Tag Archives: constipation

Three PEG Pediatric Cleanouts

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Several articles highlight the use of polyethylene glycol (Miralax) as a bowel prep for children:

  1. JPGN 2013; 56: 215-19
  2. JPGN 2013; 56: 220-24
  3. JPGN 2013; 56: 225-28

These studies and the accompanying editorial (pg 115) show fairly good results with PEG cleanout regimens.

The first study compared PEG versus senna in a blinded, prospective randomized trial.  After enrolling 30 children (6-21 years of age) at a planned interim analysis, the study showed superiority of PEG (1.5 g/kg/day) when used for 2 days prior to colonoscopy.  In addition to laxatives, patients were instructed to consume full liquid diet for 2 days prior to procedure & clear liquid on day prior (up to 3 hours before procedure).  In the PEG group, good or excellent cleanout scores were noted in 88% compared with only 29% in the senna group. There were no significant adverse effects or electrolyte changes which are well-detailed in this study (Table 2).

The second study evaluated a 1-day regimen with 46 children in a prospective open-label study.  238 g of PEG was mixed with 1.9 L of gatorade and administered over several hours.  Patients (8-18 years) were instructed to take only clears after noon the day prior to procedure Only 37 (82%) were able to take the full preparation.  43 (93%) took at least 75% of the preparation.  Despite issues with tolerance and nausea/vomiting (noted in 60%), 77% were rated as having an effective cleanout.

The third study enrolled 45 children (5-21 years) in a prospective study of a 1-day bowel preparation. Patients <45 kg received 136 g of PEG solution with 32 ounces of Gatorade; patients >45 kg received 255 g in 64 ounces.  44 children completed study.  Patients were told to take PEG over 3 hours the evening prior to procedure and allowed clears until 3 hours prior to procedure.  In this group, nausea was noted in 34% and vomiting in 16%.  However, patients reported that preparation was easy in 61% and tolerable in 39%.  The quality of the preparation was considered excellent in 23%, good in 52%, fair in 23% and poor in 2%.  There were no significant electrolyte changes.

Take Home Message:

Numerous small studies show that PEG solutions can be used as a safe, effective bowel preparation in children.  Shorter duration preparations are more convenient and may result in nausea or vomiting.

In our institution, we frequently use PEG cleanouts.  However, typically our doses of PEG are lower (eg. 136-168 g) and often combined with an enema to complete cleanout process.  Unlike adult preparations, we have not instructed families in split-dose regimens mainly due to concerns about the ability of pediatric patients to adhere to these regimens.

Related blog entry:

Miralax Safety

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Periodically questions about the safety of Miralax arise. Recently, several colleagues have received some questions about the use of Miralax due to information on the internet. You may want to familiarize yourself with this link due to the misinformation which is provided:

http://www.gutsense.org/gutsense/the-role-of-miralax-laxative-in-autism-dementia-alzheimer.html

Some of the misleading statements:

  • Miralax has never been tested for safety in children
  • Miralax makes one cancer-prone by leaving the colon unprotected
  • Miralax may result in severe malnutrition ..leading to Autism
  • Miralax can cause memory loss and neurologic side effects

It is true that there is not enough adequate long-term data on the use of Miralax, though there are studies showing its effectiveness/safety (see below).  However, according to the FDA, there are no neuropsychiatric warnings needed for Miralax:

As with all medications, one has to weigh the risks and the benefits.  Clearly, the risk and consequences of untreated defecation problems can be severe in some children and may have terrible adverse effects on daily living.  The known safety profile of Miralax is very good and its usage has been recommended by the American Gastroenterological Association (AGA) and by the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN) in position statements on the treatment of constipation:

An article from NY Times on this subject:

Related Blog Posts:

Related references:

-Aliment Pharmacol Ther 2011; 33: 33-40.  Comparison of golytely vs miralax.
-Gastro & Hep 2008; 4: 489.  Safety/effectiveness of PEG3350 as sole agent for cleanout in 245 adults.  Used 204 gram in 32 oz of water.
-Pediatrics 2006; 118: 528.  Data on safety and effectiveness in 79 children (39 c PEG, 40 c MOM).  PEG outperformed MOM.  compliance for PEG was 95%, after 12 months, 62% improved c PEG and 33% recovered (did not need med anymore).
-JPGN 2004; 39: 536. n=75.  good experience with infants & toddlers; 85% short-term/91% long-term success.
-JPGN 2004; 39: 106.  Miralax cleanout: 4 glasses of Miralax, clears , two doses of senna or bisacodyl, & 1 saline enema.
-J Pediatr 2004; 144: 358.  4 day cleanout with Miralax, 1.5g/kg/day; last day with clears.  No enemas given.
-Arch Pediatr Adolesc Med 2003 Pashankar DS et al; n=83. Rx avg 8.7mo. insignificant adverse effects. no loss of efficacy
-Clin Pediatr 2002; Gremse DA. Lactulose & Miralax equivalent , but Miralax preferred
-JPGN 2004; 39: 197.  Published use in infants, n=28
-JPGN 2003; 37: 329 (9A) use of Miralax to 2mo or older, n=23.
-J Pediatr 2002; 141: 410-14.  PEG 3350 at doses of 1-1.5g/kg/d for 3 days relieved an impaction in 95%.
-JPGN 2002; 34: 372-377. n=28 pts + 21 pts c MOM control.  61% vs  67% doing well at 12 month f/u.
-OnlineJournal of Digestive Health 1999; 1.  Miralax results in good long-term success without salt absorption.
-J Pediatr 2001; 139: 428-32.  Mean effective dose was 0.84 g/kg/day (range 0.3-1.4 g/k/d) n=24 (for 8 weeks) 18mo to 11 years.
-JPGN 2001; 32: 514. Safety of miralax & references.

AGA Constipation Guidelines

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Constipation is a ubiquitous problem.  Updated guidelines and a technical review for adults with constipation have been published (Gastroenterol 2013; 144: 211-17, Gastroenterol 2013; 144: 218-38). AGA Institute Policy and Position Statements – Gastroenterology …

For pediatric gastroenterologists, the 2006 NASPGHAN guidelines (Evaluation and Treatment of Constipation – North American Soci) are more useful.  Nevertheless, these AGA guidelines offer some helpful insights.

Definition: “physicians often regard constipation to be synonymous with infrequent bowel movements, typically fewer than 3 per week, patients have a broader set of symptoms” that are considered constipation including hard stools, abdominal discomfort, incomplete evacuation, and excessive straining.  Rome  III criteria: “symptoms for ≥ 6 months and ≥ 2 of the following symptoms for more than one-fourth of defecations during the past 3 months: straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction, manual maneuvers to facilitate defecations; ❤ defecations/wk, loose stools are not present and there are insufficient criteria for IBS”

In adults, medical testing:

  • “In the absence of other symptoms and signs, only a complete blood count is necessary.”  Not needed unless other features: TSH, calcium, colonoscopy
  • Anorectal manometry and rectal balloon expulsion should be performed in patients who fail to respond to laxatives.  Defocography should be considered subsequently.  Colonic transit should be evaluated if anorectal test results do not show a defecatory disorder.

Recommended Treatment:

  • Start with increased fiber and laxatives (e.g. PEG, milk of magnesia, bisacodyl).  Newer pharmaceutical agents (e.g. lubiprostone and linaclotide) can be considered if no improvement.
  • Both “normal transit constipation and slow transit constipation can be safely managed with long-term use of laxatives.” (strong recommendation, moderate-quality evidence).  “Contrary to earlier studies, stimulant laxatives (senna, bisacodyl) do not appear to damage the enteric nervous system.  Neurologic damage might just as readily be the cause, not the result.”
  • Pelvic floor retraining by biofeedback rather than laxatives is recommended for defecatory disorders
  • Additional workup in those who do not respond.  Surgical treatment of slow transit constipation (subtotal colectomy or colectomy with ileorectal anastomosis) only when well-documented failure of aggressive prolonged laxatives/prokinetics

The technical review has a table that lists medications associated with constipation, describes pathophysiology in detail, lists the conditions associated with constipation, and explains the testing/medical management in-depth.

Related blog entries:

PEG vs. Fiber for constipation | gutsandgrowth
Stimulants for constipation | gutsandgrowth
It’s worth the cost | gutsandgrowth
ACE report -10 year effectiveness | gutsandgrowth
Linaclotide –not for kids | gutsandgrowth
Clues about constipation and more than 2.5 million … – gutsandgrowth

Feeling the urge and stopping the shame

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So many parents misinterpret withholding behavior in children.  Many indicate that their child is trying to go but cannot and others indicate that their child does not feel an urge to defecate.  Now more insight into this common issue has emerged (JPGN 2013; 56: 19-22).

The authors reviewed their experience with colonic manometry (n=410).  150 patients were identifed as having functional constipation.  Among this group, 56 patients volunteered that they had no urge to defecate.

Yet, during colonic manometry, when the first high-amplitude propagating colonic contraction (HAPC) occurred, this was associated with retentive posturing, grimacing or denial of sensation.  When the HAPC occurred, the examiner would explain that it was causing pain that would improve if the child defecated.  Ultimately, “every patient acknowledged an urge to defecate and successfully defecated.”

One other interesting part of this publication is the discussion of psychological aspects.  Do you remember Erikson’s stages (Erik Erikson – Wikipedia, the free encyclopedia)?  The authors note, “if toilet training is not achieved or the process involves negative experiences including being shamed into the process, shame and doubt will persist.  Shame, according to Erikson, is an infantile emotion and leads to secretive behavior.  Therefore, children who failed toilet learning may deny sensations of the urge to defecate…all the while having shame and embarrassment.”

These psychological issues are important in the propagation of constipation. The authors note that, even in children with rectal distention due to chronic constipation which could result in decreased sensation, studies have shown rectal compliance was not associated with treatment failure.  Therefore, constipation and soiling are not simply due to a mechanical issue of not knowing when to go.

Related posts:

Linaclotide –not for kids

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Linaclotide has been approved for adults (≥18 years) with chronic constipation and constipation-predominat irritable bowel syndrome (IBS-C) (Gastroenterol & Hepatol 2012; 8: 653-60).

Linaclotide is a 14-amino acid peptide that stimulates guanylyl cyclase C (GCC) receptors.  It mimics the endogenous peptides guanylin (15 amino acids) and uroguanylin (16 amino acids) which activate GCC through a cascade which activates CFTR to increase luminal levels of bicarbonate, chloride and water.  This in turn improves gastrointestinal transit.

There were several trials undertaken to assess the efficacy of linaclotide in IBS-C:

  • 47 patients (36 women) with IBS-C were treated with linaclotide (100 μg or 1000 μg) or placebo –5 day study. The 1000 μg dose significantly decreased colonic transit time compared with placebo.  No serious adverse events were reported.
  • 420 patients were enrolled in a 12-week, randomized, double-blind, placebo-controlled, dose-ranging study.  The population was 92% female, 80% caucasian with a mean age of 44 years.  337 patients completed the study.  There were improvements in the number of complete spontaneous bowel movements (CSBMs) per week and in abdominal pain.  Additional results:
  1. With 300 μg dose, there were 3.93 CSBMs/week, with150 μg dose 2.79 CSBMs/week compared with 1.47 for placebo.
  2. With 300 μg dose, there was -0.90 in pain score, with 150 μg dose -0.71 compared with -0.49 for placebo.  Overall, abdominal pain improved in 31.1-38.7% of linaclotide-treated patients compared with 22.7% of placebo-treated patients.

For chronic constipation, four trials (n=42, n=310, n=630, and n=642) have shown increased CSBMs/week.  On average, a dose of 290-300 μg dose resulted in 1.8-2.7 CSBMs/week, a dose of 145-150 μg dose resulted in 1.6-2.0 CSBMs/week compared with 0.5-0.6 CSBMs/week for placebo.  Changes in stool frequency were also reflected in quality of life scores.  When linaclotide was stopped, patients reverted to similar stooling rates as placebo-treated patients but no rebound effects were noted.

Prior to approval of linaclotide, lubiprostone (Amitiza) had been the only FDA-approved medication for IBS-C.  For chronic constipation, polyethylene glycol is another approved treatment.

Related blog entries:

PEG vs. Fiber for constipation

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Which is better for childhood constipation, polyethylene glycol 3350 (PEG) or fiber? A recent study weighs in (J Pediatr 2012; 161: 710-15).

This randomized, prospective, open-label study compared PEG (with electrolytes) to a fiber supplement (acacia fiber, psyllium fiber, and fructose [AFPFF]) in 100 children with chronic functional constipation (Rome III criteria).  Mean age was 6.5 years.  Study design allowed for dosage adjustment.  Initial PEG dosing was 0.5 g/kg but could be increased to 1 g/kg. AFPFF was dosed at 16.8 g daily but could be increased to 22.4 g.  Primary outcome was ≥3 bowel movements per week and improved stool consistency (≥2 on Bristol stool scale).

Key findings:

  • Compliance was better with PEG than AFPFF: 96% for 72%.
  • After 8 weeks, improvement noted in 83% of PEG patients compared to 78% of AFPFF (P=0.788).  At this time point, PEG were having ~5.8 stools/week vs. 5.6 for AFPFF.  Mean Bristol scores were 3.7 and 3.5 respectively.
  • Conclusion: similar efficacy but PEG had better acceptance.  No mention of relative costs of these agents is noted.

Additional references:

Diagnosis and management of idiopathic childhood constipation – BMJ  NICE (Nat’L institute for Health and Clinical Excellence) recommendations 2010

Also, a recent previous post (ACE report -10 year effectiveness | gutsandgrowth) has links to multiple related blog entries.

Clues about constipation and more than 2.5 million views

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A recent article identifies some important factors contributing to constipation in Hong Kong children (JPGN 2012; 55: 56-61).

Using a territory-wide questionnaire in 2318, Hong Kong Chinese elementary school students, the authors identified several factors associated with constipation which was present in 12.2% of this cohort:

  • Refusal to pass bowel movements at school (OR 1.97).  In Hong Kong, students spend >8 hours per day at school.
  • Having dinner with one/both parents <50% of time (OR 1.52).  May indicate less time with parents and less parental prompting.
  • Nighttime sleep <7 hours (OR 1.87).  This is postulated to be related to increased homework and more stress which may affect gut motility.
  • Frequent fast food consumption (OR 1.14).  This may be associated with less fiber intake.

On a tangential note, one of my sons informed me of “bad lip reading” on YouTube; some of these clips are really funny.  Since there was one relevant to the subject at hand, with over 2.5 million views, I’ve provided a link:

“Everybody Poops” – a bad lip reading of the Black Eyed Peas …

Additional blog entries related to constipation:

Stimulants for constipation

Diagnostic tests hardly ever help patients poop

It’s worth the cost

Think twice about checking thyroid

Stimulants for constipation

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Overall, 12-19% of Americans are affected by chronic constipation (Am J Gastroenterol 2004; 9: 750-59).  Despite the fact that constipation problems are widespread, the amount of useful research available to guide treatment is quite limited.  Two recent articles do offer some information:

  • Clin Gastroenterol Hepatol 2011; 9: 577-83.
  • Gut 2011; 60: 209-18.

The first reference examined the use of bisacodyl in a randomized, double-blind placebo-controlled study in the UK.  During the 4-week treatment period, patients receiving 10mg/day bisacodyl (n=247) had increased stools, from 1.1 per week to 5.2 per week.  Stool frequency also increased to 1.9 per week in the placebo group (n=121).  All secondary endpoints including constipation-associated symptoms (eg. quality of life indices, physical discomfort) improved significantly compared to placebo.  Average age of patients in this study was 55 years.  The main adverse effect was diarrhea –mainly during the 1st week of therapy.

A selected summary in Gastroenterology (Gastroenterology 2012; 142: 402-404) reviews the first study and makes several useful points:

  • Stimulant laxative use has been hindered by myths & misconceptions along with lack of supporting data.  Most recent studies do not support a role of stimulant use in causing enteric neuropathies, a cathartic colon or increasing the risk of colon cancer
  • Osmotic laxatives have been favored in guidelines but this has not been bolstered by supporting data
  • Only recently have two large randomized controlled studies proven the efficacy and safety of stimulant laxatives over the short-term
  • Long-term prospective studies are not available on the use of stimulant laxatives.

The second reference is a systematic review and meta-analysis of randomized controlled trials (RCTs) of pharmacologic therapy for chronic idiopathic constipation.  Twenty one eligible RCTs were identified: eight laxative studies (n=1411), seven prucalopride studies (n=2639), three lubiprostone (n=610), and three linactolide trials (n=1582).  All of these studies showed treatment was superior to placebo. These studies involved subjects who were mainly adults (>90% older than 16 years).

The results showed benefit from both stimulant and osmotic laxatives.  Overall, the osmotic and stimulant laxative studies showed higher response than the pharmacologic agents like prucalopride, lubiprostone, and linaclotide.  Nevertheless, between 50% and 85% of patients did not fulfill criteria for response to therapy.

Additional references:

  • -J Clin Gastro 2003; 36: 386-389.  Safety of stimulants for long-term use.
  • -Am J Gastro 2005; 100: 232-242.  Myths about constipation.  Stimulants have not been proven to cause a “cathartic colon”
  • -J Pediatr 2009; 154: 258.  Constipation associated w 3-fold increase in health utilization/cost.
  • -Clin Gastro  Hep 2009; 7: 20.  Review of complications assoc c constipation in adults.
  • -Pediatrics 2008; 121: e1334.  Behavioral therapy ineffective in treating childhood constipation.
  • -NEJM 2008; 358: 2332, 2344.  Use of methylnatrexone for opioid-induced constipation & trial of n=620 of prucalopride for severe constipation.  Both drugs were helpful.
  • -Gastroenterology 2004; 126: S33. Review of pediatric incontinence.
  • -J Pediatr 2004; 145: 253-4.  Prevalence of encopresis 15% /constipation 23% in obese children  (n=80).  Questionnaire administered to 80 consecutive obese children.
  • -Gastroenterology 2003; 125: 357.  Longterm constipation followup.  one-third with persistent constipation; 60% better at 1 year.  (tertiary referral group)
  • -Pediatrics 2004; 113: 1753 & e520.  When constipation & toileting difficulties both occur, constipation usually precedes toileting problems

Think twice about checking thyroid

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Hypothyroidism is not a frequent cause of constipation in children (JPGN 2012; 54: 285-87).  According to this study, the yield on checking for hypothyroidism in pediatric patients with constipation is no greater than in the general population.

This retrospective study examined the records of 873 patients who underwent thyroid testing ordered by pediatric gastroenterology; 443 (51%) had isolated constipation.  In all, 56 had abnormal thyroid function testing though 40 were normal on repeat testing. Of these 16 remaining cases, 7 were known to have hypothyroidism.  Of the nine remaining “new” cases, 3 had slow growth (2 without constipation), 3 had trisomy 21, and 2 were taking medications which affect thyroid function.  This leaves only 1 patient who presented with constipation without a clear risk factor or other indication for testing.

The authors state that 1/443 (0.2%) is quite similar to background incidence of hypothyroidism (0.3%).  The costs of identifying this case would exceed $18,000 but could be considered much higher (~$200,000) when all of the costs of false-positives are considered (eg. endocrinology consultations, followup testing).  In patients with slow growth (with or without constipation), about 2.5% had hypothyroidism.

In short, think twice about checking thyroid status in patients with isolated constipation.

Additional references:

  • -JPGN 2011; 53: S2. 49, 55. ‘Rarely do children with constipation need w/u’–only if alarming features: Delayed meconium, bilious vomiting, bloody stools, fever, bladder disorders, poor growth, NO RESPONSE to conventional treatment, abnormal exam. 25% of functional constipation problems may persist into adulthood.
  • -JPGN 2010; 51: 155. Lack of utility of AXR -suggested only in uncooperative pts, concerns about abuse/concerns about psychologic impact of exam
  • -J Pediatr 2010; 156: 461-5. MRI in children with chronic constipation or not-retentive soiling (n=130, n=28) -MRI showed lumbar sacral abnormalities in 3% –none required neurosurgery (1 w spina bifida occulta, 3 w terminal filum lipomas). Prospective study.
  • JPGN 2006; 43: e1Ye13.  http://www.naspghan.org/user-assets/Documents/pdf/PositionPapers/constipation.guideline.2006.pdf  Guidelines suggest checking thyroid, calcium, celiac and lead if not responding to therapy.

It’s worth the cost

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Recently the cost of Sitzmarks® increased to $175 (for 12)–it’s worth the cost.  According to one study, the use of a transit study helps determine which patients will benefit from colonic manometry (JPGN 2012; 54: 258-62).  A retrospective review of 24 children showed that all five children with normal oral-anal transit (OTT) studies had normal colonic manometry.  In contrast, 9/19 (47%) with abnormal (slow OTT) had abnormal colonic manometry.

The authors define their approach to OTT which is helpful.

  • In patients with a fecal impaction, this was cleared prior to starting study
  • If patients had difficulty with capsule ingestion, markers were administered by embedding in part of a banana or mixed with applesauce
  • Stimulant laxatives withheld for 72hrs prior to study
  • AXR obtained on days 3 and 5
  • Slow OTT (abnormal) defined as >6 markers proximal to rectum on day 5

Of those with abnormal colonic manometry, two-thirds (6) were referred for surgical intervention; one patient with normal OTT had surgery.  Surgeries:  3 cecostomy, 4 subtotal colectomy.

Additional references:

  • -JPGN 2004; 38: 75. Colostomy in 10 children with intractable constipation.
  • -Arch Dis Child. 2004 Jan;89(1):13-6. Benninga MA, Voskuijl WP, Akkerhuis GW, Taminiau JA, Buller HA. Related Articles,  Colonic transit times and behaviour profiles in children with defecation disorders.
  • -J Pediatr Surg. 2004 Jan;39(1):73-7. Youssef NN, Pensabene L, Barksdale E Jr, Di Lorenzo C.  Is there a role for surgery beyond colonic aganglionosis and anorectal malformations in children with intractable constipation?
  • -Am J Gastroenterol. 2003 May;98(5):1052-7.  Pensabene L, Youssef NN, Griffiths JM, Di Lorenzo C. Related Articles, Colonic manometry in children with defecatory disorders. role in diagnosis and management.
  • -JPGN 2002 Jul;35(1):31-8. Gutierrez C, Marco A, Nogales A, Tebar R. Total and segmental colonic transit time and anorectal manometry in children with chronic idiopathic constipation.
  • -JPGN 2001 Nov;33(5):588-91.  Villarreal J, Sood M, Zangen T, Flores A, Michel R, Reddy N, Di Lorenzo C, Hyman PE.  Colonic diversion for intractable constipation in children: colonic manometry helps guide clinical decisions.
  • -http://www.sitzmarks.com/buyonline.aspx