Most Popular Posts 2011-2018

Since this blog’s inception, there are now more than 2500 posts; these are the most popular (most views):

Most of these posts are referenced in more recent posts on the same or similar subjects.

Near Banff

 

Low Adherence Rate with Polyethylene Glycol

The sentiment of wanting to get their kid off laxatives/stool softeners is frequently expressed at GI visits.  I certainly understand this.  Though, if a child is not stooling adequately when these medicines are withheld, this is usually detrimental for the child.

Given the frequency of this sentiment, it is not surprising that a recent study (IJN Koppen et al. J Pediatr 2018; 199: 132-9) reports low adherence with polyethylene glycol treatment in children with functional constipation.

In this cross-sectional survey using the Medication Adherence Report Scale (MARS-5), with scores of ≥23 indicating better adherence, the authors found that only 43 of 115 (37%) children were adherent.  The authors note that one of the determinants of adherence was treatment convenience.

The MARS-5 does not objectively measure the exact intake of medication; thus, the exact rate of adherence is unclear.  In addition, there is likely to wide variation in adherence among different populations.

My take: this study shows, at least in some populations, a low adherence with constipation therapy.  Sticking with treatment, for constipation and every other condition, usually results in better outcomes.

Related blog posts:

If someone is not taking their medication, perhaps this cereal would help. (I am not officially endorsing this product, but think the name is funny.)

PEG 3350 is Not Associated with Elevated Glycol Levels

Everyday parents ask me if Miralax (polyethylene glycol) is safe; this has been driven by social media claims of neurotoxicity and by articles in the NY Times (see prior blog references) indicating that more testing is needed.

A recent study (KC Williams et al. J Pediatr 2018; 195: 148-53) examines one of the areas of concern, whether miralax could result in toxic levels of glycols.  In this study with 9 treated children (ages 6-12 years) and 18 controls, careful study of potentially toxic agents, ethylene glycol (EG), diethylene glycol (DEG), and triethylene glycol (TEG), were measured every 30 minutes for 3 hours after receiving 17 g of PEG 3350.

Key findings:

  • Baseline blood levels of EG (390.51 ng/mmL) and TEG (2.21 ng/mL) did not differ between control and treated groups
  • Baseline DEG levels were lower in the PEG 3350 group (40.12 ng/mL vs 92.83 ng/mL, P=.008)
  • After PEG 3350 dose, EG and TEG levels remained well below toxic levels; DEG levels did not change.  The increases in EG and TEG, which peaked at 90 minutes, were not sustained at levels different from controls.
  • EG peaked at 1032.8 ng/mL. TEG peaked at 35.17 ng/mL
  • The highest levels of EG and DEG were actually identified in control patients. Thus, “all children are exposed routinely and have measureable amounts in the blood.”

With regard to TEG toxicity, in the discussion, the authors note that, based on animal studies, “very large doses of TEG are needed to cause side effects.” Even doses of 4000 mg/kg of TEG daily for 90 days did not result in local or systemic toxicity.  The authors note that TEG concentration in PEG 3350 is “approximately 22.1-30.6 mcg per 17 gram dose of PEG 3350.”

With regard to EG and DEG, “the average EG and DEG content of the PEG samples in this study were a 100 and 800 times less, respectively, than this required 0.2% cutoff” [FDA limit].  The agency of Toxic Substances and Disease Registry profile for EG, has indicated that “EG blood levels greater tan 0.2 mg/mL are needed for acute toxic poisoning.  The average level of EG at the 90-minute peak of 1100 +/- 350 ng/mL was 182 times lower than this level.”  For chronic exposure EG toxicity, the authors estimate that one would need to take “40 capfuls [17 gram each] of PEG 3350 per day for up to a year.”  The EPA also has advisories with regard to EG.  To achieve toxic levels for a 10-kg child, this would necessitate that the child “would have to drink 1 L of water with 50 capfuls (858 g) in 1 day or 15 capfuls (258 g) per day for 10 days.”

An important limitation of this study is that there may be other metabolites that are not measured that could cause neurotoxicity.

My take: This study shows that the theoretical risk of glycol toxicity is highly unlikely.  My advice for miralax usage: (borrowed from expert review): “Generally speaking, if your child has been prescribed PEG 3350 as part of his/her treatment plan, and you feel this medicine provides benefit, you should feel safe continuing PEG 3350. At this time, PEG 3350 appears to be safe based on current medical literature. We recommend discussing any concerns you have about the safety of PEG 3350 with your child’s health care provider. If you would prefer for your child to stop taking PEG 3350, discuss other treatments options with your child’s health care team before stopping PEG 3350 therapy. Although abruptly stopping PEG 3350 is not considered dangerous, it could lead to a relapse/worsening of constipation.”

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Related blog posts:

Last Year’s Most Popular Posts

I want to thank the many people who have helped me with this blog –now with 2180 posts over more than 6 years.  This includes my wife, my colleagues at GICareforKids, and colleagues from across the country who have provided critical feedback as well as useful publications to review.  I hope this blog continues to be a useful resource.

Here are the top dozen most popular blog posts from 2017:

 

Expert 2017 Opinion: Miralax is (Still) First Choice Laxative for Children

IJN Koppen et al. Journal of Pediatric Gastroenterology & Nutrition: October 2017 – Volume 65 – Issue 4 – p 361–363

Abstract:

 According to international guidelines, polyethylene glycol (PEG) is the laxative of first choice in the treatment of functional constipation in children, both for disimpaction and for maintenance treatment. PEG acts as an osmotic laxative and its efficacy is dose dependent. PEG is highly effective, has a good safety profile, and is well tolerated by children. Only minor adverse events have been reported. Overall the use of PEG in children has been reported to be safe, although in patients predisposed to water and electrolyte imbalances monitoring of serum electrolytes should be considered.

Because this topic is of great importance to the families that are seen by pediatric gastroenterologists (and pediatricians), I wanted to review this brief article which describes the efficacy and safety of polyethylene glycol (aka miralax).

Key Points:

  • Polyethylene glycol (PEG) is the most widely used laxative in children and adults
  • It works by interacting “with water molecules by forming hydrogen bonds, in a ratio of 100 water molecules per 1 PEG molecule, which leads to an additional increase in colonic water content.” It is minimally absorbed.
  • Studies have demonstrated that PEG is better or noninferior to all of the following: lactulose, milk of magnesia, mineral oil, and flixweed (a medicinal herb)

Safety:

  • Only minor adverse events have been reported in studies.  In randomized, placebo-controlled trials, adverse events “did not occur more frequently in patients receiving PEG compared to patients receiving placebo.”
  • The main safety issue has been when it has been administered via nasogastric administration; improper placement can lead to severe pulmonary complications.  In addition, PEG should be used “cautiously in children with swallowing problems…because of risk of aspiration.”

Combatting Myths: 

  • The authors assert that there has never been reports of physical or psychological dependence.  Weaning from PEG is to prevent relapse of constipation.
  • There is no evidence to support loss of efficacy.
  • The phenomenon of “lazy bowel syndrome” in which there is worsened colonic function has not been described due to PEG; though, patients with underlying motility problems have had these problems misattributed to PEG use.
  • Despite anecdotal reports of tremors, tics, and obsessive-compulsive behavior in children taking PEG, there has been no evidence of a causal relationship.  “These events …are still under investigation, but the FDA has decided that no action is necessary.”  The authors note that the co-occurrence of neuro-behavioral problems and constipation is well-recognized in children with and without laxative use.

Clinical Pearl: Stimulant Laxatives After Repaired Anorectal Malformations:

  • “In children with constipation after repaired anorectal malformations, …stimulant laxatives (eg. senna) should be the laxative of choice.” (J Pediatr Surg 2017; 52: 84-8)

My take (borrowed from the authors): “PEG has rapidly become the treatment of first choice for children with functional constipation.”

Related blog posts:

 

One Day Polyethylene Glycol 3350 Prep

A recent study (B Sahn et al. JPGN 2016; 63: 19-24) with 155 patients prospectively showed that a 1-day polyethylene glycol (PEG) 3350 prep was safe and fairly effective.

The prep: 4 g/kg PEG in children with weights 10-50 kg and (with 238 gm for those >50 kg along with a single dose of a stimulant: either bisacodyl 5 mg-15 mg orally (10 mg for 21-30 kg) or senna (17.6 mg for 20 kg, 26.4 mg for 21-30 kg, and 52.8 mg for >31 kg).  The PEG was mixed typically with a sports drink to a max of 64 oz.

Key findings:

  • Hypokalemia was noted in 37 (24%) but none lower than 3.3 mmil/L.
  • Hypoglycemia was identified in 5 (3 were younger than 7). The one patient with severe hypoglycemia (31 mg/dL) was a one-year-old with corticosteroid dependency and had missed his morning steroid dose.
  • Colon cleansing was excellent or good in 77%.  The authors note that this suboptimal cleansing is due in part to the difficulty of using split-dosing in pediatrics.
  • 3/4ths of patients found the prep to be easy or average to tolerate.

My take: This study validates the common approach of using 1-day PEG 3350 preps in children.  Due to the low risk of hypoglycemia, particularly in young children, and the frequent mild hypokalemia, some children may benefit from starting intravenous fluids prior to induction of anesthesia.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Arthur Ravenel Jr Bridge

Arthur Ravenel Jr Bridge

 

Refractory Constipation -Terrific Update

Recently I attended a terrific talk by my partner, Jose Garza.  This lecture provided a great deal of information on refractory constipation for both pediatricians and pediatric gastroenterologists alike.

Elements of the talk included diagnosis, pathophysiology and differential diagnosis.

Rome III Criteria -Helpful in Diagnosis of Constipation

Rome III Criteria -Helpful in Diagnosis of Constipation

JG1 pathophys

Is it Hirschsprung's Disease?

Is it Hirschsprung’s Disease?

Some of the more useful points.

  1. AXR should not be used to make diagnosis of constipation.
  2. Many refractory constipation patients are stooling fine and actually labeled as constipation instead of a functional abdominal pain disorder.  That is, they are complaining of stomach pain and have been erroneously told they are constipated (see point #1).
  3. Miralax remains a 1st line agent for constipation. In individuals with fecal soiling, if miralax is not working and they have had appropriate cleanout, then senna laxative may be helpful.
  4. Sitz markers are particularly helpful in proving stooling when teenager claims to not be stooling for a month and in proving functional fecal retention rather than nonretentive soiling.
  5. If good treatment is not working, then refer to neurogastroenterology.

Related blog posts:

JG3 -Help