Utility of pH/Multichannel Intraluminal Impedance Probe in Identifying Operative Patients in Infants with Gastroesophageal Reflux Disease

Introduction

Gastroesophageal reflux is commonly encountered in the infant population. Fortunately, after approximately 1–2 years most infants with gastroesophageal reflux will ultimately have symptom resolution. However, a subset will develop pathologic reflux severe enough to require surgical management. These are the infants who make up the population with gastroesophageal reflux disease (GERD). Complications of GERD can include aspiration pneumonia, failure to thrive, and apparent life-threatening events. Infants with suspected complications related to GERD are often referred for consideration for fundoplication. However, these complications are multifactorial, and identifying which infants have severe GERD as a source of their complication is a diagnostic dilemma despite a range of tools available for diagnosing pathologic reflux. Esophageal pH and multichannel intraluminal impedance (MII) measurements are useful diagnostic tools in adults and older children, but their diagnostic efficacy in infants is unproven. In an effort to further investigate the use of this relatively new diagnostic modality, we reviewed our experience with the pH/MII probe for the diagnosis of GERD in infants.

Subjects and Methods

After Institutional Review Board approval, we conducted a retrospective review including all patients ≤6 months of age who underwent pH/MII probe investigation for the purpose of diagnosing GERD from January 2006 to December 2009. For data analysis, patients were divided into two groups: those who underwent fundoplication (operative) and those who were managed medically (nonoperative). Demographic data points collected include gestational age, age at the time of pH/MII study and fundoplication, gender, and presence of neurologic impairment. Results of the pH probe including reflux index, Boix–Ochoa score, and the gastroenterologist's interpretation of the results were collected. The MII probe results were reviewed by a staff gastroenterologist retrospectively and included total number of reflux events, as well as number of acid and non-acid reflux events. Abnormal results for the MII probe were defined by infant data available in the current literature with normal values defined as 70 reflux events in a 24-hour period, of which 25% are acidic and 73% are non-acidic.

Length of follow-up and symptom improvement were documented. Symptom improvement was defined as the patient gaining weight, tolerating feeds with only minimal retching or occasional emesis, improved pulmonary status, and/or no apparent life-threatening event spells at last follow-up.

Statistical analysis was performed using Student's t test for continuous variables and Fisher's exact for dichotomous variables with a significance of <.05.

Results

In total, 57 patients were identified: 33 patients were in the operative group, and 24 patients were in the nonoperative group. Patient demographics of the two groups are shown in Table 1. The operative group comprised 66.7% neurologically impaired patients compared with 20.8% for the nonoperative group (P<.001). All neurologically impaired patients required a gastrostomy tube because of failure to thrive or feeding difficulties. The pH/MII probe results are shown in Table 2. There was no difference between the two groups in their pH probe results; however, the nonoperative group displayed a greater number of total reflux episodes on the MII probe.

Mean follow-up was longer in the operative group compared with the nonoperative group (15.9 versus 7.6 months, respectively; P=.006), but there was no difference in presence of symptom improvement at last follow-up between the operative and nonoperative groups (96.9% versus 100%, respectively; P=.58).

Discussion

Gastroesophageal reflux is of minimal clinical significance in the majority of infants and will generally resolve spontaneously by 2 years of age.^1–3 However, a subset of infants will develop complications related to GERD, and these patients may benefit from a fundoplication. Accurately identifying these patients is of obvious importance to the pediatric surgeon.

Traditionally, the diagnosis of GERD was predicated on an abnormal upper gastrointestinal study demonstrating reflux of contrast during fluoroscopic observation. This provides a limited scope of the disease process and has proven to be a rather ineffective means of diagnosis with an accuracy of approximately 50%.^4–6 Currently, it is most useful for identifying anatomic abnormalities and has been shown to influence the operative plan in 4% of cases. ⁶ The current gold standard for the diagnosis of GERD in adults is the 24-hour pH probe, and it is now also widely used for infants and children.^7,8 The recent addition of the MII probe, which is performed simultaneously with the pH probe, to the diagnostic armamentarium has garnered significant attention, and MII is being used frequently in infants and children. Unfortunately, experience and normal values are lacking in this population. To date, there has been a single publication proposing normal values for the population examined in our study, and this was the standard with which we compared our patients. ⁹ Although this report attempts to identify normal values in healthy infants, it cannot realistically be used to identify pathologic values. Hence, we are left with an inablilty to effectively utilize the results that are generated from MII studies and are likely using incorrect end points to identify abnormality. This is confirmed by our current study in which 100% of patients evaluated for GERD had abnormal MII studies, an extremely high sensitivity in the face of poor specificity.

An alternative to using pH/MII to identify those patients who should undergo fundoplication is to utilize the study to predict those patients who are likely to fail medical management and may require fundoplication. Several authors have evaluated the use of pH/MII in this regard. One study showed a significant difference in the reflux index of patients who were successfully managed medically compared with those who failed medical management. ¹⁰ Another study reinforced this finding, and the authors defined a reflux index >18% to be indicative of failure of medical management. ¹¹ Yet another review demonstrated that patients with GERD-related complications of apnea and pneumonia had significantly more episodes of reflux detected by the pH/MII probe than those without complications. ¹²

These studies seem to support that pH/MII data may be useful in identifying patients who will fail conservative management. However, this does not automatically translate into identifying patients who would benefit from fundoplication. In fact, a majority of studies cannot demonstrate a correlation with an abnormal test result and symptom resolution after surgery.^13,14 Recently, one study concluded that neither a positive symptom index nor a positive symptom sensitivity index predicted post-fundoplication improvement in GERD symptoms. ¹⁴ It is interesting that, in counter distinction to the use of an abnormal pH/MII as a diagnostic tool for identifying patients who will have symptom improvement after fundoplication, it has also been reported that patients with normal pH/MII test results who undergo fundoplication experience improvement in their symptoms. ¹⁵

The results of the current study support the proposal that the pH/MII probe offers no insight as to which patients will benefit from operative intervention for GERD. Our data show that the sensitivity of MII in infants is “perfect,” with 100% of infants evaluated for GERD having abnormal results, including those successfully managed with conservative treatment. To further point out the inability of MII to identify infants who will benefit from fundoplication is the finding that infants who were conservatively managed had a greater number of total reflux episodes than those who underwent fundoplication.

In the present study, successful medical and surgical management was defined as symptomatic response to acid suppression treated medically or surgically with the evidence of improvements in dysphagia, regurgitation, or respiratory complaints. Failure of medical or surgical management was evident by persistent symptoms and/or development of complications. Nonoperative patients were followed as outpatients for management of medically treated GERD by gastroenterology and pediatrics. Data were obtained from the electronic medical record outpatient visits. All operative patients were followed closely postoperatively for symptomatic improvement, and only one patient was noted to have persistence of symptoms after repair.

It should be noted that the pH/MII study is not useless, as it does identify those infants who are suffering complications of reflux. The complete clinical scenario will allow for the identification of infants with complications of reflux. Once reflux-related complications are identified, a fundoplication is often performed, which explains the symptomatic success in the patients who underwent an operation. Quite frequently, the diagnosis of GERD is made clinically by the primary team, and the pH/MII probe is used as a definitive study to document the presence of reflux prior to performing a fundoplication. Our results suggest that this test does not indicate that a patient will benefit from surgical intervention, but only reaffirms the presence of gastroesophageal reflux given that all patients evaluated for GERD in our series had a positive MII. Furthermore, our results show that even those patients managed nonoperatively improved despite having a positive MII. Therefore, until pH/MII is further refined, or a more accurate tool is developed, clinical decision-making remains paramount in differentiating those infants who should continue on their current road of medical management and those who may benefit from an operation.