Characterizing the impact of magnesium and potassium-supplemented hydration with cisplatin and the subsequent electrolyte replacement requirements.

BACKGROUND: Cisplatin-associated electrolyte dysregulation is a prevalent therapy-related adverse effect. There are numerous electrolyte-supplemented hydration regimens that have been evaluated, however these studies focused on the development of nephrotoxicity. The objective of this study was to characterize the impact of magnesium and potassium-supplemented hydration during cisplatin administration on subsequent magnesium and potassium imbalances. METHODS: A single-region retrospective study from central Texas at Baylor Scott & White Cancer Clinics who were treated with two or more cycles of cisplatin were included. Standard hydration for this study was defined as normal saline before and after cisplatin along with potassium chloride 10 mEq and magnesium sulfate 1 g added to the cisplatin bag. RESULTS: A total of 477 patients were included in the study with376 patients receiving the standard hydration. Overall, 17 percent of patients experienced a potassium level below 3.5 mEq/L, but no major depletion was observed. Thirty-three percent of the patients experienced a magnesium level below 1.8 mg/dL, and time to first rescue magnesium supplementation was 4 weeks. CONCLUSION: Our study demonstrated despite routine magnesium and potassium supplementation in hydration, magnesium imbalances were observed. Potassium levels post cisplatin administration were maintained with minimal routine supplementation in hydration.

[MODERN APPROACHES TO CORRECTION OF HYPERNATREMIA IN NEUROSURGICAL PATIENTS].

The article presents the analysis of the intensive therapy through the correction of persistent hypernatremia in neurosurgical patients after removal of brain tumors. The aim of this work was to evaluate the effectiveness of Sterofundin in the framework of complex therapy of hypernatremia in neurosurgical patients after removal of brain tumors. We analyzed the dynamics of the concentrations of sodium, potassium, chorus of the plasma, anion gap and buffer bases in the postoperative period of these patients. For obtaining reliable results, the patients were divided into groups according to the nature of the treatment: Sterofundin and symptomatic correction of hypotonic solution of sodium chloride, saluretic and Verospiron respectively. In a comparison between the groups, a distinct difference in the speed of regression of hypernatremia and durability of the achieved effect was observed. In case of treatment with Sterofundin there was a significant decrease of hypernatremia by the end of the second day of the postoperative period without tendency to re-raise. The prevalence of hypotonic solutions of sodium chloride and potassium-sparing saluretics in intensive care allowed reducing the sodium concentration non-persistently to the fourth day on the background of significant fluctuations in its concentration. The use of Sterofundin in complex therapy of electrolyte disturbances, particularly of hypernatremia in neurosurgical patients after removal of brain tumors, is reflected in the form of significant regression of increased sodium concentration in plasma compared with the method of use "hypotonic" hemodilution, saluretics and potassium-sparing diuretics.

The Role of Magnesium in Post-thyroidectomy Hypocalcemia.

BACKGROUND: The purpose of this study was to determine the prevalence of hypomagnesemia in patients undergoing thyroidectomy and evaluate the relationship of hypomagnesemia with transient and severe hypocalcemia. MATERIALS AND METHODS: This was a prospective observational study of 50 patients undergoing thyroidectomy. Blood samples were collected pre- and postoperatively for calcium, albumin, magnesium, phosphorous and parathormone (PTH). Signs, symptoms of hypocalcemia and volume of intravenous fluids used perioperatively were documented. The statistical analysis was performed using STATA I/C 10.1. RESULTS: Preoperatively, twelve patients (24 %) had hypomagnesemia and one (2 %) hypocalcemia. On the first postoperative day, hypomagnesemia was seen in 70 % and hypocalcemia in 30 %. A similar trend was observed in the fall and rise of postoperative calcium and magnesium values (p = 0.41). Severe hypocalcemia was present in three patients (6 %). All three patients had a very low postoperative PTH (<2 pg/ml). Among them, two patients (66 %) had hypomagnesemia and their hypocalcemia responded to intravenous magnesium correction. Significant risk factors for postoperative hypocalcemia include a higher volume of fluid used perioperatively and low postoperative PTH (<8 pg/ml) (p = 0.01 and 0.03, respectively). CONCLUSION: Preoperative hypomagnesemia (24 %) was prevalent in this cohort of patients. Postoperative hypomagnesemia is a common event (70 %) following total thyroidectomy, and magnesium levels tend to mimic the calcium levels postoperatively. The cause of hypocalcemia post-thyroidectomy in this study is mainly a factor of parathyroid function and fluid status. Severe hypocalcemia is a rare event, and hypomagnesemia is associated in the majority of these patients. The role of magnesium correction to alleviate severe hypocalcemia needs to be further studied.

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

Over the past decades, hypomagnesemia (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic ß-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic ß-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.

Efficacy and safety of intravenous colistin in preterm infants with nosocomial sepsis caused by Acinetobacter baumannii.

OBJECTIVES: To describe the efficacy of intravenous colistin on clinical and microbiological outcomes in preterm infants with nosocomial sepsis in neonatal intensive care unit (NICU) and define adverse events observed with this treatment. METHODS: The records of preterm infants who received colistin with or without positive cultures in the NICU were retrospectively reviewed. Patients were evaluated for response to therapy and side effects. RESULTS: A total of 21 preterm infants with medians of 28 weeks (23-36) gestational age and 870 g (620-2,650) birth weight were included. The median duration and dose of colistin therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients including all with/without positive culture was 81% (17/21). Microbiological clearance by colistin was 69% (9/13). The major side effect observed was acute kidney injury (19%). At least 24% of infants required electrolyte supplementation during the colistin therapy. Magnesium levels were significantly lower at the end of the colistin therapy (p < 0.001). Acute kidney injury and electrolyte disturbances including hypomagnesemia were reversible in all surviving patients. CONCLUSION: We suggest that renal function tests and serum electrolytes should be monitored closely and replaced in case of any need during the colistin therapy in preterm infants.

[The role of disbalance of zinc and copper in school age children with community-aquired pheumonia].

The article analyzed 60 patients with community-aquired pneumonia from ages 6 to 18 years. The dependences of trace levels of zinc and copper in the serum of these children on the activity of the inflammatory process. Analysis of survey results showed that in children with community-aquired pneumonia was observed imbalance of trace elements Zn, Cu. Severity of such violations depended mainly on severity disease and to a lesser extent on age. Normalization of detected metabolic microelement content in a period of convalescence practically advancing. In children at acute stage of community-aquired pneumonia inflammation was observed with pronounced zinc deficiency (P < 0,001), and its content in blood serum is directly dependent on the acuity and severity of inflammation. Use of the drug, which contains zinc as part of adjuvant therapy in community-aquired pneumonia in children led to more rapid normalization of serum microelement parameters, apparently due to modulating effects on microelement status and immune status. To increase the effectiveness of treatment of community-aquired pneumonia in school-age children, its recommended to use zinc containing drug.

Effect of a selective neutrophil elastase inhibitor on early recovery from body water imbalance after transthoracic esophagectomy.

The objective of the study was to evaluate the efficacy of sivelestat, a selective neutrophil elastase inhibitor, on body fluid balance after transthoracic esophagectomy. Esophagectomy with elective lymphadenectomy may induce excessive release of neutrophil elastase, which then promotes vascular permeability and an excessive water shift from the intravascular space to the peripheral compartment. Body fluid imbalance after esophagectomy often leads to circular instability, a decrease of urine output, and a delay in the shift to a diuretic state. The study was designed as a case-control study with a historical control group. A retrospective analysis was performed to examine our hypothesis that sivelestat improves abnormal body fluid retention and prevents subsequent pulmonary complications. To reveal the direct influence of sivelestat on the postoperative course, we avoided using steroids or other diuretic agents. Eighty-eight patients who underwent thoracic esophagectomy with extended lymphadenectomy from 2000 to 2008 were divided into two groups: those treated from 2003 to 2008, who all received postoperative administration of sivelestat (n=60); and those treated from 2000 to 2002, who did not receive sivelestat and were used as the control group (n=28). Both groups received fluid management using the same protocol. The time to reach a diuretic state, time until extubation of the tracheal tube, and development of delayed respiratory dysfunction were compared between the groups using univariate and multivariate analysis. The time until a shift to a diuretic state was significantly shorter after treatment with sivelestat (p<0.0001) and with a shorter operation time (p<0.0001). The tracheal tube was extubated significantly earlier in the sivelestat group (p<0.0001) and the incidence of delayed respiratory dysfunction was also significantly lower (p=0.0028) in this group. Multivariate logistic regression analysis showed that a delay in a shift to a diuretic state was a strong independent risk factor for the time to tracheal extubation (odds ratio 2.539, p=0.0056) and occurrence of delayed respiratory dysfunction (odds ratio 1.989, p=0.0104). Sivelestat treatment was not independently associated with reduced pulmonary complications, but the diuretic state was strongly regulated by sivelestat treatment (odds ratio 0.044, p=0.0003). Thus, administration of sivelestat has a beneficial influence on recovery from body water imbalance through a more rapid return to a diuretic state after esophagectomy, which contributes to prevention of subsequent pulmonary complications.

Water in health and disease: new aspects of disturbances in water metabolism.

Vasopressin is a critical regulator of water homeostasis. There are two major receptors for vasopressin: V1 and V2 receptors. Disturbances in water balance are commonly encountered in clinical practice and can be divided into disorders of urinary dilution and concentration. The major representatives of such disorders are diabetes insipidus and the syndrome of inappropriate secretion of antidiuretic hormone (SI ADH). Recent studies show that genetic forms of nephrogenic diabetes insipidus are due to mutations in the genes coding for the vasopressin V2 receptor (V2R) or aquaporin-2 (AQP2). Identification of the genes involved and analysis of the cellular fate of the V2R and AQP2 mutants are relevant for understanding the functioning of the V2R and AQP2 protein. These developments also have implications for future therapeutic options. The development of nonpeptide vasopressin receptor antagonists (VRAs) offers prospects for the treatment of euvolaemic (SI ADH) or hypervolaemic hyponatraemia (congestive heart failure or cirrhosis). Several nonpeptide VRAs are now in various stages of clinical trials. At present, only conivaptan is registered by the FD A for intravenous treatment of euvolaemic and hypervolaemic hyponatremia. A recent long-term study comparing tolvaptan with placebo in patients with chronic heart failure showed no reduction in risk of death and hospitalisation.

Cisplatin-induced hypomagnesemia and cardiac dysrhythmia.

We describe a case of a patient with cisplatin-induced hypomagnesemia who suffered brief asystole during an episode of gastroenteritis. Structural heart disease was excluded. The patient achieved complete clinical recovery after short-term administration of intravenous magnesium supplementation. Cisplatin should be considered a cause of hypomagnesemic-related cardiac dysrhythmia. Magnesium deficit may increase myocardial electrical instability and thus, the risk of life-threatening arrhythmias and sudden death. Long-term serum electrolyte measurement and appropriate replacement of magnesium are recommended.

Diagnosis and management of electrolyte emergencies.

Electrolyte and fluid imbalances are disorders frequently observed in critical care patients. In many instances patients are asymptomatic, but they may also present with neurological alterations, severe muscle weakness, nausea and vomiting or cardiovascular emergencies. Therefore, a pathophysiological understanding of these disorders is necessary for initiating an appropriate therapy. After a precise history-including drug prescriptions-has been obtained from the patient or his/her relatives, determination of the hydration status of the patient and measurement of acid-base status, plasma and urine osmolality and electrolytes are the first steps in the assessment of the disease. Once a diagnosis has been established, great attention has to be paid to the rate at which the disorder is corrected because this-if inappropriate-may cause more severe damage to the patient than the disease itself. This chapter addresses the initial diagnostic and therapeutic steps of the most common electrolyte emergencies.

Aminophylline in the treatment of fluid overload.

OBJECTIVE: Aminophylline has not been studied as an adjunct diuretic in critically ill children. Our purpose was to evaluate its use in the treatment of fluid overload in these patients. DESIGN: Open, controlled clinical trial. SETTING: Pediatric intensive care unit. PATIENTS: Study subjects ranged from 2-46 months of age, were fluid overloaded, and were receiving a continuous infusion of furosemide (> or =6 mg/kg/day). Patients with hemodynamic instability or liver dysfunction were excluded. INTERVENTIONS: A single dose of aminophylline (6 mg/kg) was given after establishing baseline values. There were no additional diuretics or changes in vasoactive agents during the study. MEASUREMENTS AND MAIN RESULTS: Urine output, creatinine clearance, and sodium and potassium excretion were measured before and after administration of the aminophylline bolus. Heart rate and mean arterial pressure (mm Hg) were recorded hourly. Urine output increased by >80% (p < .01) during the first 2 hrs after administration of the aminophylline bolus and then returned to baseline by 4 to 6 hrs. The change in urine output is consistent with the pharmacokinetics of aminophylline. Heart rate and mean arterial pressure exhibited a change of <10% from baseline. CONCLUSIONS: These results suggest that aminophylline is an effective adjunct to furosemide in increasing diuresis in critically ill children with fluid overload. The increased diuresis can be accomplished without increased risk if drug levels are adequately monitored.

Magnesium supplementation alleviates premenstrual symptoms of fluid retention.

We investigated the effect of a daily supplement of 200 mg of magnesium (as MgO) for two menstrual cycles on the severity of premenstrual symptoms in a randomized, double-blind, placebo-controlled, crossover study. A daily supplement of 200 mg of Mg (as MgO) or placebo was administered for two menstrual cycles to each volunteer, who kept a daily record of her symptoms, using a 4-point scale in a menstrual diary of 22 items. Symptoms were grouped into six categories: PMS-A (anxiety), PMS-C (craving), PMS-D (depression), PMS-H (hydration), PMS-O (other), and PMS-T (total overall symptoms). Urinary Mg output/24 hours was estimated from spot samples using the Mg/creatinine ratio. Analysis of variance for 38 women showed no effect of Mg supplementation compared with placebo in any category in the first month of supplementation. In the second month there was a greater reduction (p = 0.009) of symptoms of PMS-H (weight gain, swelling of extremities, breast tenderness, abdominal bloating) with Mg supplementation compared with placebo. Compliance to supplementation was confirmed by the greater mean estimated 24-hour urinary output of Mg (p = 0.013) during Mg supplementation (100.8 mg) compared with placebo (74.1 mg). A daily supplement of 200 mg of Mg (as MgO) reduced mild premenstrual symptoms of fluid retention in the second cycle of administration.

[Use of antihypoxants and antioxidants for pharmaco-correction of disorders of water metabolism in the liver and small intestine after vagotomy]. / Primenenie antigipoksantov i antioksidantov dlia farmakokorrektsii narushenii metabolizma vody v pecheni i tonkoi kishke posle vagotomii.

Bilateral subdiaphragmatic vagotomy in rats leads to hepatic and small intestinal water metabolic disorders appeared as higher levels of total water, longer spin-grid (T1) and spin-spin (T2) relaxation and impaired correlation between T1 and T2. The time course of changes in water metabolism in the liver is one-sided (maximum after 7 days) at the same time in the small intestine is two-sided (maximum after 7 and 30 days). The antihypoxant tomerzole and the antioxidant dibunol produce a partial normalizing effect on water metabolism in the studied viscera of the animals vagotomized (at day 30), the highest efficiency was demonstrated by dibunol whose pharmacological activity is the greatest in the small intestine.

Renal excretion of water in men under hypokinesia and physical exercise with fluid and salt supplementation.

It has been suggested that under hypokinesia (reduced number of steps/day) and intensive physical exercise, the intensification of fluid excretion in men is apparently caused as a result of the inability of the body to retain optimum amounts of water. Thus, to evaluate this hypothesis, studies were performed with the use of fluid and sodium chloride (NaCl) supplements on 12 highly trained physically healthy male volunteers aged 19-24 years under 364 days of hypokinesis (HK) and a set of intensive physical exercises (PE). They were divided into two groups with 6 volunteers per group. The first group of subjects were submitted to HK and took daily fluid and salt supplements in very small doses and the second group of volunteers were subjected to intensive PE and fluid-salt supplements. For the simulation of the hypokinetic effect, both groups of subjects were kept under an average of 4000 steps/day. During the prehypokinetic period of 60 days and under the hypokinetic period of 364 days water consumed and eliminated in urine by the men, water content in blood, plasma volume, rate of glomerular filtration, renal blood flow, osmotic concentration of urine and blood were measured. Under HK, the rate of renal excretion of water increased considerably in both groups. The additional fluid and salt intake failed to normalize water balance adequately under HK and PE. It was concluded that negative water balance evidently resulted not from shortage of water in the diet but from the inability of the body to retain optimum amounts of fluid under HK and a set of intensive PEs.

Iatrogenic hypocalcemic tetany.

The treatment of a patient with hypocalcemic tetany secondary to sodium phosphate enemas is reported. The patient presented with a serum calcium level of 5.2 mg/dL and a phosphate level of 17.5 mg/dL. Physical manifestations included tetanic contraction of the muscles of the legs and arms. There was rapid symptomatic resolution with IV calcium. The electrolyte imbalance normalized over the next two days with oral calcium supplementation.

Short-term, high-dose muzolimine treatment in patients with chronic renal failure and acute fluid retention.

Muzolimine, the new sulphonamide-free loop-diuretic with both high ceiling and long-lasting activities, was tested in 21 adult patients with chronic renal failure (CRF) (creatinine clearance ranging from 30 to 5 ml/min) and acute fluid overload. Low-protein diet and individual drug therapy were unchanged throughout the study. All patients received a single oral dose of 240 mg of muzolimine for 4 or 6 consecutive days depending on individual response. Clinical status, diuresis, body weight, blood and urine chemistry were recorded daily. In 19 out of 21 patients muzolimine treatment induced reversal of edema and congestive heart failure and a satisfactory fluid balance was achieved. Only two patients did not respond to diuretic treatment and required dialysis to control fluid balance and azotemia. In responsive patients diuresis increased by 50-100% and no rebound antidiuresis was observed after drug withdrawal. Body weight decreased meanly by 9%. No significant change occurred in serum concentration of K throughout the study, even in the 11 patients on digoxin. Except for a slight decrease of serum Cl by the end of treatment, no significant change in serum electrolytes was recorded. No effect was observed on blood glucose, urea and creatinine clearance whereas a slight increase of serum uric acid was recorded. Urinary lysozyme and gamma-GT were similar before and after the trial. Apart from a single case of muscle cramps, no significant side-effects were recorded. In conclusion, the present results indicate that short-term, high-dose oral muzolimine treatment is effective and safe in most patients with advanced CRF and acute fluid retention.