How (Un)Helpful is AD Manometry in Children with Orthostatic Intolerance?

A recent retrospective study (LN Zhang et al. J Pediatr 2019; 205: 133-44) reviewed the records of 103 consecutive children with orthostatic intolerance and gastrointestinal symptoms, all of whom had undergone antroduodenal manometry (ADM). The median age was 17 years with a 3:1 female predominance. The same group has published a smaller study in 2016 with 35 children (A Darbari et al JPGN 2016; 63: 329-35).

In their methods, the authors stated that neurogenic intestinal dysmotility was diagnosed if there was

1. lack of fasting MMC III
2. presence of simultaneous nonpropagative or retrograde phases
3. prolonged >30 min high amplitude clusters in duodenum
4. increase in basal tone >30 mmHg for >3 minutes during phase II MMC in a fasting state
5. lack of conversion from fasting MMC-III to fed MMC-II after meals
6. bursts of nonpropagating phase contractions w/in 30 minutes of meals

Key findings:

  • At baseline, the authors state that 12 (12%) had neurogenic intestinal dysmotility and 8 (8%) had significant antral hypomoility.
  • When ADM was undertaken in conjunction with tilt testing, the authors identified neurogenic intestinal dysmotility in 51 (50%), rumination/regurgitation in 23 (22%), and visceral hyperalgesia in 11 (11%).
  • Abnormalities in ADM did not have any correlation with abnormal gastric emptying studies (GES)s (which were performed in 83 of 103).  For example, among those with abnormal ADM (n=83), 48 (73%) had normal GES. And, among those with normal GES (n=58), 48 (83%) had abnormal ADM.
  • “Analysis of EGD biopsy samples revealed nonspecific esophagitis and/or gastritis in 16 of 103 patients (15%)”

While this research provides some insight into why children with orthostatic intolerance may have gastrointestinal symptoms, I remain skeptical of the usefulness of ADM as a routine study in clinical practice. The authors claim that ADM has ‘potential importance…in its utility in targeting future therapies.’

There are many hurdles, in my view, in making these studies worthwhile clinically:
  1. More uniformity in interpretation of ADM studies.  I do not have specialized neurogastroenterology training, but my understanding is that the difference between normal and abnormal is often blurry.
  2. More effective motility agents including prokinetics and agents to improve visceral hyperalgesia. How helpful is it to identify subtle manometric abnormalities without effective therapeutic agents?
  3. If GI problems are only demonstrated during tilt testing, how important is this?  I suspect that many individuals would have abnormalities if ADM was done while they were on a roller coaster, but I doubt that this would help me determine treatment for GI symptoms induced by this type of stimulus.
My take: This study confirms that EGDs are rarely useful in this setting and suggests that ADM could be.  While the study identifies frequent abnormalities when ADM was combined with tilt testing, it remains uncertain whether this will improve clinical management.
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NASPGHAN Postgraduate Course 2017 (Part 5): Refractory constipation, Extraesophageal GERD, POTS, Recurrent Abdominal Pain

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017

The child with refractory constipation

Jose Garza   GI Care for Kids & Children’s Healthcare of Atlanta

Key points:

  • Polyethylene glycol is a first-line agent and many patients require cleanout at start of therapy
  • Adequate dose of laxative is needed for sure regular painless stools
  • Don’t stop medicines before toilet training and until pattern of regular stooling established. “All symptoms of constipation should resolve for at least one month before discontinuation of treatment”
  • Gradually reduce laxatives when improved
  • An abdominal xray is NOT recommended to make the diagnosis of constipation
  • Do you have the right diagnosis? Irritable bowel is often confused with constipation.  With constipation, the pain is relieved after resolution of constipation.
  • Outlet dysfunction. Stimulant laxatives (eg. Senna) are probably underutilized. Biofeedback may help in older children.
  • Slow transit constipation. Newer prosecretory agents may be helpful –lubiprostone and linaclotide.
  • Organic constipation. Hirschsprung’s, Spina bifida, anorectal malformations etc. Testing: anorectal manometry, rectal biopsy (for Hirschsprung’s)
  • For refractory disease, consider rectal therapy –suppositories, transanal irritagations/enemas (~78% success for fecal incontinence/constipation). These treatments should be used prior to surgical therapy (eg. Malone antegrade continence enema/cecostomy)

 

 

The quest for the holy grail: Accurately diagnosing and treating extraesophageal reflux

Rachel Rosen   Boston Children’s Hospital

Key points:

  • It is frequent that EGD or impedance study will be abnormal, though this may not be causally-related.
  • No correlation with ENT exams/red airways and reflux parameters
  • No correlation with lipid laden macrophages and reflux parameters
  • No correlation with salivary pepsin and reflux parameters

Treatment:

  • Lansoprazole was not effective for colic or extraesophageal symptoms (Orenstein et al J Pediatrics 2009)
  • PPIs can increase risk of pneumonia/respiratory infections
  • Macrolides have been associated with increased risk of asthma but may be helpful for pulmonary symptoms
  • Fundoplication has not been shown to be effective for reducing aspiration pneumonia.  Fundoplication could increase risk due to worsened esophageal drainage.
  • ALTEs (BRUEs -brief resolved undefined events) need swallow study NOT PPIs

POTS and Joint Hypermobility: what do they have to do with functional abdominal pain?

Miguel Saps  University of Miami

Key points:

  • Patients with POTS and joint hypermobility have frequent functional abdominal pain as well as other comorbidities
  • Beighton Score can determine if joint hypermobility is present
  • Brighton Score determines if hypermobile Ehlers-Danlos syndrome is present
  • Patients with frequent fatigue.  Gradual progressive and regular exercise is important part of therapy.  Can start with recombant exercise – training bicycle exercise, swimming
  • Need to push salt intake and fluds

Do I need to test that C.R.A.P.?

Rina Sanghavi   Children’s Medical Center Dallas

This basic talk reviewed a broad range of issues related to functional abdominal pain.

Key points:

  • Carnett’s sign can help establish abdominal pain as due to abdominal wall pain rather than visceral pain
  • What is an appropriate evaluation?  Limited diagnostic testing for most patients.
  • Alarm symptoms include: Fevers, Nocturnal diarrhea, Dysphagia, Significant vomiting, Weight Loss/poor growth, Delayed Puberty, and Family history of IBD

What to Make of A Motility Study of Children with Orthostatic Intolerance

While a recent study (A Darbari et al JPGN 2016; 63: 329-35) provides some interesting data regarding the potential origin of gastrointestinal symptoms in the setting of orthostatic intolerance, I cannot support their conclusion that antroduodenal manometry (ADM) “should” be part of the evaluation of these affected children.

Background:

  • Retrospective study which included only subjects with a positive tilt test

What’s interesting:

  • Among 35 children with orthostatic intolerance due to either neurally mediated hypotension (NMH) or postural orthostatic tachycardia syndrome (POTS), ADM was abnormal at baseline or during tilt table testing in 26 (75%).
  • ADM studies were more often abnormal than gastric emptying studies, which were normal in 12 or 25.
  • Specific findings included neurogenic intestinal dysmotility in 15, antral hypomotility in 4, visceral hyperalgesia in 2, and regurgitation in 5.
  • GI symptoms of nausea, abdominal pain or vomiting were reproduced during tilt testing in 31 of 35 patients (89%).

Based on the discussion, the authors imply that ADM testing could help determine if the symptoms are due to neurogastrointestinal pathology or if normal, could indicate a central origin for the GI symptoms.  Thus, they conclude that motility testing “should” be part of comprehensive” orthostatic intolerance evaluation.

I would argue that this study does not show that ADM testing can reliably distinguish whether symptoms are due to a neurogastroenterological pathology or central pathology. And, in fact, there are better tests to examine for central origin.  I wouldn’t be surprised if many of their subjects had brain imaging, though this is not reported.

In addition, the authors acknowledge that ADM testing may not influence therapeutic decisions.  “The clinical response to promotility agents in children with POTS is generally low.”

My take: This study provides a useful mechanistic explanation of symptoms associated with orthostatic intolerance.  However, “I’m not there yet” on supporting ADM for all children with OI.

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Outcome with POTS –Better than Expected?

Adolescents with postural orthostatic tachycardia syndrome (POTS) are often seen in pediatric GI offices due to the associated GI symptoms.  A recent report (R Bhatia et al. J Pediatr 2016; 173: 149-53) offers up some encouraging data.

172 patients (of 502) responded to the authors’ survey.  The mean duration since the time of diagnosis was 5.4 years. Key findings:

  • 19% (n=33) reported complete resolution of their symptoms
  • 51% reported improvement, but persistent, symptoms
  • 28% reported intermittent symptoms
  • Thus, 86% reported that their POTS resolved, improved or was intermittent.

The authors note that some symptoms like dizziness and fatigue are common in patients without POTS and that “persistence of some symptoms can be part of a normal healthy life.”

My take: This study indicates that most adolescents with POTS are likely to have a good functional outcome.

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Understanding Idiopathic Nausea

A recent article describes a retrospective chart review of 45 children with chronic nausea and compares them to 49 children with chronic abdominal pain (J Pediatr 2014; 164: 1104-09).

Key findings:

  • While onset of symptoms was similar, the chronic nausea cohort presented at a median age of 15 years compared with 12 years for the pain cohort.
  • Comorbid conditions like anxiety, dizziness and fatigue were common in chronic nausea cohort.
  • Family history of migraines was note in 71% of nausea cohort compared with 22% in pain cohort
  • Extensive laboratory and imaging was much more frequent in nausea cohort.  With nausea cohort, 78% had abdominal ultrasound, 60% an upper GI, 58% brain imaging with either a CT scan or MRI, 38% gastric emptying, 31% abdominal CT or MRI, and 24% had HIDA.
  • Almost all endoscopies were normal (98% of chronic nausea group and 100% of pain cohort)
  • For nausea cohort treatment, tricyclic antidepressants showed a good response (=at least 50% symptom improvement) in 44% with a mean maximal dose of 50 mg. In contrast, with proton pump inhibitors, only 22% had some improvement (=at least 25% symptom improvement).  Similarly, ondansetron showed some improvement in 50% –though none had a “good response.”
  • Twelve patients (27%) of the nausea cohort met diagnostic criteria for cyclic vomiting syndrome (CVS) (with interepisode nausea) and another nine (20%) developed chronic nausea after ‘outgrowing’ CVS.
  • Postural (orthostatic) tachycardia syndrome (POTS) was noted in 16 of 45 in the nausea cohort based on an orthostatic screen (heart rate ≥30 beats/min during positional changes from 10 minutes in supine position to standing.

As the authors note, their study, conducted between 2006-2012, had numerous limitations, particularly the relative small size and retrospective nature.  In addition, the physician expertise in nausea/vomiting at Children’s Hospital of Wisconsin predisposes to a selection bias.

Take-home message: Nausea can be a severe symptom but is often difficult to manage. Extensive workup has a low yield in absence of other complaints or physical exam findings.

An AGA technical review on nausea and vomiting was published in 2001: GASTROENTEROLOGY 2001;120:263–286 

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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.

 

Salt for POTS –who benefits?

Individuals with postural orthostatic tachycardia syndrome (POTS) who have low baseline urinary sodium excretion (<124 mmol/24 hours) were more likely to benefit from sodium supplementation (J Pediatr 2012; 161: 281-4). In this group, “as much as 90% of patients” will improve with salt supplements.

This study from China examined the effects of sodium supplementation in 30 children (20 females, 10 males) as well as in 10 control patients to identify factors which related to therapeutic response.  Criteria for POTS included orthostatic intolerance (without orthostatic hypotension –blood pressure drop >20/10 mm Hg) accompanied by a heart rate increase of >30/min within the first 10 minutes of standing.

Despite normal serum sodium, POTS cohort had baseline 24-hr sodium excretion of 117 ± 59 compared with control of 194 ± 91.  POTS sodium-responders were similar in all aspects at baseline except for lower sodium excretion: 85 ± 35 compared to 150 ± 51 for POTS sodium-nonresponders.

The discussion reviews the theoretical reasons for POTS response to sodium (e.g.. ‘relative hypovolemia’) and points out that there are several subtypes, including ‘hypovolemic,’ hyper-adrenergic,’ and ‘autoimmune.’ Salt supplementation which has been shown to be effective only in the pediatric population targets the hypovolemic subset.

Limitations:

  • Small sample size
  • Lower sodium excreters had more symptoms at baseline & therefore may have led to bias as well

Additional references:

  • -J Pediatr 2011; 158: 20 (pg 4 editorial). n=53. GI pain in 75%, nausea/vomiting in large fraction, sleeping problems in 98%, headache, syncope, urinary symptoms. May have poor stomach emptying due to autonomic dysfunction
  • -J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):314-8. Gisela Chelimsky  “Gastric Electrical Activity Becomes Abnormal in the Upright Position in Patients With Postural Tachycardia Syndrome”
  • -J Pediatr 2011; 158: 499. Orthostatic hypotension can be treated physically: gripping hands for 15 secs before rising, lower body muscle contraction (eg pumping calf muscles/tensing legs), squatting…