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Hypernatremia is an increase in serum sodium concentration above 145 mmol/L. There are many causes of elevated sodium levels in the blood serum. One is incorrect actions performed by medical staff. The symptoms of excessively high serum sodium levels depend on the severity of hypernatremia, the rate of its increase and the accompanying volume disorders. Severe symptoms include altered consciousness, increased muscle tone and reflexes, convulsions, psychomotor hyperactivity or drowsiness (up to coma), respiratory failure, and even death. We present the case of a 45-year-old man who took seven tablets of a blood pressure-lowering drug, and paramedics subsequently administered a concentrated solution of table salt to induce vomiting. However, vomiting did not occur, leading to hypernatremia. Ultimately, the man survived but developed persistent cognitive dysfunction, including disordered short-term memory and encoding and retrieval of information from long-term memory, weakening of attention function and fatigue, and disorders in abstract thinking. The patient's family went to the prosecutor's office to investigate the possibility of medical malpractice. Experts found that the paramedics' actions were incorrect. Although it has been known for many years that table salt solutions should not be used to induce vomiting, unfortunately, both laypeople and medical professionals are still using this technique. Iatrogenic salt poisoning may end not only in serious health complications but also in legal consequences., (© 2024 American Academy of Forensic Sciences.)

Background and Objective: Hypernatremia is a possible side effect of intravenous fosfomycin. The aim of this study was to investigate the effects of changes in sodium (Na) levels on hospital stay and survival in patients hospitalized in the intensive care unit receiving fosfomycin., Subjects and Methods: This study was conducted retrospectively on the files of patients over the age of 60, who were admitted to the Internal Medicine Intensive Care Unit. Plasma sodium levels were observed and documented over a period of 14 days. The patients were divided into two groups (Hypernatremia group Na > 145 mEq/L vs normonatremia group 135-145 mEq/L). In addition, daily sodium changes were noted for 14 days in patients., Results: The mean age of the patients was 75 years. Hospitalization days were longer for hypernatremia patients (31.5 days vs 41 days, p = 0.003). Patients with hypernatremia had an extended duration of stay in the intensive care unit. (21 days vs 31 days p = 0.002). The 1-month survival rate was 61.4% in patients with hypernatremia and 24.9% in patients without hypernatremia (p = 0.004). The absence of hypernatremia increases mortality by 2.09 times (95% CI 1.35-3.23). When discharge and mortality rates were analyzed according to sodium fluctuation, discharged patients exhibited a lower sodium fluctuation (4 min/max (-10/19) vs 6 min/max (-16/32) p < 0.001)., Conclusion: In conclusion, the strength of our study is that it specifically focuses on the consequences of the sodium fluctuation on patient management and provides results., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

BACKGROUND Nephrogenic diabetic insipidus (NDI) poses a challenge in clinical management, particularly when associated with lithium ingestion. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of numerous diseases worldwide, including NDI. However, many studies have reported the diverse adverse effects of long-term use of non-selective NSAIDs. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a better drug to relieve pain and inflammation in terms of long-term safety and efficacy than non-selective NSAIDs. Nevertheless, there are few reports describing the effectiveness of celecoxib in treating NDI. CASE REPORT We report a case of a 46-year-old woman with schizophrenia who presented with severe hypernatremia and refractory polyuria due to lithium-induced NDI. Cessation of lithium ingestion and traditional treatments, including trichlormethiazide and desmopressin, yielded minimal improvement in her hypernatremia and polyuria. Her sodium level needed to be strictly controlled with the infusion of dextrose 5% in water. Given the safety of celecoxib, we decided to initiate celecoxib as the treatment of lithium-induced NDI instead of indomethacin. Notably, the introduction of celecoxib led to a substantial and sustained amelioration of polyuria and hypernatremia without any celecoxib-associated adverse effects. Even after transfer to another hospital, stability in serum sodium levels persisted with celecoxib. CONCLUSIONS We presented a case of lithium-induced NDI successfully treated with celecoxib, a selective COX-2 inhibitor. To the best of our knowledge, this is the first reported case of successful treatment of lithium-induced NDI with celecoxib, and suggests celecoxib is a viable therapeutic option warranting further exploration. Physicians should consider its use when faced with the challenging management of lithium-induced NDI.

A 15-year-old male neutered mixed breed dog weighing 28 kg presented to a referral center after developing severe tremors and altered mentation. There was hypocalcemia and hypernatremia after oral administration of sodium phosphate as a bowel cleansing agent in preparation for colonoscopy. The dog was treated intravenously with low sodium fluids and calcium gluconate. Neurologic status and electrolyte derangements normalized over the next 12 hours. Oral administration of sodium phosphate appeared to cause clinical electrolyte derangements in this dog., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been widely used. They inhibit proximal tubular glucose reabsorption, resulting in glycosuria. Herein, we report the case of a 65-year-old woman who presented with hypernatremia during the perioperative period of a subarachnoid hemorrhage. The patient continued to take dapagliflozin postoperatively and subsequently developed severe hypernatremia. Based on the urinalysis findings, we diagnosed osmotic diuresis due to glycosuria as contributing to hypernatremia. Hypernatremia improved with the discontinuation of dapagliflozin and the administration of a hypotonic infusion. In the perioperative period, physicians should discontinue SGLT2 inhibitors owing to concerns about the development of hypernatremia., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Background: Iatrogenic hyponatremia is a common complication following intravenous maintenance fluid therapy (IV-MFT) in hospitalized children. Despite the American Academy of Pediatrics' 2018 recommendations, IV-MFT prescribing practices still vary considerably., Objectives: This meta-analysis aimed to compare the safety and efficacy of isotonic versus hypotonic IV-MFT in hospitalized children., Data Sources: We searched PubMed, Scopus, Web of Science, and Cochrane Central from inception to October 1, 2022., Study Eligibility Criteria: We included randomized controlled trials (RCTs) comparing isotonic versus hypotonic IV-MFT in hospitalized children, either with medical or surgical conditions. Our primary outcome was hyponatremia following IV-MFT. Secondary outcomes included hypernatremia, serum sodium, serum potassium, serum osmolarity, blood pH, blood sugar, serum creatinine, serum chloride, urinary sodium, length of hospital stay, and adverse outcomes., Study Appraisal and Synthesis Methods: Random-effects models were used to pool the extracted data. We performed our analysis based on the duration of fluid administration (i.e., ≤ 24 and > 24 h). The Grades of Recommendations Assessment Development and Evaluation (GRADE) scale was used to evaluate the strength and level of evidence for recommendations., Results: A total of 33 RCTs, comprising 5049 patients were included. Isotonic IV-MFT significantly reduced the risk of mild hyponatremia at both ≤ 24 h (RR = 0.38, 95% CI [0.30, 0.48], P < 0.00001; high quality of evidence) and > 24 h (RR = 0.47, 95% CI [0.37, 0.62], P < 0.00001; high quality of evidence). This protective effect of isotonic fluid was maintained in most examined subgroups. Isotonic IV-MFT significantly increased the risk of hypernatremia in neonates (RR = 3.74, 95% CI [1.42, 9.85], P = 0.008). In addition, it significantly increased serum creatinine at ≤ 24 h (MD = 0.89, 95% CI [0.84, 0.94], P < 0.00001) and decreased blood pH (MD = -0.05, 95% CI [-0.08 to -0.02], P = 0.0006). Mean serum sodium, serum osmolarity, and serum chloride were lower in the hypotonic group at ≤ 24 h. The two fluids were comparable in terms of serum potassium, length of hospital stay, blood sugar, and the risk of adverse outcomes., Limitations: The main limitation of our study was the heterogeneity of the included studies., Conclusions and Implications of Key Findings: Isotonic IV-MFT was superior to the hypotonic one in reducing the risk of iatrogenic hyponatremia in hospitalized children. However, it increases the risk of hypernatremia in neonates and may lead to renal dysfunction. Given that the risk of hypernatremia is not important even in the neonates, we propose to use balanced isotonic IV-MFT in hospitalized children as it is better tolerated by the kidneys than 0.9% saline., Systematic Review Registration Number: CRD42022372359. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s).)

BACKGROUND Nephrogenic diabetes insipidus is a well-known adverse effect of lithium use. Albeit rare, there have also been documented cases of central diabetes insipidus (CDI) associated with lithium use. CASE REPORT A 31-year-old woman with a past medical history of bipolar disorder, managed with lithium 300 mg by mouth every day for 3 years, was assessed for a 1-year history of polyuria with accompanying polydipsia. During her initial hospital stay, her estimated urine output was more than 4 L per day. Initial labs showed elevated serum sodium (149 mmol/L; reference range 135-145), elevated serum osmolality (304 mOsm/kg; reference range 275-295), urine osmolality of 99 mOsm/kg (reference range 50-1200), and urine specific gravity (1.005; reference range 1.005-1.030). Lithium was at a subtherapeutic level of 0.05 mEq/L (reference range 0.6-1.2). Magnetic resonance imaging of the brain revealed no abnormalities of the pituitary gland. Two different occasions of desmopressin administration resulted in >50% increase in urine osmolality, confirming the diagnosis of CDI. Common causes of CDI, including trauma, tumors, and familial CDI, were ruled out and chronic lithium use was determined as the most probable cause for the patient's CDI. CONCLUSIONS CDI in the background of chronic lithium use is rarely reported. We present this case to consider CDI as a differential diagnosis when evaluating polyuria and hypernatremia in patients with long-term lithium use. These presentations warrant the consideration of both types of diabetes insipidus in the differential diagnoses.

Objective: To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia., Materials and Methods: A health insurance claims database and a spontaneous adverse drug reaction database were used., Results: Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 - 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 - 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 - 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years., Conclusion: It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.

Competing Interests: The authors have no conflicts of interest to declare.

We report a case of thromboembolism in a patient with hypernatremia resulting from lithium-induced nephrogenic diabetes insipidus (NDI). A 49-year-old female patient on chronic lithium therapy due to bipolar disorder was transferred to the emergency department with signs of dehydration, altered mental status, and increased oxygen demand. She was admitted to a local psychiatric clinic first because of an exacerbation of a manic episode. When she was transferred to our clinic, her blood pressure was 130/80 mmHg, she was tachycardic (110 beats/min), had tachypnea (24 breaths/min), normal body temperature (36.5 ℃), and an oxygen saturation of 94% via a face mask (10 L/min). Laboratory results showed hypertonic hypernatremia (osmolality, 363 mOsm/kg; sodium, 171 mEq/L), low urine osmolality (osmolality, 231 mOsm/kg), and normal urine sodium (Na, 63 mEq/L). Her serum lithium concentration was above the therapeutic range (1.52 mmol/L). An increase in cardiac markers and changes in electrocardiogram were detected; therefore, echocardiography was performed, which showed right ventricular dysfunction and small left ventricular chamber size. Computed tomography of the chest and lower extremities showed pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT). She was treated with hypotonic fluid to correct hypernatremia and intravenous heparin for thromboembolism. The size of the thromboembolism decreased, and hypernatremia was corrected. She was discharged with a direct oral anticoagulant (DOAC). Here, we report a case of severe hypernatremia and venous thromboembolism in lithium-induced NDI.

Background: Rapid-onset, acute hypernatremia caused by sodium overload is a rare, life-threatening condition. Although experts recommend rapid correction of sodium concentration [Na] based on pathophysiological theories, only a few reports have documented the specific details of sodium correction methods. The objective of this study was to systematically review the reported treatment regimens, achieved [Na] correction rates, and treatment outcomes., Methods: PubMed, Ichushi-database, and references without language restrictions, from inception to January 2021, were searched for studies that described ≥1 adult (aged ≥18 years) patients with rapid-onset hypernatremia caused by sodium overload, whose treatment was initiated ≤12 hours from the onset. The primary outcome of interest was the [Na] correction rate associated with mortality., Results: Eighteen case reports (18 patients; median [Na], 180.5 mEq/L) were included. The cause of sodium overload was self-ingestion in 8 patients and iatrogenic sodium gain in 10 patients; baseline [Na] and symptoms at presentation were comparable for both groups. Individualized rapid infusion of dextrose-based solutions was the most commonly adopted fluid therapy, whereas hemodialysis was also used for patients already treated with hemodialysis. The correction rates were more rapid in 13 successfully treated patients than in 5 fatal patients. The successfully treated patients typically achieved [Na] ≤160 within 8 hours, [Na] ≤150 within 24 hours, and [Na] ≤145 within 48 hours. Hyperglycemia was a commonly observed treatment-related adverse event., Conclusion: The limited empirical evidence derived from case reports appears to endorse the recommended, rapid, and aggressive sodium correction using dextrose-based hypotonic solutions., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Central pontine myelinolysis (CPM) develops due to acute hypernatremia from a normal baseline serum sodium in the setting of electrolyte abnormalities induced by topiramate use. Topiramate is a commonly used medication with several indications including migraines, myoclonic jerks and seizures. It has been reported to cause renal tubular acidosis and severe electrolyte abnormalities, which in turn predispose patients to neuropathology via renal concentration defects and osmotic shifts. Our patient is a 55-year-old woman with a history of multiple sclerosis and myoclonus on topiramate for several years who presented with weakness and was found to be profoundly hypokalemic. She went on to develop changes in mental status, motor deficits and evidence of CPM on MRI during her hospitalisation. Surprisingly, the patient never had hyponatremia; however, she had an acute rise in serum sodium from a normal baseline after fluid resuscitation with normal saline for hypotension during her admission., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Backgrounds: Tolvaptan significantly increases urine volume in acute decompensated heart failure (ADHF); serum sodium level increases due to aquaresis in almost all cases. We aimed to elucidate clinical factors associated with hypernatremia in ADHF patients treated with tolvaptan., Methods: We enrolled 117 ADHF patients treated with tolvaptan in addition to standard therapy. We examined differences in clinical factors at baseline between patients with and without hypernatremia in the initial three days of hospitalization., Results: Systolic (p = 0.045) and diastolic (p = 0.004) blood pressure, serum sodium level (p = 0.002), and negative water balance (p = 0.036) were significantly higher and serum potassium level (p = 0.026) was significantly lower on admission day in patients with hypernatremia (n = 22). In multivariate regression analysis, hypernatremia was associated with low serum potassium level (p = 0.034). Among patients with serum potassium level ≤ 3.8 mEq/L, the cutoff value obtained using receiver operating characteristic curve analysis, those with hypernatremia related to tolvaptan treatment showed significantly higher diastolic blood pressure on admission day (p = 0.004)., Conclusion: In tolvaptan treatment combined with standard therapy in ADHF patients, serum potassium level ≤ 3.8 mEq/L may be a determinant factor for hypernatremia development. Among hypokalemic patients, those with higher diastolic blood pressure on admission may be carefully managed to prevent hypernatremia.

A major goal in treatment of calves with diarrhea is to restore hydration and to correct metabolic acidosis. This can be achieved by the administration of oral electrolyte solutions (OES). However, the composition of OES products and the administration protocols in practice vary widely, which can potentially compromise the efficacy and safety of these treatments. In particular, administration of OES in milk replacer (MR) and the absence of water supply in young calves are not unusual and these conditions could compromise calf health. In this light, the objective of this study was to evaluate the efficacy and safety of OES administered in MR and in water without access to water. Forty-five male Holstein calves (16.6 ± 1.6 d of age and 45.4 ± 2.2 kg at arrival) were purchased from a collection center located in the Netherlands. After arrival, calves went through an adaptation period of 4 d. Calves that developed diarrhea within 6 d after the end of the adaptation period were enrolled in the study, and the remaining calves were sold after being weaned. Upon morning detection of abnormal fecal scores (d 1 starting point), calves were blocked based on initial BW. Within each block, calves were randomly assigned to 1 of 2 treatments, including a control consisting of a small dose of whey (CON; n = 12) and an OES treatment (OES; n = 14). Treatments were blinded to the farm staff by randomly assigning a letter to each treatment. Treatments were simultaneously administered for 4 d in MR (2.5 L at 0800 and 1730 h) and in water (3 L at 1300 and 2200 h). Calves had no supplemental access to plain water. Blood samples were taken at 0600 h for 4 d, and fecal scores (0 = normal; 1 = watery feces) were assessed daily at 0900 h for 15 consecutive days. Additionally, skin turgor and degree of enophthalmos were assessed at 1000 h from d 1 to 4 using a 3-level scoring system. Calves fed OES had a higher prevalence of diarrhea on d 3, 4, and 5 as well as higher prevalence of delayed skin turgor and increased degree of enophthalmos over the 4 monitoring days. Diarrhea duration was longer in calves receiving OES than in calves receiving CON (4.2 d vs. 2.1 d, respectively). The OES treatment resulted in hypernatremia (serum Na + >145 mmol/L) within 48 h after the first OES administration. Hypernatremia was linked with higher serum Cl - and urea concentrations and thus higher serum osmolarity in OES calves compared with CON calves. Administered under these conditions, OES resulted in various degrees of hypernatremia and a delayed recovery from diarrhea, thus defeating the purpose of OES administration., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Chinese herbal medicine is widely used globally. In many instances, it is associated with severe adverse outcomes. We report case of a Chinese herbal nephropathy occurring in a 43-year-old woman showing renal impairment, metabolic acidosis, Stokes - Adams syndrome, hypernatremia, and hypokalemia, characteristics not usually encountered in published cases.

Objective: To describe the clinical signs, clinicopathologic abnormalities, treatment, and outcome after IV administration of polyethylene glycol 3350 (PEG3350) in a cat., Case Summary: A cat was inadvertently administered 6 g/kg of PEG3350 in electrolyte solution, IV, resulting in severe hypernatremia (203 mmol/L), diffuse encephalopathy, hemolysis, and moderate azotemia. The hemolysis and acute kidney injury observed immediately following PEG3350 administration resolved with supportive care. Administration of IV and oral electrolyte-free water slowly corrected the hypernatremia and the neurologic signs subsequently improved. Complete resolution of clinical signs was documented one month following hospital discharge. The PEG3350 concentrations in serum, plasma, and urine samples confirmed toxic exposure to PEG3350. Efficacy of treatment was evident by decreasing concentrations of PEG3350 in serum after the first 24 hours of treatment. Renal elimination of PEG3350 was significant and PEG3350 was still detected in the urine 17 days after exposure., New Information Provided: This is the first report to describe the clinical signs and clinicopathologic abnormalities in a cat intoxicated with IV PEG3350. Potential pathophysiologic mechanisms are discussed, and the successful supportive medical treatment is outlined., (© Veterinary Emergency and Critical Care Society 2019.)

Introduction: Surgery is effective treatment for echinococcosis; however, there is a risk of hypertonic saline resorption and acute hypernatremia., Aim: We report two cases of severe hypernatremia following hydatid cyst removal., Case Reports: A 17-year-old girl underwent surgical removal of hepatic hydatid cyst. Following the surgery, she developed seizures evolving to status epilepticus, and was sedated and mechanically ventilated. Blood chemistry showed hypernatremia. Fluid resuscitation with 5% dextrose infusions was started in combination with furosemide. Electrolytes were monitored frequently until plasma sodium levels normalized, 30 hours later. The patient was seizure free 48 hours later. The second patient is a 70-year-old man with hepatic hydatid cyst. After the surgery he became somnolent and confused due to severe hypernatremia. Intravenous administration of five percentage dextrose was initiated and high doses of furosemide. Sodium level normalized within 38 hours. The patient's mental status improved., Conclusion: A hospital protocol was established aiming to prevent hypernatremia and neurological complications., Competing Interests: There are no conflicts of interest., (© 2019 Biljana Kuzmanovska, Andrijan Kartalov, Igor Kuzmanovski, Mirjana Shosholcheva, Nikola Jankulovski, Aleksandra Gavrilovska-Brzanov, Aleksandar Dimitrovski, Emilija Cvetkovska.)

Background: Intravenous hypotonic fluid administered in children is associated with an increased risk of developing hyponatremia. This finding has been reported from temperate countries where climate is relatively cold. But whether this risk also occurs in tropical countries has not been elucidated., Objective: The objective of this study was to determine the relationship between environmental temperature and serum sodium in non-critically ill children., Methods: A retrospective study., Results: A total of 1061 hospitalized children were enrolled. Incidences of hyponatremia were not different between patients who received isotonic and hypotonic fluids (29% vs. 31%). Subgroup analysis showed a trend of higher incidence of hyponatremia in patients who received hypotonic fluid than isotonic fluid only in patients admitted to the air-conditioned wards (29% vs. 21%, p = 0.08)., Conclusion: Children admitted to the air-conditioned wards who received hypotonic fluid seemed to carry a higher risk of developing hyponatremia than those admitted to the non-air-conditioned ward., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Rationale: Tolvaptan (TLV) is a selective vasopressin type 2 receptor antagonist, which has an active effect on patients with congestive heart failure especially combined with hyponatremia. Increasingly, evidence has demonstrated that low-dose tolvaptan can dramatically relieve patients' dyspnea and the dose would not cause severe electrolyte abnormalities. Even hypernatremia is a major adverse effect of tolvaptan, treatment with tolvaptan shows good security and is well-tolerated. Few cases have reported that patients who developed severe hypernatremia induced by low-dose Tolvaptan., Patient Concerns: A 68-year-old man was admitted to our hospital with dyspea and general fatigue. He was diagnosed with acute decompensated heart failure due to ischemic cardiomyopathy. In order to improve fluid retention and relieve his dyspnea, low-dose TLV (7.5 mg qd) was performed. After the 3-day treatment using TLV, we observed that he became delirious and his limbs shook uncontrollably. High serum sodium 173 mmol/L was noted compared to the results of the first examination (137 mmol/L). After intensive rescue, serum sodium was restored to normal (135 mol/L). Later, when the patient refused continuous renal replacement therapy (CRRT), we tried again to use a lower dose of TLV to improve diuretic resistance. Two days later, Serum sodium rose again (162 mmol/L)., Diagnoses: During the course of therapy, we did not strictly require the patient to control the fluid intake. No other medication could cause elevation of serum sodium. Therefore, we suspected a high sensitivity to the side effect of TLV., Intervention: Stop the use of TLV and encourage the patient to drink plenty of water. Gastric tube was inserted orally to increase the intake of fresh water., Outcomes: His serum sodium decreased gradually and his psychiatric symptom recovered. During this period, Overall condition of the patient was stable. After being discharged from the hospital, the patient eventually died of cardiac arrest due to critically ill heart failure., Lessons: Hypernatremia is a severe side effect of TLV. For critical patients, TLV should be used at a low dose and electrolyte should be detected in time.

Background and Objective: The endothelial glycocalyx (EG) is fragile and sensitive to damage such as exposure to hypernatremia. Our aim was to describe the influence of hypernatremia on the EG in sublingual and brain microcirculation in rabbits., Methods: Hypernatremia was induced by intravenous administration of 10% NaCl solution. The sublingual and brain microcirculation were evaluated by the Side-stream Dark Field imaging before (T1) and 20 minutes after infusion of 10% saline (T2). Damage to the EG was quantified by automated analysis of Perfused Boundary Region (PBR) indicating the amount of penetration of red blood cells into the EG. Syndecan-1 levels were also measured., Results: Hypernatremia was reached in all 20 animals, the PBR values of the sublingual area raised from 1,98 (0,3) to 2,17 (0,18) μm (p = 0,05). The levels of syndecan-1 (1,23 (0,36); 1,31 (0,33) ng/l, p = 0,3) did not mirror PBR changes., Conclusions: Hypernatremia increased the PBR within the sublingual microcirculation in our animal model, probably due to compression of the EG related to temporary intravascular hypervolemia and changes of the EG charge in RBC instead of direct damaging effect on EG, which has been excluded by rather unchanged levels of syndecan-1.

Competing Interests: Competing interests: None declared.

Background: It has been 7 years since tolvaptan was approved in Japan for the indication of heart failure in patients with volume overload; the drug can be used in patients with normonatremia. Hypernatremia was identified as a significant adverse event to be prevented., Methods and results: We compiled and analyzed data from 3,349 patients over 5 years to identify patients at high risk of hypernatremia with tolvaptan treatment. The incidence of hypernatremia, defined as serum sodium ≥150 mEq/L, was 3.65%. Baseline serum sodium concentrations, serum potassium concentrations, blood urea nitrogen : creatinine ratio, initial tolvaptan dose, and age were identified as risk factors for hypernatremia. A hypernatremia risk score was developed using the odds ratios for these factors. The high-risk population was defined as patients with a risk score ≥17.80., Conclusions: To prevent the occurrence of hypernatremic events in patients taking tolvaptan, we recommend a very low starting dose (i.e., 3.75 mg/day) in patients identified as being at high risk of hypernatremia using our new scoring process.

This quiz will discuss two patients with end-stage kidney disease (ESKD) on dialysis presenting with diaphoresis and hypernatremia.

Background: Although hypernatremia is associated with adverse outcomes, most studies examined selected populations., Methods: Discharge data of 19,072 unselected hospitalized adults were analyzed. The crude relationship between serum sodium [Na + ] and mortality defined hypernatremia as serum [Na + ] >142 mEq/L. Patients with community-acquired hypernatremia or hospital-acquired hypernatremia were compared with normonatremic patients (admission [Na + ] 138-142 mEq/L) regarding in-hospital mortality, length of stay, and discharge disposition. Patients with community-acquired hypernatremia whose hypernatremia worsened during hospitalization were compared with those without aggravation., Results: Community-acquired hypernatremia occurred in 21% of hospitalized patients and was associated with an adjusted odds ratio (OR) of 1.67 (95% confidence interval [CI], 1.38-2.01) for in-hospital mortality and 1.44 (95% CI, 1.32-1.56) for discharge to a short-/long-term care facility and an adjusted 10% (95% CI, 7-13) increase in length of stay. Hospital-acquired hypernatremia developed in 25.9% of hospitalized patients and was associated with an adjusted OR of 3.17 (95% CI, 2.45-4.09) for in-hospital mortality and 1.45 (95% CI, 1.32-1.59) for discharge to a facility, and an adjusted 49% (95% CI, 44-53) increase in length of stay. Hospital-aggravated hypernatremia developed in 11.7% of patients with community-acquired hypernatremia and was associated with greater risk of in-hospital mortality (adjusted OR, 1.84; 95% CI, 1.32-2.56) and discharge to a facility (adjusted OR, 2.14; 95% CI, 1.71-2.69), and an adjusted 16% (95% CI, 7-27) increase in length of stay., Conclusions: The hypernatremia spectrum in unselected hospitalized patients is independently associated with increased in-hospital mortality and heightened resource consumption., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: Hypernatremia is a rare but fatal complication of hypertonic saline (HS) irrigation in hepatic hydatid disease. It needs careful monitoring and treatment., Patient Concerns: A 28-year-old woman with hepatic hydatid cysts who received operation treatment developed electrolyte disturbances. We also conducted a retrospective study about influence of HS application on electrolytes in patients with hepatic hydatid disease receiving surgery., Diagnoses: Hypernatremia, developed after HS irrigation., Interventions: Normal saline, 5% dextrose and other supportive treatment were administered. In the retrospective study, a comparison of electrolyte and glucose fluctuation was made among different HS application groups., Outcomes: The patient developed hypernatremia after irrigation with HS and died from severe complications. Although some cases of complications are found, no significant relationship between HS irrigation and hypernatremia was reported according to the retrospective study., Lessons: Hypernatremia after HS irrigation remains rare but might cause severe complications. Monitoring and appropriate treatment are needed to improve prognosis.

Background: Hypernatremic dehydration is well described in exclusively breastfed neonates, although life-threatening complications are rarely reported., Materials and Methods: The present article describes a case of severe hypernatremic dehydration in a previously healthy term neonate. Other published cases of severe complications of hypernatremic dehydration are discussed., Results: The exclusively breastfed neonate described had severe hypernatremic dehydration because of inadequate milk intake, with disseminated intravascular coagulation and right lower limb gangrene that required amputation of all five toes and surgical debridement of the metatarsals. The usual etiology of hypernatremic dehydration in this age group is insufficient breast milk intake. Here, the infant's mother was treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily., Conclusions: Awareness of these complications should prompt close follow-up of the infant with poor weight gain. The role of maternal medication as a risk factor for hypernatremic dehydration among exclusively breastfed infants needs to be further explored.

There are sporadic cases of fatalities from acutely eating salt. Yet, on social media, there are "challenges to" and examples of children and some adults acutely eating salt, and recently a charity advocated eating small amounts of salt to empathize with Syrian refugees. We performed a systematic review of fatalities from ingesting salt to assess if relatively moderate doses of salt could be fatal. In 27 reports, there were 35 fatalities documented (19 in adults and 16 in children). The lethal dose was estimated to be less than 10 g of sodium (<5 teaspoons of salt) in two children, and less than 25 g sodium in four adults (<4 tablespoons of salt). The frequency of fatal ingestion of salt is not able to be discerned from our review. If investigation of the causes of hypernatremia in hospital records indicates salt overdose is relatively common, consideration could be given to placing warning labels on salt containers and shakers. Such warning labels can have the added advantage of reducing dietary salt consumption., Competing Interests: N.R.C.C. is a paid consultant to the Novartis Foundation to support their program to improve hypertension control in low to middle income countries which includes travel support for site visits and a contract to develop a survey. N.R.C.C. has also agree to provide paid consultative advice on accurate blood pressure assessment to Midway Corporation and is an unpaid member of World Action on Salt and Health (WASH); E.J.T. has no funding or conflicts of interest to disclose. E.J.T. is an unpaid volunteer board director of Open Arms Patient Advocacy Society and is a self-employed writer and administrator of the Anthony Train Corp.

In the last few years, gamma hydroxybutyric acid (GHB) has been used increasingly as a party drug; this has led to a marked increase in the number of requests for professional help with the treatment of GHB addiction. Pharmaceutical GHB (sodium oxybate, the sodium-salt of GHB), registered for cataplexia in narcolepsy patients, is used off-label to treat the withdrawal symptoms associated with GHB addiction. Pharmaceutical GHB has a high sodium load. In this report we present the cases of two patients who developed symptomatic hypernatremia following treatment with pharmaceutical GHB and who thereafter needed intensive care for the severe withdrawal symptoms that they experienced.

Purpose: The long-term efficacy of tolvaptan, a vasopressin V2 receptor antagonist, has been reported. However, the safety of long-term treatment remains to be fully elucidated. We assessed the safety profile of tolvaptan with respect to hypernatremia., Methods: This retrospective study included 371 patients treated with tolvaptan. Risk factors for hypernatremia (serum sodium concentration ≥147 mEq/L) were determined., Results: Hypernatremia occurred in 95 patients (25.6 %), of whom 71 (19.1 %) developed hypernatremia within 7 days of tolvaptan treatment (early onset). Stepwise logistic regression analysis demonstrated that baseline serum sodium ≥140 mEq/L, an initial tolvaptan dosage >7.5 mg, and a BUN/serum creatinine ratio ≥20 were independent risk factors for early onset of hypernatremia. Tolvaptan was prescribed for more than 7 days to 233 patients, of whom 123 were administrated tolvaptan for more than 1 month. Hypernatremia occurred in 24 of these patients (10.3 %) (late onset). Predictive factors for late onset of hypernatremia were an average daily dosage of tolvaptan >7.5 mg and age ≥75 years., Conclusions: A daily dosage of 7.5 mg or less was recommended to prevent hypernatremia in short- as well as long-term tolvaptan treatment, and mainly elderly patients were at risk for hypernatremia.

Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO 3 ). The purpose of this study was to determine the relationships between total NaHCO 3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS)., Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO 3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes., Results: Seventy-five patients (86%) received NaHCO 3 . Total NaHCO 3 dose averaged 136 ± 112 mEq (range: 0.0-535 mEq) per patient. Total NaHCO 3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = -0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO 3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS., Conclusion: Routine administration of NaHCO 3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO 3 was a function of the severity and duration of metabolic acidosis. NaHCO 3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO 3 dose administered was unrelated to short-term clinical outcomes.

Infusion fluids are often given to restore blood pressure (volume resuscitation), but may also be administered to replace ongoing losses, match insensible losses, correct electrolyte or acid-base disorders, or provide glucose. The development of new infusion fluids has provided clinicians with a wide range of products. Although the choice for a certain infusion fluid is often driven more by habit than by careful consideration, we believe it is useful to approach infusion fluids as drugs and consider their pharmacokinetic and pharmacodynamic characteristics. This approach not only explains why infusion fluids may cause electrolyte and acid-base disturbances, but also why they may compromise kidney function or coagulation. In this teaching case, we present a 19-year-old patient in whom severe hypernatremia developed as a result of normal saline solution infusion and explore the pharmacokinetic and pharmacodynamic effects of frequently used infusion fluids. We review clinical evidence to guide the selection of the optimal infusion fluid., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The diuretic tolvaptan has been approved for more than 5 years for the indications of euvolemic hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) secretion. In recent years many patients have been treated with tolvaptan and many physicians could gather practical experience. Other countries, such as the USA had already gained greater experience, also in the indications for hypervolemic hyponatremia. After approval was granted more than 5000 patients worldwide were included in the so-called hyponatremia register and 22 active centers in Germany with 317 patients participated. Although some details from this now concluded register have been published, the final publication of the multinational post-authorization safety study on tolvaptan in the treatment of SIADH has not yet been published. In the years 2012 and 2013 two warning letters were issued on tolvaptan. The first letter warned of the risk of a faster increase in serum sodium using tolvaptan and provided detailed information on how the risk of osmotic demeyelination can be minimized. So far only one proven case of osmotic demelination syndrome (ODS) is known; however, this occurred following incorrect use of tolvaptan in a monotherapy. The second warning letter provided information on the potential risk (reversible) of liver damage by tolvaptan, which resulted from the TEMPO 3:4 study. In this study tolvaptan was used in a higher dosage for therapy of autosomal dominant polycystic kidney disease. Although the European renal best practice (ERBP) guidelines from 2014 did not recommend tolvaptan for the indications of SIADH, other guidelines came to different conclusions. In summary, 5 years after the approval of tolvaptan there is still no consensus. At the current time many questions still remain unanswered. Initiation of therapy with tolvaptan remains reserved for experienced physicians in hospitals. Treatment must be adapted on the basis of a clinical estimation of the individual situation of each patient.

Traumatic brain injury and intracranial hypertension often require treatment to optimize patient outcome. There are a variety of complex medical conditions that can preclude standard approaches to the treatment of intracranial hypertension. We describe a case where a novel approach using continuous dialysis with trisodium citrate was used to optimize the outcome of a young male with acute renal failure and acute respiratory distress syndrome in the setting of acute traumatic brain injury., (© 2015 Marshfield Clinic.)

Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L) and severe metabolic acidosis (pH 6.65) that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurological sequelae. To the best of our knowledge, this is the first case report in adults of severe hypernatremia along with severe metabolic acidosis due to error in the preparation of dialysis fluid.

Background: Intensive care unit (ICU)-acquired hypernatremia is associated with increased mortality and ascribed to excessive sodium/insufficient free water intakes. We aimed to determine whether the volume of intravenous 0.9% saline fluid resuscitation was associated with hypernatremia in severe sepsis., Methods: We retrospectively reviewed the charts of patients admitted to our medical ICU over 1 year with severe sepsis, and recorded all fluid intakes and plasma sodium levels (Nap ) for 5 days along with clinical data. ΔNap was defined as the difference between maximal Nap reached and initial Nap . Hypernatremia was defined as Nap  > 145 mmoles/l., Results: Among 95 patients with severe sepsis, 29 developed hypernatremia within 5 days (31%), reaching a maximum Nap of 149.1 ± 2.5 mmoles/l on average 3.8 ± 1.5 days after admission. For every 50-ml/kg increase in 0.9% saline intake for the first 48 h, the odds of hypernatremia were 1.61 times larger [confidence interval (CI): 0.98-2.62; P = 0.06] and the mean of ΔNap increased by 1.86 mmoles/l (CI: 0.86-2.86; P < 0.001). Compared with non-hypernatremic patients, hypernatremic patients received more 0.9% saline within the first 48 h (111 ± 50 ml/kg vs. 92 ± 42 ml/kg, P < 0.05) and more other fluids from 48 to 96 h (64 ± 38 ml/kg vs. 42 ± 24 ml/kg, P < 0.05). Patients developing hypernatremia had increased length of mechanical ventilation (12.0 ± 12.6 vs. 9.1 ± 7.2 days, P < 0.05) and ICU mortality (38.5% vs. 13%, P < 0.01)., Conclusions: Early acquired hypernatremia is a frequent complication in severe sepsis patients and is associated with the volume of 0.9% saline received during the first 48 h of admission., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: We wanted to identify modifiable risk factors for intensive care unit (ICU)-acquired hypernatremia., Materials and Methods: We retrospectively studied sodium and fluid loads and balances up to 7 days prior to the development of hypernatremia (first serum sodium concentration, [Na+], >150 mmol/L; H) vs control (maximum [Na+] ≤150 mmol/L; N), in consecutive patients admitted into the ICU with a normal serum sodium (<145 mmol/L) and without cerebral disease, within a period of 8 months., Results: There were 57 H and 150 N patients. Severity of disease and organ failure was greater, and length of stay and mechanical ventilation in the ICU were longer in H (P<.001), with a mortality rate of 28% vs 16% in N (P=.002). Sodium input was higher in H than in N, particularly from 0.9% saline to dissolve drugs for infusion and to keep catheters open during the week prior to the first day of hypernatremia (P<.001). Fluid balances were positive and did not differ from N on most days in the presence of slightly higher plasma creatinine and more frequent administration of furosemide, at higher doses, in H than in N., Conclusions: High sodium input by 0.9% saline used to dilute drugs and keep catheters open is a modifiable risk factor for ICU-acquired H. Dissolving drugs in dextrose 5% may partially prevent potentially harmful sodium overloading and H., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Osmotic demyelination syndrome (ODS) primarily occurs after rapid correction of severe hyponatremia. There are no proven effective therapies for ODS, but we describe the first case showing the successful treatment of central pontine myelinolysis (CPM) by plasma exchange, which occurred after rapid development of hypernatremia from intravenous sodium bicarbonate therapy., Case Presentation: A 40-year-old woman presented with general weakness, hypokalemia, and metabolic acidosis. The patient was treated with oral and intravenous potassium chloride, along with intravenous sodium bicarbonate. Although her bicarbonate deficit was 365 mEq, we treated her with an overdose of intravenous sodium bicarbonate, 480 mEq for 24 hours, due to the severity of her acidemia and her altered mental status. The next day, she developed hypernatremia with serum sodium levels rising from 142.8 mEq/L to 172.8 mEq/L. Six days after developing hypernatremia, she exhibited tetraparesis, drooling, difficulty swallowing, and dysarthria, and a brain MRI revealed high signal intensity in the central pons with sparing of the peripheral portion, suggesting CPM. We diagnosed her with CPM associated with the rapid development of hypernatremia after intravenous sodium bicarbonate therapy and treated her with plasma exchange. After two consecutive plasma exchange sessions, her neurologic symptoms were markedly improved except for mild diplopia. After the plasma exchange sessions, we examined the patient to determine the reason for her symptoms upon presentation to the hospital. She had normal anion gap metabolic acidosis, low blood bicarbonate levels, a urine pH of 6.5, and a calyceal stone in her left kidney. We performed a sodium bicarbonate loading test and diagnosed distal renal tubular acidosis (RTA). We also found that she had Sjögren's syndrome after a positive screen for anti-Lo, anti-Ra, and after the results of Schirmer's test and a lower lip biopsy. She was discharged and treated as an outpatient with oral sodium bicarbonate and potassium chloride., Conclusion: This case indicates that serum sodium concentrations should be carefully monitored in patients with distal RTA receiving intravenous sodium bicarbonate therapy. We should keep in mind that acute hypernatremia and CPM can be associated with intravenous sodium bicarbonate therapy, and that CPM due to acute hypernatremia may be effectively treated with plasma exchange.

Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.

Background: Intentional massive sodium chloride ingestions are rare occurrences and are often fatal., Objectives: There are a variety of treatment recommendations for hypernatremia, ranging from dialysis to varying rates of correction. We report a case of acute severe hypernatremia corrected with rapid free-water infusions that, to our knowledge, has not been previously reported., Case Report: A 19-year-old man presented to the Emergency Department in a comatose state with seizure-like activity 2 hours after ingesting a quart of soy sauce. He was administered 6 L of free water over 30 min and survived neurologically intact without clinical sequelae. Corrected for hyperglycemia, the patient's peak serum sodium was 196 mmol/L, which, to our knowledge, is the highest documented level in an adult patient to survive an acute sodium ingestion without neurologic deficits., Conclusion: Emergency physicians should consider rapidly lowering serum sodium with hypotonic intravenous fluids as a potential management strategy for acute severe hypernatremia secondary to massive salt ingestion., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Hypernatremia and polyuria are the main symptoms of diabetes insipidus. Polyuria is characterized by a 24-h urine volume in excess of 40-50 ml/kg in adults. Dexmedetomidine, a highly selective, short-acting intravenous alpha-2 agonist, is used as a component of anesthesia, and has been suspected to induce polyuric syndrome. We report a patient who presented with severe hypernatremia and polyuria after intravenous infusion of dexmedetomidine.

Anxiety disorders are the most common psychiatric illnesses and are associated with heightened stress responsiveness. The neuropeptide oxytocin (OT) has garnered significant attention for its potential as a treatment for anxiety disorders; however, the mechanism mediating its effects on stress responses and anxiety is not well understood. Here we used acute hypernatremia, a stimulus that elevates brain levels of OT, to discern the central oxytocinergic pathways mediating stress responsiveness and anxiety-like behavior. Rats were rendered hypernatremic by acute administration of 2.0 M NaCl and had increased plasma sodium concentration, plasma osmolality, and Fos induction in OT-containing neurons relative to 0.15 M NaCl-treated controls. Acute hypernatremia decreased restraint-induced elevations in corticosterone and created an inhibitory oxytocinergic tone on parvocellular neurosecretory neurons within the paraventricular nucleus of the hypothalamus. In contrast, evaluation of Fos immunohistochemistry determined that acute hypernatremia followed by restraint increased neuronal activation in brain regions receiving OT afferents that are also implicated in the expression of anxiety-like behavior. To determine whether these effects were predictive of altered anxiety-like behavior, rats were subjected to acute hypernatremia and then tested in the elevated plus maze. Relative to controls given 0.15 M NaCl, rats given 2.0 M NaCl spent more time in the open arms of the elevated plus maze, suggesting that acute hypernatremia is anxiolytic. Collectively the results suggest that acute elevations in plasma sodium concentration increase central levels of OT, which decreases anxiety by altering neuronal activity in hypothalamic and limbic nuclei.

Objectives: Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline., Design: Retrospective chart analysis., Setting: PICU in university-affiliated children's hospital., Patients: All children from 2004 to 2009 requiring intracranial pressure monitoring (external ventricular drain or fiberoptic intraparenchymal monitor) for at least 4 days who were treated with hypertonic saline infusion for elevated intracranial pressure and did not meet exclusion criteria., Intervention: Continuous hypertonic saline infusion on a sliding scale was used to achieve target sodium levels that would keep intracranial pressure less than 20 mm Hg once the conventional therapies failed., Measurements and Main Results: Eighty-eight children met inclusion criteria. Etiologies of elevated intracranial pressure included trauma (n = 48), ischemic or hemorrhagic stroke (n = 20), infection (n = 8), acute disseminated encephalomyelitis (n = 5), neoplasm (n = 2), and others (n = 5). The mean peak serum sodium was 171.3 mEq/L (range, 150-202). The mean Glasgow Outcome Score was 2.8 (± 1.1) at time of discharge from the hospital. Overall mortality was 15.9%. Children with sustained (> 72 hr) serum sodium levels above 170 mEq/L had a significantly higher occurrence of thrombocytopenia (p < 0.001), renal failure (p < 0.001), neutropenia (p = 0.006), and acute respiratory distress syndrome (p = 0.029) after controlling for variables of age, gender, Pediatric Risk of Mortality score, duration of barbiturate-induced coma, duration of intracranial pressure monitoring, vasopressor requirements, and underlying pathology. Children with sustained serum sodium levels greater than 165 mEq/L had a significantly higher prevalence of anemia (p < 0.001)., Conclusions: Children treated by continuous hypertonic saline infusion for intracranial hypertension whose serum sodium levels exceeded certain thresholds experienced significantly more events of acute renal failure, thrombocytopenia, neutropenia, anemia, and acute respiratory distress syndrome than those whose sodium level was maintained below these thresholds.