DR. SONDHEIMER is professor of pediatrics, University of Colorado Health Sciences Center, and chief of pediatric gastroenterology,
hepatology, and nutrition at The Children's Hospital, Denver. She has nothing to disclose in regard to affiliations with,
or financial interests in, any organization that may have an interest in any part of this article.
The offices of pediatric gastroenterologists are filled with infants whose pediatricians have diagnosed gastroesophageal
reflux disease. Infants with arching, crying, spitting, and food refusal are being diagnosed with GERD. Although these babies
are treated with acid blockers and motility agents that are promoted as curative, a little digging shows that no double-blind
controlled study has confirmed the efficacy of these drugs in controlling these symptoms in infants.1-3
No doubt, acid blockade cures esophagitis and produces dramatic changes in pH probe studies. But most infants with reflux
do not have esophagitis, and treating a test result does not guarantee that symptoms will be controlled. There is a lack of
pathophysiologic data explaining why infants reflux and whether GE reflux causes these common, frustrating symptoms.
Recently, esophageal impedance monitoring has been introduced into the diagnostic armamentarium for GE reflux, and it promises
to shed welcome light on the condition. Data are beginning to accumulate from studies on children. Whether these studies will
translate into a clearer definition of disease and better control of symptoms in infancy remains to be seen. This article
focuses on what impedance studies have revealed so far about infants with suspected reflux.
Testing for reflux
The tests most commonly used to document pathologic GE reflux in infants or to correlate symptoms with acid reflux are the
barium radiograph, prolonged intraluminal esophageal pH monitoring, and upper GI endoscopy. Used less often is the esophageal
nuclear scan, which monitors the accumulation of radioisotope in the esophagus after oral administration of a radiolabeled
meal.
Another new method of monitoring esophageal acid reflux uses an intraluminal esophageal pH capsule (Bravo Capsule). This small,
wireless pH probe is clipped to the side wall of the esophagus during endoscopy and transmits pH data to a small external
recorder for up to 48 hours.
Diagnostic tests for infants in whom GERD is suspected
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All these tests have significant limitations (see the table). Endoscopy findings in infants with reflux symptoms are usually
normal. Reflux of barium during an upper GI series is so common that it should not be considered a diagnostic finding. Techniques
of nuclear scanning are poorly standardized and, because these scans monitor postprandial reflux events, they too may falsely
be read as positive. The intraluminal wireless device requires endoscopy for placement and is not small enough to be used
in infants.
For more than 30 years, physicians have measured GE reflux by prolonged monitoring of esophageal pH. Such pH probe studies
accurately describe the frequency and duration, but not the volume, of acid reflux events. Experience with pH recordings has
yielded a consensus on how much acid reflux is normal. Roughly speaking, it is probably pathologic if a child spends more
than 6% to 10% of a 24-hour period with acid material in the esophagus. Acid reflux during sleep is abnormal. More than three
or four episodes of acid reflux lasting more than five minutes in 24 hours is abnormal.
Although pH monitoring is the best diagnostic tool available, physicians have long known that these studies tell only part
of the story. The pH probe cannot detect postprandial reflux because the stomach contents are buffered by food. The probe
cannot measure the volume of the refluxate, and it cannot measure burps when only air escapes from the stomach. Although pH
studies correlate well with the presence and severity of esophagitis, this condition is rarely present in infants with reflux.
Regrettably, pH probe studies have not correlated well with typical infant symptoms linked to reflux—fussiness, arching, food
refusal, spitting, and cough.
What is impedance monitoring?
Impedance is the resistance to the flow of current between two points. Basic physics reminds us that resistance to current
flow is usually higher between electrodes submerged in air than between electrodes submerged in liquid. Using this principle,
researchers in industry and clinical medicine have developed an instrument capable of measuring impedance continuously at
multiple sites in the esophagus.
Liquid of any pH, gas, and gas-liquid mixtures cause typical changes in the baseline impedance of the empty esophageal lumen.
A sudden increase in esophageal impedance suggests that gas is surrounding the electrode pair; a sudden decrease suggests
that liquid surrounds the electrode pair; and a mid-level decrease suggests mixed contents. By watching the progression of
impedance changes up or down a linear array of several pairs of electrodes, the clinician can determine the direction of fluid
flow and distinguish a swallow from a reflux event (Figures 1 and 2).
The flow of gas and gas-liquid mixtures can also be monitored. The upward extent reached by a refluxate can be estimated by
placing several pairs of electrodes along the length of the esophagus. When a pH electrode is added to the distal tip of the
impedance catheter, we can also tell whether the fluid moving up or down the esophagus is acid or non-acid. We can even generate
an old-fashioned pH probe report.
Sound easy? In principle, it is; in practice, less so. The technology is still in development, although it is available commercially.
The recordings are complex and filled with artifacts. Although significant progress has been made in computerizing the analysis
of the records to decrease the number of artifacts, a thorough (and time-consuming) review of the recording, episode by episode,
is still required. Interpreter bias is also a big issue.
What have we learned?
Initial clinical studies of combined impedance/pH monitoring provide new insight into infant (and adult) acid reflux. The
esophagus is revealed as a much busier place than once thought. Preliminary studies in adults show that the total number of
non-acid reflux events detected by impedance is equal to or even slightly higher than the number of acid events.4
The first study in infants suggested that the non-acid events outnumbered acid events by a factor of five.5 More recent infant studies, using refined equipment and more uniform interpretation standards, have reduced this estimate.
Most infant studies now indicate that non-acid reflux events are about equal in number to acid events—similar to what is seen
in adults.6-9 In other words, impedance studies show that pH monitoring alone misses about half of reflux events in infants and adults.
Another finding that gastroenterologists learned with dismay was that treatment of GERD with an acid blocker reduces the number
of acidic reflux episodes but does not change the total number of episodes10; it just shifts the percentages, increasing the number of non-acid events as the number of acid events decreases. Impedance
monitoring confirms what adult reflux patients have often observed—namely, acid blockade improves heartburn pain but does
not eliminate the feeling of fluid rising into the esophagus.
Impedance studies in children are few in number and small in size. However, some interesting information is beginning to appear
in peer-reviewed journals. In one study of 25 babies with apparent life-threatening events (ALTEs), reflux events detected
by impedance and pH probe were monitored, while apnea events were recorded simultaneously.7 Investigators found little evidence that apnea spells and reflux, detected by impedance or by pH probe, were temporally
related. Of 527 total respiratory events, only 80 (15.2%) were linked to reflux of any sort.
In another study, 24-hour impedance and pH probe examinations were performed in 34 babies with "typical" reflux symptoms—fussiness,
pain behavior, cough, arching, burping, and spitting.8 Non-acid reflux events accounted for 60% of all reflux events in the first hour after feeding, 40% of all events in the
second postprandial hour, and 30% of events after that. Four of the 34 patients did not have any symptoms during the study.
It is also of importance to report that only four of the 34 babies referred for "reflux symptoms" actually had reflux disease
by standard pH probe analysis. The symptom index (the fraction of symptoms associated with reflux) was higher than previously
observed in studies using pH probes, but there was still no correlation between reflux and symptoms in five of the patients.
A significant symptom correlation of more that 50% was observed in 20 patients.
Taking it symptom by symptom, 50% of fussy spells were associated with reflux (half non-acid, half acid); 40% of coughing
spells were associated with reflux (one third non-acid, two thirds acid); and 50% of arching spells were associated with reflux
(half non-acid, half acid). Although few burping spells were identified, 93% were reflux-associated. Fussiness had a tighter
association with gas reflux than with any liquid reflux events.
In a recent study of children with asthma, the total number of reflux episodes detected by impedance was again approximately
twice that which would have been seen with a pH probe alone.9 Symptom correlation in these patients was very poor, with only 9% of coughing episodes associated with non-acid events and
17% of coughing episodes associated with acid reflux.
Interpreting the new data
These preliminary impedance studies in infants have confirmed that there are about twice as many reflux episodes per day than
previously measured, even in infants with what would be interpreted as normal esophageal pH studies. Impedance studies support
the idea that infant fussiness may be associated with reflux of fluid that is probably physiologic, but that only about 50%
of fussy spells on average are linked to a simultaneous reflux event. The data do not support a role for reflux in ALTEs and
do not demonstrate a relationship between reflux and coughing in asthmatic children.
What the impedance studies tell me is that regurgitation into the esophagus is more common than we thought. We still have
to determine whether these added non-acid events are, in fact, pathologic. If they are, we need to find a new therapy for
GE reflux that prevents backflow of gastric contents. Acid blockers do not accomplish this.
I hope that the impedance technique will be used in many clinical settings to get as much information as possible on the role
of non-acid reflux. The situations in which more data are needed are numerous. Can impedance help distinguish the ruminator
from the refluxer? Can it identify the patient with aspiration by monitoring the height of reflux episodes? Can it help monitor
therapy? Or clarify the source of postprandial dyspepsia? The answer to each of these questions is a qualified "Yes": Impedance
studies might do that.
I won't minimize the anxiety and frustration of families and pediatricians who are trying to help a baby with fussiness, spittiness,
and pain behavior. Everyone wants to prescribe a medicine and make the baby better. I think, however, that we have to be honest
about what we can and can't do for such patients and about the fact that the tools we have to treat suspected reflux are limited.
Acid blockers do not prevent fluid from flowing back into the esophagus. They just change the pH of the refluxate.
Before ordering a combined impedance/pH study to investigate a baby with fussy pain behavior, I would recommend the same thing
I have recommended to pediatricians who want to order a pH probe study: Ask yourself two questions. What will I do if the
results are positive? What will I do if the results are negative? If the answer to both questions is "I will try an acid
blocker," then the test results are irrelevant to your plans.
In critical situations—when surgery might be contemplated for a baby with atypical or life-threatening symptoms—impedance
may increase the sensitivity of your evaluation and help determine whether esophageal reflux of liquid of any pH is a significant
factor in the occurrence of symptoms.
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