Tag Archives: Gastroesophageal Reflux

Fundoplication in children with neurologic impairment

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A recent study questions the value of fundoplication in children with neurologic impairment who undergo gastrostomy tube placement (JAMA Pediatr doi:10.1001/jamapediatrics.2013.334).

This paper’s findings are limited by the study’s design as a retrospective, observational cohort study.  However, the study has several strengths as well.  First of all, this was a large study which identified 4163 neurologically-impaired infants who underwent either tube placement with (n=1404) or without fundoplication (n=2759).  This population was drawn from 42,796 infants admitted to neonatal intensive care units from 42 children’s hospitals.  Thus, a second advantage of this study was looking at a broad range of children from the same NICU population.

Findings:

  • Infants who underwent fundoplication did not have a reduced rate of reflux-related hospitalizations.  The authors tried to control for differences in the population with propensity score-matched analysis.
  • Only a small number had a significant preoperative GERD workup.  In total, 9.4% of infants had pH probes and 4.3% had endoscopies preoperatively.
  • Mean number of reflux-related admissions (Table 3 in study) within 1 year after discharge from NICU: overall: for gtube 0.92 compared with 1.02 for gtube/fundo, for pneumonia 0.18 (Gtube) compared with 0.23 (Gtube/fundo), aspiration pneumonia was 0.08 for both groups.

The authors note that two previous studies had shown a reduction in reflux-related hospitalizations for children who had admissions due to reflux-related conditions.  However, they note that in their study, these patients had fundoplication performed prophylactically based on clinical judgement.

But, “clinical symptoms, including dysfunctional swallowing and intolerance of gastric feedings, likely influence the decision to perform a concomitant fundoplication; however, these were unavailable in the database.”  As such, the authors propensity score model could have failed to account for factors that are essential in deciding whether a concomitant fundoplication is worthwhile.

Bottom-line: A fundoplication may not effectively prevent reflux-related hospitalizations in neurologically-impaired infants; its expected benefits may be overstated.  The only way to definitively determine how useful (or how ineffective) a fundoplication is would be a prospective study.

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What to do with ALTEs?

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While apparent life-threatening events (ALTEs) in infants are quite disturbing, the best management for these events is far from clear. A recent systematic review of ALTEs in infants was undertaken and included studies from 1970-2011 (J Pediatr 2013; 163: 94-9). The authors ultimately identified 37 relevant studies: 18 prospective observational studies and 19 retrospective observational studies.

Results:

  • None of the 37 studies yielded “a high level of evidence for diagnostic or prognostic investigations.”
  • Risk factors for ALTE: prematurity, previous ALTEs, and suspected child maltreatment.
  • Routine screening for gastroesophageal reflux, meningitis, bacteremia, and seizures are “highly unlikely to be helpful in patients who are well-appearing and have no other findings suggestive of a diagnosis.”
  • Testing for GERD “is unnecessary in children with ALTEs.”  “A positive test does not necessarily inform management because causation cannot be established.”  Patients with recurrent ALTEs “may benefit from pH monitoring in combination with symptom recording.

Additional references:

NASPGHAN Consensus guidelines on GERD (2009)

Link: Gastroesophageal Reflux Disease in the Pediatric … – NASPGHAN.o

  • In premature infants, a relationship between GER (i.e. reflux) and pathologic apnea and/or bradycardia has not been established.Despite a lack of convincing evidence, if pathological apnea occurs in the face of pre- existing reflux, then the following two statements are the most common features:
  • Although reflux causes physiologic apnea, it causes pathologic apneic episodes in only a very small number of newborns and infants.
  • When reflux causes pathological apnea, the infant is more likely to be awake and the apnea is more likely to be obstructive in nature.
  • A diagnosis of an acute life-threatening event (ALTE) warrants consideration of causes other than GER (i.e. reflux).Reflux of gastric acid seems to be related to ALTEs (episodes of combinations of apnea, color change, change in muscle tone, choking, and gagging) in < 5 % of infants with ALTE. 
  • -J Pediatr 2009; 155: 516. Bradycardia not improved in preemies treated for GER. n=18. Editorial 464 urges not using GER Rx in neonates –outside clinical trials.
  • -J Pediatr 2009; 154: 374. Apnea associated with reduction in LES tone in premature infants; therefore, GER may be secondary to apnea rather than the reverse. Small study -12 apneic event in 7 infants.
  • -J Pediatr 2008; 152: 365. Compared risk factors with SIDS. One of 153 (0.6%) with ALTE died.
  • -Pediatrics 2005; 116: 1059 & 1217 (editorial). Apnea in preemies is unrelated to GER.
  • -Pediatrics 2004; 113: e128-132. Apnea is unrelated to GER in most preemies; airway problems due to GERD is hard to establish.
  • -J Pediatr 2000; 137: 321 & 298. Poor temporal association between GER & apnea in ALTE patients.
  • -J Pediatr 2001; 138: 355. Metoclopropramide/cisapride do not help apnea in preemies with GER
  • -Pediatrics 2002; 109: 8-11. GER does not cause apnea of prematurity.

Never quite right

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After esophageal atresia (EA) repair, problems with reflux and dysphagia effect up to 75-100% of patients.  A new study, JPGN 2013; 56: 609-14, helps provide some understanding why the esophagus is never quite right in these patients.

High resolution esophageal manometry (HREM) was performed in 40 patients with a median age of 8 years at three centers. Data was obtained primarily by chart review; in addition, symptomatology at the time of HRE#M was evaluated through a self-assessment questionnaire completed by the child or his primary caregiver.  35 patients had type C EA which typically accounts for 80-85% of all EA cases. Type C EA refers to a proximal esophageal pouch and a distal tracheoesophageal fistula (TEF).  5 patients had type A. Type A EA is an EA without a distal TEF. At the time of the HREM, 7 (18%) were considered asymptomatic.

Findings:

  • Three different motility patterns were identified: aperistalsis in 15 (38%), pressurization in 6 (15%), and distal contractions in 19 (47%).
  • Aperistalsis occurred primarily in patients with long-gap defects and/or following anastomotic leaks. 8 of 15 patients with aperistalsis had undergone fundoplication.
  • Pressurization (as shown in Figure 1) was when contraction of the entire esophageal body  occurred at once rather than in a progressive manner from proximal to distal esophagus. Distal contraction pattern indicated an absence of proximal esophageal contractions. 4 of 6 patients with pressurization pattern had undergone previous fundoplication.
  • Motility patterns were not predictive of symptoms.  Asymptomatic patients were noted with all three patterns.  However, gastroesophageal symptoms predominated in the aperistalsis group.  Dysphagia was frequent in all three groups.

Study limitations included retrospective data, and small numbers of patients. Furthermore, in patients with long-standing esophageal problems, “asymptomatic” may be related to the patient not knowing what “normal” feels like and may be related to compensatory behaviors.

While HREM explains the pathophysiology in EA patients, given the lack of effective medical treatments for motility disturbances, upper endoscopy is likely to be more useful for clinical management by identifying esophagitis and possibly Barrett’s esophagus.

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Predicting duration of reflux symptoms in babies

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A recent study identified two factors on multichannel intraluminal impedance pH monitoring (MII/pH) that correlated with the duration of gastroesophageal reflux symptoms in newborns (J Pediatr 2013; 162: 770-5).

This study examined 64 newborns who underwent MII/pH in the first weeks of life and then were enrolled in followup at 1, 3, 6, 9, 12, 18. 24, and 36 months. 53 patients completed the three-year study.

These patients were enrolled consecutively.  All preterm infants had to have a minimum postmenstrual age of 36 weeks.  Other criteria included a MII/pH study with a minimum duration of 19 hours, absence of GERD pharmacology for at least 1 week, and absence of infection, metabolic disease or central nervous system disease.

Results:

  • Impedance bolus exposure index (IBEI) and proximal reflux frequency positively correlated with duration of GERD symptoms.
  • IBEI was 1.45 in the short duration group (0-3 months), 1.85 in the medium duration group (4-9 months) and 2.46 in the long duration group (> 9 months).
  • Proximal reflux frequency (events/hour) was 1.56 in the short duration group (0-3 months), 1.95 in the medium duration group (4-9 months) and 2.38 in the long duration group (> 9 months).
  • Overall, one-half of patients were asymptomatic within the fifth month of age and the vast majority were asymptomatic by one year of age.
  • Weakly acidic events but not acid reflux events were significant in determining the differences in IBEI and proximal reflux.  As such, this study adds weight to the idea that acid blockers have little benefit in the first months of life.

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Trouble Sleeping and Gastroesophageal Reflux

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Determining whether reflux is causing an infant to have trouble sleeping is quite difficult as a practical matter.  A recent retrospective study adds information to this topic but opens up a can of worms (JPGN 2013; 56: 431-35).

The main problem is that clinical reflux occurs in the majority of infants and that sleeping problems are ubiquitous as well.  This leaves the door open to testing a lot of infants. At the  same time, effective therapeutic options are limited.  So, identifying that reflux is causing trouble sleeping, when feasible, may be akin to getting the license plate of the truck that ran you over.

In this retrospective study (2008-2010) of 24 infants with a median age of 5 months, 18 were receiving acid-suppressing medications prior to evaluation.  Determination that reflux was causally associated with awakenings and arousals was determined with symptom association probabilities (SAP) based on 2-minute measurement intervals with multichannel intraluminal impedance/pH monitoring/simultaneous polysomnography; SAP was considered significant if ≥95%.

Findings: Seven patients had a positive SAP for arousals due to GER (5 exclusively related to non-acid GER).  Nine patients had a positive SAP for awakenings due to GER (4 exclusively related to non-acid GER).

There were several limitations of the study.  Besides the small size, the main limitation of this retrospective study was a selection bias.  Other limitations included a large number of patients with comorbid conditions and the coincident usage of acid-suppressing medications.  19 of 24 patients had one or more significant comorbid conditions: laryngomalacia in 10, prematurity in 5, genetic syndromes in 3, esophageal atresia in 1, and SLE in 1.

Take-home point: This study is in agreement with the general consensus that GER (acid and non-acid) may trigger sleep interruptions in infants. Nevertheless, given the lack of impact on management, only rarely will infants with poor sleep benefit from these investigations.

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Off-label medications in pediatrics

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In the U.S., multiple legislative changes have been improving the information available for off-label use of medications (JPGN 2013; 56: 113-4).

The Pediatric Research Equity Act (PL 108-155) and the Best Pharmaceuticals for Children Act (PL 107-109) help the Food and Drug Administration (FDA) promote pediatric trials and better information.

  • Pediatric data must be included in labeling whether results are positive, negative or inconclusive
  • If pediatric trials are not completed because the drug would be ineffective or unsafe, this information must go into labeling
  • Public internet posting of certain FDA pediatric reviews is required regardless of whether the trials led to an approval

Despite these improvements, the data may be difficult to interpret.  The authors of this commentary note that only “48% of trials of products that had pediatric safety information added to the product’s labeling were reported in the peer-reviewed literature.”  Furthermore, in about half of the published articles, the studies did not emphasize the same information as the FDA labeling.

Even when a fair amount of data is provided, it is frequently ignored.  A specific example given by the authors: lansoprazole. Lansoprazole is not approved in patients younger than 1 year and labeling describes a negative trial in this age group. Yet, in the U.S., lansoprazole was dispensed off-label in this population approximately 358,000 times in 2010.

Pharmaceutical companies benefit whether the prescription is for an approved indication or for an off-label use.  Even with approved uses, there have been substantial concerns about adverse effects.  The likelihood of more risk and less benefit is much greater for off-label use.

So with the next prescription, it might be worth thinking about whether the medication works, whether there is sufficient data to support an approved indication, and how much risk is involved.

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Stopping reflux with magnets

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Gastroesophageal reflux disease (GERD) can be treated by bolstering the lower esophageal sphincter with a surgically-implanted bracelet of powerful magnets (NEJM 2013; 368: 719-27).

In a prospective study, 100 patients with GERD were enrolled in this study.  The study was conducted in 13 centers in the U.S. and 1 in the Netherlands.  It was designed by Torax Medical.  There was no control group. The primary outcome was normalization of esophageal acid exposure or a 50% greater reduction in exposure at 1 year.

Patient selection:

  • Inclusion criteria: 18-75 years with at least 6-month history of GERD and partial response to proton pump inhibitor treatment.  All patients had to have abnormal pH probe studies at baseline.
  • Exclusion criteria: large hiatal hernia, grade C or D esophagitis (Los Angeles classification), BMI >35, Barrett’s esophagus, motility disorder, dysphagia more than three times a week, or allergy to implant components.

Results:

  • Primary outcome was achieved in 64% of patients.
  • Secondary outcomes: a reduction of proton-pump inhibitor (PPI) use of 50% or more was achieved in 93%.  In fact, at 3 years, 87% had completely eliminated the use of PPIs. Quality of life scores improved in 92%.
  • Adverse effects: most common was dysphagia (68% postop, 11% at 1 year, 4% at 3 years).  This often resolved after esophageal dilatation.
  • Six patients had the device removed.

The bracelet of beads contained sealed magnetic neodymium iron boride.  Each bead is connected by a small wire to the next.  The small wires allow for expansion of the bracelet. It is also designed to avoid compression of the esophagus as the beads can rest against each other.  In addition, the beads separate with the transport of food or if increased intragastric pressure (eg. belch or vomit).

The median time for the procedure of laparascopic placement was 36 minutes. This study brings the worldwide clinical experience to 497 magnetic implants.  To date, there have been no reported erosions or migrations.

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Failure of PPI test

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Identifying patients gastroesophageal reflux with a so-called ‘PPI test’ is not effective (Clin Gastroenterol Hepatol 2012; 10: 1360-66).

This study examined data from the previous Diamond study (Gut 2010; 59: 714-21).

In short, among 308 patients who were evaluated by endoscopy and pH probe, 197 had GERD identified by the presence of reflux esophagitis, pH <4 for 5.5% or positive symptom association monitoring.  Then all patients were given esomeprazole 40 mg once a day for two weeks.

A positive response to PPI Rx was observed in 69% of those with GERD and in 51% of those without GERD.  If response was defined as ‘the absence of the most bothersome symptom in the last 3 days of treatment,’ then GERD patients had a 54% response compared to 35% of Non-GERD patients.

While the PPI test is a failure, in many clinical situations, symptom response to therapy may be more important than the reason for the symptoms. The attached link provides a nice synopsis: Study Finds ‘PPI Test’ a Poor Predictor of GERD : Internal Medicine …

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Impedance recommendations from PIG

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The ESPGHAN Pediatric Impedance Group (PIG) has published a review/consensus statement on the use of pH-Impedance monitoring (MII-pH) in children (JPGN 2012; 55: 230-34).

Conclusions from this group:

  • MII-pH provides more information than conventional pH probe.  Whether this information will “inform prognosis, or predict response to therapy in pediatric patients has yet to be determined”
  • ‘As long as there is no effective medical therapy for weakly acid and nonacid reflux, the clinical relevance of MII-pH remains debatable’
  • “There are no data on the results of antireflux surgery based solely on the detection of weakly acid and nonacid reflux”
  • MII-pH is investigational technique needing standardization before routine diagnostic use can be recommended.
  • Major indications: need to identify weakly acid and nonacid reflux, persisting symptoms during antireflux treatment, use in identifying rumination syndrome, and research
  • Limitations of MII-pH: high cost, limited contribution to change in medical care, lack of evidence-based parameters for assessment of GER

Related blog entries:

Gastroesophageal Reflux: I know it when I see it

Treating reflux does not help asthma

The Medical Pendulum and Gastroesophageal Reflux

Treatment for rumination and belching

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Treatment options for rumination and for belching are limited.  Baclofen improves symptoms and decreases events in both of these disorders (Clin Gastroenterol Hepatol 2012; 10: 379-84).

Rumination is characterized by effortless regurgitation of recently ingested food into the mouth (or beyond). It is easily mistaken for vomiting disorders and motility disturbances.  With rumination, patients have retrograde flow of gastric contents into the esophagus through voluntary, though unintentional, abdominal muscle contractions with increased intragastric pressure increases.

Supragastric belching occurs when air is sucked into the esophagus by decreasing the intrathoracic pressure or by contracting pharyngeal muscles.

Baclofen is an agonist of the γ-aminobutyric acid B (GABA) receptor which results in increased lower esophageal sphincter (LES) pressures and reduced swallowing rates. Baclofen has been shown to improve reflux, mainly by reducing transient LES relaxations (TLESRs) but also by increasing basal LES pressures.

In the majority of patients, the mainstay of treatment has been behavioral which use diaphragmatic breathing to compete/extinguish these behaviors.  There are a shortage of therapists familiar with this approach.  As such, alternative treatments are needed.  In this study, high-resolution manometry-impendance recordings were taken from 16 patients (10 women; mean age 43 years; range 18-89 years); eight of the patients had rumination.  Only 12 patients were included in the final analysis; four patients refused repeat manometry.  Manometry was performed before and after treatment along with recording symptoms.  Both symptoms and manometry recordings improved with Baclofen therapy.  This was a one-week open-label study.  Baclofen was dosed at 10 mg TID.  At baseline the total number of “flow events” was 473; after treatment, this was reduced to 282 events.  In total, rumination events decreased by 68% during treatment.   This improvement correlated with increased LES pressures.

Four of the 12 patients reported mild side effects mainly sleepiness and difficulty concentrating.

Additional references:

  • -Clin Gastroenterol & Hep 2007; 5:772. Review. Supragastric belching usually due to aerophagia and is very frequen (up to 20/hr)t. GERD related belching is less infrequent, has sour taste, usually less loud & after meals. Gum chewing, excessive beverage drinks, rapid eating or drinking,  smoking or using straw for drinking may increase air in the stomach and lead to burping which can be behavioural problem as well.
  • -“Behavioral Treatment of Chronic Belching Due to Aerophagia in a  Normal Adult” Behav Modif 2006; 30; 341
  • -JPGN 2011; 52: 414. Mgt of severe rumination @ Columbus Ohio. n=5. Definitive dx established with AD manometry with typical r-wave pattern (when regurgitates after a meal)
  • -JPGN 2010; 50: 103. Rumination occurring in NL intelligent adolescents. May start with regurgitation and progress to inability to swallow saliva.
  • -Clin Gastro & Hep 2006; 4: 1314. Review of management of rumination/case presentation
  • -Chitkara et al: Teaching diaphragmatic breathing for rumination syndrome. Am J Gastroenterol. 2006 Nov;101(11):2449-52. Review. Can use behavioral interventions such as deep breathing exercises/ diaphragmatic breathing to break the spasms..
  • -Gastroenterology 2006; 130: 1527-28. Review and criteria of rumination.
  • -Pediatrics 2003; 111: 158-62. Review of rumination dx, Rx, & prognosis.
  • -Clin Persp in Gastro 2000; 3 (5): 277.

Additional Baclofen references:

  • -J Pediatr 2006; 149: 436, 468. Baclofen reduces GER. 0.5mg/kg/day
  • -JPGN 2004; 38: 317. Effectiveness of baclofen in neurologically-impaired children w GER. (0.7/kg/day), n=8.
  • -Gastroenterology 2000; 118: 7-13. Use of baclofen to reduce TLESR.
  • -Aliment Pharm Ther 2003; 17: 243-51. Baclofen reduced GER (acid & nonacid). side effects -N, V, dizzy. dose: in adults, start at 5mg tid, increase c 5mg increments every 4th day to 10-20mg tid.