Efficacy of oral sodium chloride in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy: A randomized controlled trial (SCHO Trial).

INTRODUCTION: Hyponatremia is a well-documented adverse effect of oxcarbazepine treatment, but no clinical trial has yet been conducted to explore any intervention for reducing the incidence of hyponatremia. MATERIALS AND METHODS: This open-label trial evaluated the efficacy of add-on daily oral sodium chloride supplementation of 1-2 g/day for 12 weeks in reducing the incidence of hyponatremia in children receiving oxcarbazepine monotherapy aged 1-18 years. Apart from comparing the incidence of symptomatic and severe hyponatremia, serum and urine sodium levels, serum and urine osmolality, changes in behavior and cognition, and the number of participants with recurrence of seizures and requiring additional antiseizure medication (ASM) were also compared. RESULTS: A total of 120 children (60 in each group) were enrolled. The serum sodium level at 12 weeks in the intervention group was higher than that of the control group (136.5 ± 2.6 vs 135.4 ± 2.5 mEq/L, p = 0.01). The number of patients with hyponatremia was significantly lower in the intervention group (4/60vs14/60, p = 0.01). However, the incidence of symptomatic and severe hyponatremia (0/60vs1/60, p = 0.67 for both), changes in social quotient and child behavior checklist total score (0.6 ± 0.8 vs 0.7 ± 0.5, p = 0.41 and 0.9 ± 1.2 vs 1.1 ± 0.9, p = 0.30 respectively), the number of patients with breakthrough seizures (9/60vs10/60, p = 0.89), and the number of patients requiring additional ASMs (8/60vs10/60, p = 0.79) were comparable in both groups. CONCLUSIONS: Daily oral sodium chloride supplementation is safe and efficacious in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy. However, sodium chloride supplementation does not significantly reduce more clinically meaningful outcome measures like symptomatic and severe hyponatremia. Trial registry No. CTRI/2021/12/038388.

A balancing act: drifting away from the reflexive use of "ab"normal saline.

Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient.

Choosing fluids to reduce the risks of acute electrolyte disturbances in children after a kidney transplant.

Intravenous (i.v.) fluid therapy is critically important in pediatric kidney transplantation. Because of the high volumes given perioperatively, transplant recipients can develop significant electrolyte abnormalities depending on the types of fluids used. Current practices in pediatric transplantation aim to balance risks of hyponatremia from traditionally used hypotonic fluids, such as 0.45% sodium chloride, against hyperchloremia and acidosis associated with isotonic 0.9% sodium chloride. Using the balanced solution Plasma-Lyte 148 as an alternative might mitigate these risks.

Prevention and Correction of Dysnatremia After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Dysnatremia occurs commonly in patients with aneurysmal subarachnoid hemorrhage (aSAH). The mechanisms for development of sodium dyshomeostasis are complex, including the cerebral salt-wasting syndrome, the syndrome of inappropriate secretion of antidiuretic hormone, diabetes insipidus. Iatrogenic occurrence of altered sodium levels plays a role, as sodium homeostasis is tightly linked to fluid and volume management. METHODS: Narrative review of the literature. RESULTS: Many studies have aimed to identify factors predictive of the development of dysnatremia, but data on associations between dysnatremia and demographic and clinical variables are variable. Furthermore, although a clear relationship between serum sodium serum concentrations and outcomes has not been established-poor outcomes have been associated with both hyponatremia and hypernatremia in the immediate period following aSAH and set the basis for seeking interventions to correct dysnatremia. While sodium supplementation and mineralocorticoids are frequently administered to prevent or counter natriuresis and hyponatremia, evidence to date is insufficient to gauge the effect of such treatment on outcomes. CONCLUSIONS: In this article, we reviewed available data and provide a practical interpretation of these data as a complement to the newly issued guidelines for management of aSAH. Gaps in knowledge and future directions are discussed.

Effect of an Albumin Infusion Treatment Protocol on Delayed Cerebral Ischemia and Relevant Outcomes in Patients with Subarachnoid Hemorrhage.

BACKGROUND: An institutional management protocol for patients with subarachnoid hemorrhage (SAH) based on initial cardiac assessment, permissiveness of negative fluid balances, and use of a continuous albumin infusion as the main fluid therapy for the first 5 days of the intensive care unit (ICU) stay was implemented at our hospital in 2014. It aimed at achieving and maintaining euvolemia and hemodynamic stability to prevent ischemic events and complications in the ICU by reducing periods of hypovolemia or hemodynamic instability. This study aimed at assessing the effect of the implemented management protocol on the incidence of delayed cerebral ischemia (DCI), mortality, and other relevant outcomes in patients with SAH during ICU stay. METHODS: We conducted a quasi-experimental study with historical controls based on electronic medical records of adults with SAH admitted to the ICU at a tertiary care university hospital in Cali, Colombia. The patients treated between 2011 and 2014 were the control group, and those treated between 2014 and 2018 were the intervention group. We collected baseline clinical characteristics, cointerventions, occurrence of DCI, vital status after 6 months, neurological status after 6 months, hydroelectrolytic imbalances, and other SAH complication. Multivariable and sensitivity analyses that controlled for confounding and considered the presence of competing risks were used to adequately estimate the effects of the management protocol. The study was approved by our institutional ethics review board before study start. RESULTS: One hundred eighty-nine patients were included for analysis. The management protocol was associated with a reduced incidence of DCI (hazard ratio 0.52 [95% confidence interval 0.33-0.83] from multivariable subdistribution hazards model) and hyponatremia (relative risk 0.55 [95% confidence interval 0.37-0.80]). The management protocol was not associated with higher hospital or long-term mortality, nor with a higher occurrence of other unfavorable outcomes (pulmonary edema, rebleeding, hydrocephalus, hypernatremia, pneumonia). The intervention group also had lower daily and cumulative administered fluids compared with historic controls (p < 0.0001). CONCLUSIONS: A management protocol based on hemodynamically oriented fluid therapy in combination with a continuous albumin infusion as the main fluid during the first 5 days of the ICU stay appears beneficial for patients with SAH because it was associated with reduced incidence of DCI and hyponatremia. Proposed mechanisms include improved hemodynamic stability that allows euvolemia and reduces the risk of ischemia, among others.

Pediatric perioperative fluid management.

The purpose of perioperative fluid management in children is to maintain adequate volume status, electrolyte level, and endocrine system homeostasis during the perioperative period. Although hypotonic solutions containing glucose have traditionally been used as pediatric maintenance fluids, recent studies have shown that isotonic balanced crystalloid solutions lower the risk of hyponatremia and metabolic acidosis perioperatively. Isotonic balanced solutions have been found to exhibit safer and more physiologically appropriate characteristics for perioperative fluid maintenance and replacement. Additionally, adding 1-2.5% glucose to the maintenance fluid can help prevent children from developing hypoglycemia as well as lipid mobilization, ketosis, and hyperglycemia. The fasting time should be as short as possible without compromising safety; recent guidelines have recommended that the duration of clear fluid fasting be reduced to 1 h. The ongoing loss of fluid and blood as well as the free water retention induced by antidiuretic hormone secretion are unique characteristics of postoperative fluid management that must be considered. Reducing the infusion rate of the isotonic balanced solution may be necessary to avoid dilutional hyponatremia during the postoperative period. In summary, perioperative fluid management in pediatric patients requires careful attention because of the limited reserve capacity in this population. Isotonic balanced solutions appear to be the safest and most beneficial choice for most pediatric patients, considering their physiology and safety concerns.

Postoperative free water administration is associated with dysnatremia after congenital heart disease surgery in infants.

Dysnatremia after congenital heart disease (CHD) surgery is common. European guidelines on intraoperative fluid therapy in children recommend isotonic solutions to avoid hyponatremia, but prolonged cardiopulmonary bypass and administration of high sodium-containing solutions (i.e., blood products and sodium bicarbonate) are associated with postoperative hypernatremia. The aim of the study was to describe fluid composition prior to and during the development of postoperative dysnatremia. A retrospective observational, single-center study including infants undergoing CHD surgery. Demographics and clinical characteristics were registered. Highest and lowest plasma sodium values were recorded and associations with perioperative fluid administration, blood products, crystalloids, and colloids were explored in relation to three perioperative periods. Postoperative dysnatremia occurred in nearly 50% of infants within 48 h after surgery. Hypernatremia was mainly associated with administration of blood products (median [IQR]: 50.5 [28.4-95.5] vs. 34.5 [18.5-61.1] mL/kg; p = 0.001), and lower free water load (1.6 [1.1-2.2] mL/kg/h; p = 0.01). Hyponatremia was associated with a higher free water load (2.3 [1.7-3.3] vs. 1.8 [1.4-2.5] mL/kg/h; p = 0.001) and positive fluid balance. On postoperative day 1, hyponatremia was associated with higher volumes of free water (2.0 [1.5-2.8] vs. 1.3 [1.1-1.8] mL/kg/h; p < 0.001) and human albumin, despite a larger diuresis and more negative daily fluid balance. Postoperative hyponatremia occurred in 30% of infants despite restrictive volumes of hypotonic maintenance fluid, whereas hypernatremia was mainly associated with blood product transfusion. Individualized fluid therapy, with continuous reassessment to reduce the occurrence of postoperative dysnatremia is mandatory in pediatric cardiac surgery. Prospective studies to evaluate fluid therapy in pediatric cardiac surgery patients are warranted.

Fluid Restriction Reduces Delayed Hyponatremia and Hospital Readmissions After Transsphenoidal Surgery.

CONTEXT: Postoperative hyponatremia leads to prolonged hospital length of stay and readmission within 30 days. OBJECTIVE: To assess 3 strategies for reducing rates of postoperative hyponatremia and analyze risk factors for hyponatremia. DESIGN: Two retrospective analyses and 1 prospective study. SETTING: Tertiary referral hospital. PATIENTS: Patients undergoing transsphenoidal surgery for pituitary adenomas and other sellar and parasellar pathologies. INTERVENTION(S): Phase 1: no intervention. Phase 2: postoperative day (POD) 7 sodium testing and patient education. Phase 3: fluid restriction to 1 L/day on discharge in addition to phase 2 interventions. MAIN OUTCOME MEASURES: Rates of early and delayed hyponatremia and readmissions. Secondary outcomes were risk factors for hyponatremia and readmission costs. RESULTS: In phase 1, 296 patients underwent transsphenoidal surgery. Twenty percent developed early and 28% delayed hyponatremia. Thirty-eight percent underwent POD 7 sodium testing. Readmission rates were 15% overall and 4.3% for hyponatremia. In phase 2 (n = 316), 22% developed early and 25% delayed hyponatremia. Eighty-nine percent complied with POD 7 sodium testing. Readmissions were unchanged although severity of hyponatremia was reduced by 60%. In phase 3 (n = 110), delayed hyponatremia was reduced 2-fold [12.7%, relative risk (RR) = 0.52] and readmissions 3-fold [4.6%, RR = 0.30 (0.12-0.73)]; readmissions for hyponatremia were markedly reduced. Hyponatremia readmission increased costs by 30%. CONCLUSIONS: Restricting fluid to 1 L/day on discharge decreases rates of delayed hyponatremia and readmissions by 50%. Standardized patient education and POD 7 sodium testing decreases severity of hyponatremia but does not impact readmission rates. These protocols should be considered standard practice for patients undergoing transsphenoidal surgery.

Correction and Prevention of Hyponatremia in Patients With Cirrhosis and Ascites: Post Hoc Analysis of the ANSWER Study Database.

INTRODUCTION: We assessed the impact of long-term albumin administration to hyponatremic patients with ascites enrolled in the ANSWER trial. METHODS: The normalization rate of baseline hyponatremia and the 18-month incidence rate of at least moderate hyponatremia were evaluated. RESULTS: The hyponatremia normalization rate was higher with albumin than with standard medical treatment (45% vs 28%, P = 0.042 at 1 month). Long-term albumin ensured a lower incidence of at least moderate hyponatremia than standard medical treatment (incidence rate ratio: 0.245 [CI 0.167-0.359], P < 0.001). DISCUSSION: Long-term albumin administration improves hyponatremia and reduces episodes of at least moderate hyponatremia in outpatients with cirrhosis and ascites.

Hyponatremia after Autologous Breast Reconstruction: A Cohort Study Comparing Two Fluid Management Protocols.

BACKGROUND: Perioperative fluid management is an important component of enhanced recovery pathways for microsurgical breast reconstruction. Historically, fluid management has been liberal. Little attention has been paid to the biochemical effects of different protocols. This study aims to reduce the risk of postoperative hyponatremia by introducing a new fluid management protocol. METHODS: A single-institution cohort study comparing a prospective series of patients was managed using a new "modestly restrictive" fluid postoperative fluid management protocol to a control group managed with a "liberal" fluid management protocol. RESULTS: One-hundred thirty patients undergoing microsurgical breast reconstruction, at a single institution during 2021, are reported. Hyponatremia is demonstrated to be a significant risk with the original liberal fluid management protocol. At the end of the first postoperative day, mean fluid balance was +2,838 mL (± 1,630 mL). Twenty-four patients of sixty-five (36%) patients had low blood sodium level, 14% classified as moderate-to-severe hyponatremia. Introducing a new, "modestly-restrictive" protocol reduced mean fluid balance on day 1 to +844 mL (±700) (p ≤ 0.0001). Incidence of hyponatremia reduced from 36 to 14% (p = 0.0005). No episodes of moderate or severe hyponatremia were detected. Fluid intake, predominantly oral water, between 8am and 8pm on the first postoperative day is identified as the main risk factor for developing hyponatremia (odds ratio [OR]: 7; p = 0.019). Modest fluid restriction, as guided by the new protocol, protects patients from low sodium level (OR: 0.25; confidence interval: 95%; 0.11-1.61; p = 0.0014). CONCLUSION: The original "liberal" fluid management protocol encouraged unrestricted postoperative oral intake of water. Patients were often advised to consume in excess of 5 L in the first 24 hours. This unintentionally, but frequently, was associated with moderate-to-severe hyponatremia. We present a new protocol characterized by early cessation of intravenous fluid and an oral fluid limit of 2,100 mL/day associated with a significant reduction in the incidence of hyponatremia and fluid overload.

Postoperative fluid restriction to prevent hyponatremia after transsphenoidal pituitary surgery: An updated meta-analysis and critique.

BACKGROUND: Hyponatremia is a common and potentially dangerous complication of transsphenoidal surgery. Prophylactic postoperative fluid restriction has been trialled as a method to reduce the incidence of postoperative hyponatremia. METHODS: A systematic review of the literature was performed in accordance with the PRISMA statement. Risk of bias was assessed using the MINORS criteria. Meta-analysis was performed using the random-effects model. RESULTS: A total of 6 retrospective cohort studies were available for analysis. Fluid restriction was commonly between 1000 and 1500 ml/day and limited to the first postoperative week. Overall, the rate postoperative hyponatremia was fourfold less in the fluid restricted cohorts (3.4 % vs 11.2 %, OR 0.24 (95 %CI 0.15-0.38), p < 0.01). There was no difference in readmission rates (1.4 % vs 3.9 %, OR 0.32 (95 %CI 0.09-1.13), p = 0.08) or postoperative diabetes insipidus (14.5 % vs 18.6 %, OR 0.82 (95 %CI 0.50-1.36), p = 0.45) between fluid restricted and control cohorts. CONCLUSION: Prophylactic postoperative fluid restriction is a cheap, easily implemented intervention that appears to reduce the rate of postoperative hyponatremia, but not necessarily re-admission rates. Whether these prevented cases of hyponatremia are clinically significant remains to be demonstrated.

0.45% Versus 0.9% Saline in 5% Dextrose as Maintenance Fluids in Children Admitted With Acute Illness: A Randomized Control Trial.

BACKGROUND: The safety of giving intravenous (IV) maintenance fluids according to Holliday and Segar's recommendations of 1957 has recently been questioned after reports of complications caused by iatrogenic hyponatremia in children receiving hypotonic fluids. However, the current practice of choice of maintenance IV fluids for hospitalized children varies worldwide. This study was planned to compare 0.45% and 0.9% saline in 5% dextrose at standard maintenance rates in hospitalized children aged 3 months to 12 years. OBJECTIVE: Primary objective was to study change in serum sodium level at 24 hours in children receiving total IV fluid maintenance therapy as 0.45% or 0.9% normal saline in 5% dextrose. Secondary objectives of this study were to estimate change in serum sodium levels from the baseline to 48 or 72 hours, if IV fluids were continued, and to find incidence of hyponatremia and hypernatremia after administering these 2 types of maintenance fluids. METHODS: This study was an open-label, randomized control trial conducted at the Department of Pediatrics of a tertiary care hospital from July 22, 2019, to October 28, 2019. Two hundred children aged 3 months to 12 years admitted in pediatric emergency and requiring IV maintenance fluid were randomized into 2 groups (group A received 0.45% saline in 5% dextrose, group B received 0.9% normal saline in 5% dextrose) with 100 in each group. RESULTS: Both groups were comparable for baseline characteristics. Fall in mean serum sodium from baseline was more with increasing duration of IV fluids until 24 hours in 0.45% saline group as compared with 0.9% saline group, which was statistically significant (P < 0.001). The incidence of mild and moderate hyponatremia was significantly more in hypotonic group at 12 hours (P < 0.001) and 24 hours (P < 0.001). However, there was no significant difference at 48 hours. CONCLUSIONS: The fall in serum sodium values was significant, and there was significant risk of hyponatremia with the use of hypotonic fluids at 12 and 24 hours. Hence, the use of isotonic fluids seems to be more appropriate among the hospitalized children.Trial Registration: CTRI/2019/10/021791.

Marathon Runners' Knowledge and Strategies for Hydration.

OBJECTIVE: To study hydration plans and understanding of exercise-associated hyponatremia (EAH) among current marathon runners. DESIGN: Cross-sectional study. SETTING: Southern California 2018 summer marathon. PARTICIPANTS: Two hundred ten marathon runners. INTERVENTIONS: Survey administered 1 to 2 days before the race. Race times were obtained from public race website. MAIN OUTCOME MEASURES: Planned frequency of hydration; awareness of, understanding of, and preventative strategies for dehydration and EAH; resources used to create hydration plans; drink preferences. RESULTS: When the participants were split into 3 equal groups by racing speed, the slower tertile intended to drink at every mile/station (60%), whereas the faster tertile preferred to drink every other mile or less often (60%), although not statistically significant. Most runners (84%) claimed awareness of EAH, but only 32% could list a symptom of the condition. Both experienced marathoners and the faster tertile significantly had greater understanding of hyponatremia compared with first-time marathoners and the slower tertile, respectively. Less than 5% of marathoners offered "drink to thirst" as a prevention strategy for dehydration or EAH. CONCLUSION: Slower runners plan to drink larger volumes compared with their faster counterparts. Both slower and first-time marathoners significantly lacked understanding of EAH. These groups have plans and knowledge that may put them at higher risk for developing EAH. Most marathon runners did not know of the guidelines to "drink to thirst," suggesting the 2015 EAH Consensus statement may not have had the desired impact.

Restoration of dysnatremia and acute kidney injury benefits outcomes of acute geriatric inpatients.

Dysnatremia and dyskalemia are common problems in acutely hospitalized elderly patients. These disorders are associated with an increased risk of mortality and functional complications that often occur concomitantly with acute kidney injury in addition to multiple comorbidities. In a single-center prospective observational study, we recruited 401 acute geriatric inpatients. In-hospital outcomes included all-cause mortality, length of stay, and changes in functional status as determined by the Activities of Daily Living (ADL) scale, Eastern Cooperative Oncology Group (ECOG) performance, and Clinical Frailty Scale (CFS). The prevalence of dysnatremia alone, dyskalemia alone, and dysnatremia plus dyskalemia during initial hospitalization were 28.4%, 14.7% and 32.4%, respectively. Patients with electrolyte imbalance exhibited higher mortality rates and longer hospital stays than those without electrolyte imbalance. Those with initial dysnatremia, or dysnatremia plus dyskalemia were associated with worse ADL scores, ECOG performance and CFS scores at discharge. Subgroup analyses showed that resolution of dysnatremia was related to reduced mortality risk and improved CFS score, whereas recovery of renal function was associated with decreased mortality and better ECOG and CFS ratings. Our data suggest that restoration of initial dysnatremia and acute kidney injury during acute geriatric care may benefit in-hospital survival and functional status at discharge.

Fluid Restriction After Transsphenoidal Surgery for the Prevention of Delayed Hyponatremia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Delayed hyponatremia is the primary cause of readmission after transsphenoidal surgery, with a reported incidence of 9% to 30.7%. Studies have failed to identify consistent predictive factors for postoperative hyponatremia; thus, it is difficult to determine patients that are at a high risk. Fluid restriction is one approach for the prevention of hyponatremia. We have performed a meta-analysis and systematic review of the literature to evaluate the impact of fluid restriction on hyponatremia and hospital readmissions. METHODS: Ovid EMBASE, PubMed, Scopus, and Cochrane were searched from inception to May 2021, using the Population, Intervention, Comparison, Outcome, and Study question format: Do patients who underwent transsphenoidal surgery and followed a postoperative fluid restriction regimen differ in terms of hyponatremia and readmission rates? Studies that implemented fluid restriction and reported hyponatremia and/or readmission rates were included for analysis. Data were pooled by meta-analysis and analyzed using fixed effect and random effect models. RESULTS: A total of 143 manuscripts representing 103 unique studies were identified, with 5 studies included for analysis, yielding a pooled cohort of 1586 patients: 594 on fluid restriction protocols and 992 control patients. Fluid restriction protocols ranged from 1.0 to 2.5 L and varied in the length time between postoperative days 1 to 15. Patients on fluid restriction had a decreased risk of hyponatremia (risk ratio: 0.34; 95% CI, 0.21-0.57; P < .00001) and readmission due to hyponatremia (risk ratio: 0.24; 95% CI, 0.09-0.63; P = .0038). CONCLUSION: Postoperative fluid restriction after transsphenoidal surgery represents an effective method for the prevention of hyponatremia and hospital readmission and has the potential to decrease health care costs.

Improving Isotonic Maintenance Intravenous Fluid Use in the Emergency Department.

BACKGROUND: Maintenance intravenous fluids (IVFs) are commonly used in the hospital setting. Hypotonic IVFs are commonly used in pediatrics despite concerns about high incidence of hyponatremia. We aimed to increase isotonic maintenance IVF use in children admitted from the emergency department (ED) from a baseline of 20% in 2018 to >80% by December 2019. METHODS: We included patients aged 28 days to 18 years receiving maintenance IVFs (rate >10 mL/hour) at the time of admission. Patients with active chronic medical problems were excluded. Interventions included institutional discussions on isotonic IVF based on literature review, education on isotonic IVF use per the American Academy of Pediatrics guideline (isotonic IVF use with appropriate potassium chloride and dextrose), electronic medical record changes to encourage isotonic IVF use, and group practice review with individual physician audit and feedback. Balancing measures were the frequency of serum electrolyte checks within 24 hours of ED admission and occurrence of hypernatremia. Data were analyzed by using statistical process control charts. RESULTS: Isotonic maintenance IVF use improved, with special cause observed twice; the 80% goal was met and sustained. No difference was noted in serum electrolyte checks within 24 hours of admission (P > .05). There was no increase in occurrence of hypernatremia among patients who received isotonic IVF compared with those who received hypotonic IVF (P > .05). CONCLUSIONS: The application of improvement methods resulted in improved isotonic IVF use in ED patients admitted to the inpatient setting. Institutional readiness for change at the time of the American Academy of Pediatrics guideline release and hardwiring of preferred fluids via electronic medical record changes were critical to success.

Oleuropein Protects Against Cerebral Ischemia Injury in Rats: Molecular Docking, Biochemical and Histological Findings.

This study was designed to evaluate the underlying protective mechanisms of oleuropein involved in alleviating brain damage in a rat model of ischemic stroke. Male Wistar rats were divided into four groups; Control, stroke (MCAO), MCAO + clopidogrel (Clop) and MCAO + oleuropein (Ole). Results showed that the MCAO group evidenced significant brain edema (+ 9%) as well as increases of plasma cardiac markers such as lactate deshydrogenase (LDH), creatine kinase (CK-MB), fibrinogen and Trop-T by 11 %, 43%, 168 and 590%, respectively, as compared to the control group. Moreover, infarcted rats exhibited remarkable elevated levels of angiotensin converting enzyme (ACE), both in plasma and brain tissue, with astrocyte swelling and necrotic neurons in the infarct zone, hyponatremia, and increased rate of thiobarbituric acid-reactive substances (TBARS) by 89% associated with decreases in the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) by 51%, 44 and 42%, respectively, compared to normal control rats. However, MCAO rats treated with oleuropein underwent mitigation of cerebral edema, correction of hyponatremia, remarkable decrease of plasma fibrinogen and cardiac dysfunctional enzymes, inhibition of ACE activity and improvement of oxidative stress status in brain tissue. Furthermore, in silico analysis showed considerable inhibitions of ACE, protein disulfide isomerase (PDI) and TGF-ß1, an indicative of potent anti-embolic properties. Overall, oleuropein offers a neuroprotective effect against ischemic stroke through its antioxidative and antithrombotic activities.

Rehydration during Endurance Exercise: Challenges, Research, Options, Methods.

During endurance exercise, two problems arise from disturbed fluid-electrolyte balance: dehydration and overhydration. The former involves water and sodium losses in sweat and urine that are incompletely replaced, whereas the latter involves excessive consumption and retention of dilute fluids. When experienced at low levels, both dehydration and overhydration have minor or no performance effects and symptoms of illness, but when experienced at moderate-to-severe levels they degrade exercise performance and/or may lead to hydration-related illnesses including hyponatremia (low serum sodium concentration). Therefore, the present review article presents (a) relevant research observations and consensus statements of professional organizations, (b) 5 rehydration methods in which pre-race planning ranges from no advanced action to determination of sweat rate during a field simulation, and (c) 9 rehydration recommendations that are relevant to endurance activities. With this information, each athlete can select the rehydration method that best allows her/him to achieve a hydration middle ground between dehydration and overhydration, to optimize physical performance, and reduce the risk of illness.

Risks of severe hyponatremia in children receiving hypotonic fluids.

Intravenous fluids are frequently used in hospitalized children. Hypotonic fluids have been the standard of care in pediatrics for many years. This might be explained by the empiricism of early recommendations favoring fluids with dextrose, but an insufficient amount of sodium. The risk of hyponatremia (<135mmol/L) might be increased by the occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in the course of common acute diseases (e.g., bronchiolitis, acute gastroenteritis, encephalitis, meningitis) in children. Severe hyponatremia (<130mmol/L) is often associated with neurologic complications leading to sequelae or even death. Over the last few years, hyponatremia induced by hypotonic fluids has been increasingly reported, and significant progress has been made in the understanding of cerebral edema and osmotic demyelination. Several randomized clinical trials have shown weak but significant evidence that isotonic fluids were superior to hypotonic solutions in preventing hyponatremia. However, clinical practices have not changed much in France, as suggested by the analysis of intravenous fluids ordered from the Assistance Publique-Hôpitaux de Paris (AP-HP) central pharmacy (PCH) in 2017. Therefore, it would be advisable that national guidelines be released under the French Health Authorities regarding the safe infusion of infants and children.