Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department

Lindner, Gregor; Funk, Georg‐Christian; Leichtle, Alexander Benedikt; Fiedler, Georg Martin; Schwarz, Christoph; Eleftheriadis, Theodoros; Mohaupt, Markus; Exadaktylos, Aristomenis K.; Arampatzis, Spyridon

doi:10.1111/ijcp.12469

Cited by 31 publications

(19 citation statements)

References 32 publications

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“…Cancer, chronic kidney disease, diabetes and alcoholism have each been associated with Ca, Mg and PO 4 abnormalities . Medications, including vitamin D, proton pump inhibitors and glucocorticoids have been associated with hypercalcaemia, hypomagnesaemia and hypophosphataemia, respectively . Although we did not find a significant association between vitamin D and any electrolyte abnormality, there were trends towards some associations (ORs 1.3, 1.4).…”

Section: Discussioncontrasting

confidence: 80%

“…We did not examine a number of very uncommon variables previously demonstrated to be associated with Ca, Mg or PO 4 abnormalities, for example granulomatous disease, immobilisation, inherited renal tube defects and tissue breakdown. [13][14][15] Therefore, although the risk variables of the present study are incomplete, the most commonly reported risks have been included. Furthermore, it is unlikely that future studies would have sufficient power to adequately examine such uncommon conditions.…”

Section: Limitationsmentioning

confidence: 99%

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Risk variables associated with abnormal calcium, magnesium and phosphate levels among emergency department patients

Taylor

Date

Ugoni

et al. 2019

Emerg Medicine Australasia

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Objective The utility of calcium, magnesium and phosphate measurement in the ED is limited. We aimed to determine clinical risk variables for abnormal levels of these electrolytes in order to inform the development of an ordering guideline. Methods We performed a retrospective, observational study of patients who presented to a tertiary referral ED between January and June 2017. Adult patients who had serum calcium, magnesium or phosphate tests completed during their ED stay were included. Presenting symptoms and signs, comorbidities, medication use and laboratory values were extracted from the medical record. Patients with missing data items were excluded. Logistic regression models determined clinical risk variables associated with low and high levels of each electrolyte. Results A total of 33 120 adults presented during the study period. Of the 1679 calcium, 1576 magnesium and 1511 phosphate tests, 228 (13.6%), 158 (10.0%) and 387 (25.6%) were abnormal, respectively. Significant risk variables (P < 0.05) for abnormal levels were: hypocalcaemia – vomiting, perioral numbness, hand/foot spasm, calcium and phosphate supplements and chemotherapy (odds ratio [OR] range 5.9–17.3); hypercalcaemia – female sex, vomiting, polyuria, confusion, hyperparathyroidism, cancer and type 1 diabetes (OR range 2.3–9.7); hypomagnesemia – female sex, proton pump inhibitor use, tacrolimus use, alcohol abuse and type 2 diabetes (OR range 2.2–13.1); hypermagnesemia – lethargy, thiazide use and chronic kidney disease (OR range 4.3–4.5); hypophosphatemia – nausea, seizure and glucocorticoid use (OR range 1.7–2.1); and hyperphosphataemia – polyuria, diuretics and chronic kidney disease (OR range 1.9–5.0). Conclusion A range of demographic, comorbid, medication and clinical variables are associated with abnormal calcium, magnesium and phosphate levels. These findings will inform the development of clinical guidelines to rationalise calcium, magnesium and phosphate testing. Justification may be required for testing patients with no risk variables.

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Section: Discussioncontrasting

confidence: 80%

Section: Limitationsmentioning

confidence: 99%

Risk variables associated with abnormal calcium, magnesium and phosphate levels among emergency department patients

Taylor

Date

Ugoni

et al. 2019

Emerg Medicine Australasia

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“…Some observational data have been published, with the majority reporting on the relationship between PPI use and hypomagnesemia in hospitalized patients . A few studies have shown this association in the outpatient setting .…”

Section: Discussionmentioning

confidence: 99%

Hypomagnesemia as a predictor of mortality in hemodialysis patients and the role of proton pump inhibitors: A cross‐sectional, 1‐year, retrospective cohort study

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Shindo

Banshodani

et al. 2016

Hemodialysis International

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Introduction This study aimed to evaluate the association between proton pump inhibitor (PPI) use and serum magnesium levels, and the role of hypomagnesemia and PPI use as a risk factor for mortality in hemodialysis patients. Methods An observational study, including a cross-sectional and 1-year retrospective cohort study. The study comprised 399 hemodialysis patients at a single center, and was conducted from January to September 2014. Multiple linear regression analysis was used to investigate the independent relationship between serum magnesium levels and baseline demographic and clinical variables, including PPI and histamine-2 receptor antagonist use. Cox regression model was used to identify lower serum magnesium level and PPI as a predictor of 1-year mortality. Findings Serum magnesium levels were lower with PPI use than non-PPI use (2.39 ± 0.36 vs. 2.56 ± 0.39 mg/dL, P < 0.001). Multiple linear regression analysis showed that PPI use, low serum albumin levels, and low serum potassium and high-sensitivity C-reactive protein (hs-CRP) levels were significantly associated with low serum magnesium levels. A total of 29 deaths occurred during the follow-up period. According to Cox regression analysis stratified by hs-CRP, only high serum hs-CRP levels (>4.04 mg/L) in association with low serum magnesium levels was an independent risk factor for 1-year mortality (hazard ratio: 2.92; 95% CI: 1.53-6.40, P < 0.001). Discussion Serum magnesium levels are lower in PPI use. In the inflammatory state, a low serum magnesium level is a significant predictor of mortality in hemodialysis patients.

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“…Previous cross sectional studies have demonstrated a small decrease in serum magnesium [27,28] in PPI users. Though we were unable to replicate this finding in either our cross sectional or prospective study arms, we did find a statistically significant downward trend of serum magnesium following initiation of PPI therapy in our cohort of patients who were previously PPI naïve.…”

Section: Discussionmentioning

confidence: 87%

Proton pump inhibitor associated hypomagnasaemia ‐ a cause for concern?

Begley

Smith²,

Barnett

et al. 2016

Brit J Clinical Pharma

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AIMSIn recent years, there have been a number of case reports of severe hypomagnesaemia associated with proton pump inhibitor (PPI) use, such that both the FDA and MHRA have issued drug safety warnings. They have recommended periodic serum magnesium testing in patients prescribed PPIs but provide no guidance on timing of these measurements. METHODSTo our knowledge, we are the first to perform a prospective study to explore specifically proton pump inhibitor associated hypomagnesaemia (PPIAH). We followed 56 patients new to PPIs prospectively as well as a further 100 patients on long term PPIs crosssectionally to identify what factors may be influencing the development of significant hypomagnesaemia. RESULTSFor the prospective arm of the study, we measured serum magnesium levels prior to starting a PPI and again at regular intervals for the next 8 months. For the cross-sectional arm of the study we measured serum magnesium levels on patients on PPI therapy ranging from less than 1 year to over 5 years. CONCLUSIONWe found that, although there was a significant downward trend in serum magnesium levels in patients new to PPI therapy with time, clinically relevant hypomagnesaemia was not readily identifiable on regular blood testing. We did however identify patients on concurrent diuretic therapy as being at higher risk and so would recommend regular serum magnesium testing alongside their regular renal function monitoring on a more frequent basis such as annually. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The FDA and MHRA have issued drug safety warnings regarding the use of proton pump inhibitors (PPIs) and the risk of hypomagnesaemia, recommending regular serum magnesium monitoring but are unable to specify how regularly to do so.• With so many patients prescribed both short and long term PPI therapy, regular blood test monitoring could represent a significant logistical and financial burden on the NHS. WHAT THIS STUDY ADDS• We demonstrate the limited benefit in annual measurement of serum magnsesium in all patients on PPI therapy, as recommended by previous authors.• We were able to identify patients on concurrent diuretic therapy as being at greatest risk of hypomagnesaemia.

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Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department

Abstract: Use of PPIs predisposes patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of the underlying morbidity, posing a critical concern.

Cited by 31 publications

References 32 publications

Risk variables associated with abnormal calcium, magnesium and phosphate levels among emergency department patients

Risk variables associated with abnormal calcium, magnesium and phosphate levels among emergency department patients

Hypomagnesemia as a predictor of mortality in hemodialysis patients and the role of proton pump inhibitors: A cross‐sectional, 1‐year, retrospective cohort study

Proton pump inhibitor associated hypomagnasaemia ‐ a cause for concern?

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