Urea for Treatment of SIAD Induced Hyponatremia: Experience of an Oncology Center.

Electrolytes Disturbances and Seizures

Hyponatremia is Associated with Poor Prognosis in Left Ventricular Assist Device Patients

Common Endocrine Issues in the Pediatric Intensive Care Unit

Diagnosis and Treatment of Hyponatremia

Risk of pre-existing hyponatremia and mortality in patients with traumatic brain injury across age groups

SMALL CELL LUNG CARCINOMA WITH THREE PARANEOPLASTIC SYNDROMES IN ONE PATIENT

Hyponatraemia for the clinical endocrinologist

Introduction: When a patient with severe hyponatremia requires renal replacement therapy, a too rapid correction of sodium levels may occur. Manual dilution of the fluids during continuous renal replacement therapy (CRRT) is a method that can lead to a controlled correction of sodium. We present a case and add a systematic review to determine the feasibility of this method. Case Presentation: A female was admitted to the intensive care unit with acute kidney failure due to anti-glomerular basement membrane antibody glomerulonephritis, anuria, and an initial sodium level of 100 mmol/L. She received CRRT with manually diluted fluids for 6 days, in which sodium levels increased from 108 mmol/L to 130 mmol/L. A search in Medline, Web of Science, and Google Scholar was added for the systematic review. The search yielded 49 cases, including the current report, of which 47 were anuric or oliguric, in which the fluids were diluted to a median of 8 mmol/L (interquartile range 5–11) (range 0–17) above the serum sodium, the median CRRT dose was 27 mL/kg/h (22–30) (13–77.5). This led to an increase in serum sodium of 0.2 mmol/L/h (0.1–0.3) (0–0.7). Conclusion: CRRT with manually diluted fluids in patients with severe hyponatremia and anuria can lead to a controlled increase serum sodium, while allowing sufficient RRT dose and fluid removal. Still, errors in dilution may occur and we recommend 4 hourly monitoring of serum sodium levels to timely detect an inadvertent increase in sodium. Introduction: When a patient with severe hyponatremia requires renal replacement therapy, a too rapid correction of sodium levels may occur. Manual dilution of the fluids during continuous renal replacement therapy (CRRT) is a method that can lead to a controlled correction of sodium. We present a case and add a systematic review to determine the feasibility of this method. Case Presentation: A female was admitted to the intensive care unit with acute kidney failure due to anti-glomerular basement membrane antibody glomerulonephritis, anuria, and an initial sodium level of 100 mmol/L. She received CRRT with manually diluted fluids for 6 days, in which sodium levels increased from 108 mmol/L to 130 mmol/L. A search in Medline, Web of Science, and Google Scholar was added for the systematic review. The search yielded 49 cases, including the current report, of which 47 were anuric or oliguric, in which the fluids were diluted to a median of 8 mmol/L (interquartile range 5–11) (range 0–17) above the serum sodium, the median CRRT dose was 27 mL/kg/h (22–30) (13–77.5). This led to an increase in serum sodium of 0.2 mmol/L/h (0.1–0.3) (0–0.7). Conclusion: CRRT with manually diluted fluids in patients with severe hyponatremia and anuria can lead to a controlled increase serum sodium, while allowing sufficient RRT dose and fluid removal. Still, errors in dilution may occur and we recommend 4 hourly monitoring of serum sodium levels to timely detect an inadvertent increase in sodium.

Objective:The aim of this study is to compare the adherence to the guidelines in patients presenting with hyponatremia defined as a sodium (Na) level ⩽120 mEq/L, treated with 3% hypertonic saline or normal saline. The comparison included 3% hypertonic saline use, safe serum sodium increases within 24 and 48 h, frequency of hyponatremia-related complications, and length of stay.Methods:This retrospective observational study enrolled 122 patients with serum sodium ⩽120 mEq/L admitted to the Internal Medicine Department, King Abdulaziz Medical City, National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia, from January 2016 to December 2017. The patients were treated with either 3% hypertonic saline or normal saline.Results:Of the 122 patients, 105 (83.3%) received normal saline, and 17 (13.5%) received hypertonic saline. In the normal saline group, the mean serum sodium increase at 24 h was lower (6.60 ± 4.75) compared to the hypertonic saline group (9.24 ± 5.04). The length of stay was longer in the normal saline group (10.35 ± 13.90) compared to the hypertonic saline group (4.35 ± 3.39). A small proportion (8.7%) of the normal saline group had a serum sodium increase >12 mg/dL at 24 h compared to 29.4% for the hypertonic saline group, and the difference was statistically significant (p value = 0.013). Almost one-third of the sample (36%) presented with complications, the majority (77.3%, n = 34) had a serum sodium of ⩽115 mg/dL, and 22.7% (n = 10) with a serum sodium of 116–120 mg/dL (p value = 0.041).Conclusion:Despite the strong recommendation for 3% hypertonic saline use in severe hyponatremia, many practitioners still use normal saline, even in patients with serum sodium ⩽120 mEq/L. Normal saline showed some efficacy in managing hyponatremia in asymptomatic cases; however, severe cases may have a delayed correction, hyponatremia-related complications, and an extended length of stay.

Hyponatremia causes significant morbidity, mortality, and disability. This review considers the literature of the past 18 months to improve understanding of these complications and to identify therapeutic strategies to prevent them. Acute hyponatremia causes serious brain swelling that can lead to permanent disability or death. A 4-6 mEq/l increase in serum sodium is sufficient to reverse impending herniation. Brain swelling is minimal in chronic hyponatremia, and to avoid osmotic demyelination, correction should not exceed 8 mEq/l/day. In high-risk patients, correction should not exceed 4-6 mEq/l/day. Inadvertent overcorrection of hyponatremia is common and preventable by controlling unwanted urinary water losses with desmopressin. Even mild chronic hyponatremia is associated with increased mortality, attention deficit, gait instability, osteoporosis, and fractures, but it is not known if the correction of mild hyponatremia improves outcomes. Controlled trials are needed to identify affordable treatments for hyponatremia that reduce the need for hospitalization, decrease hospital length of stay, and decrease morbidity. Such trials could also help answer the question of whether hyponatremia causes excess mortality or whether it is simply a marker for severe, lethal, underlying disease.

Chapter 8. Hyperosmolar therapy

Standardized Oral Urea for the Treatment of Hyponatraemic Conditions: Pharmacological and Pharmacoeconomic Consideration

In recent, it has been reported that alternative splicing variant of AIMP2, AIMP2/DX2 (DX2), is frequently expressed in human lung cancer and is related with p53-mediated tumor suppression pathway. Here we show that DX2 can promote tumor progression and increase incidence, cooperatively with oncogenic K-Ras in transgenic mouse model. Moreover, it can induce small cell lung carcinoma (SCLC) as well as contribute to progression of non-small cell lung carcinoma (NSCLC). In fact, DX2 expression is elevated in human small cell lung cancer cell lines. Based on the cellular localization and responsibility of si-DX2, we revealed that DX2 is an inhibitor of p14/ARF. Elimination of DX2 can induce p14/ARF expression and DX2 Transgenic (Tg) mouse cells show the low expression of p19/ARF. Since DX2, but not its original product AIMP2, is selectively interacted with p14/ARF, we screened the specific binding inhibitor and obtained the single compound (SLC36) from about 9000 chemicals. This chemical can block the interaction of p14/ARF-DX2 and also AIMP2-DX2, but not the binding of p14/ARF-p53 or AIMP2-p53. In addition, it can induce p14/ARF expression and cell death in human lung cancer cell lines including SCLC cell lines. In our in vivo study, treatment of SLC36, combined with low dosage of adriamycin (1 mg/kg) can suppress the cancer incidence as well as progression in K-RasLA2 and K-Ras/DX2 double Tg model. These results indicate that DX2 can contribute to lung cancer progression and development, including SCLC, through inhibition of p14/ARF, and blocking of DX2-p14/ARF binding would be useful therapeutic strategy of human lung cancers including SCLC as well as NSCLC. Citation Format: Ah Young Oh, Youn-Sang Jung, Su-Jin Lee, Jung Hyun Jo, Ho Young Chun, Bum-Joon Park. Blocking of p14/ARF and DX2 binding by novel small chemical can improve the chemo-sensitivity of small cell lung cancer and non-small cell lung carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4602. doi:10.1158/1538-7445.AM2014-4602

The treatment of hyponatremia, especially euvolemic and hypervolemic hyponatremia, has changed with the development of drugs which function as vasopressin receptor antagonists. These agents increase solute-free water excretion by the kidney resulting in an aquaresis. Conivaptan, a vasopressin receptor antagonist, has recently been approved by the FDA in the United States for use in the therapy of both euvolemic and hypervolemic hyponatremia. This report summarizes one center's experience with ten patients treated with this new drug. The patients had euvolemic hyponatremia with serum sodium levels less than 128 mEq/l. The same protocol was used in all patients with the conivaptan being given as a 20-mg intravenous loading dose followed by a 20-mg continuous 24-h infusion. Review of the data revealed that six of the ten patients had an excellent response to the therapy, with serum sodium increasing by a mean of 8.5+/-0.8 mEq/l (increases ranged from 7 to 12 mEq/l over 24 h). No significant changes in serum potassium levels or mean arterial pressures were noted. Two of the ten patients experienced a decrease in urine osmolality without a significant increase in serum sodium. Two other patients had only slight decreases in urine osmolality, and no significant increase in serum sodium levels. The data reveal that conivaptan is useful in the management of significant hyponatremia. There were no significant untoward effects, with the exception of one patient whose blood pressure decreased during the conivaptan infusion and who responded to cessation of the infusion and saline replacement therapy. This new class of drugs holds great promise for the treatment of dilutional hyponatremic disorders.

Hyponatremia is the most common electrolyte disorder present in hospitalized patients. Acute and severe hyponatremia can cause significant morbidity and mortality. The present review discusses the epidemiology, causes, and a practical approach to the diagnosis and management of acute and chronic hyponatremia, including the appropriate use of hypertonic saline and potential future use of the new V2 vasopressin receptor antagonists in critically ill patients. The increasing knowledge of aquaporin water channels and the role of vasopressin in water homeostasis have enhanced our understanding of hyponatremic disorders. Increased vasopressin secretion due to nonosmotic stimuli leads to decreased electrolyte-free water excretion with resulting water retention and hyponatremia. Vasopressin receptor antagonists induce electrolyte-free water diuresis without natriuresis and kaliuresis. Phase three trials indicate that these agents predictably reduce urine osmolality, increase electrolyte-free water excretion, and raise serum sodium concentration. They are likely to become a mainstay of treatment of euvolemic and hypervolemic hyponatremia. The correct diagnosis and management of hyponatremia is complex and requires a systematic approach. Vasopressin receptor antagonists are potential tools in the management of hyponatremia. Further studies are needed to determine their role in the treatment of acute, severe, life-threatening hyponatremia as well as chronic hyponatremia.