Anxiolytic effect of chronic intake of supplemental magnesium chloride in rat.

Evidence suggest that magnesium dietary supplementation has several health benefits including lowering blood pressure, reducing insulin resistance, and improving symptoms of depression, anxiety, and migraine. Here, we aimed to study the effect of chronic magnesium supplementation on anxiety-like behavior in rats by supplementing with magnesium their drinking water for 30 days. Anxiety-like behavior was induced by subcutaneous injection of veratrin 30 min before performing elevated plus maze and open field tests to measure anxiety levels and locomotion, respectively. We quantify the concentration of magnesium in plasma and cerebrospinal fluid. We used diazepam to compare the efficacy of magnesium supplementation as an anxiolytic agent. Our results show that rats supplemented with magnesium had a statistically significant decrease in anxiety levels with not effects on locomotion and a statistically significant increase in concentration of magnesium in plasma and cerebrospinal fluid. However, the anxiolytic effect of magnesium supplementation washes-out in 12 days. We discuss the advantages of using supplemental magnesium as anxiolytic.

When All Else Fails: Alternative Methods of Euthanasia.

Barbiturate overdose as a method of euthanasia is becoming unacceptable. This has made alternative methods of euthanasia very important. Gunshot or captive bolt euthanasia is among methods that are acceptable, but they may not be esthetically acceptable. This has led to the use of other methods of euthanasia. Inducing anesthesia prior to euthanasia offers an easier method of control. Adjunctive techniques using intravenous potassium or magnesium salts administered intravenously and intracardiac administration of potassium chloride or intrathecal lidocaine offer alternatives that work well and are more environmentally safer than barbiturates. Pithing and exsanguination are also environmentally safer but may not be as esthetically acceptable as the other methods.

The effects of 0.9% saline versus Plasma-Lyte 148 on renal function as assessed by creatinine concentration in patients undergoing major surgery: A single-centre double-blinded cluster crossover trial.

OBJECTIVES: Saline and Plasma-Lyte have different physiochemical contents; consequently, they may differently affect patients' renal function. We compared the effects of fluid therapy with 0.9% saline and with Plasma-Lyte 148 on renal function as assessed by creatinine concentration among patients undergoing major surgery. METHODS: We conducted a prospective, double-blinded cluster crossover trial comparing the effects of the two fluids on major surgery patients. The primary aim was to establish the pilot feasibility, safety and preliminary efficacy evidence base for a large interventional trial to establish whether saline or Plasma-Lyte is the preferred crystalloid fluid for managing major surgery patients. The primary efficacy outcome was the proportion of patients with changes in renal function as assessed by creatinine concentration during their index hospital admission. We used changes in creatinine to define acute kidney injury (AKI) according to the RIFLE criteria. RESULTS: The study was feasible with 100% patient and clinician acceptance. There were no deviations from the trial protocol. After screening, we allocated 602 patients to saline and 458 to Plasma-Lyte. The median (IQR) volume of intraoperative fluid received was 2000 mL (1000:2000) in both groups. Forty-nine saline patients (8.1%) and 49 Plasma-Lyte patients (10.7%) developed a postoperative AKI (adjusted incidence rate ratio [aIRR]: 1.34; 95% CI: 0.93-1.95; p = 0.120). No differences were observed in the development of postoperative complications (aIRR: 0.98; 95% CI: 0.89-1.08) or the severity of the worst complication (aIRR: 1.00; 95% CI: 0.78-1.30). The median (IQR) length of hospital stay was six days (3:11) for the saline group and five days (3:10) for the Plasma-Lyte group (aIRR: 0.85; 95% CI: 0.73-0.98). There were no serious adverse events relating to the trial fluids, nor were there fluid crossover or contamination events. CONCLUSIONS: The study design was feasible to support a future follow-up larger clinical trial. Patients treated with saline did not demonstrate an increased incidence of postoperative AKI (defined as changes in creatinine) compared to those treated with Plasma-Lyte. Our findings imply that clinicians can reasonably use either solution intraoperatively for adult patients undergoing major surgery. TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; ACTRN12613001042730; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364988.

Effect of 0.9% NaCl compared to plasma-lyte on biomarkers of kidney injury, sodium excretion and tubular transport proteins in patients undergoing primary uncemented hip replacement - a randomized trial.

BACKGROUND: Isotonic saline (IS) is widely used to secure perioperative cardiovascular stability. However, the high amount of chloride in IS can induce hyperchloremic acidosis. Therefore, IS is suspected to increase the risk of acute kidney injury (AKI). Biomarkers may have potential as indicators. METHODS: In a double-blinded, placebo-controlled study, 38 patients undergoing primary uncemented hip replacement were randomized to IS or PlasmaLyte (PL). Infusion was given during surgery as 15 ml/kg the first hour and 5 ml/kg the following two hours. Urinary samples were collected upon admission and the day after surgery. As surgery was initiated, urine was collected over the course of 4 h. Hereafter, another urine collection proceeded until the morning. Urine was analyzed for markers of AKI neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Arterious and venous blood samples for measurements of pH and plasma electrolytes including chloride (p-Cl) were collected as surgery was initiated, at the end of surgery and the following morning. RESULTS: IS induced an increase in p-Cl (111 ± 2 mmol/L after IS and 108 ± 3 after PL, p = 0.004) and a decrease in pH (7.39 ± 0.02 after IS and 7.43 ± 0.03 after PL, p = 0.001). Urinary NGAL excretion increased in both groups (ΔNGAL: 5.5 [4.1; 11.7] µg/mmol creatinine p = 0.004 after IS vs. 5.5 [2.1;9.4] µg/mmol creatinine after PL, p < 0.001). No difference was found between the groups (p = 0.839). Similarly, urinary KIM-1 excretion increased in both groups (ΔKIM-1: IS 115.8 [74.1; 156.2] ng/mmol creatinine, p < 0.001 vs. PL 152.4 [120.1; 307.9] ng/mmol creatinine, p < 0.001). No difference between the groups (p = 0.064). FENa increased (1.08 ± 0.52% after IS and 1.66 ± 1.15% after PL, p = 0.032). ENaC excretion was different within groups (p = 0.019). CONCLUSION: A significantly higher plasma chloride and a lower pH was present in the group receiving isotonic saline. However, u-NGAL and u-KIM-1 increased significantly in both groups after surgery despite absence of changes in creatinine. These results indicate that surgery induced subclinical kidney injury. Also, the IS group had a delayed sodium excretion as compared to the PL group which may indicate that IS affects renal sodium excretion differently from PL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:  NCT02528448 , 19/08/2015.

Circulating Ionized Magnesium as a Measure of Supplement Bioavailability: Results from a Pilot Study for Randomized Clinical Trial.

Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL·24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL·24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg·24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.

EVALUATION OF EUTHANASIA OF MOON JELLYFISH (AURELIA AURITA) USING SIMPLE SALT SOLUTIONS.

Immersion euthanasia methods reported over the most recent decades for aquatic invertebrates use organic alcohols or halogenated hydrocarbons that can interfere with nuclear magnetic resonance (NMR) analysis. A rolling study design evaluated potassium chloride (KCl), magnesium chloride (MgCl2), and magnesium sulfate (MgSO4) as potential ion-based euthanasia methods for moon jellyfish (Aurelia aurita) destined for metabolomic analysis by NMR spectroscopy. Death was defined as the cessation of autonomous bell pulsing and response to external stimulus. MgCl2 applied at a dose of 142 g/L provided euthanasia within 32 sec of applications without the untoward effects observed with the other two salts. Euthanasia with KCl at the doses tested was associated with abnormal behavior and tissue degradation during dissection. MgSO4 at the doses tested resulted in abnormal behavior and failed to provide rapid euthanasia.

Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study.

Magnesium (Mg) is an essential biomineral that acts as an intracellular cofactor for more than 300 enzymes. It is an important modulator of the N-methyl-D-aspartate (NMDA) receptor which is involved in memory function and depression. The purpose of this study was to compare the dose dependent effect of oral supplementation of Magnesium chloride (MgCl2), Magnesium sulphate (MgSO4) and Magnesium-L-threonate (MgT) on memory and depression-related behaviors in rats. Rats were orally administered with different doses (50 mg/kg, 100 mg/kg and 150 mg/kg) of each Mg salt. Following 28 days of oral supplementation, animals were subjected to behavioral tests. After completion of behavioral test, rats were decapitated. Brain and plasma samples were used for neurochemical and biochemical analysis. Assessment of behaviors in elevated plus maze (EPM) test and forced swim test (FST) showed that MgT more significantly improved memory of rats and decreased depression-like symptoms in healthy rats as compared to controls. Biochemical analysis indicated significant increase in plasma Mg levels dose dependently following MgT administration. This increase might be related to observe enhanced cholinergic functions and decline in oxidative stress in rats in the present study. This comparative study highlights that MgT (100mg/kg) is the most appropriate Mg salt and dose for oral treatment that strengthens cholinergic system and improves brain related functions through attenuation of oxidative burden in adult healthy rats.

Physico-chemical stability of Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose with eight common intravenous medications.

BACKGROUND: Plasma-Lyte 148® is a balanced, crystalloid intravenous (IV) fluid which is both calcium-free and isotonic. It prevents the hyperchloremic metabolic acidosis and iatrogenic hyponatremia seen with use of 0.9% sodium chloride and hypotonic solutions, respectively. However, data on compatibility with commonly used drugs are lacking. AIMS: To investigate the stability of Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose with eight commonly used therapeutic agents when compared with 5% glucose and 0.9% sodium chloride as diluents. We aimed to provide vital data which may facilitate the introduction of what appears to be a safer and more economic fluid. METHODS: Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose were mixed with morphine, midazolam, fentanyl, ketamine, clonidine, aminophylline, salbutamol, and furosemide at set concentrations. Comparisons were made to 0.9% sodium chloride and 5% glucose fluid controls. Six repeats of each IV fluid and drug admixture were analyzed through high-performance liquid chromatography at three time points: 0, 2, and 24 hours. A concentration change of <5% was defined as chemically stable. Physical stability was assessed by observation of precipitate formation or color change. pH changes were measured using a Fisherbrand Hydrus 300 pH meter. RESULTS: Relative to starting concentration, all drugs except midazolam were stable to ±3%. All examined therapeutic agents were chemically stable at 2 and 24 hours relative to control solutions. No precipitate formed in any of the samples. All Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose drug admixtures remained in a safe, peripheral administration pH range of 5-9 and were closer to the pH of blood than standard fluid-drug admixtures. CONCLUSION: Morphine, fentanyl, ketamine, salbutamol, aminophylline, and clonidine are stable for 24 hours when mixed with Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose for administration at concentrations equivalent to those found at a typical Y-site with maintenance fluid. Furosemide is stable at lower concentrations than those seen at a Y-site, but midazolam displayed instability.

Magnesium therapy improves outcome in Streptococcus pneumoniae meningitis by altering pneumolysin pore formation.

BACKGROUND AND PURPOSE: Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults and is characterized by high lethality and substantial cognitive disabilities in survivors. Here, we have studied the capacity of an established therapeutic agent, magnesium, to improve survival in pneumococcal meningitis by modulating the neurological effects of the major pneumococcal pathogenic factor, pneumolysin. EXPERIMENTAL APPROACH: We used mixed primary glial and acute brain slice cultures, pneumolysin injection in infant rats, a mouse meningitis model and complementary approaches such as Western blot, a black lipid bilayer conductance assay and live imaging of primary glial cells. KEY RESULTS: Treatment with therapeutic concentrations of magnesium chloride (500 mg·kg-1 in animals and 2 mM in cultures) prevented pneumolysin-induced brain swelling and tissue remodelling both in brain slices and in animal models. In contrast to other divalent ions, which diminish the membrane binding of pneumolysin in non-therapeutic concentrations, magnesium delayed toxin-driven pore formation without affecting its membrane binding or the conductance profile of its pores. Finally, magnesium prolonged the survival and improved clinical condition of mice with pneumococcal meningitis, in the absence of antibiotic treatment. CONCLUSIONS AND IMPLICATIONS: Magnesium is a well-established and safe therapeutic agent that has demonstrated capacity for attenuating pneumolysin-triggered pathogenic effects on the brain. The improved animal survival and clinical condition in the meningitis model identifies magnesium as a promising candidate for adjunctive treatment of pneumococcal meningitis, together with antibiotic therapy.

Effect of 0.9% Saline or Plasma-Lyte 148 as Crystalloid Fluid Therapy in the Intensive Care Unit on Blood Product Use and Postoperative Bleeding After Cardiac Surgery.

OBJECTIVE: To evaluate the effect of Plasma-Lyte 148 (PL-148) compared with 0.9% saline (saline) on blood product use and postoperative bleeding in patients admitted to the intensive care unit (ICU) following cardiac surgery. DESIGN: A post hoc subgroup analysis conducted within a multicenter, double-blind, cluster-randomized, double-crossover study (study 1) and a prospective, single-center nested-cohort study (study 2). SETTING: Tertiary-care hospitals. PARTICIPANTS: Adults admitted to the ICU after cardiac surgery requiring crystalloid fluid therapy as part of the 0.9% saline vs. PL-148 for ICU fluid therapy (SPLIT) trial. INTERVENTIONS: Blinded saline or PL-148 for 4 alternating 7-week blocks. MEASUREMENTS AND MAIN RESULTS: 954 patients were included in study 1; 475 patients received PL-148, and 479 received saline. 128 of 475 patients (26.9%) in the PL-148 group received blood or a blood product compared with 94 of 479 patients (19.6%) in the saline group (OR [95% confidence interval], 1.51 [1.11-2.05]; p = 0.008). In study 2, 131 patients were allocated to PL-148 and 120 patients were allocated to saline. There were no differences between groups in chest drain output from the time of arrival in the ICU until 12 hours postoperatively (geometric mean, 566 mL for the PL-148 group v 547 mL in the saline group; p = 0.60). CONCLUSIONS: The findings did not support the hypothesis that using PL-148 for fluid therapy in ICU following cardiac surgery reduces transfusion requirements compared to saline. The significantly increased proportion of patients receiving blood or blood product with allocation to PL-148 compared to saline was unexpected and requires verification through further research.

Study protocol for the Balanced Solution versus Saline in Intensive Care Study (BaSICS): a factorial randomised trial.

BACKGROUND: The effectiveness and safety of balanced crystalloid fluids compared with saline (0.9% sodium chloride) as a fluid of choice in critically ill patients remain unclear. The effects of different fluid infusion rates on outcomes are also unknown. OBJECTIVES: To test the hypothesis that a balanced crystalloid solution, compared with saline, decreases 90-day all-cause mortality among critically ill patients; and to test the hypothesis that slow, compared with rapid, infusion rate decreases 90-day mortality in this population of patients. METHODS: The Balanced Solution versus Saline in Intensive Care Study (BaSICS) is a pragmatic, 2 ??2 factorial, randomised controlled trial. A total of 11 000 patients will be recruited from at least 100 Brazilian intensive care units. Patients will be randomised to receive Plasma-Lyte 148 or saline, and to rapid infusion (999 mL/h) or slow infusion (333 mL/h). Study fluids will be used for resuscitation episodes (at rapid or slow infusion rates), dilution of compatible medications and maintenance solutions. Patients, health care providers and investigators will be blinded to the solutions being tested. The rate of bolus infusion will not be blinded. OUTCOMES: The primary outcome is 90-day all-cause mortality. Secondary outcomes are: incidence of renal failure requiring renal replacement therapy within 90 days, incidence of acute kidney injury (Kidney Disease: Improving Global Outcomes stages 2 and 3), incidence of non-renal organ dysfunction assessed by Sepsis-related Organ Failure Assessment score at Days 3 and 7, and number of mechanical ventilationfree days within the first 28 days after randomisation. RESULTS AND CONCLUSIONS: The BaSICS trial will provide robust evidence on whether a balanced crystalloid, compared with saline, improves important patient outcomes in critically ill patients. BaSICS will also provide relevant information on whether bolus infusion rate affects outcomes in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02875873.

Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.

BACKGROUND: Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel. METHODS: Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. RESULTS: DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. CONCLUSIONS: These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. SIGNIFICANCE: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.

A randomized-controlled trial of high- or low-volume intravenous Plasma-Lyte(®) to prevent hypotension during sedation for colonoscopy.

PURPOSE: The purpose of this study was to compare the incidence of hypotension during sedation in adults presenting for elective colonoscopy and randomized to intravenous Plasma-Lyte 148(®) at either 2 mL·kg(-1) (low volume) or 20 mL·kg(-1) (high volume). METHODS: Patients aged ≥ 18 yr presenting for elective colonoscopy, with or without gastroscopy, after oral bowel preparation were randomized to receive the intervention immediately before the start of the procedure. Hypotension was defined as a ≥ 25% decrease in systolic blood pressure (SBP) from baseline during the procedure. Secondary outcomes included SBP < 90 mmHg, lowest SBP during sedation, duration of hypotension, use of vasopressors, postoperative outcomes, and cost. RESULTS: Seventy-five patients were randomly allocated to either the low-volume or high-volume group, respectively (total n = 150). The incidence of hypotension was similar in the two groups (59% vs 56%, respectively; odds ratio, 0.90; 95% confidence interval, 0.47 to 1.71; P = 0.74). The incidence of SBP < 90 mmHg, the lowest SBP during sedation, the duration of hypotension, the use of vasopressors, and postoperative outcomes were also similar in the two groups. CONCLUSIONS: This study does not support the routine use of 20 mL·kg(-1) of intravenous Plasma-Lyte 148 to prevent hypotension and other complications during sedation for elective colonoscopy in adult patients. Clinical Trials Registry (ANZCTR 12615001288516).

The Evaluation of Magnesium Chloride within a Polyethylene Glycol Formulation in a Porcine Model of Acute Spinal Cord Injury.

A porcine model of spinal cord injury (SCI) was used to evaluate the neuroprotective effects of magnesium chloride (MgCl2) within a polyethylene glycol (PEG) formulation, called "AC105" (Acorda Therapeutics Inc., Ardsley, NY). Specifically, we tested the hypothesis that AC105 would lead to greater tissue sparing at the injury site and improved behavioral outcome when delivered in a clinically realistic time window post-injury. Four hours after contusion/compression injury, Yucatan minipigs were randomized to receive a 30-min intravenous infusion of AC105, magnesium sulfate (MgSO4), or saline. Animals received 4 additional infusions of the same dose at 6-h intervals. Behavioral recovery was tested for 12 weeks using two-dimensional (2D) kinematics during weight-supported treadmill walking and the Porcine Injury Behavior Scale (PTIBS), a 10-point locomotion scale. Spinal cords were evaluated ex vivo by diffusion-weighted magnetic resonance imaging (MRI) and subjected to histological analysis. Treatment with AC105 or MgSO4 did not result in improvements in locomotor recovery on the PTIBS or in 2D kinematics on weight-supported treadmill walking. Diffusion weighted imaging (DWI) showed severe loss of tissue integrity at the impact site, with decreased fractional anisotropy and increased mean diffusivity; this was not improved with AC105 or MgSO4 treatment. Histological analysis revealed no significant increase in gray or white matter sparing with AC105 or MgSO4 treatment. Finally, AC105 did not result in higher Mg2+ levels in CSF than with the use of standard MgSO4. In summary, when testing AC105 in a porcine model of SCI, we were unable to reproduce the promising therapeutic benefits observed previously in less-severe rodent models of SCI.

The effect of an acute and 7-day administration of magnesium chloride on magnesium concentration in the serum, erythrocytes, and brain of rats.

BACKGROUND: Magnesium (Mg) is one of the most essential cations in human body that is involved in a variety of physiological processes. Despite the variations in the extracellular Mg level, specific transport systems are involved in maintaining the intracellular free Mg at a relatively constant level. We aimed to investigate the changes of Mg level in the brain, erythrocytes, and serum of rats after an acute and subchronic administration of Mg. METHODS: Magnesium chloride (MgCl2) solution was administered intraperitoneally (ip) either once at a dose of 50mg/kg or for 7 days at a single daily dose of 50mg/kg. Blood and brains of animals were collected 15, 30, 60, 120, and 240min after the acute or the last injection. Total Mg concentration in blood serum, erythrocytes, and the whole brain was determined spectrophotometrically. RESULTS: The highest Mg concentration was detected in the brain tissue, while the most significant changes in Mg level were found in serum. CONCLUSIONS: Neither the brain nor the erythrocyte showed a change in the Mg level considerably after an increase in serum Mg level induced by the acute and subchronic administration of MgCl2 solution.

Sodium reduction during cardiopulmonary bypass: Plasma-Lyte 148 versus trial fluid as pump primes.

OBJECTIVES: We compared effects on plasma sodium concentrations plus calculated plasma tonicity of two "balanced" crystalloid solutions used as 2 L pump primes during cardiopulmonary bypass (CPB): Plasma-Lyte 148 (sodium concentration, 140 mmol/L; potassium concentration, 5 mmol/L) versus a bicarbonate-balanced fluid (sodium concentration, 140 mmol/L; potassium concentration, 0 mmol/L). DESIGN, SETTING AND PARTICIPANTS: We analysed pooled data from two prospective interventional studies performed in university-affiliated hospitals, from 50 patients undergoing elective cardiac surgery. INTERVENTIONS: Participants were allocated equally to Plasma-Lyte 148 or bicarbonate-balanced fluid, with plasma electrolytes measured by direct ion selective electrodes immediately before bypass (pre-CPB), within 3 minutes of commencement (T2), and before bypass cessation (end-CPB). RESULTS: Plasma sodium fell at T2 in 46 patients (92%) (P<0.0005). With Plasma-Lyte 148, the mean sodium decreased by 3.0 mmol/L (SD, 1.7 mmol/L), and with bicarbonate-balanced fluid it decreased by 2.2 mmol/L (SD, 1.1 mmol/L) (P=0.002). The mean tonicity fell by >5 mOsm/kg for both groups (P<0.0005). At end-CPB, the mean sodium for both groups remained reduced by >2 mmol/L (P<0.0005). In the group receiving Plasma-Lyte 148, 52% of patients were hyponatraemic (sodium<135 mmol/L) at T2 and end-CPB. CONCLUSIONS: Sodium reductions were common with both priming solutions, but more severe with Plasma-Lyte 148. Crystalloid priming solutions require sodium concentrations>140mmol/L to ensure normonatraemia throughout CPB.

Effects of transdermal magnesium chloride on quality of life for patients with fibromyalgia: a feasibility study.

BACKGROUND: Fibromyalgia is a syndrome characterized by chronic pain, fatigue, depression, and sleep disturbances. Its primary cause is unclear. Several studies have reported decreased intracellular magnesium levels in patients with fibromyalgia and have found negative correlation between magnesium levels and fibromyalgia symptoms. OBJECTIVE: To gather preliminary data on whether transdermal magnesium can improve quality of life for women who have fibromyalgia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a patient questionnaires and survey in a fibromyalgia clinic at a tertiary medical center. Forty female patients with the diagnosis of fibromyalgia were enrolled. Each participant was provided a spray bottle containing a transdermal magnesium chloride solution and asked to apply 4 sprays per limb twice daily for 4 weeks. Participants were asked to complete the Revised Fibromyalgia Impact Questionnaire, SF-36v2 Health Survey, and a quality-of-life analog scale at baseline, week 2, and week 4. MAIN OUTCOME MEASURE: Questionnaire and survey scores, evaluated through intent-to-treat and per-protocol analyses. RESULTS: Twenty-four patients completed the study (mean [SD] age, 57.2 [7.6] years; white, 95%; mean body mass index, 31.3 kg/m2). With intention-to-treat analysis, Revised Fibromyalgia Impact Questionnaire subscale and total scores were significantly improved at week 2 and week 4 (total score, P=0.001). Per-protocol analysis results were similar: all subscales of the Revised Fibromyalgia Impact Questionnaire were significantly improved at week 2 and week 4 (total score, P=0.001). CONCLUSION: This pilot study suggests that transdermal magnesium chloride applied on upper and lower limbs may be beneficial to patients with fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov.ldentifier NCT01968772.

Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: A double-blind placebo-controlled randomized trial.

AIM: This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia. METHODS: A total of 116 men and non-pregnant women, aged 30 to 65 years with hypomagnesaemia and newly diagnosed with prediabetes, were enrolled into a randomized double-blind placebo-controlled trial to receive either 30 mL of MgCl2 5% solution (equivalent to 382 mg of magnesium) or an inert placebo solution once daily for four months. The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels. RESULTS: At baseline, there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups. At the end of follow-up, fasting (86.9 ± 7.9 and 98.3 ± 4.6 mg/dL, respectively; P = 0.004) and post-load glucose (124.7 ± 33.4 and 136.7 ± 23.9 mg/dL, respectively; P = 0.03) levels, HOMA-IR indices (2.85 ± 1.0 and 4.1 ± 2.7, respectively; P = 0.04) and triglycerides (166.4 ± 90.6 and 227.0 ± 89.7, respectively; P = 0.009) were significantly decreased, whereas HDL cholesterol (45.6 ± 10.9 and 46.8 ± 9.2 mg/dL, respectively; P = 0.04) and serum magnesium (1.96 ± 0.27 and 1.60 ± 0.26 mg/dL, respectively; P = 0.005) levels were significantly increased in those taking MgCl2 compared with the controls. A total of 34 (29.4%) people improved their glucose status (50.8% and 7.0% in the magnesium and placebo groups, respectively; P < 0.0005). CONCLUSION: Our results show that magnesium supplementation reduces plasma glucose levels, and improves the glycaemic status of adults with prediabetes and hypomagnesaemia.