Lung squamous cell carcinoma with severe hypomagnesemia due to cisplatin plus gemcitabine in combination with necitumumab therapy: A case report.

A 72-year-old man, diagnosed with advanced lung squamous cell carcinoma, was administered of cisplatin plus gemcitabine with necitumumab, a human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), as a sixth-line treatment. Tumor shrinkage was observed, but asymptomatic grade 4 hypomagnesemia occurred on day 8 of the second cycle. He received magnesium replenishment and hypomagnesemia recovered on day 40, but tumor progression was observed during the period of magnesium correction. Hypomagnesemia is known as a major adverse event of treatment with anti-EGFR antibodies, but there have been no case reports of severe hypomagnesemia or its clinical course.

Symptomatic hypomagnesemia induced by proton-pump inhibitors (PPIs). A known adverse event that is worth recalling.

In 2016, the Sociedad Española de Patología Digestiva published a paper on the adverse effects of PPIs, including a position statement on their safety, with the conclusion that they are uncommon and usually of little importance. Magnesium deficiency was assessed among PPI adverse events.

[Neurological symptoms of hypomagnesemia]. / Neurologische symptomen bij hypomagnesiëmie.

BACKGROUND: An epileptic seizure is a common neurological presentation in the Emergency Department (ED). Electrolyte disturbances are an important cause of neurological symptoms like seizures and hypomagnesemia is one of them. PPI's can cause hypomagnesemia and are readily prescribed. Therefore patients taking PPI's are at risk of developing neurological symptoms due to hypomagnesemia. CASE: A 82-year old woman was seen in ED with a history of nausea, vomiting and vertigo. A vertical nystagmus was observed with attacks of mydriasis followed by a phase of encephalopathy and restlessness. These were recognized as epilepsy. Hypokaliemia, hypocalcemia and a deep hypomagnesemia were present. The PPI accounted for hypomagnesemia. After 2 days of intravenous magnesium suppletion all symptoms disappeared. CONCLUSION: PPI's can cause hypomagnesemia and magnesium levels should be obtained in patients presenting with encephalopathy or atypical neurological symptoms.

Hypomagnesemia and survival in patients with head and neck cancers who received primary concurrent chemoradiation.

BACKGROUND: Prior research has confirmed that persistent hypomagnesemia was predictive of shorter survival among patients with ovarian cancer who received carboplatin-based chemotherapy. In the current retrospective study, the authors examined the association between hypomagnesemia and survival in patients with head and neck cancer who received concurrent chemoradiation with weekly infusions of cisplatin and/or carboplatin. METHODS: Patients with head and neck cancers who had undergone chemoradiation with cisplatin and/or carboplatin between January 1, 2010, and December 31, 2014, were included. Patients were aged ≥18 years with pathology of squamous cell carcinoma of the larynx, oral cavity, or oropharynx who had received at least 30 fractions of radiotherapy with concurrent weekly cisplatin and/or carboplatin. Pathology features, laboratory results, Eastern Cooperative Oncology Group performance status, social histories, and survival were recorded. The association between hypomagnesemia and survival was analyzed controlling for known prognostic factors. RESULTS: The final cohort consisted of 439 patients with a median age of 59 years. A greater frequency of hypomagnesemia during the treatment course was found to be significantly associated with shorter survival (hazard ratio [HR], 1.13; P = .033) independent of age (HR, 1.65; P = .042), cancer site (nonoropharynx vs oropharynx: HR, 2.15 [P = .003]), Eastern Cooperative Oncology Group performance status (>1 vs ≤1: HR, 2.64 [P < .001]), and smoking history (smoker vs nonsmoker: HR, 1.88 [P = .012]). In addition, more severe hypomagnesemia was associated with shorter survival compared with the milder form. CONCLUSIONS: The frequency and severity of hypomagnesemia during treatment are prognostic of survival for patients with head and neck cancers who are receiving concurrent chemoradiation with cisplatin and/or carboplatin. A prospective study is needed to investigate the impact of the prevention of hypomagnesemia on survival in this patient population.

Total gastrectomy for severe proton pump inhibitor-induced hypomagnesemia in a MEN1/Zollinger Ellison syndrome patient.

We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.

La hipomagnesemia en hemodiálisis se asocia a mayor riesgo de mortalidad: su relación con el líquido de diálisis / Hypomagnesaemia in haemodialysis is associated with increased mortality risk: its relationship with dialysis fluid

La hipomagnesemia en hemodiálisis (HD) se asocia a mayor riesgo de mortalidad: su relación con el líquido de diálisis (LD). INTRODUCCIÓN: Concentraciones bajas de magnesio (Mg) en sangre se han relacionado con el desarrollo de diabetes, hipertensión arterial, arritmias, calcificaciones vasculares y con mayor riesgo de muerte, en población general y en hemodiálisis. La composición del LD y su concentración de Mg es uno de los principales determinantes de la magnesemia en los pacientes en HD. OBJETIVO: Estudiar las concentraciones de magnesio en los pacientes en HD, su valor predictivo de mortalidad y qué factores se asocian a la hipomagnesemia y mortalidad en HD. MÉTODOS: Estudio retrospectivo de una cohorte de pacientes prevalentes en HD seguidos 2 años. Cada 6 meses se determina el Mg sérico. En el análisis se utiliza el Mg inicial y el medio de cada paciente, comparando los pacientes con Mg por debajo de la media, 2,1mg/dl, con los que están por encima. Durante el seguimiento se han utilizado 3 tipos de LD: tipo 1, magnesio de 0,5 mmol/l y tipo 3, Mg 0,37 mmol/l ambos con acetato y tipo 2, 0,5 mmol/l de Mg con citrato. RESULTADOS: Se han incluido en el estudio 137 pacientes en hemodiálisis, 72 hombres y 65 mujeres, con una edad media de 67(15) [26-95] años. Cincuenta y siete pacientes eran diabéticos y 70 pacientes estaban en hemodiafiltración en línea (HDF-OL) y 67 en hemodiálisis de alto flujo (HD-HF). El Mg medio de los 93 pacientes con LD tipo 1 era: 2,18(0,37) mg/dl, en 27 con el tipo 3: 2,02 (0,42) mg/dl y los 17 con tipo 2: 1,84 (0,24)mg/dl (p = 0,01). El Mg se relaciona de forma directa significativa con el P y con la albúmina. Después de un seguimiento medio de 16,6(8,9)[3-24] meses, 77 seguían activos, 24 habían fallecido y 36 se habían trasplantado o trasladado. Los pacientes con un Mg superior a 2,1mg/dl tienen una supervivencia mayor, p = 0,008. La supervivencia de los pacientes con los tres tipos de LD no difería significativamente, Log-Rank, p = 0,424. Corregido por la magnesemia, los pacientes con LD con citrato tienen mejor supervivencia, p = 0,009. En el análisis de regresión de COX se observa cómo la edad, albúmina sérica, Mg, técnica de diálisis y tipo de LD tienen valor predictivo de mortalidad independiente. CONCLUSIONES: Los magnesios séricos bajos respecto a los altos se asocian a mayor riesgo de mortalidad. El tipo de LD influye en la concentración de Mg y en el riesgo de muerte

Hypomagnesaemia in haemodialysis (HD) is associated with increased mortality risk: its relationship with dialysis fluid (DF). INTRODUCTION: Low concentrations of magnesium (Mg) in blood have been linked to the development of diabetes, hypertension, arrhythmias, vascular calcifications and an increased risk of death in the general population and in haemodialysis patients. The composition of the dialysis fluid in terms of its magnesium concentration is one of the main determinants of magnesium in haemodialysis patients. OBJECTIVE: To study magnesium concentrations in haemodialysis patients, their predictive mortality rate and what factors are associated with hypomagnesaemia and mortality in haemodialysis. METHODS: Retrospective study of a cohort of prevalent haemodialysis patients followed up for two years. Serum magnesium was measured every six months. The analysis used the initial and average magnesium values for each patient, comparing patients with magnesium below the mean (2.1mg/dl) with those with magnesium above the mean. During the follow-up, three types of dialysis fluid were used: type 1, magnesium 0.5 mmol/l; type 3, magnesium 0.37 mmol/l (both with acetate); and type 2, magnesium 0.5 mmol/l with citrate. RESULTS: We included 137 haemodialysis patients in the study, of which 72 were male and 65 were female, with a mean age of 67 (15) [26-95] years old. Of this group, 57 patients were diabetic, 70 were on online haemodiafiltration (OL-HDF) and 67 were on high-flow haemodialysis (HF-HD). The mean magnesium of the 93 patients with dialysis fluid type 1 was 2.18 (0.37) mg/dl. In the 27 patients with dialysis fluid type 3 it was 2.02 (0.42) mg/dl. And in the 17 with dialysis fluid type 2 it was 1.84 (0.24) mg/dl (p=.01). There was a pronounced direct relationship between Mg and P and albumin. After a mean follow-up of 16.6 (8.9) [3-24] months, 77 remained active, 24 had died and 36 had been transplanted or transferred. Patients with magnesium above than 2.1mg/dl had a longer survival (p=.008). The survival of patients with the three types of dialysis fluid did not differ significantly (Log-Rank, p=.424). Corrected for blood magnesium, patients with dialysis fluid with citrate have better survival (p=.009). The COX regression analysis shows how age, serum albumin, magnesium, dialysis technique and type of dialysis fluid have an independent predictive mortality rate. CONCLUSIONS: Low serum magnesium levels have a greater association with an increased risk of mortality compared to high levels. The type of dialysis fluid affects the magnesium concentration and the risk of death

Parathyroid hormone resistance from severe hypomagnesaemia caused by cisplatin.

Not required for Clinical Vignette.

[Atrial fibrillation and QT prolongation due to proton pump inhibitor-induced hypomagnesemia]. / Fibrillation atriale et allongement du QT sur hypomagnésémie secondaire à un traitement par inhibiteur de la pompe à protons.

Proton pump inhibitors are widely prescribed but their long-term use can expose patients to adverse effects. Some of these are not very well known, including hypomagnesemia. Hypomagnesemia can be manifested by cardiac complications such as supraventricular arrhythmia or QT prolongation, increasing the risk of torsade de pointe. We present a case of atrial fibrillation triggered by severe hypomagnesemia secondary to proton pump inhibitor use and exacerbated by thiazide diuretic treatment. Conversion to sinus rhythm showed a prolonged corrected QT interval. We approach the pathophysiology and the electrophysiologic effects of hypomagnesemia.

Omeprazole-induced hypomagnesaemia, causing renal tubular acidosis with hypokalaemia, hypocalcaemia, hyperlactacidaemia and hyperammonaemia.

A 72-year-old Japanese man treated with omeprazole for 11 years was admitted due to loss of consciousness and muscle weakness. Wolff-Parkinson-White syndrome-induced tachycardia was considered as the cause of syncope. His blood examination revealed rhabdomyolysis, hypokalaemia, hypomagnesaemia, hypocalcaemia, hyperlactacidaemia, hyperammonaemia and high-anion-gap metabolic acidosis. Hypomagnesaemia could be caused by magnesium malabsorption due to omeprazole use. Hypocalcaemia might be caused by the inhibitory effect of hypomagnesemia on the parathyroid gland hormone secretion. Hyperammonaemia might be caused by two reasons: (1) renal ammonium production induced by hypokalaemia; (2) inhibition of ammonium secretion by omeprazole. Both hypocalcaemia and hypokalaemia might cause chronic elevation of serum creatinine phosphokinase which ended up with rhabdomyolysis. Correction of serum electrolytes rapidly improved his muscle weakness. Discontinuation of omeprazole no longer caused these abnormalities. A physician should be aware of unexplained signs and symptoms of patients using proton-pump inhibitors to avoid life-threatening electrolyte and physiologic disturbances.

Pathophysiology of Drug-Induced Hypomagnesaemia.

Magnesium (Mg2+) is the second most abundant intracellular and fourth extracellular cation found in the body and is involved in a wide range of functions in the human cell and human physiology. Its role in most of the enzyme processes (ATP-ases)-stabilisation of nucleic acids (DNA, RNA), regulation of calcium and potassium ion channels, proliferation, glucose metabolism and apoptosis-make it one of the most important cations in the cell. Three pathogenetic mechanisms are mainly implicated in the development of hypomagnesaemia: reduced food intake, decreased intestinal absorption and increased renal excretion of Mg2+. This review presents the function of Mg2+, how it is handled in the kidney and the drugs that cause hypomagnesaemia. The frequency and the number of drugs like diuretics and proton-pump inhibitors (PPIs) that are used daily in medical practice are discussed in order to prevent and treat adverse effects by providing an insight into Mg2+ homeostasis.

Adverse cardiovascular and blood pressure effects of drug-induced hypomagnesemia.

Introduction: The objective of this study was to review the current status of drug-induced hypomagnesemia and its adverse effects on cardiovascular disease (CVD) and hypertension. Since magnesium is a potent vasodilator, which modulates vasomotor tone, peripheral blood flow, and hypertension, its deficiency could have significant cardiovascular and blood pressure (BP) effects.Areas covered: Studies have shown that several factors can contribute to magnesium deficiency including age, diet, disease, and certain drugs such as diuretics and proton-pump inhibitors (PPIs). For an updated perspective of drug-induced hypomagnesemia, a Medline search of the English language literature was conducted between 2010 and 2019 using the terms diuretics, proton-pump inhibitors, hypomagnesemia, cardiovascular disease, hypertension, and 35 pertinent papers were retrieved.Expert opinion: The data showed that magnesium deficiency is difficult to occur since it is plentiful in green leafy vegetables, cereals, nuts, and the drinking water. However, magnesium deficiency can occur with the use of diuretics for the treatment of hypertension and heart failure, or the use of PPIs for the treatment of gastroesophageal reflux disease. Therefore, magnesium deficiency should be detected and treated to prevent the aggravation of hypertension and the onset of CVD and serious cardiac arrhythmias including torsades de points.

Proton pump inhibitors and hypomagnesemia: A meta-analysis of observational studies.

BACKGROUND: Previous meta-analyses have suggested that there might be an association between the use of proton pump inhibitors (PPIs) and the development of hypomagnesemia, although the conclusions were no definitive. METHODS: To provide an update on this topic, we performed a meta-analysis of all observational studies that examined the association between the use of PPIs and the development of hypomagnesemia. A literature search was conducted in MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (January 1970 to June 2018) to identify observational studies that examined the association between the use of PPIs and the incidence and prevalence of hypomagnesemia. STUDY ELIGIBILITY CRITERIA: In the absence of randomized controlled trials, we focused primarily on observational studies, including cross-sectional, case-control, retrospective, and prospective cohort studies. There was no limitation on sample size or study duration. Random-effect models meta-analyses were used to compute pooled unadjusted and adjusted odds ratios (ORs) for binary variables. RESULTS: Sixteen observational studies were identified, including 13 cross-sectional studies, 2 case-control studies, and 1 cohort study, with a total of 131,507 patients. The pooled percentage of PPI users was 43.6% (95% confidence interval [CI] 25.0%, 64.0%). Among PPI users, 19.4% (95% CI 13.8%, 26.5%) had hypomagnesemia compared to 13.5% (95% CI 7.9%, 22.2%) among nonusers. By meta-analysis, PPI use was significantly associated with hypomagnesemia, with a pooled unadjusted OR of 1.83 (95% CI 1.26, 2.67; P = .002) and a pooled adjusted OR of 1.71 (95% CI 1.33, 2.19; P < .001). In subgroup analyses, high-dose PPI use was associated with higher odds for hypomagnesemia relative to low-dose PPI use (pooled adjusted OR 2.13; 95% CI 1.26, 3.59; P = .005). CONCLUSION: Our findings are in support of the results of the previous meta-analyses. Furthermore, we found a dose-response between the PPI use and development of hypomagnesemia.

Proton-pump Inhibitor-induced Severe Hypomagnesemia and Hypocalcemia are Clinically Masked by Thiazide Diuretic.

Hypomagnesemia, a side effect of proton-pump inhibitors (PPIs), can be asymptomatic. The presence of hypocalcemia or hypokalemia is indicative of hypomagnesemia; however, the concomitant use of PPIs and thiazide may mask hypocalcemia. A 79-year-old woman with a history of chronic heart failure and chronic kidney disease developed symptomatic hypocalcemia and hypomagnesemia. Five weeks earlier, she had developed thiazide-induced hyponatremia, so thiazide had been discontinued. Reviewing the patient's charts revealed that three discontinued thiazide administrations in the clinical course had unmasked hypocalcemia. Our case demonstrates that thiazide-induced hypercalcemia can be so prominent as to mask PPI-induced hypocalcemia and hypomagnesemia.

Does the use of proton pump inhibitors increase the risk of hypomagnesemia: An updated systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly used in the treatment of acid-related diseases; however, the association between the use of PPIs and potential risk of hypomagnesemia is controversial. METHODS: In the present study, databases including PubMed, EMBASE, MEDLINE, PsycINFO, CINAHL, the Cochrane Library, and 4 Chinese databases were searched since the inception until April 2018. Previous observational studies on the incidence of hypomagnesemia in individuals exposed to PPIs were included. RESULTS: This systematic review involved 15 studies including 129,347 participants, and the sample size varied from 52 to 95,205. Meta-analysis of 14 studies indicated that the use of PPIs increased the risk of hypomagnesemia [RR, 1.44, 95% CI, 1.13-1.76; I, 85.2%]. Subgroup analysis revealed that the use of PPI was not associated with the incidence of hypomagnesemia in outpatients [RR, 1.49; 95% CI, 0.83-2.14; I, 41.4%] and hospitalized patients [RR, 1.05; 95% CI, 0.81-1.29; I, 62.1%], respectively. The use of PPIs was not related to the risk of hypomagnesemia based on the cut-off values of 1.8 mg/dL [RR, 1.73; 95% CI, 0.87-2.58; I, 65.2%], 1.7 mg/dL [RR, 1.48; 95% CI, 0.90-2.06; I, 87.6%], and 1.6 mg/dL [RR, 0.98; 95% CI, 0.69-1.27; I, 67.9%]. CONCLUSION: The association between the exposure to PPI and the incidence of hypomagnesemia remained unclear. Due to the remarkable heterogeneity in previous studies, a definitive conclusion could not be drawn. Further research should be conducted to investigate the relationship between the use of individual PPI and potential risk of hypomagnesemia, and a dose-response analysis may be required.

The Association between the Use of Proton Pump Inhibitors and the Risk of Hypomagnesemia in a National Cohort of Veteran Patients with HIV.

OBJECTIVES: To examine the risk of hypomagnesemia of HIV-positive patients adherent to proton pump inhibitors (PPIs). METHODS: A cohort study utilizing the Veterans Affairs Informatics and Computing Infrastructure was conducted on patients with (1) a complete antiretroviral therapy, (2) a serum magnesium measure during the study period, and (3) adherent to PPIs. Statistical analyses evaluated baseline characteristics between cohorts and a Cox proportional hazards model evaluating the association of hypomagnesemia while adjusting for baseline covariates. RESULTS: A total of 6047 patients met the study inclusion criteria, 329 patients in the PPI cohort and 5718 patients in the non-PPI cohort. The stratified Cox proportional hazards model results revealed that the risk of hypomagnesemia for the PPI cohort is 3.16 times higher compared to the non-PPI cohort (adjusted hazard ratio = 3.16, 95% confidence interval = 2.56-3.9). CONCLUSIONS: Proton pump inhibitors medication usage in HIV-positive patients is associated with a higher risk of hypomagnesemia compared to non-PPI patients.

Influence of oral magnesium-containing supplement and antacid administration on hypomagnesemia induced by panitumumab.

PURPOSE: Hypomagnesemia is a common side effect of panitumumab. The effect of magnesium-containing supplement as a laxative and concomitant antacid (proton pump inhibitor and histamine H2 antagonist) administration on panitumumab-induced hypomagnesemia was retrospectively investigated. METHODS: Patients with advanced or recurrent colorectal cancer who received panitumumab were included in this study. Serum magnesium levels were extracted from the electronic medical records of 1753 administrations in 221 patients who received panitumumab. Serum magnesium levels in patients with or without oral magnesium-containing supplement and antacid treatment were compared using analysis of covariance as the number of panitumumab administration up to 16 times for covariates. RESULTS: The mean serum magnesium levels were significantly decreased with increasing number of panitumumab administrations (2.13 mg/dL at 1st vs. 1.55 mg/dL at 16th, p < 0.001). The use of oral magnesium-containing supplement significantly inhibited the decline in mean serum magnesium level (1.98 mg/dL vs. 1.78 mg/dL, p < 0.001). However, antacid use in patients receiving oral magnesium-containing supplement significantly decreased the effectiveness of the magnesium supplement on serum magnesium level (2.02 mg/dL vs. 1.93 mg/dL, p < 0.05). CONCLUSION: The use of oral magnesium-containing supplement might function as magnesium supplement based on the finding that use of oral magnesium-containing supplement during panitumumab administration decreased hypomagnesemia. However, combination of antacid decreased the supplemental effect of oral magnesium on hypomagnesemia. These results suggest the possibility that use of antacids during anti-EGFR antibody administration may promote hypomagnesemia.

Drug use is associated with lower plasma magnesium levels in geriatric outpatients; possible clinical relevance.

BACKGROUND: Hypomagnesemia has been associated with diabetes, cardiovascular disease, and other disorders. Drug use has been suggested as one of the risk factors for low magnesium (Mg) levels. In the elderly population, prone to polypharmacy and inadequate Mg intake, hypomagnesemia might be relevant. Therefore, we aimed to investigate associations between drug use and plasma Mg. METHODS: Cross-sectional data of 343 Dutch geriatric outpatients were analysed by Cox and linear regression, while adjusting for covariates. Drug groups were coded according to the Anatomical Therapeutic Chemical classification system; use was compared to non-use. Hypomagnesemia was defined as plasma Mg < 0.75 mmol/l and <0.70 mmol/l. RESULTS: Prevalence of hypomagnesemia was 22.2% (Mg < 0.75 mmol/l) or 12.2% (Mg < 0.70 mmol/l); 67.6% of the patients used ≥5 medications (polypharmacy). The number of different drugs used was inversely linearly associated with Mg level (beta -0.01; p < 0.01). Fully adjusted Cox regression showed significant associations of polypharmacy with hypomagnesemia (Mg < 0.75 mmol/l) (prevalence ratio (PR) 1.81; 95%CI 1.08-3.14), proton pump inhibitors (PR 1.80; 95%CI 1.20-2.72), and metformin (PR 2.34; 95%CI 1.56-3.50). Moreover, stratified analyses pointed towards associations with calcium supplements (PR 2.26; 95%CI 1.20-4.26), insulins (PR 3.88; 95%CI 2.19-6.86), vitamin K antagonists (PR 2.01; 95%CI 1.05-3.85), statins (PR 2.44; 95%CI 1.31-4.56), and bisphosphonates (PR 2.97; 95%CI 1.65-5.36) in patients <80 years; selective beta blockers (PR 2.01; 95%CI 1.19-3.40) if BMI <27.0 kg/m2; and adrenergic inhalants in male users (PR 3.62; 95%CI 1.73-7.56). Linear regression supported these associations. CONCLUSION: As polypharmacy and several medications are associated with hypomagnesemia, Mg merits more attention, particularly in diabetes, cardiovascular disease, and in side-effects of proton pump inhibitors and calcium supplements.