Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial.

AIMS/HYPOTHESIS: Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. METHODS: Using a randomised, double-blind (both participants and investigators were blinded to the participants' treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18-40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic-euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. RESULTS: We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg-1 min-1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. CONCLUSIONS/INTERPRETATION: Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. TRIAL REGISTRATION: EudraCT number 2021-001243-27. FUNDING: This study was supported by a grant from the Dutch Diabetes Research Foundation (2017-81-014).

Magnesium and Hematoma Expansion in Intracerebral Hemorrhage: A FAST-MAG Randomized Trial Analysis.

BACKGROUND: Observational studies suggest that magnesium may have hemostatic effects. FAST-MAG (Field Administration of Stroke Therapy-Magnesium) was a pragmatic clinical trial of magnesium sulfate administered prehospital for acute clinical stroke syndromes and included patients with intracerebral hemorrhage. Exploratory secondary analysis by the treatment group found no reduction in hematoma expansion (HE) associated with magnesium treatment in intracerebral hemorrhage but did not consider serum magnesium levels achieved. We analyzed FAST-MAG intracerebral hemorrhage data for associations between serum magnesium level, HE, and early neurological deterioration, accounting for groupwise biases. METHODS: HE was defined as hematoma volume increase ≥3 mL within 24 hours and early neurological deterioration as ≥1-point Glasgow Coma Scale decline from arrival to hospital day 4. Comparing treatment and placebo groups confirmed biased availability of neuroimaging data. Therefore, HE and neurological deterioration were analyzed and stratified by treatment and placebo groups using univariate tests and adjusted logistic regression. RESULTS: Spontaneous intracerebral hemorrhage was present in 381 patients. Placebo patients had fewer serial neuroimaging studies available (123 [65.4%] versus 145 [75.1%]; P=0.038). Necessary data were available in 104 magnesium- and 85 placebo-treated patients (age, 64.9 [13.0] years; 67.7% male). In the magnesium group, higher magnesium level was associated with less HE (adjusted odds ratio, 0.64 per mg/dL [95% CI, 0.42-0.93]) and less neurological deterioration (adjusted odds ratio, 0.54 per mg/dL [95% CI, 0.33-0.82]). In the placebo group, magnesium level was not associated with either HE or neurological deterioration. CONCLUSIONS: Magnesium may exhibit a hemostatic effect that was only observable in the FAST-MAG magnesium treatment group. Equipoise should be maintained, and specific trials are needed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00059332.

Revolution in sepsis: a symptoms-based to a systems-based approach?

Severe infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy and multiple organ dysfunction. Males appear to have a higher risk of mortality than females. Currently, there are few or no effective drug therapies to protect the brain, maintain the blood brain barrier, resolve excessive inflammation and reduce secondary injury in other vital organs. We propose a major reason for lack of progress is a consequence of the treat-as-you-go, single-nodal target approach, rather than a more integrated, systems-based approach. A new revolution is required to better understand how the body responds to an infection, identify new markers to detect its progression and discover new system-acting drugs to treat it. In this review, we present a brief history of sepsis followed by its pathophysiology from a systems' perspective and future opportunities. We argue that targeting the body's early immune-driven CNS-response may improve patient outcomes. If the barrage of PAMPs and DAMPs can be reduced early, we propose the multiple CNS-organ circuits (or axes) will be preserved and secondary injury will be reduced. We have been developing a systems-based, small-volume, fluid therapy comprising adenosine, lidocaine and magnesium (ALM) to treat sepsis and endotoxemia. Our early studies indicate that ALM therapy shifts the CNS from sympathetic to parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces inflammation, corrects coagulopathy, and maintains tissue O2 supply. Future research will investigate the potential translation to humans.

Long-term cisplatin nephrotoxicity after childhood cancer: a systematic review and meta-analysis.

BACKGROUND: Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced glomerular filtration rate and hypomagnesaemia. Existing literature regarding the epidemiology of long-term nephrotoxicity in childhood cancer describes large variation in prevalence and risk factors. OBJECTIVES: This study is to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment for childhood cancer. STUDY ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they: (i) evaluated participants treated with cisplatin who were diagnosed with cancer < 18 years of age; (ii) investigated any author-defined measure of nephrotoxicity; and (iii) performed this evaluation 3 or more months after cisplatin cessation. Studies whose scope was broader than this were included if appropriate subgroup analysis was performed. RESULTS: Prevalence of reduced glomerular filtration rate (GFR) ranged between 5.9 and 48.1%. Pooled prevalence of reduced GFR using studies with a modern consensus threshold of 90 ml/min/1.73 m2 was 29% (95% CI 0.0-58%). Prevalence of hypomagnesaemia ranged between 8.0 and 71.4%. Pooled prevalence of hypomagnesaemia was 37% (95% CI 22-51%). Substantial heterogeneity was present, with I2 statistics of 94% and 73% for reduced GFR and hypomagnesaemia respectively. All large, long-term follow-up studies described increased risk of reduced GFR with increasing cumulative cisplatin dose. Included studies varied as to whether cisplatin was a risk factor for proteinuria, and whether age was a risk factor for cisplatin nephrotoxicity. LIMITATIONS: A wide range of study methodologies were noted which impeded analysis. No studies yielded data from developing health-care settings. No non-English studies were included, further limiting generalisability. CONCLUSIONS: Both of the most common manifestations of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing cumulative dose conferring increased risk of nephrotoxicity. Further work is needed to characterise the relationship between reduced GFR and hypomagnesaemia, investigate other risk factors and understand the interindividual variation in susceptibility to nephrotoxicity.

Risk Evaluation of Proton Pump Inhibitors for Panitumumab-Related Hypomagnesemia in Patients with Metastatic Colorectal Cancer.

Hypomagnesemia commonly occurs as a side effect of panitumumab treatment. In severe cases, temporary discontinuation or dose reduction of panitumumab may be necessary. Proton pump inhibitors (PPIs) are reportedly potential risk factors for hypomagnesemia. We conducted a multicenter study to assess the impact of PPIs on the risk of grade 3-4 hypomagnesemia in patients with metastatic colorectal cancer (mCRC) receiving panitumumab. We adjusted for potential bias using a propensity score-matched analysis and retrospectively reviewed the medical records of patients. Hypomagnesemia severity was graded according to the Common Terminology Criteria for Adverse Events, version 5.0. A total of 165 patients were enrolled in this study. The incidence of grade 3-4 hypomagnesemia was significantly higher in the PPI group than in the non-PPI group, both before (20.0% [30/60] vs. 8.0% [8/105], p = 0.026) and after propensity score matching (16.2% [6/37] vs. 0% [0/37], p = 0.025). In the propensity score-matched cohort, the risk of grade 3-4 hypomagnesemia was significantly higher in the PPI group (odds ratio, 2.19; 95% confidence interval, 1.69-2.84; p = 0.025). These findings suggest that concomitant use of PPIs significantly increases the risk of grade 3-4 hypomagnesemia in patients with mCRC receiving panitumumab. Therefore, close monitoring of these patients is imperative.

Risk Factors of Cetuximab-Induced Hypomagnesemia and the Effect of Magnesium Prophylaxis in Patients with Head and Neck Cancer: A Retrospective Study.

Hypomagnesemia is a characteristic adverse event of cetuximab in patients with head and neck cancer (HNC). However, there is limited information about its prevalence, risk factors, and preventive strategies. This study aimed to investigate the risk factors of hypomagnesemia and examine the preventive effects of prophylactic magnesium (Mg) administration. We initially investigated HNC patients treated with cetuximab between 2013 and 2019. Our institute started prophylactic Mg treatment (20-mEq Mg sulfate administration before cetuximab) in practice during this period. We retrospectively assess the preventive efficacy by comparing patients before and after its implementation. In total, 109 patients were included. In 60 patients without prophylaxis, all-grade and grade ≥2 hypomagnesemia at 3 months occurred in 61.7 and 15.0% of patients. The incidence of hypomagnesemia was not affected by regimens and concomitant medications. In 49 patients treated with prophylactic Mg treatment, there was no significant decrease in the cumulative incidence of hypomagnesemia. However, the preventive Mg treatment eliminated the need for additional Mg repletion to maintain Mg levels in patients treated with paclitaxel + cetuximab. A risk factor in patients without prophylaxis was a low Mg level at pre-treatment (≤2.0 mg/dL) (odds ratio: 6.03, 95% confidence interval: 1.78-20.4, p = 0.004), whereas that in patients with prophylaxis was the number of cetuximab doses (≥10) (odds ratio: 5.50, 95% confidence interval: 1.52-19.87, p = 0.009). In conclusion, a low pre-treatment Mg level was the only risk factor that could be avoided by prophylactic Mg administration. This preventive intervention is recommended for managing cetuximab-induced hypomagnesemia.

A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation.

BACKGROUND: Nephrotoxicity remains the most serious side effect of cisplatin therapy. Cisplatin-induced nephrotoxicity (CIN) limits the use of this drug and affects up to 20% of patients. Several possible interventions such as magnesium supplementation may prevent CIN. This study aimed to review different types of hydration protocols and we conducted a meta-analysis of magnesium supplementation to understand its effect in protecting against CIN. METHODS: A search of the PubMed, Embase, and Cochrane databases was performed. Trials were eligible if they enrolled patients who received cisplatin and different hydration protocols to prevent CIN. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the efficacy of different protocols. RESULTS: We initially identified 1113 different studies and included 33 of them which met the selection criteria. A meta-analysis of 11 retrospective studies that examined magnesium supplementation during hydration showed that this treatment provided significant protection against CIN (OR = 0.22, 95% CI = 0.14 to 0.35). CONCLUSION: There has been uncertainty regarding the best method to prevent CIN. Our results highlight the potentially protective effect of magnesium supplementation during hydration. This study is registered in PROSPERO, CRD42020212682.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Nutritional Support: The Use of Antioxidants in Inflammatory Bowel Disease.

The problem of treating inflammatory bowel disease continues to be a topic of great interest for researchers. Despite the complexity surrounding their treatment and strategies to prolong periods of remission, there is a promising exploration of various compounds that have potential in combating inflammation and alleviating symptoms. Selenium, calcium, magnesium, zinc, and iron are among these compounds, offering a glimpse of hope in the treatment of IBD. These essential minerals not only hold the promise of reducing inflammation in these diseases, but also show the potential to enhance immune function and possibly influence the balance of intestinal microflora. By potentially modulating the gut microbiota, they may help support overall immune health. Furthermore, these compounds could play a crucial role in mitigating inflammation and minimising complications in patients with IBD. Furthermore, the protective effect of these compounds against mucosal damage in IBD and the protective effect of calcium itself against osteoporosis in this group of patients are notable.

The analgesic effects of magnesium in veterinary patients: a qualitative evidence synthesis.

OBJECTIVE: To perform a qualitative evaluation of the analgesic effects of magnesium in domestic animals, including its anaesthetic sparing effects. STUDY DESIGN: All database searches were made using PubMed and Google Scholar. Studies published after 1990, evaluating the use of magnesium and reporting information on analgesia, in dogs, cats, horses, cows, goats and sheep were selected (last search in August 2023). A reference check in the selected papers was performed to identify any study which was omitted. The CERQual (Confidence in Evidence from Reviews of Qualitative research) approach was used to assess confidence and analyse the evidence. RESULTS: A total of 20 studies relevant to the analgesic effects of magnesium in veterinary patients and two reviews were included. All were published after 2006. Of the 20, five studies provided information about analgesia in the postoperative period in dogs with heterogenous results. Magnesium added epidurally increased the duration of the sensory block in several species. Motor block was also observed when added to spinal analgesia. Results regarding volatile agents sparing effect were conflicting. Occasional moderate adverse effects were reported in dogs, such as nausea and vomiting, when administered as a bolus in conscious animals, and hypotension when administered intraperitoneally. Collapse was reported in horses after epidural administration. CONCLUSIONS AND CLINICAL RELEVANCE: The evidence of an analgesic effect of magnesium in veterinary patients remains scarce considering the paucity and low quality of published data. Further research may be helpful to establish the efficacy and indications of magnesium in multimodal analgesia in animals.

Differential Protective Effect of Zinc and Magnesium for the Hepatic and Renal Toxicity Induced by Acetaminophen and Potentiated with Ciprofloxacin in Rats.

Background and Objectives: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. Material and Methods: The experiment was performed on five animal groups: group 1-control, treated for 6 weeks with normal saline, 1 mL/kg; group 2-AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3-AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4-AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl2 10 mg/ kg/day was added; and group 5-AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (p < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < p < 0.01 and 0.01 < p < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < p < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < p < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < p < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < p < 0.05 group 5 vs. group 4). Conclusions: This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney's function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.

Effectiveness and Safety of Nebulized Magnesium as Last Line Treatment in Adults with Acute Asthma Attack: A Systematic Review and Meta-Analysis.

BACKGROUND: Asthma is a disease characterized by chronic airway inflammation, however one-third of asthmatic cases did not respond adequately. Inhaled magnesium has been proposed as a treatment for unresponsive asthma cases. However, its role remains controversial. This review evaluates the effectiveness and safety of nebulized magnesium compared to standard therapy (Beta Agonist, Anticholinergic, Corticosteroid) in adults with acute asthma attacks. METHODS: The protocol has been registered in PROSPERO. A literature search was conducted through PubMed/MEDLINE, Cochrane, ProQuest, and Google Scholar, and using the keywords "inhaled magnesium" and "asthma". Manual searches were carried out through data portals. Journal articles included are randomized controlled trials. The assessment risk of bias was performed using Version 2 of the Cochrane risk-of-bias tool for randomized trials. RESULTS: There are five articles included in this review. There is no significant difference in readmission rate and oxygen saturation in the magnesium group compared to control (RR 1; 95% CI 0.92 to 1,08; p= 0,96 and MD 1,82; 95% CI -0.89 to 4.53; p= 0.19, respectively). There is a significant reduction of respiratory rate and clinical severity in magnesium (MD -1,72; 95% CI -3,1 to 0.35; p= 0.01, RR 0.29; 95% CI 0.17 to 0.69; p <0.001, respectively). There was a higher risk of side effects in the magnesium group (HR 1.56; 95%CI 1.05 to 2.32; p= 0.03). However, the side effects are relatively mild such as hypotension and nausea. CONCLUSION: Inhaled magnesium improves the outcome of asthmatic patients, especially in lung function, clinical severity, and respiratory rate. Moreover, inhaled magnesium is safe to be given.

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.

BACKGROUND/IMPORTANCE: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases. OBJECTIVE: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults. EVIDENCE REVIEW: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence. FINDINGS: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies. CONCLUSIONS: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.

Effect of Magnesium on Deterioration and Symptomatic Hemorrhagic Transformation in Cerebral Ischemia: An Ancillary Analysis of the FAST-MAG Trial.

BACKGROUND: Magnesium (Mg) is a neuroprotectant in preclinical models. Lower serum Mg levels have been associated with symptomatic hemorrhagic transformation (HT) in patients with ischemic stroke. Early treatment of acute ischemic stroke with Mg may reduce rates of symptomatic HT. METHODS: In this post hoc study of the Field Administration of Stroke Therapy Magnesium (FAST-MAG) trial, 1,245 participants with a diagnosis of cerebral ischemia received 20 g of Mg or placebo initiated in the prehospital setting. Posttreatment serum Mg level was measured for 809 participants. Cases of clinical deterioration, defined as worsening by ≥4 points on the National Institute of Health Stroke Scale (NIHSS), were imaged and evaluated for etiology. Symptomatic HT was defined as deterioration with imaging showing new hemorrhage. RESULTS: Clinical deterioration occurred in 187 and symptomatic HT in 46 of 1,245 cases of cerebral ischemia. Rates of deterioration and symptomatic HT were not significantly lower in those who received Mg (15.7% vs. 14.4%, p = 0.591; 2.8% vs. 4.6%, p = 0.281). In cases where serum Mg level was obtained posttreatment, lower serum Mg level (<1.7 mg/dL) was associated with significantly higher rates of deterioration and symptomatic HT (27.5% vs. 15.5%, p = 0.0261; 11.6% vs. 3.65%, p = 0.00819). CONCLUSIONS: Treatment with Mg did not significantly reduce rates of clinical deterioration or symptomatic HT. Future analysis should address whether treatment with Mg could have influenced the subgroup with low serum Mg at baseline.

High-dose IV magnesium in mesothelioma patients receiving surgery with hyperthermic intraoperative cisplatin: Pilot studies and design of a phase II randomized clinical trial.

INTRODUCTION: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans. METHODS: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B. RESULTS: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium. CONCLUSIONS: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. MATERIAL AND METHODS: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. RESULTS: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was -0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. CONCLUSIONS: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS.

Hypomagnesemia with Secondary Hypocalcemia (HSH): a Case Report.

BACKGROUND: Hypomagnesemia with secondary hypocalcemia (HSH) is a genetic disorder arising from the body's impaired capacity to absorb and retain magnesium (Mg2+) consumed through diet. Consequently, Mg2+ levels in blood are significantly reduced, a condition referred to as hypomagnesemia. Insufficient levels of Mg2+ and calci-um (Ca2+) can lead to neurological complications that manifest during infancy, such as painful muscle spasms (tet-any) and seizures. METHODS: We reported a case of HSH involving a 10-year-old male patient from a Han Chinese family. He was admitted due to recurrent convulsions experienced over the past two years. The patient's initial episode occurred two years prior, when he collapsed without apparent cause and exhibited limb numbness, convulsions, and a disordered state of consciousness, accompanied by hypocalcemia. Cranial CT scans revealed multiple symmetrical calcifications in the basal ganglia, corona radiata, and cerebellar dentate nucleus. RESULTS: During the hospital stay, the patient was administered the following treatments: Calcium Carbonate and Vitamin D3 Tablets (1.5 g of calcium carbonate and 125 IU of Vitamin D3 per tablet, 1 tablet/time) once daily, Calcitriol Soft Capsules (0.25 µg of calcitriol per capsule, 1 capsule/time) twice daily, Potassium Chloride Sustained-release Tablets (0.5 g of potassium chloride per tablet, 1 tablet/time) thrice daily, Potassium Aspartate and Mag-nesium Aspartate Tablets (158 mg of potassium aspartate and 140 mg of magnesium aspartate per tablet, 1 tablet/ time) thrice daily, and intravenous infusions of Magnesium Sulfate Injection (2.5 g/time) twice daily. After three days in the hospital, the patient's initial symptoms subsided, resulting in discharge with a prescription of ongoing oral medications including Calcium Carbonate and Vitamin D3 Tablets, Calcitriol Soft Capsules, and Potassium Aspartate and Magnesium Aspartate Tablets, with the same usage and dosage as the above three drugs. A month subsequent, the serum levels of Mg2+, Ca2+, potassium (K+), and phosphorus were 0.96 mmol/L, 2.52 mmol/L, 4.06 mmol/L, and 1.63 mmol/L, respectively. CONCLUSIONS: Primary HSH is an uncommon manifestation of parathyroid hypoplasia, clinically characterized by low levels of Mg2+, Ca2+, and K+ in the blood. Our findings serve to enrich and consolidate the knowledge for future case studies and follow-up investigations.

Effect of magnesium sulfate perioperative infusion on postoperative catheter-related bladder discomfort in male patients undergoing laparoscopic radical resection of gastrointestinal cancer: a prospective, randomized and controlled study.

BACKGROUND: Laparoscopic radical resection of gastrointestinal cancer is associated with a high incidence of postoperative catheter-related bladder discomfort (CRBD). Studies on the benefits of magnesium sulfate intravenous infusion during the perioperative period post-laparoscopic surgery are yet lacking. METHODS: A total of 88 gastrointestinal cancer male patients scheduled for laparoscopic radical resection were randomly divided into two groups: normal saline (control) and magnesium. In the magnesium group, a 40 mg/kg loading dose of intravenous magnesium sulfate was administered for 10 min just after the induction of anesthesia, followed by continuous intravenous infusion of 15 mg/kg/h magnesium sulfate until the end of the surgery; the control group was administered the same dose of normal saline. Subsequently, 2 µg/kg sufentanil was continuously infused intravenously by a postoperative patient-controlled intravenous analgesia (PCIA) device. The primary outcome was the incidence of CRBD at 0 h after the surgery. The secondary outcomes included incidence of CRBD at 1, 2, and 6 h postsurgery, the severity of CRBD at 0, 1, 2, and 6 h postsurgery. Remifentanil requirement during surgery, sufentanil requirement within 24 h postsurgery, the postoperative numerical rating scale (NRS) score at 48 h after the surgery, magnesium-related side effects and rescue medication (morphine) requirement were also assessed. RESULTS: The incidence of CRBD at 0, 1, 2, and 6 h postoperatively was lower in the magnesium group than the control group (0 h: P = 0.01; 1 h: P = 0.003; 2 h: P = 0.001; 6 h: P = 0.006). The incidence of moderate to severe CRBD was higher in the control group at postoperative 0 and 1 h (0 h: P = 0.002; 1 h: P = 0.028), remifentanil requirement during surgery were significantly lower in the magnesium group than the control group. Sufentanil requirements during the 24 h postoperative period were significantly lower in the magnesium group than the control group. The NRS score was reduced in the magnesium group compared to the control group in the early postoperative period. Magnesium-related side effects and rescue medication (morphine) did not differ significantly between the two groups. CONCLUSIONS: Intravenous magnesium sulfate administration reduces the incidence and severity of CRBD and remifentanil requirement in male patients undergoing radical resection of gastrointestinal cancer. Also, no significant side effects were observed. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2100053073. The study was registered on 10/11/2021.

Serum concentration-guided intravenous magnesium sulfate administration for neuroprotection in patients with aneurysmal subarachnoid hemorrhage: a retrospective evaluation of a 12-year single-center experience.

Delayed cerebral infarction (DCI) is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). The benefits of magnesium sulfate as an alternative treatment are controversial, and most previous studies examined its benefits only as adjunctive treatment to traditional nimodipine. We retrospectively analyzed aSAH patients records with magnesium sulfate between 2010 and 2021. We aimed for a serum magnesium concentration of 2-2.5 mmol/l between post-hemorrhage days 3 and 12. The patients were separated in three groups based on average serum magnesium concentration (magnesium >2 mmol/l, reduced magnesium 1.1-1.9 mmol/l, and no magnesium). Additionally, we assessed delayed cerebral infarction (DCI) and clinical outcome at follow-up, using the modified Rankin Scale (mRS), categorized in favorable (0-3) and unfavorable outcome (4-5). In this analysis, 548 patients were included. Hereof, radiological evidence of DCI could be found in 23.0% (n = 126) of patients. DCI rates were lower if patients' average serum magnesium was higher than 2 mmol/l (magnesium 18.8%, n = 85; reduced magnesium 38.3%, n = 23; no magnesium 51.4%, n = 18; p < 0.001). Also, at the last follow-up, patients in the group with a higher serum magnesium concentration had better outcome (favorable outcome: magnesium 64.7%, n = 293; reduced magnesium 50.0%, n = 30; no magnesium 34.3%, n = 12; p < 0.001). This 12-year study reveals the value of serum concentration-guided magnesium administration in aSAH patients. Our findings demonstrate the safety and efficacy when titrated to a serum concentration of 2-2.5 mmol/l. We observed higher rates of delayed cerebral infarction and unfavorable outcomes in patients with serum concentrations below 2 mmol/l.

Pain management after cardiac surgery via median sternotomy: A systematic review with procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND: Pain after cardiac surgery via median sternotomy can be difficult to treat, and if inadequately managed can lead to respiratory complications, prolonged hospital stays and chronic pain. OBJECTIVES: To evaluate available literature and develop recommendations for optimal pain management after cardiac surgery via median sternotomy. DESIGN: A systematic review using PROcedure-SPECific Pain Management (PROSPECT) methodology. ELIGIBILITY CRITERIA: Randomised controlled trials and systematic reviews published in the English language until November 2020 assessing postoperative pain after cardiac surgery via median sternotomy using analgesic, anaesthetic or surgical interventions. DATA SOURCES: PubMed, Embase and Cochrane Databases. RESULTS: Of 319 eligible studies, 209 randomised controlled trials and three systematic reviews were included in the final analysis. Pre-operative, intra-operative and postoperative interventions that reduced postoperative pain included paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), intravenous magnesium, intravenous dexmedetomidine and parasternal block/infiltration. CONCLUSIONS: The analgesic regimen for cardiac surgery via sternotomy should include paracetamol and NSAIDs, unless contraindicated, administered intra-operatively and continued postoperatively. Intra-operative magnesium and dexmedetomidine infusions may be considered as adjuncts particularly when basic analgesics are not administered. It is not clear if combining dexmedetomidine and magnesium would provide superior pain relief compared with either drug alone. Parasternal block/surgical site infiltration is also recommended. However, no basic analgesics were used in the studies assessing these interventions. Opioids should be reserved for rescue analgesia. Other interventions, including cyclo-oxygenase-2 specific inhibitors, are not recommended because there was insufficient, inconsistent or no evidence to support their use and/or due to safety concerns.