Nocturnal Acid Breakthrough Research Articles

An evaluation of the clinical implications of acid breakthrough in patients on proton pump inhibitor therapy.

Some patients with gastro-oesophageal reflux disease continue to experience symptoms despite therapy with proton pump inhibitors. One recently proposed cause is the occurrence of nocturnal acid breakthrough. : To investigate the relationship between acid breakthrough occurrence (nocturnal and daytime) and refractory symptoms among patients with gastro-oesophageal reflux disease on proton pump inhibitors. Fifty-two consecutive patients with persistent symptoms of gastro-oesophageal reflux disease despite proton pump inhibitor therapy underwent 24-h pH study at the Mayo Clinic between January 1 and November 10, 1999. Relevant data were extracted and analysed. Fifty-two patients, 18 males and 34 females, were eligible for the study. The mean age was 53 +/- 2.2 years. Thirty-seven patients (71%) had nocturnal acid breakthrough, and 36 (69%) had daytime acid breakthrough. Sixty per cent of patients experienced both nocturnal and daytime acid breakthrough, whereas 19% had neither. Among those with nocturnal and daytime acid breakthrough, only 36% and 33% of symptoms, respectively, were associated with gastro-oesophageal reflux episodes. The proportion of patients with symptoms and the mean symptom scores were not significantly different between those with and without acid breakthrough. Gastric acid breakthrough occurs nocturnally and during the daytime in patients on proton pump inhibitor therapy. With less than 36% of refractory symptoms associated with gastro-oesophageal reflux, gastric acid breakthrough cannot explain symptom refractoriness to proton pump inhibitor therapy in a significant majority of patients evaluated by 24-h pH study.

Combination Drug Therapy for Gastroesophageal Reflux Disease

OBJECTIVE:To evaluate the role of combination therapy with proton-pump inhibitors (PPIs) and histamine2 receptor antagonists in gastroesophageal reflux disease (GERD).DATA SOURCES:Clinical literature identified through MEDLINE (January 1966–August 2001). Key search terms included gastroesophageal reflux, benzimidazoles; omeprazole; lansoprazole; pantoprazole; rabeprazole; receptor antagonists, histamine2; therapy, combination drug; therapy, combined modality; and combinations, drug.DATA SYNTHESIS:Approximately 80–90% of patients show healing of reflux esophagitis after 8 weeks of once-daily PPI therapy. Patients taking PPI therapy twice daily still have nocturnal acid breakthrough (periods of gastric pH <4 lasting for ≥60 min during the night) as much as 70% of the time. The clinical application of this finding has not been shown. One trial has shown that omeprazole in the morning plus ranitidine at bedtime is not as effective as omeprazole twice daily given before the morning and evening meals at controlling nocturnal acid breakthrough. Further, 1 small trial in healthy subjects without GERD showed that the addition of a 1-time dose of ranitidine at bedtime to a twice-daily regimen of omeprazole may decrease the occurrence of nocturnal acid breakthrough. However, the clinical significance of this finding is not clear.CONCLUSIONS:No studies in patients with GERD demonstrate that the addition of histamine2 receptor antagonists to twice-daily PPI therapy provides any further benefit above that derived from PPIs alone. The parameter used to measure the efficacy of combination regimens for GERD thus far — Nocturnal acid breakthrough — Has not been proven to correlate with improvement of GERD symptoms in any controlled or prospective clinical trials. Further investigation is needed to determine optimal therapy in patients refractory to standard doses of PPIs.

Combination drug therapy for gastroesophageal reflux disease.

To evaluate the role of combination therapy with proton-pump inhibitors (PPIs) and histamine(2) receptor antagonists in gastroesophageal reflux disease (GERD). Clinical literature identified through MEDLINE (January 1966-August 2001). Key search terms included gastroesophageal reflux, benzimidazoles; omeprazole; lansoprazole; pantoprazole; rabeprazole; receptor antagonists, histamine(2); therapy, combination drug; therapy, combined modality; and combinations, drug. Approximately 80-90% of patients show healing of reflux esophagitis after 8 weeks of once-daily PPI therapy. Patients taking PPI therapy twice daily still have nocturnal acid breakthrough (periods of gastric pH <4 lasting for > or =60 min during the night) as much as 70% of the time. The clinical application of this finding has not been shown. One trial has shown that omeprazole in the morning plus ranitidine at bedtime is not as effective as omeprazole twice daily given before the morning and evening meals at controlling nocturnal acid breakthrough. Further, 1 small trial in healthy subjects without GERD showed that the addition of a 1-time dose of ranitidine at bedtime to a twice-daily regimen of omeprazole may decrease the occurrence of nocturnal acid breakthrough. However, the clinical significance of this finding is not clear. No studies in patients with GERD demonstrate that the addition of histamine(2) receptor antagonists to twice-daily PPI therapy provides any further benefit above that derived from PPIs alone. The parameter used to measure the efficacy of combination regimens for GERD thus far--nocturnal acid breakthrough--has not been proven to correlate with improvement of GERD symptoms in any controlled or prospective clinical trials. Further investigation is needed to determine optimal therapy in patients refractory to standard doses of PPIs.

Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough

Adding histamine 2 receptor antagonists (H2RAs) to proton pump inhibitor (PPI) therapy is a common practice to block nocturnal acid breakthrough (NAB). Controversy exists over its efficacy because of H2RA intolerance. No prospective study has addressed this issue. Twenty-three healthy volunteers and 20 gastroesophageal reflux disease (GERD) patients were studied. Ambulatory pH monitoring was performed with one electrode in the gastric fundus and the other 5 cm above the lower esophageal sphincter. Baseline pH testing was performed and repeated after 2 weeks on PPI twice daily before meals (omeprazole 20 mg). All subjects then received 28 days of PPI plus H2RA Qhs (ranitidine 300 mg) with repeat pH testing on days 1, 7, and 28. Eighteen controls and 16 GERD patients completed all 5 studies. Compared with baseline, all 4 medication regimens decreased supine % time pH < 4 (P = 0.001). The administration of PPI + 1 day of H2RA was the only therapy that significantly decreased % time gastric pH < 4 for the supine period compared with PPI twice daily alone (P < 0.001). There was no difference in % time supine gastric pH < 4 between 2 weeks of PPI twice daily alone and either 1 week or 1 month of PPI + bedtime H2RA. The combination of H2RA and PPI therapy reduced NAB only with the introduction of therapy. Because of H2RA tolerance, there is no difference in acid suppression between PPI twice daily and PPI twice daily + H2RA after 1 week of combination therapy.

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis.

Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.

Esophageal pH and reflux symptom response to various treatment regimens: clinical relevance of nocturnal acid breakthrough

Esophageal pH and reflux symptom response to various treatment regimens: clinical relevance of nocturnal acid breakthrough

Effect of CYP2C19 polymorphism on rabeprazole induced nocturnal acid breakthrough

Effect of CYP2C19 polymorphism on rabeprazole induced nocturnal acid breakthrough

Efficacy of histamine blockade in the suppression of nocturnal acid breakthrough and gastroesophageal reflux

Efficacy of histamine blockade in the suppression of nocturnal acid breakthrough and gastroesophageal reflux

H2RAs do not provide sustained supression of nocturnal acid breakthrough

H2RAs do not provide sustained supression of nocturnal acid breakthrough

Effect of CYP2C19 polymorphism on rabeprazole induced nocturnal acid breakthrough

Effect of CYP2C19 polymorphism on rabeprazole induced nocturnal acid breakthrough

Efficacy of histamine blockade in the suppression of nocturnal acid breakthrough and gastroesophageal reflux

Efficacy of histamine blockade in the suppression of nocturnal acid breakthrough and gastroesophageal reflux

H2RAs do not provide sustained supression of nocturnal acid breakthrough

H2RAs do not provide sustained supression of nocturnal acid breakthrough

Nocturnal acid breakthrough and H 2RAs—another viewpoint

The concept of nocturnal acid breakthrough (NAB), defined as intragastric pH <4 for 1 hour overnight on PPI therapy, has gained much attention. Controversy exists over the ability of bedtime H2RAs to block NAB. No prospective study conducted to evaluate the effect of long term H2RA use on NAB.

The effect of bedtime ranitidine on the symptoms of nocturnal acid breakthrough in patients with refractory gastroesophageal reflux disease

Background: Bedtime ranitidine, combined with twice daily dosing of proton pump inhibitors (PPI's) has been shown to reduce nocturnal acid breakthrough (NAB) in normal individuals. We investigated the subjective improvement of bedtime ranitidine on patients with documented acid breakthrough on PPI's.

Nocturnal acid breakthrough and H2RAs-another viewpoint

Nocturnal acid breakthrough and H2RAs-another viewpoint

The effect of bedtime ranitidine on the symptoms of nocturnal acid breakthrough in patients with refractory gastroesophageal reflux disease

The effect of bedtime ranitidine on the symptoms of nocturnal acid breakthrough in patients with refractory gastroesophageal reflux disease

Helicobacter pylori infection influences nocturnal gastric acid breakthrough.

Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions. To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough. Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was determined by the 13C-urea breath test and an assay for serum anti-H. pylori antibody. Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H2-receptor antagonist at bedtime. Only one patient with nocturnal gastric acid breakthrough had H. pylori infection. The absence of H. pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.

Acid suppression therapy in Barrett's esophagus: the importance of pH monitoring.

It is generally accepted that intestinal metaplasia of the esophageal mucosa results from chronic injuries caused by acid gastroesophageal reflux (GER). It would seem to follow, therefore, that appropriate therapy of Barrett’s esophagus, once recognized, should attempt to eliminate any continuing esophageal acid exposure. Indeed, the usual standard of care in this disease includes the use of potent acid-suppressing medications (or surgery) in an attempt to accomplish this goal. Such therapies have been well documented to result in resolution of the patient’s reflux symptoms and healing of associated esophagitis. There is, however, no present evidence that either of these therapeutic approaches results in regression of the metaplastic epithelium or elimination of the malignant potential in this disease. The observation that patients with Barrett’s esophagus have a decreased sensitivity to esophageal acid exposure indicates that control of heartburn in these patients does not ensure the absence of continuing acid reflux [1]. This possibility was initially documented by the study from our laboratory using ambulatory intra-esophageal pH monitoring, which showed that Barrett’s patients rendered asymptomatic on omeprazole frequently were having continued abnormal GER [2]. Subsequently, this phenomenon was better clarified by the observation that recovery of gastric acidity overnight, so-called “nocturnal acid breakthrough” occurs with high frequency even with twice-daily dosing of omeprazole [3]. These observations form the basis for the suggestion that long-term control of GER in patients with Barrett’s esophagus requires monitoring of intragastric and distal esophageal pH during the time when the patient is undergoing therapy. This concept has gained acceptance by many clinical investigators in this field. Does continuing acid reflux, even in diminished amount, constitute a threat to the patient with Barrett’s esophagus? The first suggestion that this might be true was provided by cell culture studies from esophageal biopsies of patients with Barrett’s esophagus showing that in vitro exposure to pulses of acid resulted in greater proliferation and less differentiation of the metaplastic epithelium [4]. A subsequent study by the same investigators provided the clinical link to the in vitro experiments. Using ambulatory pH monitoring during therapy with proton pump inhibitors (PPI) to establish the presence or absence of control of GER, these investigators documented that patients with continuing abnormal GER showed greater evidence of proliferation activity and less differentiation from their endoscopic biopsies than did patients with well-controlled GER [5]. Thus, experimental evidence both at the basic and clinical level supports the need for ambulatory pH monitoring to establish adequacy of acid suppression therapy and to guide titration of medication dosing in these patients. Does dose adjustment based on pH monitoring result in evidence of regression of the abnormal metaplastic epithelium in Barrett’s esophagus patients? Two recent clinical observations suggest an affirmative answer to this question. Our approach to patients with Barrett’s esophagus has been to use pH monitoring to adjust

Nocturnal acid breakthrough - prevalence & clinical implications

Nocturnal acid breakthrough - prevalence & clinical implications

Nocturnal acid breakthrough cannot be eliminated in patients with atypical gastroesophageal reflux disease

Nocturnal acid breakthrough cannot be eliminated in patients with atypical gastroesophageal reflux disease