Magnesium Replacement Research Articles

Prevalence of Hypomagnesaemia among Obese Type 2 Diabetic Patients Attending the National Center for Diabetes, Endocrinology and Genetics (NCDEG).

Background:Some observations suggested that magnesium supplementation could be helpful in the treatment of diabetic patients by improving glycemic control and preventing the development of diabetes-related complications.Objectives:To estimate the prevalence of hypomagnesaemia among obese patients with type 2 diabetes attending the National Center for Diabetes, Endocrinology and Genetics (NCDEG) in Amman, Jordan.Patients and Methods:A cross-sectional study was carried out at the National Center for diabetes, Endocrinology and Genetics (NCDEG) in Amman-Jordan. A total of 1105 patients with type 2 diabetes (51.9% females and 48.1% males) who attended this center between first of October 2011and end of February 2012 were included in the study. The mean age and duration of diabetes were 57.1 years and 5.1 years, respectively and the mean value of HbA1c was 7.9%. Our study also performed a comparison of the prevalence of hypomagnesaemia between our studied sample and 3600 individuals enrolled in the National Vitamin D study completed in Jordan in 2009. The obtained data included patients’ age, gender, smoking history, HbA1c level, comorbid history including hypertension, dyslipidemia, and presence of neuropathy and retinopathy.Results:Out of 1105 patients with type 2 diabetes, 210 patients (19%) (95% CI, 16.8%-21.4%) were hypomagnesaemic. Female gender, hypertension, statin therapy, HbA1c between 7-7.9% or ≥ 9% and patients with diabetes duration more than five years were independent risk factors for hypomagnesaemia. No association between hypomagnesaemia and age distribution, smoking history, neuropathy and retinopathy was found. In comparison with individuals enrolled in the National Vitamin D study, diabetic patients in this study had a much higher prevalence of hypomagnesaemia (19% vs. 0.7%) with odd’s ratio of 32 (95% CI, 21-48.2).Conclusions:As the prevalence of hypomagnesaemia among patients with type 2 diabetes treated at the NCDEG was found to be 19% (95% CI, 16.8%-21.4%), we recommend periodic determination of magnesium level and appropriate magnesium replacement therapy particularly among the above defined groups.

Magnesium protects against cisplatin-induced acute kidney injury by regulating platinum accumulation

Despite its success as a potent antineoplastic agent, ∼25% of patients receiving cisplatin experience acute kidney injury (AKI) and must discontinue therapy. Impaired magnesium homeostasis has been linked to cisplatin-mediated AKI, and because magnesium deficiency is widespread, we examined the effect of magnesium deficiency and replacement on cisplatin-induced AKI in physiologically relevant older female mice. Magnesium deficiency significantly increased cisplatin-associated weight loss and markers of renal damage (plasma blood urea nitrogen and creatinine), histological changes, inflammation, and renal cell apoptosis and modulated signaling pathways (e.g., ERK1/2, p53, and STAT3). Conversely, these damaging effects were reversed by magnesium. Magnesium deficiency alone significantly induced basal and cisplatin-mediated oxidative stress, whereas magnesium replacement attenuated these effects. Similar results were observed using cisplatin-treated LLC-PK1 renal epithelial cells exposed to various magnesium concentrations. Magnesium deficiency significantly amplified renal platinum accumulation, whereas magnesium replacement blocked the augmented platinum accumulation after magnesium deficiency. Increased renal platinum accumulation during magnesium deficiency was accompanied by reduced renal efflux transporter expression, which was reversed by magnesium replacement. These findings demonstrate the role of magnesium in regulating cisplatin-induced AKI by enhancing oxidative stress and thus promoting cisplatin-mediated damage. Additional in vitro experiments using ovarian, breast, and lung cancer cell lines showed that magnesium supplementation did not compromise cisplatin's chemotherapeutic efficacy. Finally, because no consistently successful therapy to prevent or treat cisplatin-mediated AKI is available for humans, these results support developing more conservative magnesium replacement guidelines for reducing cisplatin-induced AKI in cancer patients at risk for magnesium deficiency.

Cost-minimization analysis of two fluid products for resuscitation of critically injured trauma patients

Results of a study to determine potential cost benefits of substituting an alternative electrolyte solution for 0.9% sodium chloride injection for the initial fluid resuscitation of trauma patients are presented. Using data from a randomized clinical trial that compared 24-hour fluid resuscitation outcomes in critically injured trauma patients treated with 0.9% sodium chloride injection and those who received a balanced electrolyte solution (Plasma-Lyte A, Baxter Healthcare), a cost-minimization analysis was performed at a large medical center. The outcomes evaluated included fluid and drug acquisition costs, materials and nurse labor costs, and costs associated with electrolyte replacement. The use of Plasma-Lyte A was associated with a relatively higher fluid acquisition cost but a reduced need for magnesium replacement. During the first 24 hours of hospitalization, 4 of 24 patients (17%) treated with 0.9% sodium chloride injection and none of the patients who received the comparator product (n = 22) required supplemental magnesium. Patients treated with 0.9% sodium chloride injection received a median of 4 g of magnesium (interquartile range [IQR], 2.5-4.0 g), compared with a median of 0 g (IQR 0-2 g) in the comparator group. Taking into account the costs of consumable supplies and nursing labor, the cost-minimization analysis indicated a 24-hour cost differential of $12.35 in favor of Plasma-Lyte A. Substitution of Plasma-Lyte A for 0.9% sodium chloride injection for fluid resuscitation during the first 24 hours after traumatic injury was associated with decreased magnesium replacement requirements and a net cost benefit to the institution.

Patient care services: What pharmacists do

Patient care services: What pharmacists do

APhA honors outstanding achievements at Annual Meeting

Each year, APhA recognizes exceptional contributors to the profession at the Annual Meeting. The following award winners will be honored at APhA2014 in Orlando.

Magnesium replacement does not improve insulin resistance in patients with metabolic syndrome: a 12-week randomized double-blind study.

BackgroundTo evaluate the effect of magnesium (Mg) replacement on insulin resistance and cardiovascular risk factors in women with metabolic syndrome (MS) without diabetes.MethodsThis 12-week clinical randomized double-blind study compared the effects of 400 mg/day of Mg with those of a placebo (n = 72) on fasting glucose, insulin, HOMA-IR, lipid profile and CRP. Mg was measured in serum (SMg) and in mononuclear cells (MMg).ResultsHypomagnesemia (SMg < 1.7 mg/dL) was seen in 23.2% of patients and intracellular depletion in 36.1% of patients. The MMg means were lower in patients with obesity (0.94 ± 0.54 μg/mg vs. 1.19 ± 0.6 μg/mg, P = 0.04), and insulin resistance (0.84 ± 0.33 μg/mg vs. 1.14 ± 0.69 µg/mg, P < 0.05). Mg replacement did not alter SMg (1.82 ± 0.14 mg/dL vs. 1.81 ± 0.16 mg/dL, P = 0.877) and tended to increment MMg (0.90 ± 0.40 μg/mg vs. 1.21 ± 0.73 μg/mg, P = 0.089). HOMA-IR did not alter in interventions nor in placebo group (3.2 ± 2.0 to 2.8 ± 1.9, P = 0.368; 3.6 ± 1.9 to 3.2 ± 1.8, respectively), neither did other metabolic parameters.ConclusionSerum and intracellular Mg depletion is common in patients with MS; however, Mg replacement in recommended dosage did not increase significantly Mg levels, neither reduced insulin resistance or metabolic control.

Photocatalytic hydrogen production from water under visible light irradiation using a dye-sensitized attapulgite nanocrystal photocatalyst

Attapulgite (ATP), not only as a type of natural and low cost silicate clay mineral but also as a high quality nanosized material with large surface area, layered and lath-like structure, has been found to have a wide variety of industrial applications. The ideal composition of ATP is Mg5Si8O20(OH)2(OH2)4. However, according to previous reports from different countries in the world, it is very important for our research that the actual composition of ATP varies because of partial replacement of magnesium by aluminum, iron, titanium and other elements. Herein, we have successfully used this dye sensitized clay mineral (raw and purified) to effectively reduce water for hydrogen generation under visible light irradiation. Further chemical analysis as well as computational simulation (CS) proposed that the natural Fe-doping (two ATP crystal cells sharing one Fe atom) can promote the photocatalytic process.

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Introduction: The effectiveness and potential complexity of electrolyte replacement protocols in the surgical population have been described in the literature. Previously, in our SICU and TICU, the electrolyte replacement protocol was not integrated into our computerized physician order entry (CPOE) system. This analysis was undertaken to determine if an electronic protocol integrating clinical decision support (CDS) in our CPOE system would improve electrolyte protocol replacement rates. Methods: This was a single-center, retrospective analysis investigating our nursing-driven electrolyte replacement protocol compliance in June 2010, prior to the CDS ordering process update, and in September 2012, 5 months after the update. Patients were included if at least 16 years of age and admitted to the SICU or TICU with protocol orders for greater than 24 hours. Compliance was assessed with respect to potassium (K), magnesium (Mg), and phosphorus (Phos) replacement doses and follow-up laboratory monitoring. The Mann-Whitney U test was used for continuous data and Fischer’s Exact was used for categorical data. Results: 150 patients were included in this study. 60 patients were in the pre-update 2010 group, and 90 patients were in the post-update 2012 group. Baseline characteristics were similar between groups. Overall initial compliance with K, Mg, and Phos replacement occurred in 2% of patients in 2010 group compared to 17% of patients in the 2012 group (p<0.001). K doses missed per 100 K levels drawn were significantly decreased in the 2012 group (23 per 100 vs 15 per 100 K lab draws, p=0.013). K doses higher than prescribed by the protocol were reduced in the 2012 group, with 8 per 100 vs 3 per 100 K lab draws (p=0.001). Improvements were similar for K doses that were lower than directed. Mg doses missed per 100 Mg levels drawn were improved (37 per 100 vs 13 per 100 Mg lab draws, p<0.001), along with fewer Mg doses that here too high in 2012 (2 per 100 vs 0 per 100 Mg lab draws, p=0.03). No difference in phosphorus replacement was observed. Missed follow-up K levels were reduced in the 2012 group (52 per 100 vs 2 per 100 protocol days, p<0.001). Of the patients with missed doses of K, Mg, and Phos, the average electrolyte values were minimally below the replacement threshold. Conclusions: The electrolyte replacement protocol update integrating CDS in our CPOE system did improve overall compliance, reduced missed K and Mg doses, and helped ensure doses given were correct. We also were able to improve K monitoring in hypokalemic surgical and trauma patients.

Treatment of Hypomagnesemia

Serum magnesium concentration is determined by the interplay of intestinal absorption and renal excretion. Hypomagnesemia can occur as a result of insufficient magnesium intake, increased gastrointestinal or renal loss, or redistribution from extracellular to intracellular compartments. A number of drugs are known to cause hypomagnesemia, including proton pump inhibitors (PPIs). We report the case of a patient with symptomatic hypomagnesemia due to short bowel syndrome and PPI therapy. Investigations revealed low 24-hour urinary magnesium excretion and secondary hypocalcemia. PPI treatment was withdrawn and the patient was managed with intravenous and oral magnesium and calcium replacement. This teaching case provides an evidence-based discussion of the treatment of hypomagnesemia.

Acute Decrease in Serum Magnesium Level after Ischemic Stroke May Not Predict Decrease in Neurologic Function

Higher serum levels of magnesium (Mg2+) may contribute to improved outcome following ischemic stroke, and this may be related to vessel recanalization. Patients with low or normal serum magnesium levels during the acute phase of ischemic stroke may be more susceptible to neurologic deterioration (ND) and worse outcomes. All patients who presented to our center within 48 hours of acute ischemic stroke (July 2008 to December 2010) were retrospectively identified. Patient demographics, laboratory values, and multiple outcome measures, including ND, were compared across admission serum Mg2+ groups and change in Mg2+ from baseline to 24-hour groups. Three hundred thirteen patients met inclusion criteria (mean age: 64.8 years, 42.2% female, 64.0% black). Mg2+ groups at baseline were not predictive of poor functional outcome, death, or discharge disposition. Patients whose serum Mg2+ decreased during the first 24 hours of admission were also not at greater odds of ND or poor outcome measures compared with patients with unchanging or increasing Mg2+ levels. Our results suggest that patients who have low Mg2+ at baseline or a reduction in Mg2+ 24 hours after admission are not at a higher risk of experiencing ND or poor short-term outcome. Ongoing prospective interventional trials will determine if hyperacute aggressive magnesium replacement affords neuroprotection in stroke.

Hypomagnesemia as a possible explanation behind episodes of severe pain in cancer patients receiving palliative care

Within an oncology setting, certain chemotherapy drugs, such as cisplatin, may lead to magnesium loss causing nephropathy. Neurological and cardiovascular symptoms caused by hypomagnesaemia are well known. The relationship between serious hypomagnesemia and severe pain is not well documented but nevertheless, when faced with unexplained episodes of pain which do not respond to powerful analgesics, it is important to review blood magnesium levels. We present two cases of opioid-refractory pain attacks. Patients received drugs which have been linked to hypomagnesemia. In both cases, endovenous magnesium replacement led to a drastic improvement in pain management.

Magnesium

Magnesium

The Effects of Serum Potassium and Magnesium Levels in a Patient with Gitelman's Syndrome on the Timing of Ventricular Wall Motion and the Pattern of Ventricular Strain and Torsion

Gitelman's syndrome is a primary renal tubular hypokalemic metabolic alkalosis. Hypokalemia and hypomagnesemia can cause cardiac tissue excitability and conduction. Global ventricular mechanical function is directly related to the contractile properties of cardiac myocytes, which are largely dependent on the flow of ions such as potassium and magnesium. Here, we show that increased levels of potassium, in addition to magnesium, in a patient with Gitelman's syndrome significantly impacts the timing of ventricular wall motion and the pattern of ventricular strain and torsion. Two-dimensional speckle tracking echocardiography was used for evaluation of the hypokalemic-hypomagnesemic period (first day) and third day after potassium chloride and magnesium replacement therapy. The transthoracic echocardiography showed that the percent ejection fraction was similar in hypokalemic-hypomagnesemic (63%) and normokalemic-normomagnesemic (after potassium and magnesium therapy, 67%) hearts. However, decreased left ventricular apical 4-chamber peak systolic longitudinal strain, left ventricle global peak systolic strain, and global torsion values increased after potassium chloride and magnesium replacement therapy.

Magnesium Augments Platelet Activation and Coagulation in Citrated Blood Product

AbstractAbstract 3438Massive transfusion is defined as infusion of 10 units of red blood cells in 24 hours during treatment of uncontrolled bleeding. Mortality rates are 28.3% higher for patients that undergo massive transfusion. Administered blood products are collected from donors using citrate inhibition for anti-coagulation. Citrate chelates calcium, thus preventing its interactions with clotting enzymes and eliminating coagulation activity. Severe trauma patients suffer compromised liver function slowing citrate clearance and further reducing calcium availability. Under this scenario, calcium is empirically replaced due to concerns regarding hemostasis, however magnesium, which is also chelated by citrate, is not empirically replaced. Our goal was to describe both platelet aggregation and coagulation under conditions of increasing magnesium concentration following citrate chelation to ascertain the true spectrum of magnesium influence upon hemostasis.To analyze platelet activation/aggregation, de-identified whole blood (WB) was anti-coagulated with citrate (10.9mM) and corn trypsin inhibitor (CTI) (0.1mg/mL), or citrate and 50μL pPACK (final). Platelet-rich plasma (PRP) was prepared through centrifugation at 200g for 10 minutes. Subsequent spin at 2000g for 10 minutes yielded platelet-poor plasma (PPP). Remaining packed red blood cells were combined with PRP (platelets calcein-tagged to 10μM final) to simulate 40% hematocrit. Shear rate of 920/sec was induced for arterial flow conditions for 10 minutes at 37°C through a microchannel (350μm W × 70μm H × 5000μm L) pre-coated with a solution of 100μg/mL type-I collagen blocked with 0.5% BSA/1X PBS. Fluorescent signal intensity of calcein-tagged platelets was quantified through sequential image capture every 30 seconds using Fluxion BioFlux 1000. For coagulation analyses, citrate/CTI inhibited WB, PRP, and PPP was analyzed via thromboelastograph (TEG) following large volume pre-mixing with tissue factor (1:5000). TEG cups were preloaded with varying concentrations of calcium chloride (0M, 5.5mM, 10.9mM, 15mM), or calcium chloride (15mM) with magnesium sulfate (0M, 3mM, 3.5mM, 4.5mM) before blood or component addition. TEG data were collected for 90 minutes. Statistical analyses were performed with GraphPad Prism 5 software. Comparisons were drawn using linear analysis and area under the curve.Data indicate that re-attainment of physiological magnesium concentration in citrated blood: (1) facilitates platelet activation/aggregation, and (2) augments coagulation parameters through accelerated clot time and increased clot strength. Rate of platelet aggregation was significantly increased at final magnesium concentrations of 1.5mM (p<0.01), and 3mM (p<0.005) when added to re-calcified WB. Further, addition of magnesium to PPP reduced time to initiation of clot formation (4.5mM), increased clot strength (1mM, 3mM), and increased rate of clot formation (1mM, 3mM). These data suggest supplemental magnesium improves hemostatic properties in citrated WB and PPP with or without re-calcification. The incidence and severity of hypocalcemia and hypomagnesimia in massive transfusion, and effects on hemostatic function remain to be established. Replacement of magnesium during massive transfusion may represent a therapeutic opportunity. Disclosures:No relevant conflicts of interest to declare.

Comparison of intravenous and oral magnesium replacement in hospitalized patients with cardiovascular disease

The results of an investigation of serum magnesium concentrations (SMCs) after i.v. versus oral delivery of magnesium in cardiovascular critical care are presented. A retrospective case review was conducted to compare the net gain of magnesium after i.v. (n = 188) or oral (n = 164) magnesium therapy for the prevention of ventricular fibrillation and arrhythmias in patients hospitalized for serious cardiovascular disorders, as determined by assessing SMCs. The primary study outcome was the change from baseline SMC values 6-24 hours after the completion of magnesium courses; secondary outcomes included the impact of renal impairment, concomitant medication use, and other clinical variables on SMC changes. Although consistent elevations in SMC were produced by oral magnesium delivery, i.v. administration resulted in greater and more rapid elevations relative to baseline SMC. The degree of change in SMC was significantly influenced by the timing of SMC measurement after a magnesium course, by renal function, and by concomitant use of i.v. loop diuretics. A comparison of 24-hour courses of magnesium replacement therapy showed that magnesium sulfate 2 g i.v. was associated with larger changes in SMC than magnesium oxide 800, 1200, or 1600 mg orally when the baseline SMC was 1.4-1.8 mg/dL. At baseline SMCs of 1.4-1.8 mg/dL, oral magnesium oxide provided a consistent median increase in SMC of 0.1 mg/dL. The change in the number of bowel movements did not differ significantly between courses of i.v. magnesium sulfate and oral magnesium oxide.

Influence of Urine Output on Magnesium Level in Aneurysmal Subarachnoid Hemorrhage (P02.210)

Objective: To investigate whether high urine output after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a decrease in serum magnesium level. Background Hypomagnesemia frequently occurs in critically ill patients and may be correlated with worse outcome in the subset of aneurysmal subarachnoid hemorrhage (aSAH) patients. These patients are at risk of developing cardiac arrhythmias and cerebral vasospasm, and maintaining normal serum magnesium levels may help to prevent these complications. However, the mainstay of prevention and treatment of cerebral vasospasm includes “Triple-H Therapy” (hypertension, hypervolemia and hemodilution), which may artificially increase patients9 urine outputs and subsequently lower magnesium levels. Design/Methods: A retrospective chart review at an Academic Hospital from July 1 st 2010 to December 31 st 2010 yielded 16 patients with the diagnosis of aSAH. Serum magnesium level, magnesium repletion, total fluid intake and total urine output were recorded daily. Statistical correlation was used for statistical analysis. Results: Of the 16 patients, one patient was excluded from the study due to short hospital stay. Three patients showed strong correlation (r= -0.8831; -0.7039 and -0.5840 respectively) between high daily urine output and low serum magnesium level. All three patients needed multiple magnesium replacements to maintain a stable magnesium level. Six patients showed moderate correlation (r= -0.4021; -0.3976; -0.3657; -0.3557; -0.3285 and -0.3120 respectively), and 6 showed weak and very weak correlation. Daily serum magnesium level tended to fluctuate around the admission magnesium level. Conclusions: There is no significant correlation between daily urine output and daily serum magnesium level. However, there is a tendency that more hypomagnesemia occurs when daily urine output is higher than 5 liters (L). Serum magnesium level tends to fluctuate around the admission level. Admission serum magnesium may indicate the relative magnesium level throughout the acute aSAH period. Disclosure: Dr. Gu has nothing to disclose. Dr. Klinger has nothing to disclose. Dr. Boudreaux has nothing to disclose. Dr. Botros has nothing to disclose. Dr. Griffith has nothing to disclose. Dr. Rickert has nothing to disclose. Dr. White has nothing to disclose. Dr. Samson has nothing to disclose.

Resolving basal ganglia calcification in hereditary hypomagnesemia with secondary hypocalcemia due to a novel TRMP6 gene mutation

Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare condition caused by mutations in the transient receptor potential melastatin 6 (TRPM6) gene. Patients usually present during early infancy with symptomatic hypocalcemia; however, intracranial calcification has not been previously reported in HSH. We report on a three-month-old Saudi girl who presented with hypocalcemic convulsions and was initially treated as nutritional rickets. However, further biochemical analysis of blood and urine were suggestive of HSH. This diagnosis was confirmed by mutation analysis, which identified a novel homozygous frame shift mutation (ins 2999T) of the TRPM6 gene. A computed tomography brain scan, done around the time of diagnosis, identified bilateral basal ganglia calcification (BGC). Her serum calcium and the BGC improved with magnesium replacement. BGC can be added as a new feature of HSH and the case highlights the importance of measuring serum Mg in patients with hypocalcemic convulsions, particularly in children of consanguineous parents.

Recurrent symptomatic hypocalcemia during rifampicin therapy for brucellosis

Drug-associated hypocalcemia is rare, but may occur during routinely administered drugs. We reported a case of vertebral brucellosis, which developed two hypocalcemic episodes associated with hypokalemic alkalosis with two drug combinations including rifampicin. Possible underlying mechanisms of hypocalcemia were discussed. The patient had carpopedal spasm at both hypocalcemic presentations. Laboratory analysis revealed hypocalcemia, hypokalemia, alkalosis with hypercalciuria, and low-normal parathormone (PTH) at first and elevated PTH at the second admission. The patient improved with cessation of drugs and appropriate management of hypocalcemia and hypokalemia with calcium, vitamin D, magnesium, and potassium replacement. The underlying mechanism of hypocalcemia in this patient seemed to be due to tubular damage resulting with Bartter-like syndrome, which is well defined with aminogylcosides. But the recurrence of hypocalcemia with an aminoglycoside-free antibiotic combination including rifampicin suggests a possible role of rifampicin on hypocalcemia associated Bartter-like syndrome that has never been reported before.

Nanomechanics of the Cadherin Ectodomain: “CANALIZATION” BY Ca2+ BINDING RESULTS IN A NEW MECHANICAL ELEMENT

Cadherins form a large family of calcium-dependent cell-cell adhesion receptors involved in development, morphogenesis, synaptogenesis, differentiation, and carcinogenesis through signal mechanotransduction using an adaptor complex that connects them to the cytoskeleton. However, the molecular mechanisms underlying mechanotransduction through cadherins remain unknown, although their extracellular region (ectodomain) is thought to be critical in this process. By single molecule force spectroscopy, molecular dynamics simulations, and protein engineering, here we have directly examined the nanomechanics of the C-cadherin ectodomain and found it to be strongly dependent on the calcium concentration. In the presence of calcium, the ectodomain extends through a defined ("canalized") pathway that involves two mechanical resistance elements: a mechanical clamp from the cadherin domains and a novel mechanostable component from the interdomain calcium-binding regions ("calcium rivet") that is abolished by magnesium replacement and in a mutant intended to impede calcium coordination. By contrast, in the absence of calcium, the mechanical response of the ectodomain becomes largely "decanalized" and destabilized. The cadherin ectodomain may therefore behave as a calcium-switched "mechanical antenna" with very different mechanical responses depending on calcium concentration (which would affect its mechanical integrity and force transmission capability). The versatile mechanical design of the cadherin ectodomain and its dependence on extracellular calcium facilitate a variety of mechanical responses that, we hypothesize, could influence the various adhesive properties mediated by cadherins in tissue morphogenesis, synaptic plasticity, and disease. Our work represents the first step toward the mechanical characterization of the cadherin system, opening the door to understanding the mechanical bases of its mechanotransduction.

Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin.

Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity.