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Special Issue "Hyponatremia: Advances in Diagnosis and Management"

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383).

Deadline for manuscript submissions: closed (31 July 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Lewis S. Blevins

California Center for Pituitary Disorders, University of California, San Francisco, 400 Parnassus Ave., A-808, San Francisco, California 94143-0350, USA
Website | E-Mail
Phone: 1-866/559-5543
Fax: 415/353-4970
Interests: pituitary tumors; hypopituitarism; acromegaly; prolactinoma; transsphenoidal pituitary surgery

Special Issue Information

Dear Colleagues,

Advances in molecular in cell biology have led to important discoveries leading to new therapies in all fields of medicine. This is particularly true in the story of the syndrome of inappropriate anti-diuresis (SIADH), wherein the cloning of the vasopressin receptor has led to drug development for the treatment of euvolemic and hypervolemic hyponatremia, disorders that have been recognized since the advent of accurate and reliable laboratory determinations of the serum sodium. Evaluation and management of patients with hyponatremia has always been based on clinical judgment and is subject to individual interpretation of findings in the clinical context of presentation and recent treatments. Therapies for hyponatremia, including fluid restriction, saline and lasix, 3% saline, and demeclocycline are less than ideal, poorly understood, and often ineffective. Development of a class of drugs known as the vaptans has revolutionized the treatment of euvolemic and hypervolemic hyponatremia.

This Special Issue focuses on compulsive particles that reflect our understanding of the pathophysiology and treatment of hyponatremia and associated consequences.

Prof. Dr. Lewis S. Blevins
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • hyponatremia
  • SIADH
  • cerebral salt wasting
  • osmotic demyelination
  • arginine vasopressin receptor
  • arginine vasopressin receptor blockers
  • vaptans, tolvaptan

Published Papers (16 papers)

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Research

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Open AccessArticle Implications of Hyponatremia in Liver Transplantation
J. Clin. Med. 2015, 4(1), 66-74; doi:10.3390/jcm4010066
Received: 8 August 2014 / Accepted: 5 December 2014 / Published: 29 December 2014
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Abstract
Although there are a limited number of quality studies, appropriate peri-operative management of serum electrolytes seems to reduce adverse outcomes in liver transplantation. Hyponatremia is defined as the presence of serum concentration of sodium equal ≤130 mmol/L and it is detected in approximately
[...] Read more.
Although there are a limited number of quality studies, appropriate peri-operative management of serum electrolytes seems to reduce adverse outcomes in liver transplantation. Hyponatremia is defined as the presence of serum concentration of sodium equal ≤130 mmol/L and it is detected in approximately 20% of patients with end stage liver disease waiting for a liver transplant (LT). This paper will focus on the pathogenesis of dilutional hyponatremia and its significance in terms of both candidacy for LT and post-operative outcomes. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessCommunication Hyponatremia and the Thyroid: Causality or Association?
J. Clin. Med. 2015, 4(1), 32-36; doi:10.3390/jcm4010032
Received: 29 August 2014 / Accepted: 5 December 2014 / Published: 26 December 2014
Cited by 2 | PDF Full-text (86 KB) | HTML Full-text | XML Full-text
Abstract
Thyroid disorders, particularly hypothyroidism, have historically been implicated in the development of serum hyponatremia. However, in more recent years, this paradigm has been challenged, and it has been suggested that the link between hypothyroidism and hyponatremia may merely be an association. This review
[...] Read more.
Thyroid disorders, particularly hypothyroidism, have historically been implicated in the development of serum hyponatremia. However, in more recent years, this paradigm has been challenged, and it has been suggested that the link between hypothyroidism and hyponatremia may merely be an association. This review will focus on the thyroid and its link with serum hyponatremia, and review the available literature on the topic. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessArticle Hyponatremia in Patients with Spontaneous Intracerebral Hemorrhage
J. Clin. Med. 2014, 3(4), 1322-1332; doi:10.3390/jcm3041322
Received: 29 August 2014 / Revised: 28 October 2014 / Accepted: 31 October 2014 / Published: 20 November 2014
PDF Full-text (144 KB) | HTML Full-text | XML Full-text
Abstract
Hyponatremia is the most frequently encountered electrolyte abnormality in critically ill patients. Hyponatremia on admission has been identified as an independent predictor of in-hospital mortality in patients with spontaneous intracerebral hemorrhage (sICH). However, the incidence and etiology of hyponatremia (HN) during hospitalization in
[...] Read more.
Hyponatremia is the most frequently encountered electrolyte abnormality in critically ill patients. Hyponatremia on admission has been identified as an independent predictor of in-hospital mortality in patients with spontaneous intracerebral hemorrhage (sICH). However, the incidence and etiology of hyponatremia (HN) during hospitalization in a neurointensive care unit following spontaneous intracerebral hemorrhage (sICH) remains unknown. This was a retrospective analysis of consecutive patients admitted to Detroit Receiving Hospital for sICH between January 2006 and July 2009. All serum Na levels were recorded for patients during the ICU stay. HN was defined as Na <135 mmol/L. A total of 99 patients were analyzed with HN developing in 24% of sICH patients. Patients with HN had an average sodium nadir of 130 ± 3 mmol/L and an average time from admission to sodium <135 mmol/L of 3.9 ± 5.7 days. The most common cause of hyponatremia was syndrome of inappropriate antidiuretic hormone (90% of HN patients). Patients with HN were more likely to have fever (50% vs. 23%; p = 0.01), infection (58% vs. 28%; p = 0.007) as well as a longer hospital length of stay (14 (8–25) vs. 6 (3–9) days; p < 0.001). Of the patients who developed HN, fifteen (62.5%) patients developed HN in the first week following sICH. This shows HN has a fairly high incidence following sICH. The presence of HN is associated with longer hospital length of stays and higher rates of patient complications, which may result in worse patient outcomes. Further study is necessary to characterize the clinical relevance and treatment of HN in this population. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessArticle Hyponatraemia in Emergency Medical Admissions—Outcomes and Costs
J. Clin. Med. 2014, 3(4), 1220-1233; doi:10.3390/jcm3041220
Received: 16 August 2014 / Revised: 6 October 2014 / Accepted: 10 October 2014 / Published: 29 October 2014
Cited by 1 | PDF Full-text (1018 KB) | HTML Full-text | XML Full-text
Abstract
Healthcare systems in the developed world are struggling with the demand of emergency room presentations; the study of the factors driving such demand is of fundamental importance. From a database of all emergency medical admissions (66,933 episodes in 36,271 patients) to St James’
[...] Read more.
Healthcare systems in the developed world are struggling with the demand of emergency room presentations; the study of the factors driving such demand is of fundamental importance. From a database of all emergency medical admissions (66,933 episodes in 36,271 patients) to St James’ Hospital, Dublin, Ireland, over 12 years (2002 to 2013) we have explored the impact of hyponatraemia on outcomes (30 days in-hospital mortality, length of stay (LOS) and costs). Identified variables, including Acute Illness Severity, Charlson Co-Morbidity and Chronic Disabling Disease that proved predictive univariately were entered into a multivariable logistic regression model to predict the bivariate of 30 days in-hospital survival. A zero truncated Poisson regression model assessed LOS and episode costs and the incidence rate ratios were calculated. Hyponatraemia was present in 22.7% of episodes and 20.3% of patients. The 30 days in-hospital mortality rate for hyponatraemic patients was higher (15.9% vs. 6.9% p < 0.001) and the LOS longer (6.3 (95% CI 2.9, 12.2) vs. 4.0 (95% CI 1.5, 8.2) p < 0.001). Both parameters worsened with the severity of the initial sodium level. Hospital costs increased non-linearly with the severity of initial hyponatraemia. Hyponatraemia remained an independent predictor of 30 days in-hospital mortality, length of stay and costs in the multi-variable model. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Figures

Open AccessArticle Incidence, Etiology and Outcomes of Hyponatremia after Transsphenoidal Surgery: Experience with 344 Consecutive Patients at a Single Tertiary Center
J. Clin. Med. 2014, 3(4), 1199-1219; doi:10.3390/jcm3041199
Received: 30 July 2014 / Revised: 23 September 2014 / Accepted: 27 September 2014 / Published: 28 October 2014
Cited by 2 | PDF Full-text (839 KB) | HTML Full-text | XML Full-text
Abstract
Hyponatremia is often seen after transsphenoidal surgery and is a source of considerable economic burden and patient-related morbidity and mortality. We performed a retrospective review of 344 patients who underwent transsphenoidal surgery at our institution between 2006 and 2012. Postoperative hyponatremia was seen
[...] Read more.
Hyponatremia is often seen after transsphenoidal surgery and is a source of considerable economic burden and patient-related morbidity and mortality. We performed a retrospective review of 344 patients who underwent transsphenoidal surgery at our institution between 2006 and 2012. Postoperative hyponatremia was seen in 18.0% of patients at a mean of 3.9 days postoperatively. Hyponatremia was most commonly mild (51.6%) and clinically asymptomatic (93.8%). SIADH was the primary cause of hyponatremia in the majority of cases (n = 44, 71.0%), followed by cerebral salt wasting (n = 15, 24.2%) and desmopressin over-administration (n = 3, 4.8%). The incidence of postoperative hyponatremia was significantly higher in patients with cardiac, renal and/or thyroid disease (p = 0.0034, Objective Risk (OR) = 2.60) and in female patients (p = 0.011, OR = 2.18) or patients undergoing post-operative cerebrospinal fluid drainage (p = 0.0006). Treatment with hypertonic saline (OR = −2.4, p = 0.10) and sodium chloride tablets (OR = −1.57, p = 0.45) was associated with a non-significant trend toward faster resolution of hyponatremia. The use of fluid restriction and diuretics should be de-emphasized in the treatment of post-transsphenoidal hyponatremia, as they have not been shown to significantly alter the time-course to the restoration of sodium balance. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessArticle Neurosurgical Hyponatremia
J. Clin. Med. 2014, 3(4), 1084-1104; doi:10.3390/jcm3041084
Received: 3 August 2014 / Revised: 11 September 2014 / Accepted: 22 September 2014 / Published: 14 October 2014
Cited by 1 | PDF Full-text (1051 KB) | HTML Full-text | XML Full-text
Abstract
Hyponatremia is a frequent electrolyte imbalance in hospital inpatients. Acute onset hyponatremia is particularly common in patients who have undergone any type of brain insult, including traumatic brain injury, subarachnoid hemorrhage and brain tumors, and is a frequent complication of intracranial procedures. Acute
[...] Read more.
Hyponatremia is a frequent electrolyte imbalance in hospital inpatients. Acute onset hyponatremia is particularly common in patients who have undergone any type of brain insult, including traumatic brain injury, subarachnoid hemorrhage and brain tumors, and is a frequent complication of intracranial procedures. Acute hyponatremia is more clinically dangerous than chronic hyponatremia, as it creates an osmotic gradient between the brain and the plasma, which promotes the movement of water from the plasma into brain cells, causing cerebral edema and neurological compromise. Unless acute hyponatremia is corrected promptly and effectively, cerebral edema may manifest through impaired consciousness level, seizures, elevated intracranial pressure, and, potentially, death due to cerebral herniation. The pathophysiology of hyponatremia in neurotrauma is multifactorial, but most cases appear to be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Classical treatment of SIADH with fluid restriction is frequently ineffective, and in some circumstances, such as following subarachnoid hemorrhage, contraindicated. However, the recently developed vasopressin receptor antagonist class of drugs provides a very useful tool in the management of neurosurgical SIADH. In this review, we summarize the existing literature on the clinical features, causes, and management of hyponatremia in the neurosurgical patient. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessArticle Actual Therapeutic Indication of an Old Drug: Urea for Treatment of Severely Symptomatic and Mild Chronic Hyponatremia Related to SIADH
J. Clin. Med. 2014, 3(3), 1043-1049; doi:10.3390/jcm3031043
Received: 25 July 2014 / Revised: 26 August 2014 / Accepted: 9 September 2014 / Published: 18 September 2014
Cited by 5 | PDF Full-text (707 KB) | HTML Full-text | XML Full-text
Abstract
Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH) or
[...] Read more.
Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH) or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS) in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessArticle Hyponatremia: A Risk Factor for Early Overt Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation
J. Clin. Med. 2014, 3(2), 359-372; doi:10.3390/jcm3020359
Received: 11 February 2014 / Revised: 4 March 2014 / Accepted: 7 March 2014 / Published: 4 April 2014
Cited by 1 | PDF Full-text (345 KB) | HTML Full-text | XML Full-text
Abstract
Hepatic encephalopathy (HE) is a frequent complication in cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). Hyponatremia (HN) is a known contributing risk factor for the development of HE. Predictive factors, especially the effect of HN, for the development of overt HE within
[...] Read more.
Hepatic encephalopathy (HE) is a frequent complication in cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). Hyponatremia (HN) is a known contributing risk factor for the development of HE. Predictive factors, especially the effect of HN, for the development of overt HE within one week of TIPS placement were assessed. A single-center, retrospective chart review of 71 patients with cirrhosis who underwent TIPS creation from 2006–2011 for non-variceal bleeding indications was conducted. Baseline clinical and laboratory characteristics were collected. Factors associated with overt HE within one week were identified, and a multivariate model was constructed. Seventy one patients who underwent 81 TIPS procedures were evaluated. Fifteen patients developed overt HE within one week. Factors predictive of overt HE within one week included pre-TIPS Na, total bilirubin and Model for End-stage Liver Disease (MELD)-Na. The odds ratio for developing HE with pre-TIPS Na <135 mEq/L was 8.6. Among patients with pre-TIPS Na <125 mEq/L, 125–129.9 mEq/L, 130–134.9 mEq/L and ≥135 mEq/L, the incidence of HE within one week was 37.5%, 25%, 25% and 3.4%, respectively. Lower pre-TIPS Na, higher total bilirubin and higher MELD-Na values were associated with the development of overt HE post-TIPS within one week. TIPS in hyponatremic patients should be undertaken with caution. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)

Review

Jump to: Research

Open AccessReview Hyponatremia Associated with Heart Failure: Pathological Role of Vasopressin-Dependent Impaired Water Excretion
J. Clin. Med. 2015, 4(5), 933-947; doi:10.3390/jcm4050933
Received: 8 August 2014 / Revised: 19 February 2015 / Accepted: 7 April 2015 / Published: 8 May 2015
Cited by 3 | PDF Full-text (432 KB) | HTML Full-text | XML Full-text
Abstract
An exaggerated increase in circulatory blood volume is linked to congestive heart failure. Despite this increase, reduction of the “effective circulatory blood volume” in congestive heart failure is associated with decreased cardiac output, and can weaken the sensitivity of baroreceptors. Thereafter, tonic inhibition
[...] Read more.
An exaggerated increase in circulatory blood volume is linked to congestive heart failure. Despite this increase, reduction of the “effective circulatory blood volume” in congestive heart failure is associated with decreased cardiac output, and can weaken the sensitivity of baroreceptors. Thereafter, tonic inhibition of the baroreceptor-mediated afferent pathway of vagal nerves is removed, providing an increase in non-osmotic release of arginine vasopressin (AVP). In the renal collecting duct, the aquaporin-2 (AQP2) water channel is regulated by sustained elevation of AVP release, and this leads to augmented hydroosmotic action of AVP, that results in exaggerated water retention and dilutional hyponatremia. Hyponatremia is also a predictor for worsening heart failure in patients with known/new onset heart failure. Therefore, such a dilutional hyponatremia associated with organ damage is predictive of the short- and long-term outcome of heart failure. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessReview Diagnosis and Management of Hyponatremia in Patients with Aneurysmal Subarachnoid Hemorrhage
J. Clin. Med. 2015, 4(4), 756-767; doi:10.3390/jcm4040756
Received: 26 September 2014 / Revised: 26 December 2014 / Accepted: 10 April 2015 / Published: 21 April 2015
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Abstract
Hyponatremia is the most common, clinically-significant electrolyte abnormality seen in patients with aneurysmal subarachnoid hemorrhage. Controversy continues to exist regarding both the cause and treatment of hyponatremia in this patient population. Lack of timely diagnosis and/or providing inadequate or inappropriate treatment can increase
[...] Read more.
Hyponatremia is the most common, clinically-significant electrolyte abnormality seen in patients with aneurysmal subarachnoid hemorrhage. Controversy continues to exist regarding both the cause and treatment of hyponatremia in this patient population. Lack of timely diagnosis and/or providing inadequate or inappropriate treatment can increase the risk of morbidity and mortality. We review recent literature on hyponatremia in subarachnoid hemorrhage and present currently recommended protocols for diagnosis and management. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessReview Hyponatremia in Patients with Cirrhosis of the Liver
J. Clin. Med. 2015, 4(1), 85-101; doi:10.3390/jcm4010085
Received: 22 October 2014 / Accepted: 18 December 2014 / Published: 31 December 2014
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Abstract
Hyponatremia is common in cirrhosis. It mostly occurs in an advanced stage of the disease and is associated with complications and increased mortality. Either hypovolemic or, more commonly, hypervolemic hyponatremia can be seen in cirrhosis. Impaired renal sodium handling due to renal hypoperfusion
[...] Read more.
Hyponatremia is common in cirrhosis. It mostly occurs in an advanced stage of the disease and is associated with complications and increased mortality. Either hypovolemic or, more commonly, hypervolemic hyponatremia can be seen in cirrhosis. Impaired renal sodium handling due to renal hypoperfusion and increased arginine-vasopressin secretion secondary to reduced effective volemia due to peripheral arterial vasodilation represent the main mechanisms leading to dilutional hyponatremia in this setting. Patients with cirrhosis usually develop slowly progressing hyponatremia. In different clinical contexts, it is associated with neurological manifestations due to increased brain water content, where the intensity is often magnified by concomitant hyperammonemia leading to hepatic encephalopathy. Severe hyponatremia requiring hypertonic saline infusion is rare in cirrhosis. The management of asymptomatic or mildly symptomatic hyponatremia mainly rely on the identification and treatment of precipitating factors. However, sustained resolution of hyponatremia is often difficult to achieve. V2 receptor blockade by Vaptans is certainly effective, but their long-term safety, especially when associated to diuretics given to control ascites, has not been established as yet. As in other conditions, a rapid correction of long-standing hyponatremia can lead to irreversible brain damage. The liver transplant setting represents a condition at high risk for the occurrence of such complications. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Figures

Open AccessReview Differentiating SIADH from Cerebral/Renal Salt Wasting: Failure of the Volume Approach and Need for a New Approach to Hyponatremia
J. Clin. Med. 2014, 3(4), 1373-1385; doi:10.3390/jcm3041373
Received: 7 July 2014 / Revised: 26 August 2014 / Accepted: 9 September 2014 / Published: 8 December 2014
Cited by 3 | PDF Full-text (122 KB) | HTML Full-text | XML Full-text
Abstract
Hyponatremia is the most common electrolyte abnormality. Its diagnostic and therapeutic approaches are in a state of flux. It is evident that hyponatremic patients are symptomatic with a potential for serious consequences at sodium levels that were once considered trivial. The recommendation to
[...] Read more.
Hyponatremia is the most common electrolyte abnormality. Its diagnostic and therapeutic approaches are in a state of flux. It is evident that hyponatremic patients are symptomatic with a potential for serious consequences at sodium levels that were once considered trivial. The recommendation to treat virtually all hyponatremics exposes the need to resolve the diagnostic and therapeutic dilemma of deciding whether to water restrict a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or administer salt and water to a renal salt waster. In this review, we briefly discuss the pathophysiology of SIADH and renal salt wasting (RSW), and the difficulty in differentiating SIADH from RSW, and review the origin of the perceived rarity of RSW, as well as the value of determining fractional excretion of urate (FEurate) in differentiating both syndromes, the high prevalence of RSW which highlights the inadequacy of the volume approach to hyponatremia, the importance of changing cerebral salt wasting to RSW, and the proposal to eliminate reset osmostat as a subtype of SIADH, and finally propose a new algorithm to replace the outmoded volume approach by highlighting FEurate. This algorithm eliminates the need to assess the volume status with less reliance on determining urine sodium concentration, plasma renin, aldosterone and atrial/brain natriuretic peptide or the BUN to creatinine ratio. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessReview Physiopathological, Epidemiological, Clinical and Therapeutic Aspects of Exercise-Associated Hyponatremia
J. Clin. Med. 2014, 3(4), 1258-1275; doi:10.3390/jcm3041258
Received: 21 August 2014 / Revised: 24 October 2014 / Accepted: 24 October 2014 / Published: 12 November 2014
PDF Full-text (334 KB) | HTML Full-text | XML Full-text
Abstract
Exercise-associated hyponatremia (EAH) is dilutional hyponatremia, a variant of inappropriate antidiuretic hormone secretion (SIADH), characterized by a plasma concentration of sodium lower than 135 mEq/L. The prevalence of EAH is common in endurance (<6 hours) and ultra-endurance events (>6 hours in duration), in
[...] Read more.
Exercise-associated hyponatremia (EAH) is dilutional hyponatremia, a variant of inappropriate antidiuretic hormone secretion (SIADH), characterized by a plasma concentration of sodium lower than 135 mEq/L. The prevalence of EAH is common in endurance (<6 hours) and ultra-endurance events (>6 hours in duration), in which both athletes and medical providers need to be aware of risk factors, symptom presentation, and management. The development of EAH is a combination of excessive water intake, inadequate suppression of the secretion of the antidiuretic hormone (ADH) (due to non osmotic stimuli), long race duration, and very high or very low ambient temperatures. Additional risk factors include female gender, slower race times, and use of nonsteroidal anti-inflammatory drugs. Signs and symptoms of EAH include nausea, vomiting, confusion, headache and seizures; it may result in severe clinical conditions associated with pulmonary and cerebral edema, respiratory failure and death. A rapid diagnosis and appropriate treatment with a hypertonic saline solution is essential in the severe form to ensure a positive outcome. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Figures

Open AccessReview Review of Tolvaptan’s Pharmacokinetic and Pharmacodynamic Properties and Drug Interactions
J. Clin. Med. 2014, 3(4), 1276-1290; doi:10.3390/jcm3041276
Received: 22 August 2014 / Revised: 15 October 2014 / Accepted: 24 October 2014 / Published: 12 November 2014
Cited by 3 | PDF Full-text (189 KB) | HTML Full-text | XML Full-text
Abstract
Tolvaptan is an arginine vasopressin (AVP) antagonist that acts to increase excretion of free water (aquaresis) in patients without introducing electrolyte abnormalities or worsening renal function. It works via blockade of vasopressin-2 receptors at the renal collecting duct. Since the approval of tolvaptan
[...] Read more.
Tolvaptan is an arginine vasopressin (AVP) antagonist that acts to increase excretion of free water (aquaresis) in patients without introducing electrolyte abnormalities or worsening renal function. It works via blockade of vasopressin-2 receptors at the renal collecting duct. Since the approval of tolvaptan for the treatment of hypervolemic and euvolemic hyponatremia in 2009, new studies have been reported to better characterize its pharmacokinetic and pharmacodynamic profile of tolvaptan. This paper is a review of both these clinical studies, as well as previous literature, in order to help guide appropriate clinical use of tolvaptan in patients. With appropriate monitoring of serum sodium, tolvaptan may be safely dose escalated from 15 mg once daily to a maximum effective dose of 60 mg once daily for multiple days, to achieve optimal aqauretic effects. In terms of drug interactions, co-administration of moderate to potent CYP3A4 inhibitors and inducers should be avoided. Tolvaptan should also be co-administered with caution and proper monitoring in the presence of P-glycoprotein substrate and strong inhibitors. Co-administration of tolvaptan with diuretic therapy did not appear to alter the aquaretic effect of tolvaptan; and was shown to be safe and well tolerated. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessReview Effects of Hyponatremia on the Brain
J. Clin. Med. 2014, 3(4), 1163-1177; doi:10.3390/jcm3041163
Received: 25 July 2014 / Revised: 18 September 2014 / Accepted: 10 October 2014 / Published: 28 October 2014
Cited by 3 | PDF Full-text (1254 KB) | HTML Full-text | XML Full-text
Abstract
Hyponatremia is a very common electrolyte disorder, especially in the elderly, and is associated with significant morbidity, mortality and disability. In particular, the consequences of acute hyponatremia on the brain may be severe, including permanent disability and death. Also chronic hyponatremia can affect
[...] Read more.
Hyponatremia is a very common electrolyte disorder, especially in the elderly, and is associated with significant morbidity, mortality and disability. In particular, the consequences of acute hyponatremia on the brain may be severe, including permanent disability and death. Also chronic hyponatremia can affect the health status, causing attention deficit, gait instability, increased risk of falls and fractures, and osteoporosis. Furthermore, an overly rapid correction of hyponatremia can be associated with irreversible brain damage, which may be the result of the osmotic demyelination syndrome. This review analyzes the detrimental consequences of acute and chronic hyponatremia and its inappropriate correction on the brain and the underlying physiopathological mechanisms, with a particular attention to the less known in vivo and in vitro effects of chronic hyponatremia. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)
Open AccessReview Hyponatremia: Special Considerations in Older Patients
J. Clin. Med. 2014, 3(3), 944-958; doi:10.3390/jcm3030944
Received: 17 June 2014 / Revised: 7 July 2014 / Accepted: 18 July 2014 / Published: 18 August 2014
Cited by 6 | PDF Full-text (752 KB) | HTML Full-text | XML Full-text
Abstract
Hyponatremia is especially common in older people. Recent evidence highlights that even mild, chronic hyponatremia can lead to cognitive impairment, falls and fractures, the latter being in part due to bone demineralization and reduced bone quality. Hyponatremia is therefore of special significance in
[...] Read more.
Hyponatremia is especially common in older people. Recent evidence highlights that even mild, chronic hyponatremia can lead to cognitive impairment, falls and fractures, the latter being in part due to bone demineralization and reduced bone quality. Hyponatremia is therefore of special significance in frail older people. Management of hyponatremia in elderly individuals is particularly challenging. The underlying cause is often multi-factorial, a clear history may be difficult to obtain and clinical examination is unreliable. Established treatment modalities are often ineffective and carry considerable risks, especially if the diagnosis of underlying causes is incorrect. Nevertheless, there is some evidence that correction of hyponatremia can improve cognitive performance and postural balance, potentially minimizing the risk of falls and fractures. Oral vasopressin receptor antagonists (vaptans) are a promising innovation, but evidence of their safety and effect on important clinical outcomes in frail elderly individuals is limited. Full article
(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)

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