0.18-1.14 g/kg/d).
The children had been under clinical monitoring for urticaria, diarrhea, nausea, abdominal pain, headache, dizziness, tingling sensation, convulsion, change in consciousness, and biochemical monitoring, such as complete blood count with reticulocyte, liver function test, glucose, blood urea nitrogen, creatinine, calcium, phosphate, electrolytes (including tCO2) and serum osmolality, for several months.
The compliance and effect of medication were guaranteed with defecation diary which was kept by the patient or guardian
Analysis of the duration of therapy and hyperphosphatemia, and between the dose of PEG 4000 and hyperphosphatemia was made using Student's T-test.
Results
The key findings were as follows.
1. None of the children complained of clinical adverse effects, including those of urticaria, diarrhea, abdominal pain, headache, dizziness, numbness, seizure, or change of consciousness.
2. The first biochemical test was performed at 8.05 months after the beginning of PEG 4000. Serum phosphate (SP) value was high in 10 children, and leucopenia was noted in one child.
3. The second test was performed in 44 children at 7.57 months after the first test. The SP value was high in four children, including the three children whose initial SP value was high and one new child. Six out of 10 children with high initial SP value became normal and one was lost. Hypernatremia was noted in one child.
4. The third test was done in 15 children at 7.5 months after the second test. The SP value of the new child from the second test was high but became normal after finishing treatment. Two out of 3 children with high SP value at the second test became normal and one was lost.
5. The fourth test was done in 2 children a few months after the third test. All of the results were normal.
6. There was no relation between the duration of therapy and hyperphosphatemia, or between the dose of PEG 4000 and hyperphosphatemia.
Discussion
Considering that functional constipation is usually treated for 6 to 24 months, the long term safety of the medicine is more important than the efficacy of the medication. The researchers made some important observations from the study results.
ï‚· In the present study, 100 children were enrolled and the mean duration of treatment was about 17 months (7-46 months). Significant clinical problems were not noted during observation.
ï‚· Many biochemical parameters were analyzed, and the serum phosphate level was elevated in some children. Generally, serum phosphate increases in cases of acute, chronic renal failure, aggravated catabolic stress, lactic acidosis, hypocalcemia, cytolysis during chemotherapy, administration of a large quantity of phosphate, or hypoparathyroidism, but, in the present study, the etiology of hyperphosphatemia remained unclear.
ï‚· It was noted that hyperphosphatemia resolved spontaneously despite continuance of treatment except in one child.
"PEG 4000 is safe for long-term therapy in children with chronic constipation in terms of biochemical parameters. However, pediatricians require biochemical follow-up, especially for serum phosphate." the authors concluded.
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on PEG 4000, click here
REFERENCES
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8. Lee JH, Lee R, Bae SH. Efficacy and safety of electrolytes-free polyethylene glycol (PEG) 4000 for disimpaction in children with chronic functional constipation. Korean J Pediatr2008;51:391-5.
9. Lee SH, Bae SH. Maintenance dose of electrolyte free polyethylene glycol (PEG) 4000 in Korean children with chronic functional constipation. Korean J Pediatr 2007; 50:1212-6.
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