Metabolic alkalosis in a hemodialysis patient--successful treatment with a proton pump inhibitor

Hemodialysis patients develop metabolic acidosis due to their impaired excretion of daily produced protons (H+). The following report will show a rare case of severe metabolic alkalosis (predialysis pH 7.52, base excess (BE) +17) in a hemodialysis woman caused by self-provoked upper gastrointestinal H+ losses based on an eating disorder. Treatment with a proton pump inhibitor resulted in the normalization of acid/base homeostasis (predialysis pH 7.40, BE +1.6).     

The efficacy of preanesthetic proton pump inhibitor treatment for patients on long-term H2 antagonist therapy

We previously reported that H2-antagonist medication given for longer than 4 wk may produce complete tolerance to preanesthetic H2 antagonist therapy. In this study, we evaluated the efficacy of preanesthetic proton pump inhibitor (PPI; oral rabeprazol) use in patients receiving regular H2-antagonist (oral famotidine) therapy for more than 4 wk. Forty-eight patients with assumed complete tolerance to H2 antagonists undergoing elective surgery were recruited and randomly assigned to receive either a preanesthetic PPI (rabeprazol 20 mg; n = 24) or H2-antagonist (H2 group; roxatidine 75 mg; n = 24) at 9:00 pm on the day before surgery and 2 h before the induction of anesthesia. Volume of gastric contents and pH values were measured after the induction of anesthesia. Gastric pH value in the PPI group (5.38 +/- 2.42) was significantly higher than in the H2 group (3.27 +/- 1.98; P < 0.01). Gastric volume in the PPI group (8.6 +/- 1.5 mL) was significantly smaller than in the H2 group (15.4 +/- 2.8 mL; P < 0.05; cf. PPI). Fourteen patients in the H2 group were at risk of acid aspiration pneumonia (gastric pH <2.5 or volume >25 mL), whereas only four patients in the PPI group (P < 0.05) were at risk. These data suggest that in patients receiving H2-antagonist therapy for longer than 4 wk, prophylaxis for acid aspiration pneumonia should include preanesthetic PPI medication. IMPLICATIONS: We previously reported that more than 4 wk of administration of H2-antagonists may produce a full tolerance to preanesthetic H2-antagonists. The present study suggests that a proton pump inhibitor may be effective for prophylaxis of acid aspiration pneumonia in patients showing the full tolerance to H2 antagonists.     

The effects of risedronate administered in combination with a proton pump inhibitor for the treatment of osteoporosis

This study was performed to investigate the effects of the co-administration of proton pump inhibitor (PPI) on the efficacy of bisphosphonate (BP) treatment for osteoporosis. A total of 180 women with low bone mineral density were randomly divided into four groups, one in which sodium risedronate was administered with sodium rabeprazole and one in which only risedronate was administered (BP + PPI and BP groups, respectively). The biomarkers were measured at the baseline and every 3 months, inlcuding: N-terminal telopeptide of type I collagen corrected for creatinine, bone-specific alkaline phosphatase (BAP), parathyroid hormone, bone mineral density (BMD) of the lumbar spine and physical parameters evaluated according to the SF-36v2? Health Survey. Statistical comparisons of these parameters were performed after 9 months. Data were available for a total of 137 patients (62 in the BP group and 75 in the BP + PPI group). The Δ % value of increase in BMD and improvement of physical functioning in the BP + PPI group were significantly larger, and its decrease in BAP in the BP + PPI group was significantly smaller than that in the BP group. It is expected that risedronate administration in combination with a PPI may be more effective not only for treating osteoporosis but also improving physical fitness than treatment with risedronate alone.     

Unexpected consequences of proton pump inhibitor use

Proton pump inhibitors (PPIs) are among the most widely prescribed classes of medications for gastroesophageal and laryngopharyngeal reflux diseases. There is emerging evidence that the pathogenesis of disease in laryngeal mucosa is not just related to refluxed acid, but also the presence of pepsin and acidic microenvironments. The widespread use of PPIs is also calling into question potential complications of PPI use. This commentary expands upon these issues with other potential unexpected consequences, and considers the importance of determining a proper approach to patient management.     

Effect of long-term proton pump inhibitor therapy on hemoglobin and serum iron levels after sleeve gastrectomy

BackgroundIron deficiency anemia and iron deficiency are commonly seen after bariatric surgery. Gastroesophageal reflux disease is commonly associated with sleeve resections and warrants postoperative acid reducing therapy.ObjectiveTo analyze the impact of long-term proton pump inhibitors on iron deficiency or iron deficiency anemia in laparoscopic sleeve gastrectomy (LSG) patients.SettingUniversity hospital, USA.MethodsA single-institution case control study included 2 groups of bariatric patients who underwent LSG. Patient characteristics such as age, sex, American Society of Anesthesiologists risk, body mass index, nutritional status, and co-morbidities were comparable. Postoperative follow-up was scheduled at 1-week, and 1-, 3-, 6-, and 12-month durations. All received standard postoperative iron, multivitamin therapy, and nutritional screening and evaluation. All patients were placed on postoperative proton pump inhibitors (PPI) therapy for at least 3 months. At third postoperative visit, anemia indicators were assessed by serum iron concentration, total iron binding capacity, transferrin saturation, red blood cell count, hemoglobin concentration, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Postoperative hemoglobin and serum iron levels were compared between those patients still taking PPIs to those not taking PPIs at 12 months.ResultsA total of 287 patients underwent LSG from January 2016 to December 2017, 203 were included and 84 patients were excluded. Patients taking long-term PPIs (>12 mo, n = 85) were compared with those not taking PPIs (n = 118) and outcomes were respectively as follows: mean pre- and postoperative hemoglobin levels (in g/DL) were 13.2 and 10.7, and 13.3 and 13.7; mean postoperative serum iron levels (in μg/DL) were 41.7 and 88.7. Results were computed using paired t test and odds ratio that showed iron deficiency anemia in 12.9% (11/85) in PPI group compared with 4.23% (5/118) in the non-PPI group (odds ratio of 3.3, 95% confidence interval [1.21–10], and P = .03). Iron deficiency was seen in 22.3% (19/85) in the PPI group and 11% (13/118) in the non-PPI group (odds ratio of 2.3, 95% confidence interval [1.07–5.02] and P = .031).ConclusionsOur study indicates that PPIs can increase the severity of iron deficiency and iron deficiency anemia in patients who underwent LSG. Aggressive surveillance is needed in those taking long-term PPIs after LSG. It is encouraged to further analyze these findings in a larger randomized study model design.     

质子泵抑制剂联合生长抑素治疗肠梗阻疗效观察

目的探讨质子泵抑制剂（proton pump inhibitor PPI）和生长抑素（somatostin SS）联合使用治疗肠梗阻的临床疗效。方法将97例非手术治疗的肠梗阻患者按入院先后随机分为试验组（50例）和对照组（47例）。试验组入院即联合使用SS（善宁）和PPI（奥美拉唑）,对照组单用SS（善宁）,两组其他基础治疗相同。于治疗后24、48、72、96、120h检查患者症状,体征,腹部X片,血常规和胃肠减压液的性状、量、pH值。结果试验组中46例非手术治疗成功,平均症状缓解时间为（28±4．7）h,3—5d（平均3．6d）后症状消失,4例在非手术治疗过程中中转手术,非手术治疗治愈率为92．00％;对照组40例非手术治疗成功,平均症状缓解时间为（46±5．6）h,4—6d（平均5．2d）后症状消失,7例在非手术治疗过程中中转手术,非手术治疗治愈率为85．11％。两组在住院时间、住院费用差异有统计学意义。结论SS和PPI联合使用,能提高非手术治疗肠梗阻的疗效,缩短住院时间、降低住院费用。     

Successful treatment of proton pump inhibitor induced sporadic fundic gland polyps with an argon plasma coagulator in a patient with polycythaemia vera

IntroductionProton pump inhibitor (PPI) use is associated with the development of fundic gland polyps (FGPs); discontinuing PPIs is associated with regression of FGPs. Here, we report a rare case of non-respondent FGPs after discontinuation of PPI that were successfully treated using an argon plasma coagulator (APC).Presentation of caseWe present the case of a 68-year-old woman with a history of polycytheamia vera. She also had gastroesophageal reflux disease (GERD) and had been taking 10 mg of omeprazole daily for the past three years. Esophagogastroduedenoscopy (GF) revealed over 100 pedunculated polyps in the gastric body and fundus. Histological examination of the specimens showed dilated oxyntic glands with flattened parietal and mucous cells. Based on these findings and the clinical history, a diagnosis of FGPs was made. Omeprazole use was then discontinued. Repeat GF performed 6 months and 1 year later showed a significant increase in the number and size of the polyps. APC treatment was performed every 6 months for 3 years. Further GF showed a significant decrease in the number and size of the FGPs 4 years after discontinuing PPI.DiscussionWe conclude that PPI use is a strong risk factor for the development of FGPs and discontinuing PPI is associated with regression of FGPs, but not in patients with polycythaemia vera. However, the mechanism involved in the interaction between FGP and polycytheamia vera remains unknown.ConclusionNon-respondent FGPs after discontinuation of PPI use may be successfully treated using APC.     

Pharyngeal pH measurements in patients with respiratory symptoms before and during proton pump inhibitor therapy.

BACKGROUND: Pharyngeal pH monitoring is a diagnostic tool used to identify Gastroesophageal reflux disease (GERD) as an etiology of respiratory symptoms. We performed pharyngeal pH monitoring on 14 patients with respiratory symptoms thought to be induced by GERD. METHODS: Symptoms and pH monitoring (esophageal and pharyngeal) were assessed prior to and 3 months after the initiation of double-dose proton pump inhibitor therapy. RESULTS: Symptoms included cough, hoarseness, and throat clearing. Ten patients had at least one episode of pharyngeal reflux (PR+) and 4 patients had no pharyngeal reflux (PR-). Pharyngeal reflux episodes in PR+ patients decreased from 3.5 to 0.9 (P <0.05) per day with 8 of 10 (80%) patients having elimination or reduction of such episodes. Eight of 9 PR+ patients (89%) with suppressed pharyngeal reflux on medical therapy had resolution of respiratory symptoms. Three of 4 PR- patients (75%) had persistent symptoms on medical therapy. CONCLUSIONS: Proton pump inhibitor therapy improves clinical symptoms and decreases pharyngeal reflux episodes in patients with respiratory symptoms related to GERD. Direct measurement of pharyngeal pH is helpful in the identification of patients likely to respond to antireflux therapy.     

Gastroesophageal reflux disease with proton pump inhibitor use is associated with an increased risk of osteoporosis: a nationwide population-based analysis

Summary

Gastroesophageal reflux disease (GERD) with proton pump inhibitor (PPI) use is associated with an increased risk of osteoporosis. The risk of hip fracture is not increased in GERD patients with PPI use.

Introduction

The relationship between GERD with PPI treatment and the risk of osteoporosis is unclear. We aimed to determine the risk of developing osteoporosis in patients diagnosed with GERD.

Methods

Patients diagnosed with GERD and received PPI treatment between 2000 and 2010 were identified from the Longitudinal Health Insurance Database as the study cohort (n?=?10,620), which was frequency matched with the comparison cohort (n?=?20,738) sampled from the general population according to age, sex, index year, and comorbidities. Both cohorts were followed until the end of 2011. The risk of osteoporosis was evaluated in both groups by using Cox proportional hazards regression models.

Results

The GERD patients with PPI treatment had a greater incidence (31.4 vs 20.7 per 1000 person-year; crude hazard ratio [cHR] 1.51; 95 % confidence interval [CI] 1.40–1.63) and a higher risk (adjusted HR [aHR] 1.50; 95 % CI 1.39–1.62) of osteoporosis than that of the comparison cohort. However, the overall incidence of hip fracture was not different between the GERD with PPI use and the control cohorts (aHR 0.79; 95 % CI 0.53–1.18).

Conclusion

GERD with PPI use is associated with an increased risk of osteoporosis. The findings of our study do not support an increased risk of hip fracture in GERD patients treated with a PPI.

     

Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial

BACKGROUND: Adequate analgesic medication is mandatory after cardiac operations. Cyclooxygenase-2 inhibitors represent a new therapeutic option, acting primarily on the response to inflammation. METHODS: We compared a cyclooxygenase-2 inhibitor (etodolac) with two traditional drugs: a nonselective cyclooxygenase inhibitor (diclofenac) and a weak opioid (tramadol) on postoperative pain and renal function in patients undergoing coronary artery bypass operations. Sixty consecutive patients were randomized into three groups: (1) group A patients who received tramadol; (2) group B patients who received diclofenac; and (3) group C patients who received etodolac. For measurement of analgesic effect, the visual analogue scale was assessed up to postoperative day 4. Creatinine-clearance was determined before and at the end of study medication, and serum creatinine and urea were monitored daily for renal effects. Study medication was given on postoperative days 2 and 3. Side effects and additional pain medication were recorded. RESULTS: The visual analogue scale was lower in group C (p < 0.05) from postoperative days 2 to 4 and in group B (p < 0.05) from postoperative days 3 to 4 compared with group A. Amount of additional pain medication and incidence of side effects were significantly less in group C compared with group A. We observed a short-lasting elevation of serum creatinine and urea in groups B and C compared with group A (p < 0.05). CONCLUSIONS: At the doses analyzed, etodolac and diclofenac produced better postoperative pain relief with less side-effects than tramadol. A short-lasting impairment of renal function was found in patients treated with etodolac and diclofenac.     

Sporadic duodenal bulb gastrin-cell tumors: association with Helicobacter pylori gastritis and long-term use of proton pump inhibitors

We reviewed the clinicopathologic profile of a series of recently diagnosed sporadic duodenal gastrin-cell (G-cell) tumors. All cases were discovered incidentally and had a unique clinicopathologic profile: all 18 cases were gastrin-positive tumors located in the duodenal bulb, were small in size (mean size 5.4 mm), demonstrated an insular architectural pattern, and were localized to the lamina propria and submucosa. None of the patients had Zollinger-Ellison or carcinoid syndrome. The behavior was indolent and there was no evidence of metastasis at diagnosis or during follow-up. In our sampled population, the presence of Helicobacter pylori gastritis and the use of proton pump inhibitors (PPIs) were significantly associated with the presence of G-cell tumors. Both the presence of H. pylori gastritis and use of PPI remained significant in a logistic regression model adjusted for age, race/ethnicity, and sex with P values of 0.0016 (odds ratio=10.1, 95% confidence interval: 2.3 to 42.4) and 0.008 (odds ratio=8.9, 95% confidence interval: 1.76 to 45.4), respectively. Most patients with tumors showed G-cell hyperplasia in the nontumorous regions of the duodenum. The high incidence of sporadic duodenal G-cell tumors in patients with H. pylori gastritis and long-term PPI use suggests an association that needs to be further explored. Presence of G-cell hyperplasia in the nontumorous duodenal mucosa suggests that these may originate from a proliferative phase, similar to the hyperplasia-dysplasia-neoplasia sequence seen in other endocrine tumors.     

质子泵抑制剂对犬胰腺外分泌功能影响的研究

目的 探索质子泵抑制剂（proton pump inhibitor,PPI）对犬胰腺外分泌功能的影响。方法健康成年犬24只平均随机分成4组：对照组（A组）、对照给药组（B组）、胰腺炎组（C组）、胰腺炎给药组（D组）。A组和B组制备犬胰液外引流模型,C组和D组制备犬急性水肿型胰腺炎胰液外引流模型。采用5%牛磺胆酸钠（0.5 mL/kg）以1 mL/min胰管逆行注射制备急性水肿型胰腺炎模型。B组和D组建模成功后立即给予泮托拉唑（0.7 mg/kg+生理盐水50 mL,q12 h）,A组和C组给予等量的生理盐水。各组每12 h收集胰液一次,并测量胰液的分泌量,胰液中的淀粉酶、脂肪酶、总蛋白含量和pH值。胰腺组织送病理学和电镜检查。结果 B组与A组比较,胰液的分泌量,胰液中淀粉酶、脂肪酶的浓度和pH值在第1天和第2天均降低（P ＜0.05）。胰液中总蛋白的含量第1天B组和A组无明显统计学差异（P ＞0.05）,第2天B组低于A组（P ＜0.05）。D组与C组比较,胰液的分泌量,胰液中淀粉酶、脂肪酶、总蛋白的浓度和pH值无明显变化（P ＞0.05）。D组和C组在不同时间段的血淀粉酶、脂肪酶浓度无明显差别（P ＞0.05）。病理学检查未见明显的差别。电镜下可见PPI作用后胰腺腺泡细胞内酶原颗粒增多。结论 质子泵抑制剂能够明显抑制正常犬的胰腺外分泌,但对急性水肿型胰腺炎犬的胰腺外分泌功能影响不大。     

Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux.

OBJECTIVE: To describe the occurrence of relative proton pump inhibitor (PPI) drug resistance in the treatment of laryngopharyngeal reflux (LPR). STUDY DESIGN AND SETTING: A retrospective review was performed for 1053 consecutive adults undergoing double-probe (simultaneous esophageal and pharyngeal) pH testing in our laboratory. Two hundred five patients who had pH studies performed while taking at least a daily dose of PPI therapy were identified; 167 qualified for further analysis. The pH data was reviewed for the presence of abnormalities in either esophageal or pharyngeal acid exposure to evaluate drug efficacy. RESULTS: Forty-four percent (74/167) of the study patients demonstrated abnormal levels of acid exposure. Results were further analyzed to compare failure rates based on different dosage regimens. Patients on once daily doses of PPI failed at a rate of 56%, with lower failure rates for higher-dose regimens. CONCLUSIONS: A significant number of LPR patients on PPI therapy demonstrate relative drug resistance.     

COX‐2 mRNA is increased in oesophageal mucosal cells by a proton pump inhibitor

Background: Barrett's oesophagus develops in some individuals with gastro‐oesophageal reflux and is the precursor to oesophageal adenocarcinoma. Proton pump inhibitors (PPIs) suppress gastric acid production and are used to treat reflux. Clinical trials suggest that cyclooxygenase (COX) inhibitors might prevent oesophageal cancer, although PPIs could offset this by increasing COX‐2 expression in Barrett's oesophagus. To investigate this, we evaluated the impact of a PPI on COX expression in oesophageal mucosal cells. Methods: The effect of the PPI esomeprazole on COX‐1 and COX‐2 mRNA levels in oesophageal cells was determined. Oesophageal cell lines OE33 (adenocarcinoma‐derived) and HET‐1A (immortalized squamous cells) and a control intestinal cell line HT29 (colon carcinoma) were treated for 24 h, with increasing concentrations of the esomeprazole. Results: COX‐2, but not COX‐1, mRNA levels dose‐dependently increased in OE33 and HET‐1A cells versus esomeprazole concentration. COX‐2 mRNA levels did not increase in HT29 cells. Conclusions: Exposure to esomeprazole increases COX‐2 mRNA in oesophageal cells. This might contribute to the lack of benefit for COX inhibitors for oesophageal cancer prevention in recent clinical studies.     

Persistent acid and bile reflux in asymptomatic patients with Barrett esophagus receiving proton pump inhibitor therapy

HYPOTHESIS: Symptom control does not reflect elimination of abnormal acid reflux or abnormal bile reflux in patients with long-segment Barrett esophagus receiving proton pump inhibitors (PPIs). DESIGN: Prospective survey. SETTING: University hospital. PATIENTS: Thirty-two patients with long-segment Barrett esophagus who were asymptomatic with PPIs. MAIN OUTCOME MEASURES: Twenty-four-hour ambulatory pH and bile reflux monitoring while continuing PPIs. RESULTS: Abnormal acid reflux (pH <4 for 11.9% [interquartile range, 6.8%-19.6%) of 24 hours] persisted in 15 patients (47%) who could not be distinguished from those with normal acid reflux (pH <4 for <4.5% of 24 hours) by any endoscopic, manometric, or therapeutic characteristic. Abnormal bile reflux (absorbance >0.14 for 8.7% [interquartile range, 3.9%-8.7%] of 24 hours) was detected in 11 (48%) of 23 patients, such that both normal bile reflux (absorbance >0.14 for <1.8% of 24 hours) and normal acid reflux were observed in only 8 patients (35%). There was no association between abnormal acid reflux and abnormal bile reflux. CONCLUSIONS: Despite symptom control with PPIs, both acid reflux and bile reflux were controlled in only one third of patients. Posttherapeutic monitoring of acid and bile reflux is recommended in future clinical trials of PPI treatment vs laparoscopic antireflux surgery.     

Haemorrhoidectomy: randomised controlled clinical trial of Ligasure compared with Milligan-Morgan operation.

OBJECTIVE: To evaluate the efficacy of the Ligasure system in the management of haemorrhoids. DESIGN: Unblinded randomised clinical trial. SETTING: Teaching hospital, Spain. PATIENTS: 112 patients with third and fourth degree haemorrhoids. INTERVENTIONS: For 56 patients we used Ligasure system and a variant of Milligan and Morgan's technique. For the other 56, we used the traditional technique. MAIN OUTCOME MEASURES: Postoperative pain. RESULTS: Operating times varied from 100 seconds for each haemorrhoidal cushion with Ligasure system to the 313 seconds by the traditional technique. The blood loss was not quantifiable in patients operated on with Ligasure. Pain was scored on a visual analogue scale. In the Ligasure group, the mean scores were 4.9 (immediate postoperative period) and 2.3 (24 hours later). In the other group, the scores were 7.8 and 6.9. These differences were significant. CONCLUSION: Haemorrhoidectomy using Ligasure as a technical variant of Milligan and Morgan's technique has important advantages.     

Proton pump inhibitor therapy for chronic laryngo-pharyngitis: a randomized placebo-control trial.

OBJECTIVE: To determine the efficacy of proton-pump inhibitor (PPI) therapy for chronic laryngo-pharyngitis treated with lifestyle modification. STUDY DESIGN AND METHODS: Double-blind, randomized trial comparing two-month Rabeprazole (20 mg b.i.d.) to placebo control. RESULTS: Compared to baseline, both PPI and control patients had significant improvement in total reflux symptoms (P = 0.002 and P = 0.03 respectively), with significant improvement in "laryngo-pharyngeal" but not "typical" reflux symptoms. No significant difference was noted for change in reflux symptoms between PPI-treated and control patients (P = 0.44). Significant global improvement was noted by 50% of control and 53% of PPI-treated patients (P = 1.0). No significant differences were noted within or between treatment groups for change in health status or videostrobolaryngoscopy grade. Lifestyle modification compliance correlated significantly with global improvement. CONCLUSION: Compared to baseline, lifestyle modification for 2 months significantly improved chronic laryngo-pharyngitis symptoms. When compared to control, treatment with a PPI failed to demonstrate significantly greater improvement in reflux symptoms, health status, or laryngeal appearance.