Value of pH Impedance Monitoring While on Twice-Daily Proton Pump Inhibitor Therapy to Identify Need for Escalation of Reflux Management

Gastroenterology. 2021 Nov;161(5):1412-1422. doi: 10.1053/j.gastro.2021.07.004. Epub 2021 Jul 14.


Background and aims: Acid exposure time (AET) and reflux episode thresholds from the Lyon Consensus may not apply for pH impedance studies performed while on proton pump inhibitor (PPI) therapy. We aimed to determine metrics from "on PPI" pH impedance studies predicting need for escalation of therapy.

Methods: De-identified pH impedance studies performed while on twice-daily PPI (Diversatek, Boulder, CO) in healthy volunteers (n = 66, median age 37.5 years, 43.9% female), and patients with proven gastroesophageal reflux disease (GERD) (European heartburn-predominant cohort: n = 43, median age 57.0 years, 55.8% female; North American regurgitation-predominant cohort: n = 42, median age 41.6 years, 42.9% female) were analyzed. Median values and interquartile ranges for pH impedance metrics in healthy volunteers were compared with proven GERD patients with and without 50% symptom improvement on validated measures. Receiver operating characteristic (ROC) analyses identified optimal thresholds predicting symptom response.

Results: Both conventional and novel reflux metrics were similar between PPI responders and nonresponders (P ≥ .1 for each) despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (AET >4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, respectively, 57.1% and 82.4% of whom reported nonresponse; and 85% with these metrics improved with invasive GERD management. On ROC analysis, AET threshold of 0.5% modestly predicted nonresponse (sensitivity, 0.62; specificity, 0.51; P = .22), and 40 reflux episodes had better performance characteristics (sensitivity, 0.80; specificity, 0.51; P = .002); 79% with these metrics improved with invasive GERD management.

Conclusion: Combinations of abnormal "on PPI" pH impedance metrics are associated with PPI nonresponse in proven GERD patients, and can be targeted for treatment escalation, including surgery, particularly in regurgitation-predominant GERD.

Keywords: Acid Exposure Time; Gastroesophageal Reflux Disease; Proton Pump Inhibitor; Reflux Episodes; pH Impedance Monitoring.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Drug Administration Schedule
  • Drug Monitoring*
  • Electric Impedance
  • Esophageal pH Monitoring*
  • Europe
  • Female
  • Gastroesophageal Reflux / diagnosis
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / physiopathology
  • Heartburn / diagnosis
  • Heartburn / drug therapy*
  • Heartburn / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Proton Pump Inhibitors / administration & dosage*
  • Proton Pump Inhibitors / adverse effects
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • United States
  • Young Adult


  • Proton Pump Inhibitors