[Risk Factors Analysis for Hypermagnesemia with Magnesium Oxide].

While decreased renal function is a known risk factor for hypermagnesemia caused by magnesium oxide (MgO), few studies have comprehensively investigated other contributing factors. In this study, the researchers analyzed the risk factors for hypermagnesemia development in 256 inpatients receiving MgO treatment at the Matsuyama Shimin Hospital. Multivariate analysis identified blood urea nitrogen ≧22 mg/dL, estimated glomerular filtration rate ≦43.1 mL/min, and MgO ≧1000 mg/d as risk factors. Additionally, the researchers' findings suggest a correlation between the number of risk factors and the incidence of hypermagnesemia, including the prevalence of Grade 3 cases. Interestingly, low body mass index emerged as a potential risk factor even in patients without the three identified factors. These findings highlight the importance for pharmacists to advocate for routine serum Mg level monitoring in patients with the risk factors identified in this study.

A case-control study showing low creatinine clearance and high magnesium intake as risk factors for hypermagnesemia in older individuals.

According to epidemiological studies, constipation has a negative effect on life expectancy, necessitating appropriate treatment. According to the Pharmaceuticals and Medical Devices Agency (PMDA), patients who have been taking magnesium oxide (MgO) for constipation over a prolonged period, especially those with impaired renal function and older individuals, are at high risk of hypermagnesemia. Therefore, serum Mg levels, which are often not checked in clinical practice, should be monitored in these patients. Thus, to predict elevated serum Mg levels and prevent the development of hypermagnesemia, we aimed to identify the risk factors of hypermagnesemia, especially in the older population. Our study included patients who were prescribed MgO at our hospital between January 1, 2014, and March 31, 2016. Patients who did not meet the inclusion criteria were excluded and matched to adjust for background factors; finally, 35 patients in the hypermagnesemia arm and 140 patients in the non-hypermagnesemia arm were included in the analysis. Multivariate analysis identified estimated creatinine clearance (eCcr) ≤ 28.2 mL/min as a statistically significant risk factor. In addition, MgO dose ≥ 900 mg/day was identified as a risk factor for clinical consideration, although not statistically significant. Furthermore, the incidence of hypermagnesemia was shown to increase to 11.6% for those with MgO dose ≥ 900 mg/day, 27.0% for those with eCcr ≤ 28.2 mL/min, and 53.1% for those with both. Hypermagnesemia may occur in older patients with eCcr ≤ 28.2 mL/min who take more than 900 mg/day of MgO.

Exploratory Study of Pharmacists' Monitoring Methods Based on Left Ventricular Function for Hypermagnesemia by Magnesium Oxide in Heart Failure.

Serum magnesium (Mg) monitoring in patients with heart failure (HF) receiving magnesium oxide (MgO) is not adequately performed. Furthermore, the relationship between left ventricular function (LVF) and hypermagnesemia in HF is unknown. Here, we investigated the efficacy of serum Mg monitoring by protocol-based pharmaceutical management (PBPM) and the effect of LVF on hypermagnesemia. This protocol is for patients with an estimated glomerular filtration rate of <45 mL/min, receiving MgO, and admitted to the cardiology unit. The pharmacist includes the measurement of Mg when a blood test is ordered for a patient by their physician. Rates of serum Mg measurement and hypermagnesemia detection were compared at 2 years pre-PBPM (n = 88) and at 2 years post-PBPM (n = 55). LVF parameters and reported factors for hypermagnesemia were selected as explanatory factors on multivariate logistic regression. The measurement rate of serum Mg concentration significantly increased from 19.3% pre-PBPM to 80.0% post-PBPM (P < .001). The detection rate of hypermagnesemia also increased from 3.4% to 27.3%, respectively (P < .001). Our results suggest that serum Mg monitoring by PBPM may contribute to the early detection of hypermagnesemia and prevent its progression in HF. According to logistic regression, the adjusted odds ratio for hypermagnesemia with an exacerbation of HF was 9.57 (95% confidence interval: 1.594-57.477, P = .014), and the E/e' > 15, an index of reduced left ventricular diastolic capacity, was 6.46 (95% confidence interval: 1.291-32.364, P = .023). We propose that serum Mg monitoring should be performed during exacerbations of HF in patients with left ventricular diastolic dysfunction, with a pharmacist's assistance.

Prophylactic Administration of Magnesium Oxide Prevents Dextran Sulfate Sodium-Induced Colonic Injury in Mice.

We previously demonstrated that per os administration and ad libitum ingestion of a magnesium chloride (MgCl2) solution had a prophylactic effect on dextran sulfate sodium (DSS)-induced colitis in mice, magnesium being considered to play a role in this preferable action. Magnesium oxide (MgO) is a commercially available magnesium formulation, but whether or not it prevents development of colitis is unknown. In this study, we investigated the effect of MgO administration on development of colitis in DSS-treated male C57BL/6J mice. Experimental colitis was induced by ad libitum ingestion of 1% (w/v) DSS, and the colitis severity was evaluated by disease activity index (DAI) scores, histological assessment and colonic expression of inflammatory cytokines. A 1 mg/mL MgO solution was administered to mice through ad libitum ingestion from a day before DSS treatment to the end of the experimental period of 12 d. In addition, the effects of DSS, MgO and their combination on the gut microbiota were investigated by 16S ribosomal RNA metagenome analysis. DSS-induced elevation of DAI scores was partially but significantly decreased by MgO administration, while MgO administration had no apparent effect on the shortened colonic length, elevated mRNA expression of colonic interleukin-1ß and tumor necrosis factor-α, increased accumulation of colonic mast cells, or altered features of the gut microbiota in DSS-treated mice. Overall, we demonstrated that MgO had a prophylactic effect on the development of colitis in DSS-treated mice by preventing histological colonic damage, but not colonic inflammation or alteration of the gut microbiota.

Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial.

Background Magnesium supplements may have beneficial effects on arterial stiffness. Yet, to our knowledge, no head-to-head comparison between various magnesium formulations in terms of effects on arterial stiffness has been performed. We assessed the effects of magnesium citrate supplementation on arterial stiffness and blood pressure and explored whether other formulations of magnesium have similar effects. Methods and Results In this randomized trial, subjects who were overweight and slightly obese received either magnesium citrate, magnesium oxide, magnesium sulfate, or placebo for 24 weeks. The total daily dose of magnesium was 450 mg/d. The primary outcome was carotid-to-femoral pulse wave velocity, which is the gold standard method for measuring arterial stiffness. Secondary outcomes included blood pressure and plasma and urine magnesium. Overall, 164 participants (mean±SD age, 63.2±6.8 years; 104 [63.4%] women) were included. In the intention-to-treat analysis, neither magnesium citrate nor the other formulations had an effect on carotid-to-femoral pulse wave velocity or blood pressure at 24 weeks compared with placebo. Magnesium citrate increased plasma (+0.04 mmol/L; 95% CI, +0.02 to +0.06 mmol/L) and urine magnesium (+3.12 mmol/24 h; 95% CI, +2.23 to +4.01 mmol/24 h) compared with placebo. Effects on plasma magnesium were similar among the magnesium supplementation groups, but magnesium citrate led to a more pronounced increase in 24-hour urinary magnesium excretion than magnesium oxide or magnesium sulfate. One serious adverse event was reported, which was considered unrelated to the study treatment. Conclusions Oral magnesium citrate supplementation for 24 weeks did not significantly change arterial stiffness or blood pressure. Magnesium oxide and magnesium sulfate had similar nonsignificant effects. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03632590.

Intoxicación por leche magnesia en una paciente pediátrica con constipación crónica: a propósito de un caso / Milk of magnesia intoxication in a pediatric patient with chronic constipation: case report

Resumen Las intoxicaciones accidentales siguen siendo un problema importante que genera gran cantidad de casos de autopsia médico legal, sobre todo cuando ocurren en pacientes pediátricos donde se deben descartar otras causas de muerte y que no se trate de un homicidio. La intoxicación con leche magnesia es un diagnóstico poco frecuente por lo que se hace necesario conocer sus características, evolución y las alteraciones metabólicas por las que se produce la muerte. La hipermagnesemia constituye una condición iatrogénica, generalmente secundaria a la administración de fármacos que contienen magnesio, entre ellos laxantes en pacientes con estreñimiento crónico, en muchas ocasiones sin supervisión médica; que puede producir depresión respiratoria, hipotensión, paro cardiorrespiratorio y la muerte. El diagnóstico de intoxicación con leche magnesia es clínico y se correlaciona con la concentración de magnesio detectada en análisis de muestras de sangre. A continuación se presenta un caso de intoxicación por leche magnesia en una paciente en edad pediátrica con antecedente de parálisis cerebral infantil y constipación crónica que desarrolló una hipermagnesemia posterior a la administración de dicho laxante por parte de sus padres.

Abstract Accidental intoxications continue to be an important problem in the Forensic Pathology field, mostly when they occur in pediatric patients where it is necessary to dismiss other causes of death and to rule out homicide. Milk of magnesia intoxication is a rare diagnosis, therefore it is important to know it´s characteristics, evolution and the metabolic disorders that lead to death. Hypermagnesemia is an iatrogenic condition, usually caused by the administration of medications that contain magnesium, such as laxatives in patients with chronic constipation, without medical supervision; that can lead to respiratory distress, hypotension, cardiac arrest and death. The diagnosis of milk of magnesia intoxication is clinical and can be correlated to the levels of magnesium found in blood sample analysis. We present a case of milk of magnesia intoxication in a 6-year-old girl with cerebral palsy and chronic constipation that was given laxatives by her parents and developed a fatal hypermagnesemia.

Magnesium Oxide in Constipation.

Magnesium oxide has been widely used as a laxative for many years in East Asia, yet its prescription has largely been based on empirical knowledge. In recent years, several new laxatives have been developed, which has led to a resurgence in interest and increased scientific evidence surrounding the use of magnesium oxide, which is convenient to administer, of low cost, and safe. Despite these advantages, emerging clinical evidence indicates that the use of magnesium oxide should take account of the most appropriate dose, the serum concentration, drug-drug interactions, and the potential for side effects, especially in the elderly and in patients with renal impairment. The aim of this review is to evaluate the evidence base for the clinical use of magnesium oxide for treating constipation and provide a pragmatic guide to its advantages and disadvantages.

Association of drugs with special caution in the guidelines with falls: A case-control and case-crossover study in Japan.

AIM: To determine the relationship between multiple medications and falls. METHODS: This case-control and case-crossover study was carried out at Kudanzaka Hospital in Chiyoda, Tokyo, Japan. A total of 325 patients who experienced their first falls when hospitalized between January 2016 and November 2018, and 1285 controls matched by sex, age and clinical departments were included in this study. Hospitalization duration and fall risk score were adjusted for in the analyses. RESULTS: In the case-control study, multivariable logistic regression showed that increasing the intake of oral medications was not significantly associated with the incidence of falls (odds ratio 1.02, 95% confidence interval 0.998-1.049). In contrast, drugs prescribed with special caution in accordance with the Elderly Oral Medication Guidelines were significantly associated with falls (odds ratio 1.17, 95% confidence interval 1.09-1.26). A similar pattern was observed in the case-crossover analysis. Among the drugs to be prescribed with special caution according to the guidelines, atypical antipsychotics, non-benzodiazepine hypnotics and magnesium oxide were significantly associated with the risk of falls. CONCLUSION: The drugs to be prescribed with special caution according to the guidelines were associated with an increased fall risk. The risk of falls in hospitalized older people due to multiple medications varies among medications. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; ••: ••-••.

Pediatric bowel preparation: Sodium picosulfate, magnesium oxide, citric acid vs polyethylene glycol, a randomized trial.

BACKGROUND: Bowel preparation in children can be challenging. AIM: To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid (SPMC) bowel preparation in children. METHODS: Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ½ dose × 2, SPMC 1 dose × 2, or polyethylene glycol (PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders (rating of 'excellent' or 'good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: 78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ½ dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was 'very easy' or 'easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG. CONCLUSION: SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.

Magnesium oxide and hip fracture in the elderly: a population-based retrospective cohort analysis.

Using national insurance claims of Taiwan, we found that magnesium oxide (MgO) use is associated with an increased risk of hip fracture in the elderly. Further studies are warranted to explore the mechanisms associated with MgO use that lead to hip fracture. PURPOSE: The purpose of this study was to investigate the association between MgO use and hip fracture risk in the elderly (age > 65 years). METHODS: This nationwide population-based retrospective study was conducted from 1996 to 2013. Individuals with (n = 26,069) and without (n = 26,069) MgO use were enrolled after propensity score matching. Primary outcome was a hip fracture. After adjusting for age, sex, comorbidities, and medications, multivariate Cox proportional hazards regression models were used to calculate incidences and risk of hip fracture [hazard ratio (HR)]. RESULTS: During the mean follow-up duration of 4.8 years in the MgO cohort and 5.7 years in the non-MgO cohort, respectively 1547 and 1107 cases developed a hip fracture. MgO use was identified as a risk factor for hip fracture in both univariate [crude HR, 1.68; 95% confidence interval (CI), 1.55-1.81; p < 0.001] and multivariate [adjusted HR (aHR), 1.66; 95% CI, 1.54-1.80; p < 0.001] Cox proportional hazards regression models. The cumulative incidence of hip fracture was significantly higher in the MgO cohort than in the non-MgO cohort (1.23 per 100 person-years vs. 0.74 per 100 person-years, logrank test, p < 0.001). CONCLUSION: MgO use is an independent risk factor for hip fracture in the elderly.

"Candido's List": the workers of Collotta Cis & Figli at Molina di Ledro in Trento Province, Italy. A tale of magnesia, asbestos and work.

The study entitled "Candido's List" (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to "virtually' enter the remaining worksites and listen to these spaces "tell" their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.

Histopathological Effects of Bone Cement on Cartilage Tissue.

INTRODUCTION: Glass ionomer bone cement is frequently applied with cartilage grafts in otology, even as a single unit. OBJECTIVE: This experimental study was performed to investigate the histopathological effects of bone cement on cartilage tissue. METHODS: The study was conducted between January 2018 and April 2018 and used 12 New Zealand White rabbits. The right ears of the rabbits constituted the study group, while the left ears were the controls. Ketac Cem Radiopaque (3 M Germany) was used as glass ionomer cement. Tissue samples from the rabbits were subjected to histopathological analysis to compare acute and chronic inflammation, foreign body reaction, angiogenesis, collagenesis, fibrosis, necrosis, cartilage fracture, osseous metaplasia, and loss of chondrocyte nuclei between the groups. RESULTS: The rates of cartilage fracture (P = 0.044), foreign body reaction (P < 0.001), acute inflammation (P = 0.009), chronic inflammation (P = 0.002), and angiogenesis (P = 0.003) were significantly higher in the study group compared with the controls. The study group showed some degree of necrosis; no necrosis was observed in the control group, but the difference was not statistically significant (P = 0.101). There were no significant differences in fibrosis, collagenesis, osseous metaplasia, or loss of chondrocyte nuclei between the groups. CONCLUSIONS: This study showed that application of bone cement can cause acute and chronic inflammation, foreign body reactions, angiogenesis, and cartilage fractures. Further studies are needed to determine the long-term effects of bone cement on cartilage.

Severe hypermagnesemia induced by magnesium oxide ingestion: a case series.

Hypermagnesemia is generally considered an exceptional iatrogenic condition usually caused by magnesium-containing cathartics. In particular, this condition often develops when magnesium-containing cathartics are administered to elderly patients with renal insufficiency or bowel movement dysfunction. Although magnesium oxide (MgO) is widely prescribed as a laxative, serum magnesium concentration has not been examined in most cases. In this report, we present the cases of four elderly patients with constipation and symptomatic hypermagnesemia caused by MgO ingestion, one of which had a lethal course. All of the patients were older than 65 years and with renal dysfunction. In addition, they had difficulties in expressing their symptoms because of cerebrovascular events or dementia. These cases suggest that hypermagnesemia caused by magnesium-containing cathartics is more likely to develop than previously recognized and that physicians should be aware that patients with chronic kidney disease and the elderly are at risk of hypermagnesemia on magnesium administration. We recommend serum magnesium monitoring for high-risk patients after initial prescription or dose increase.

Effects of Magnesium Oxide on the Serum Duloxetine Concentration and Antidepressant-Like Effects of Duloxetine in Rats.

Duloxetine is a serotonin/noradrenaline reuptake inhibitor that is used as an antidepressant. However, it is known to cause constipation as a side effect. Magnesium compounds, such as magnesium oxide and magnesium hydroxide aqueous solution, are often combined with duloxetine to ameliorate the constipation caused by duloxetine. However, there is concern that these magnesium compounds might alter the effects of duloxetine via physicochemical interactions. In this study, we attempted to clarify the interactions that take place between duloxetine and magnesium oxide using in vivo and in vitro experiments. We evaluated the influence of magnesium oxide on in vitro duloxetine concentrations using HPLC. In addition, we examined the in vivo antidepressant-like effects and serum concentrations of duloxetine in rats. In the in vitro experiment, the duloxetine concentration was significantly decreased by co-treatment with magnesium oxide. In the in vivo experiment, the antidepressant-like effects of duloxetine were not affected by the combined oral administration of magnesium oxide and a duloxetine formulation although the serum duloxetine level was significantly decreased. However, the antidepressant-like effects of a duloxetine reagent were significantly attenuated by the co-administration of magnesium oxide. These results suggest that duloxetine and magnesium oxide directly interact and that such interactions affect the absorption and antidepressant-like effects of duloxetine.

A Pilot Randomized Trial of Oral Magnesium Supplementation on Supraventricular Arrhythmias.

Low magnesium may increase the risk of atrial fibrillation. We conducted a double-blind pilot randomized trial to assess adherence to oral magnesium supplementation (400 mg of magnesium oxide daily) and a matching placebo, estimate the effect on circulating magnesium concentrations, and evaluate the feasibility of using an ambulatory heart rhythm monitoring device (ZioPatch) for assessing premature atrial contractions. A total of 59 participants were randomized; 73% were women, and the mean age was 62 years. A total of 98% of the participants completed the follow-up. In the magnesium supplement group, 75% of pills were taken, and in the placebo group, 83% were taken. The change in magnesium concentrations was significantly greater for those given the magnesium supplements than for those given the placebo (0.07; 95% confidence interval: 0.03, 0.12 mEq/L; p = 0.002). The ZioPatch wear time was approximately 13 of the requested 14 days at baseline and follow-up. There was no difference by intervention assignment in the change in log premature atrial contractions burden, glucose, or blood pressure. Gastrointestinal changes were more common among the participants assigned magnesium (50%) than among those assigned the placebo (7%), but only one person discontinued participation. In sum, compliance with the oral magnesium supplementation was very good, and acceptance of the ZioPatch monitoring was excellent. These findings support the feasibility of a larger trial for atrial fibrillation (AF) prevention with oral magnesium supplementation.

A Magnesium Oxide Bezoar.

A 75-year-old Japanese woman presented with nausea and appetite loss. Computed tomography showed a radiopaque substance in the stomach. Esophagogastroduodenoscopy revealed bezoars in the stomach, which were endoscopically retrieved. The bezoars were mainly composed of magnesium and oxide. Although bezoar formation associated with magnesium oxide consumption is infrequently encountered, the present case indicates that pharmacobezoar should be considered among the differential diagnoses in patients who demonstrate a radiopaque mass in the digestive tract and have a history of magnesium oxide use.

Fatal Hypermagnesemia Due to Laxative Use.

We report a case of fatal hypermagnesemia in a 53-year-old woman admitted for acute exacerbation of chronic obstructive pulmonary disease and with a history of chronic constipation treated regularly with magnesium-containing laxatives. On admission, her magnesium level was 2.0mg/dL, which rose to a peak of 10.8mg/dL despite hydration and diuresis in the presence of a normal kidney function. Continuous renal replacement therapy was promptly initiated, which reduced her serum magnesium levels, but her condition continued to deteriorate precipitously progressing to shock leading to oligoanuric renal failure, and she died 2 days later. A review of the literature shows that though rare and often unsuspected, severe hypermagnesemia frequently results in death even in individuals with normal renal function despite renal replacement therapy. In patients with constipation, retention of magnesium-based laxative in the gut apparently serves as a reservoir for continuous magnesium absorption and contributes to mortality.