Introduction

Proton pump inhibitors (PPIs) have been the mainstay treatment for upper gastrointestinal acid-related disorders. However recent reports have expressed concern over the safety aspects associated with the long term use of PPIs. Few studies have demonstrated lowering of serum magnesium levels in PPIs users taking diuretics concomitantly. The US FDA also recommended screening of serum magnesium in PPI users, especially the ones with additional risk factors for hypomagnesemia.

Aim

To evaluate if low or high doses of PPIs, taken with or without diuretics, cause hypomagnesemia in PPI users.

Method

Study design

• The records of patients at the time of hospitalization in 2 tertiary care hospitals were retrospectively reviewed
• Patients >39 years were included
• Patient characteristics such as age, gender and medical history was reviewed
• A total of 12,058 tests to estimate the serum magnesium (Mg) levels were conducted at or within 24 hours of hospital admission
• The total cohort of 2400 patients were selected and categorized into 6 groups on the basis of the PPI and diuretics usage at the time of admission
• Group 1 – No PPI or diuretic use
• Group 2 – PPI and low dose diuretics
• Group 3 – PPI and high dose diuretics
• Group 4 – PPI only
• Group 5 – Low dose diuretics and no PPI
• Group 6 – High dose diuretics and no PPI
• Low dose PPIs corresponded to omeprazole 20 mg qd, esomeprazole 20 mg, pantoprazole 20 mg, dexlansoprazole 30 mg lansoprazole 15 mg and rabeprazole 20 mg
• High dose PPIs included omeprazole >40 mg qd, esomeprazole >40 mg, pantoprazole >40 mg, dexlansoprazole >60 mg lansoprazole >30 mg and rabeprazole >40 mg
• Low dose diuretics were defined as furosemide 20 mg qd, torsemide 10 mg qd or thiazide diuretics
• High dose diuretics were defined as furosemide >40 mg, torsemide >20 mg qd or any combination of loop and thiazide diuretics

Endpoints

• Hypomagnesemia defined as serum Mg level <1.6 mg/dl
• Severe hypomagnesemia (serum Mg level<1 mg/dl)

Results

• Mean age of patients was 66.6+13 years and 45% were men
• Cohort comprised of 1200 PPI users and 1200 PPI non-users
• There was no significant difference in the mean serum magnesium levels in PPI users as well as PPI non-users (1.84+0.29 mg/dL vs 1.85+0.30 mg/dL respectively; p=0.40).
• The prevalence of hypomagnesemia in PPI users and non-users was also similar (p=0.77) as seen in figure 1.

• The difference in the prevalence of severe hypomagnesemia was also insignificant (p=0.3) as seen in figure 2.

• The prevalence of hypomagnesemia in the PPI users irrespective of the concomitant use of diuretics was similar (p=0.8)
• 14.3% of the PPI users with diuretics reported hypomagnesemia vs 13.4% of the group on diuretics alone (p=0.61)
• 27.8% of the PPI users were associated with liver disease as compared to 18.5% of the PPI non-users (p=0.04)
• Further multivariate analysis revealed that subjects with liver disease and diabetes mellitus were at an increased risk of developing hypomagnesemia, with an odds ratio of 1.6 and 2.2 (p=0.001 and p<0.001) respectively.
• Liver disease and diabetes mellitus were independent predictors of hypomagnesemia
• The difference in the prevalence of hypomagnesemia was insignificant across the 6 groups as seen in figure 3. Group 1 vs 2 p=0.82, group 1 vs 3 p=0.73, group 1 vs 4 p=0.84, group 1 vs 5 p=0.93 and group 1 vs 6 p=0.16.

• Omeprazole was most commonly used PPI by 45.5%, followed by pantoprazole by 26.1%, esomeprazole by 13%, dexlansoprazole by 7.4% and lansoprazole by 5.1%

Conclusion

• The use of proton pump inhibitors (PPIs), irrespective of the dose, taken with or without diuretics, did not lower the levels of serum magnesium in non-critically ill patients.
• These findings of a recent retrospective review supported the recent American Gastroenterological Association Practice Update, which does not recommend routine screening of serum magnesium in PPI users.

J Gastroenterol Hepatol. 2018 Mar 7. Doi: 10.1111/jgh.14141.