Nocturnal Acid Breakthrough -- Approach to Management

Radu Tutuian, MD; Donald O. Castell, MD

Disclosures
In This Article

Abstract and Introduction

Nocturnal acid breakthrough is defined as the presence of intragastric pH < 4 during the overnight period for at least 60 continuous minutes in patients taking a proton-pump inhibitor (PPI). Nocturnal acid breakthrough occurs in more than 70% of Helicobacter pylori-negative patients on PPI therapy and has clinical consequences in particular in patients with complicated gastroesophageal reflux disease (GERD), Barrett's esophagus, and esophageal motility abnormalities. The clinical importance of nocturnal acid breakthrough and the benefit of adding histamine-2 receptor antagonists (H2RAs) to PPI therapy have been debated ever since these concepts were introduced. In our experience, the addition of bedtime H2RAs is clinically effective in controlling nocturnal acid breakthrough and GERD symptoms.

The final step in gastric acid secretion is the exchange of intracellular protons (H+) for extracellular potassium (K+). The energy required to transfer protons across the high concentration gradient (intracellular pH is approximately 7 while the intragastric pH is close to 1) comes from cleaving ATP molecules. The H+/K+ ATP-ase responsible for this process is also known as the "proton pump," and is inhibited by substituted benzimidazoles or PPIs. The introduction of PPIs in the 1980s changed the clinical approach to and management of peptic diseases such as gastric ulcers, duodenal ulcers, and GERD.

The initial, basic science reports on the PPIs described these medications as irreversible inhibitors of the proton pump, underscoring the need for synthesis of new proton pumps before acid secretion could be resumed.[1] The concern about iatrogenic achlorhydria and its consequences led to an initial "black box" warning regarding the duration of treatment with PPIs. Subsequent clinical data revealed that PPIs, even though they significantly decrease acid secretion, do not completely eliminate intragastric acidity.[2] Reasons for this phenomenon include the relative short serum half-life of PPIs (2-4 hours), the fact that not all proton pumps are active at the same time, and that generation of new proton pumps is a continuous process.[3] Recovery of intragastric acidity, primarily during nighttime while on PPI therapy, should not be regarded as a failure of, or resistance to, these compounds, but rather as an expected phenomenon that may require attention in some patients.

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