For those wanting a state-of-the-art review on constipation:
YouTube (1:01) ANMS Virtual Symposia on Constipation
Dr. Jose Garza (one of my partners) gives the first lecture focused on pediatrics -first 18 minutes.
A few points:
- Miralax is safe (time: 13:45)
- Senna and bisacodyl are safe and have not been shown to cause dependence (time 14:55)
A recent retrospective study (S Bonilla et al. JPGN 2020; 71: 288-291. Long-term Use of Bisacodyl in Pediatric Functional Constipation Refractory to Conventional Therapy) provides some reassuring information about the use of bisacodyl for pediatric constipation, n=164. Bisacodyl’s mechanism of action is due to its ability to cause mucosal secretion and a prokinetic effect on colonic mucosa.
- Bisacodyl median dose was 5 mg/day, median duration of treatment was 14 months
- Median number of BM/wk doubled after initiation of bisacodyl from 2 to 4 bm/w (P < 0.001)
- Approximately 57% of patients had successful response. At long-term follow-up 55% of patients were successfully weaned off bisacodyl (median time of 18 months)
- Side effects: 8 patients reported abdominal pain, 4 had diarrhea, and 1 had nausea
- Limitations: open-label study, retrospective study, lack of a placebo-control
My take (from authors): “We observed no long-term complications with its long-term use in children.” Prospective studies are needed.
Related blog posts:
The images below show how much more prevalent problems with regurgitation, colic, functional diarrhea, dyschezia, and functional constipation in the first 3 months of life compared to later in the first year of life.
A recent cross-sectional study (LM Little et al. J Pediatr 2019; 210: 141-5) which examined sensory processing and constipaiton included 66 children and 66 control children.
- Children with chronic constipation had significantly higher sensory scores than matched controls. This included sensory avoiding (P<.001) and sensory sensitivity (P<.05).
The authors utilized the Child Sensory Profile-2 and the Toileting Habit Profile Questionnaire.
The finding that sensory problems contribute to chronic constipation. In those with over-responsiveness, which was more frequent in this study, this can lead to avoidance behaviors. In under-responsiveness, children may not realized that they need to defecate which can lead to problems as well.
My take: This study suggests that recognition of how sensory problems contribute to chronic constipation could improve counseling/treatment approaches.
Related blog posts:
Salt Creek Falls, OR
A recent study (LLD Zhong et al. Clin Gastroenterol Hepatol 2019; 17: 1303-10) shows that a Chinese remedy MaZiRenWan (MZRW) which is a combination of 6 herbs is an effective agent for constipation based on a double-blind, double-dummy trial of 291 patients with functional constipation. Thanks to Ben Gold for this reference.
MZRW was dosed at 7.5 mg BID and Senna was dosed at 15 mg per day. Mean age of study participants was 45 years.
- Complete response, defined as an increase of stooling by 1 or more BM per week, was similar between MZRW (68%) and Senna (58%) at week 8. Both were superior to placebo which had a 33% complete response.
- At week 16, MZRW had better response than senna or placebo, with complete responses of 47%, 21%, and 18% respectively.
- No serious adverse effects were reported and there were no significant differences in renal or liver function between the groups.
My take: The authors note that this remedy has been around for 2000 years. Their data show it appears to be a well-tolerated alternative for the management of constipation in adults.
Mount Batchelor, OR
A recent study (Vilanova-Sanchez A, et al. J Pediatr Surg 2018; 53: 722-7) provides reassurance regarding the safety of senna-based laxatives in kids.
The authors performed a literature review and reviewed their personal experience (2014 to 2017) of prescribing Senna in 640 patients. In this cohort, 230 (36%) had functional constipation.
- Besides abdominal cramping or diarrhea during the first weeks of administration, there were no other long-term side effects from Senna found in the pediatric literature with long-term treatment
- At their institution, 83 (13%) patients presented minor side effects such as abdominal cramping, vomiting or diarrhea, almost half (48%) of which resolved spontaneously within two weeks.
- “We did not see any side effects in 540 (84.3%) patients.” The median length of treatment was 338 days and median dose was 17.5 mg. “430 (80%) of them are currently taking Senna.”
- 17 patients (2.2%) developed blisters during their treatment. Patients who developed blisters had higher doses 60 mg/day; 60 [12–100] vs. 17.5 [1.7–150] (p < 0.001). All of the blistering episodes were related to night-time accidents, with a long period of stool to skin contact.
In their discussion, the authors note that senna and other anthranoid glycosides are not absorbed in the small intestine. They are maintained as prodrugs until they reach the large intestine where they are metabolized to the active form. In addition, “despite an extensive search of both the medical and lay literature we did not find any reference to long term tolerance due to treatment which we find is a frequently mentioned concern by families and clinicians”
The authors comments on the study from Nationwide Children’s Hospital website:
- “The safety profile of senna is as good as or better than many common medications a person would be on, including over-the-counter medications routinely given to very young children, and tolerance does not appear to be a concern,” says Dr. Levitt, who is also a professor of Surgery at The Ohio State University College of Medicine. “We hope this paper will make physicians more comfortable in using senna-based laxatives, and that they will be more widely used.”
- Senna is often more effective than polyethylene glycol. This study shows that it is safe as well. “A physician should consider senna as the first line medication,” says Dr. Levitt.
My take: Many patients who come to pediatric gastroenterologists have not responded to polyethylene glycol. Senna has been effective in many of these patients as part of a bowel regimen which usually includes behavior modification and diet.
Related blog posts:
Pictures from Joshua Tree National Park
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.)
A recent study (MH Vriesman et al. J Pediatr 2017; 190: 69-73) with 1835 children examined the issue of stool consistency, comparing the Bristol Stool Scale (BSS) and the Questionnaire on Pediatric Gastrontestinal Symptoms-Rome III (QPGS-RIII). Most of the patients in this study were older children, with 803 (43.7%) age 8-12 years and 1032 (56.3%) ≥13 years.
- Surprisingly (to me) there only slight agreement between BSS and QPGS-RIII for assessing stool consistency (κ = .046; P=.022).
- With the BSS, hard stools (types 1 & 2) were reported more frequently than QPGS-RIII: 18.0% vs. 7.1%.
- Both scales reported similar levels of functional constipation, 9.3% for BSS and 8.6% for QPGS-RIII. The presence of hard stools or painful defecation is only 1 of 6 Rome criteria for the diagnosis of functional constipation.
These results indicate significant variability in how often pediatric patients considered their stools hard based on the instrument (BSS vs QPGS-RIII). The reason why there is fairly close agreement on functional constipation is due to the fact that Rome III criteria combine the presence of hard stools and painful defecation into a single criteria and the fact that there are multiple criteria needed. “Not all children with hard stools have painful defecation and vice versa, with only 21% of children with painful defecation reporting hard stools.”
My take: This study suggests that painful defecation is more important to ascertain than if the stools are hard. In addition, this may explain why softening the stools as a stand alone strategy is not effective in many children.
Related study: S Muddasani et al. J Pediatr 2017; 190: 74-8. This retrospective study showed that pelvic floor physical therapy was effective in the majority of children (n=64,mean age 8.7 yrs) with fecal incontinence due to pelvic floor dyssynergia. It is notable that there were only two physical therapists involved; thus, in order to replicate these results, one would need quite capable PTs.
Related blog posts:
IJN Koppen et al. Journal of Pediatric Gastroenterology & Nutrition: October 2017 – Volume 65 – Issue 4 – p 361–363
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).
- 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)
- 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.”
- 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:
A personal pet peeve is having to explain to so many parents that their child is not constipated. The typical scenario is that their child went to the ER for abdominal pain and had an abdominal radiograph (AXR); then, the parents are informed that their child is constipated based on ‘fecal loading’ noted on the AXR. In this scenario, it is common for the child to have the following:
- regular bowel movements
- lack of a rectal exam
- lack of improvement with laxatives (though some do improve, perhaps due to the fact that symptoms often have regression to the mean)
- often a normal AXR when interpreted by radiologist rather than ED physician (it is normal to have some stool in the colon)
So, I like to see publications that support my viewpoint that this approach is misguided. Two recent studies provide some insight into this topic:
- SB Freedman et al. J Pediatr 2017; 186: 87-94
- CC Ferguson et al. Pediatrics 2017; 140 (1):e20162290 (thanks to Ben Gold for this reference)
Freedman et al performed a retrospective cohort study (children <18 yrs) who were diagnosed with constipation at 23 EDs from 2004-2015. This study used the PHIS database. Key findings:
- 185,439 of 282,225 had AXR at index ED visit
- Revisits to ED occurred in 3.7%
- 0.28% returned with a clinically important alternate diagnosis, most commonly appendicitis (34% in this category)
- Children who had AXR were more likely to have a 3-day revisit with a clinically important alternate diagnosis (0.33% vs. 0.17%)
Recognizing that AXRs are “unnecessary and potentially misleading,” Ferguson et al aimed to decrease AXR utilization in low-acuity patients who were suspected of having constipation. Using quality tools, the authors performed four plan-do-study-act cycles which included holding grand rounds, sharing best practices, metrics reporting, and academic detailing. Key finding:
- Over 12 months, we observed a significant and sustained decrease from a mean rate of 62% to a mean rate of 24% in the utilizaiton of AXRs in the ED for patients suspected of having constipation.
My take: These studies support my view that routine use of AXR in the diagnosis of constipation is a mistake and can be misleading.
Related blog posts: