Prevalence and risk factors of long-term proton pump inhibitors-associated hypomagnesemia: a cross-sectional study in hospitalized patients

Abstract

Proton pump inhibitors (PPI)-related hypomagnesemia is a potentially life-threatening adverse event first described in 2006. PPIs are widely used in the general population. Information regarding prevalence and risk factors is scarce. We conducted a cross-sectional study in inpatients to evaluate prevalence and associated factors with hypomagnesemia in chronic PPIs users. This is a cross-sectional study of hospitalized adult patients with chronic use of PPIs from January 01, 2012, to December 31, 2018. Chronic use was defined as taking PPIs at least 6 months before hospital admittance. Data were collected from informatized medical records from a University Hospital (Hospital Italiano de Buenos Aires). Hypomagnesemia was defined as a value equal to or less than 1.7 mg/dl. The first hospitalization measurement was retrieved. Thirty-six percent of patients (95% CI 30-43) with chronic PPI use presented hypomagnesemia at admission. Patients with hypomagnesemia presented a higher prevalence of chronic kidney disease (18.6% vs 8%, p < 0.05), more use of oral magnesium supplementation (20.9% vs 8%, p < 0.05), use of corticosteroids (32.6% vs 19.3%, p = 0.06) and calcineurin inhibitors (17.4% vs 6.7%, p < 0.05). Regarding laboratory findings, they presented lower hematocrit (28.7% vs 32.8%, p < 0.05), phosphatemia (3 mg/dl vs 3.4 mg/dl, p < 0.05), natremia (135 mg/dl vs 136 mg/dl, p < 0.05) and albumin levels (2.8 g/dl vs 3.2 g/dl p < 0.05) when compared to those who presented normomagnesemia. Hypocalcemia was more frequent among patients with hypomagnesemia (57% vs 38.7%, p < 0.05). In the multivariate analysis, hyponatremia, decreasing levels of hematocrit (odds ratio, OR 0.93-CI 95% 0.88-0.98) and malignant bone compromise (OR 2.83-CI 95% 1.04-7.7) were associated with hypomagnesemia. Adult patients with long-term use of PPIs have a high prevalence of hypomagnesemia. Increasing age, female sex, concomitant use of drugs that impair tubular function and chronic kidney disease may enhance this phenomenon. Anemia, hyponatremia and malignant bone compromise were associated factors with PPIs-related hypomagnesemia.

Keywords: Drug safety; Hypomagnesemia; Proton pump inhibitor use.