| Candy et al. Treatment of faecal impaction with polyethelene glycol plus electrolytes (PGE + E) followed by a double-blind comparison of PEG + E versus lactulose as maintenance therapy. 2006. Journal of Pediatric Gastroenterology and Nutrition 43[1], 65-70 | Study Type:
Prospective case series (phase 1 of the study)*
Evidence level:
3
Study aim:
to assess the efficacy of polyethylene glycol 3350 plus electrolytes (PEG + E; Movicol ®) as oral monotherapy in the treatment of faecal impaction in children and to compare PEG + E with lactulose as maintenance therapy in a randomised trial | 65 children
Inclusion criteria:
children aged 2 to 11 years with intractable constipation that had failed to respond to conventional treatment and would require hospital admission for disimpaction (otherwise been admitted for enemas, manual removal or intestinal lavage with PEG + E solutions)
Exclusion criteria: any condition contraindicating the use of PEG+E or lactulose, including intestinal perforation or obstruction, allergy to any of the ingredients of the trial products, paralytic ileus, toxic megacolon, Hirschsprung's disease, severe inflammatory bowel disease, uncontrolled renal/hepatic/ cardiac disease, uncontrolled endocrine disorder or any neuromuscular condition affecting the bowel
Setting:
hospital | 65 children
Mean age: 5.7 years(56% children 5 to 11 years)
68% boys
Country:
UK | Intervention:
Polyethylene glycol 3350 (13.8 g powder dissolved in at least 125 ml water per sachet) plus electrolytes (PEG + E; Movicol ®) administered orally in hospital according to an escalating dosing regimen until disimpaction was achieved (up to 7 days)
- -
PEG + E dosing regime
No. PEG + E sachets :
2 to 4 years Day 1: 1 Day 2: 2 Day 3: 2 Day 4: 3 Day 5: 3 Day 6: 4 Day 7: 4
5 to 11 years Day 1: 2 Day 2: 3 Day 3: 4 Day 4: 5 Day 5: 6 Day 6: 6 Day 7: 6
Comparison: none
| Follow-up period:
9 days
Outcome Measures:
Successful disimpaction without any additional intervention Time to disimpaction (primary efficacy endpoint) Maximum dose required to achieve disimpaction Safety
|
Successful disimpaction (No, %): - -
total (n=63) - -
age 2 to 4 (n=28) - -
age 5 to 11 (n=35)
Time to disimpaction (days) (mean, SD; median, range): - -
total (n=63) - -
age 2 to 4 (n=28) - -
age 5 to 11 (n=35)
Maximum dose required (sachets/day): - -
total (n=63): 6 - -
age 2 to 4 (n=28): 4 - -
age 5 to 11 (n=35): 6
4. Mean number (SD) of sachets required to achieve disimpaction: - -
total (n=63): 19.6 (7.5) - -
age 2 to 4 (n=28): 14.3 (4.5) - -
age 5 to 11 (n=35): 23.6 (6.8)
No significant differences between the two age groups for any of the outcomes measured The 2 children who failed to disimpact in the 7 days specified in the study protocol were continued on PEG+E administration and eventually disimpacted Safety: - -
Number of children experiencing adverse effects: 39 (62%). (non of these judged by investigator to be serious)
Most commonly reported events: gastrointestinal (51% children) (abdominal pain, nausea, pruritus, ani / proctalgia and vomiting)
No differences in the overall incidence of adverse effects or of gastrointestinal effects for the two age groups, except for vomiting (32% of age 2 to 4 children vs. 9% of aged 5 to 11 children) ) results showed a direct correlation between incidence of vomiting and day of dosing | Additional information from study:
Definition of impaction was functional or procedural: Children were eligible if they would, in the normal course of events, have been admitted and treated for faecal impaction
Phase 1 of the study planned as noncomparative because of good success rate obtained at initial experience in treating impacted children with PEG + E in the authors' unit: it was considered unethical to randomise the children to an alternative treatment
Sample size: intended to recruit 60 children to obtain approximately 45 children continuing to end of phase 2
Successful disimpaction indicated by the passage of watery stools.
Dose regime chosen because it had shown to be effective in a previous study from the same unit
After disimpaction children continued to received PEG + E at the dose that achieved disimpaction for 2 more days to ensure that complete disimpaction of the bowel had occurred
Use of additional interventions necessary to achieve disimpaction (laxatives, suppositories, enemas, washouts or manual removal) necessary to achieve disimpaction was also recorded
3 children withdrew before receiving any study medication and 2 children failed to disimpact within the time allowed, but they were included in results
Reviewer comments:
No explicit definition of “watery stools” given
It is not clear who assessed the outcome “passage of watery stools”, although it looks like it was probably the researchers
Individual assessing outcomes not reported blinded to study objectives
Not reported whether there were any differences between the children who withdrew before receiving any medication, those who failed to disimpact and the ones who completed the study and disimpacted during the time allowed
Not clear whether vomiting affected the dose required to achieve disimpaction or whether children receive any medication to prevent / stop vomiting
Source of funding: supported by Norgine Pharmaceuticals Ltd.
|
| Youssef et al. Dose response of PEG 3350 for the treatment of childhood fecal impaction. 2002. Journal of Pediatrics 141[3], 410-414 | Study Type:
RCT
Evidence level:
1-
Study aim:
to investigate the efficacy and safety of 4 different doses of polyethylene glycol (PEG) 3350 in the treatment of childhood faecal disimpaction | 41 children
Inclusion criteria:
children with functional faecal retention as defined by Rome criteria, aged 3 to 18, male or female, with evidence of faecal impaction at physical examination
Exclusion criteria:
previous gastrointestinal surgery, no allergy /sensitivity to PEG solution or phosphates, signs and symptoms suggestive of obstruction (vomiting, abdominal distension and abdominal mass that extended beyond the level of the umbilicus) | 41 children
27 male
median age 7.5 years (3.,3 to 13.1)
Country:
USA | Intervention:
Polyethylene glycol PEG 3350
Comparisons (4 arms):
0.25 g/kg per day 0.5 g/kg per day 1.0 g/kg per day 1.5 g/kg per day
Each of them to be taken for 3 consecutive days, premixed with a solution flavoured in orange Crystal Light (Kraft Food, Inc) in the morning with breakfast at a dose of 10mL/kg/day. If volume exceeded 240 ml, the remaining daily dose was equally divided throughout the remaining meals. Maximum dose 100 g daily | Follow-up period:
5 days after starting treatment (48 hour after their last drug use)
Outcome Measures:
Primary outcome: - -
clearance of faecal impaction
Secondary outcomes: - -
number of bowel movements - -
characteristics of stools - -
safety
| Clearance of faecal impaction (number of patients, %)
- -
Achieved total: 30 (75)
(Values for each group are estimates taken from a Bar chart.):
0.25 g/kg per day (n=10): 5 0.5 g/kg per day (n=10): 4 1.0 g/kg per day (n=10): 9 1.5 g/kg per day (n=9): 10
p<0.05 c and d (95%) vs. a and b (55%)
Number of bowel movements in 5 days:
>3 bowel movements during the 5-day study: 33 (83%) of total sample
(Values for each group are estimates taken from a Bar chart. Baseline value is less than 2 for all groups):
0.25 g/kg per day (n=10): 6 0.5 g/kg per day (n=10): 8 1.0 g/kg per day (n=10): 11 1.5 g/kg per day (n=9): 12
p<0.005 for each group compared to the others
- -
time of first bowel movement after initiation of treatment (mean ± SD) 1.89 ± 0.46 days (total sample)
Characteristics of stools and symptoms during treatment
No significant differences in any of the following parameters among the 4 groups:
straining, consistency, stool amount, gas and cramping (copy actual results)
Adverse effects:
- -
Nausea (5%) - -
Vomiting (5%) - -
Bloating/flatulence: 18% - -
Pain/cramping: 5% - -
Loose stools (13%) - -
Diarrhoea: higher doses groups (5/20) vs. lower doses group (2/20); p<0.02
Acceptability of study medication by children:
95% of children took PEG 3350 on the first attempt
Mean daily volumes required to take the appropriate study dose:
no significant differences between groups
All children said they would repeat a 3-day regimen of PEG3350 to help treat future faecal impaction
Duration of constipation at baseline significantly longer for the group receiving 1.5 g/kg per day as compared to the group receiving 0.5 g/kg per day (p<0.03) | Additional information from study:
Functional faecal retention: difficulty passing stools >3 months (straining, grunting, stool “getting stick”) and passage of stools <3 times/week
Planned to enrol 10 children in each group
All medications for constipation discontinued 7 days before baseline examination and also during the duration of study
Faecal impaction: a palpable mass in the left abdomen and/or a dilated rectum filled with a large amount of hard stool on rectal examination
Presence or absence of faecal impaction assessed by abdominal and rectal examination. Physical examinations performed by 2 examiners to confirm presence of faecal impaction
Investigators blinded to randomisation allocation sequence and concealment maintained until patients enrolled completed
All medications dispensed to families in a clear container labelled with only a random sequence number generated by manufacturer. All containers initially contained PEG 3350: 50g, 100g, 200g or 300g. Each container was then constituted to a 2000 ml solution for respective four doses
Characteristics of stools measured by diaries provided to parents. Diaries had visual analog scales marked from 0 to 10, each mark evenly spaced 1 cm apart, 0 minimum and 10 maximum. Children and parents asked to report each defecation and its associated straining (0, very easy and no pushing; 1 to 10, very difficult and much effort), consistency of stool (0, too loose and watery; 1 to 10 very hard), amount of stools per defecation (0, very little; 1 to 10, a lot) associated gas (0, none; 1 to 10 too much) and cramping (0, none; 1 to 10 very painful)
5th day after initiation of treatment chosen for follow-up visit because of author's previous clinical experience with PEG 3350 showed initial effect between 1 and 2 days after beginning use of medication
Clearance of faecal impaction defined as rectal vault that was either empty or had a small amount of soft stools. In those with abdominal examination findings, resolution of the left lower quadrant mass in addition to an empty rectal vault was defined as successful disimpaction. Clearance of faecal impaction confirmed by 2 examiners
Success of disimpaction not significantly related to the independent factors of age, duration of constipation, current use of medication for constipation and baseline constipation score
One child receiving 1.5 g/kg/day did not show up at follow-up visit
Reviewer comments:
Small sample, no sample size calculation
Methods of randomisation and allocation concealment not described
Examiners performing physical examination not clearly reported blinded. Unclear whether the two examiners who confirmed clearance of faecal impaction were the same who assessed children at baseline
Unclear who prepared the 2000 ml solution for respective four doses
Source of funding: supported by Braintree Laboratories Incorporated, General Clinical Research Centre, Children's Hospital of Pittsburgh, Pennsylvania |
| Tolia et al. A prospective randomized study with mineral oil and oral lavage solution for treatment of faecal impaction in children. 1993. Alimentary Pharmacology and Therapeutics 7[5], 523-529 | Study Type:
RCT
Evidence level:
1-
Study aim:
to compare the efficacy and acceptability of the treatment of faecal impaction using either mineral oil or pineapple isotonic intestinal lavage solution containing polyethylene glycol-3350 (Colyte) | 48 children
Inclusion criteria:
children aged > 2 years with constipation, normal growth and development, absence of Hirschsprung's disease excluded on the basis of history and physical examination by the presence of firm to hard faecal impaction in the anal canal and rectal ampulla on an otherwise normal; complete physical examination
Exclusion criteria:
medical history of recurrent vomiting and/or aspiration, central nervous system problems or known history of liver, kidney and heart disease | 48 children
Data available for 36 patients who completed study:
- -
Group I (mineral oil): 11 males Mean age: 6.88 ± 3.26 years - -
Group II (flavoured lavage solution): 6.44 ± 2.36 years
Country:
USA | Intervention:
2-8 tablespoons of mineral oil in 2 divided doses for 2 days. Dose empirically determined (30 ml/10 kg of body weight)
If parents had difficulty in administering the oil they were asked to disguise it by blending it with 120-180 ml of orange juice
Comparison:
pineapple flavoured balanced oral lavage solution containing polyethylene glycol-3350 (Colyte) (sweetened with Nutra-Sweet) to drink in the dose of 20 ml/kg/h for 4 h once daily on 2 consecutive days. Maximum amount/hour: 1 litre
In addition patients received a single oral dose of metoclopramide (0.1 mg/kg) before dinking the lavage solution on both days to prevent nausea and vomiting | Follow-up period:
2 days
Outcome Measures:
History: - -
number of bowel movements after treatment - -
vomiting - -
compliance - -
cramps/bloating - -
first bowel movement after treatment consider same treatment
Physical examination: - -
palpable abdominal masses - -
abdominal distension) - -
consistency of stool - -
anal fissure - -
anal sphincter tone - -
perineal soiling
| Frequencies (%) (total sample for all outcomes, n=36)
History: number of bowel movements after treatment (>5 / 1 to 5/ none): - -
Group I (mineral oil, n=17): 2/10/5 - -
Group II (lavage solution, n=19): 9/8/2 p<0.005
vomiting (none/occasional/a lot): - -
Group I (mineral oil, n=17):17/0/0 - -
Group II (lavage solution, n=19): 12/6/1 p<0.005
compliance (good/fair/poor): - -
Group I (mineral oil, n=17): 14/3/0 - -
Group II (lavage solution, n=19): 6/7/6 p<0.01
cramps/bloating (none/ a few/a lot): - -
Group I (mineral oil, n=17): 13/4/0 - -
Group II (lavage solution, n=19): 10/8/1 N.S
first bowel movement after treatment (< 1 day/>1 day/none): - -
Group I (mineral oil, n=17): 6/6/5 - -
Group II (lavage solution, n=19): 14/3/2 p<0.01
consider same treatment (yes/maybe/no): - -
Group I (mineral oil, n=17): 12/3/2 - -
Group II (lavage solution, n=19): 11/6/2 N.S
Physical examination: - -
palpable abdominal masses (none/a few/many): - -
Group I (mineral oil, n=17): 10/4/3 - -
Group II (lavage solution, n=19): 17/1/1 p<0.005
- -
abdominal distension (none/some): - -
Group I (mineral oil, n=17): 11/6 - -
Group II (lavage solution, n=19): 11/8 N.S
- -
consistency of stool (soft/firm/hard): - -
Group I (mineral oil, n=17): 12/3/2 - -
Group II (lavage solution, n=19): 14/3/2 N.S
- -
anal fissure (none/healing): - -
Group I (mineral oil, n=17): 15/2 - -
Group II (lavage solution, n=19): 15/4 N.S
- -
anal sphincter tone (normal/decreased): - -
Group I (mineral oil, n=17): 14/3 - -
Group II (lavage solution, n=19): 15/4 N.S
- -
perineal soiling (absent/present): - -
Group I (mineral oil, n=17): 10/7 - -
Group II (lavage solution, n=19): 13/6 N.S
| Additional information from study:
Constipation defined as the passage of infrequent, large sized, firm to hard stools with or without associated rectal pain or bleeding
Randomisation performed by a computer-generated table
Significantly more patients in the lavage group gave a history of previous treatment with mineral oil (p<0.05). No significant differences at baseline between 2 groups regarding: duration of constipation, frequency of stooling, associated encopresis, rectal bleeding, previous treatments with enemas/fibre diet, palpable abdominal masses, abdominal distension, anal fissure, perineal soiling, sphincter tone and consistency of stool.
Parents kept diaries assessing: compliance of child with medication, time of first bowel movement after treatment, number of bowel movements on each day, consistency of bowel movements, abdominal distension, cramps, nausea and vomiting, and willingness to repeat the same treatment in the future if impaction recurred
After treatment patients re-evaluated by the same physician who repeated the abdominal and rectal examination in the same way as before
12 patients failed to return for reassessment in two days
Post-treatment history and physical examination further analysed after stratifying for previous use of mineral oils and stratified results did not differ significantly from unstratified analysis. Results presented are unstratified
Reviewer comments:
Small sample size. No sample calculation made
Method of allocation concealment not described
Physician-researchers not reported blinded
Intention to treat analysis not performed
Unclear how descriptive outcomes converted to numerical before analysis
Source of funding: Block Drug Company, Inc. (Jersey City, NJ, USA) provided the supplies for the study |
| Guest et al. Clinical and economic impact of using macrogol 3350 plus electrolytes in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction based on actual clinical practice in England and Wales. 2007. Current Medical Research and Opinion 23[9], 2213-2225 | Study Type:
Multicentre retrospective cohort
Evidence level:
2-
Study aim:
to estimate the clinical and economic impact of using macrogol 3350 plus electrolytes (macrogol 3350; Movicol, Movicol Paediatric Plain) in an outpatient setting compared to enemas and Suppositories and manual evacuation to treat paediatric faecal impaction | 224 children
Inclusion criteria:
aged between 2 and 11 years, suffering from intractable constipation and initially disimpacted between 01/01/01 and 31/01/06
Exclusion criteria:
not initially disimpacted between previous dates or had any condition contraindicating the use of macrogol 3350 | 224 children aged 2 to 11 years
5 centres in England and Wales
- -
macrogol 3350 plus electrolytes n=112 children n=5 centres - -
enemas and suppositories n=101 children n=5 centres - -
manual evacuation of the bowel under anaesthesia n=11 children n= 2 centres
Country:
UK | Intervention:
macrogol 3350 plus electrolytes
Comparison 1:
enemas and suppositories
Comparison 2:
manual evacuation of the bowel under anaesthesia | Follow-up period:
12 weeks
(including maintenance treatment)
Outcome Measures:
- -
Percentage of patients disimpacted within 5 days - -
Time to initial disimpaction - -
time for disimpaction for those who did not disimpact within 5 days - -
reported adverse effects
| Percentage of patients disimpacted within 5 days (%, Confidence limit)
- -
macrogol 3350 plus electrolytes (n=5 centres): 97% (94%, 100%) - -
enemas and suppositories (n=5 centres): 73% (58%, 89%) - -
manual evacuation of the bowel under anaesthesia (n=2 centres): 89% (67%, 100%)
p<0.001
Time to initial disimpaction and time for disimpaction for those who did not disimpact within 5 days:
No significant differences amongst the 3 groups
Doses required for successful disimpaction within 5 days (mean, 95% CI):
- -
macrogol 3350 plus electrolytes (sachets): 29 (13 to 44) - -
enemas (units): 2 (1 to 3) - -
suppositories (units): 1 (1 to 2)
Percentage of patients on different treatments during the week before initial treatment:
Significantly more children disimpacted with manual evacuation were taking lactulose and senna compared with other 2 groups (p<0.001)
Significantly more children disimpacted with Macrogol were taking picosulfate compared with other 2 groups (p<0.01)
Significantly more children disimpacted with enemas and suppositories were taking lactulose and other combinations (p<0.01), other laxatives (p<0.001) or were not treated ((p<0.001) when compared with other 2 groups
No significant differences between the 3 groups for patients taking lactulose only or those taking Senna
Adverse effects:
a. Vomiting (%): -macrogol 3350 plus electrolytes (n=112 patients): 2
- -
enemas and suppositories (n=101 patients): 2 - -
manual evacuation of the bowel under anaesthesia (n=11 patients): 18
p<0.01
No significant differences among 3 groups for: urinary tract infection, dermatitis around anus, thrush and gastric illness | Additional information from study:
Clinical data contained in patients' case notes transcribed onto case report forms designed specifically for this study by one independent nurse, who examined the case notes of all patients at all centres
Patients stratified according to centre and initial treatment for disimpaction. Individual clinical outcomes quantified for each treatment at each centre. Clinical centre was the unit of analysis
Reviewer comments:
No clear definition of “intractable constipation” given
Very small sample size for the manual evacuation of the bowel
Not reported which enemas and suppositories children were treated with for disimpaction
Having another nurse (or other professional) independently examining the case notes or reviewing the transcriptions might have decreased the risk of potential bias
According to the reported results it is unclear that clinical centre was the unit of analysis
Source of funding: sponsored financially by Norgine Pharmaceuticals Ltd, Harefiled, UK, manufactures of Movicol (macrogol 3350 plus electrolytes) |
| Pashankar et al. Efficacy and optimal dose of daily polyethylene glycol 3350 for treatment of constipation and encopresis in children. 2001. Journal of Pediatrics 139[3], 428-432 | Study Type:
Prospective case series
Evidence level:
3
Study aim:
to examine the efficacy and dosing of PEG in children with constipation | 24 children
Inclusion criteria:
constipated children between ages of 18 months and 12 years
Exclusion criteria:
history of Hirschsprung's disease, anorectal malformations, abdominal surgery or any systemic illness that could lead to constipation | (data available for only 20 children who completed study)
9 boys aged 18 months to 11 years
Mean age 6.09 ± 4.2 years
11 children: constipation alone
9 children: constipation + soiling
Country:
USA | Intervention:
PEG solution, initial dose ~1g/kg body weight per day (14 ml/kg/d solution) given in 2 divided doses for 8 weeks
Parents instructed to dissolve 17 g of PEG powder in each 240 ml (8 ounces) of water, juice or other clear-liquid beverage, families allowed free choice of clear liquid beverage. For determination of best dose for each child, parents asked to increase or decrease volume of PEG solution by 20% every 3 days as required to yield 2 soft-to-loose stools (consistency score of 3 to 4) per day
Comparison:
none | Follow-up period:
8 weeks
Outcome Measures:
- -
soiling frequency - -
presence of abdominal faecal mass - -
presence of faecal rectal impaction - -
dilated rectal vault - -
painful defecation - -
fear of defecation /stool withholding
| Soiling frequency (n=9) (mean ± SEM) :
before treatment: 10.0 ± 2.4
during treatment: 1.3 ± 0.7 p= 0.003
Total resolution of soiling: 4 patients (44.4%)
Presence of abdominal faecal mass (n=18)
before treatment: 44%
during treatment: 0%
p<0.0029
Presence of faecal rectal impaction (n=18)
before treatment: 83%
during treatment: 22%
p<0.0006
Dilated rectal vault (n=18)
before treatment: 78%
during treatment: 11%
p<0.0001
Painful defecation (n=20)
before treatment: 75%
during treatment: 0%
p<0.0001
Fear of defecation /stool withholding (N=20)
before treatment: 70%
during treatment: 5%
p<0.0001
Final effective dose during last 2 weeks of treatment (mean ± SEM) (g/kg/day):
0.84 ± 0.27 (range 0.27 to 1.42)
Palatability:
all children reported willingness to take PEG and found it highly palatable (to prepare PEG patients used sweeteners, fruit juices, water and cow's milk)
Adverse effects:
no significant except for diarrhoea during adjustment of dose. Flatulence (n=2) Abdominal pain (n=10) | Additional information from study:
Diagnosis of constipation based on symptoms of at least 3 months' duration including at least 2 of: hard stools, painful defection, withholding of stools, faecal soiling, palpable faecal mass and fewer than 3 bowel movements/week
Administration of all other medications for constipation stopped on enrolment. No enemas or cathartics given either. Initial doses of PEG prescribed based on authors' previous experience with this agent
Stool consistency assessed by history on a scale of 1 to 5 as follows: 1, hard; 2, firm; 3, soft; 4, loose and 5, watery
Patients examined on enrolment and at the end of 8 weeks of therapy for the presence or absence of a palpable faecal mass, faecal impaction and rectal dilatation
Children of appropriate developmental status advised to sit on toilet for 5 minutes after each meal
Patients bowel habits before PEG treatment compared with those recorded on diary forms during the last 2 weeks (weeks 7 and 8) of treatment
4 subjects dropped from study because of failure to return required symptoms diaries: 2 of these had an excellent response to therapy by parent report and two were lost to follow up
Reviewer comments:
Small sample size, no sample size calculation
No data reported on who performed physical examination on enrolment and at the end of 8 weeks of therapy
Not clear why data on physical examination available for only 18 children
Source of funding: not stated |
