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• W1964485917 abstract "To the Editor: An 83-year-old man was diagnosed with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in 2009, when he developed severe symptomatic hyponatremia (sodium 119 mmol/L) after a respiratory tract infection. He was taking levothyroxine for hypothyroidism. He was unable to tolerate demeclocycline because he had hepatitis, and since then, his sodium had been maintained at approximately 125 mmol/L with fluid restriction. In December 2011, he fell and fractured his hip. At that time, his sodium was 123 mmol/L. He had a hemiarthroplasty and was hospitalized for 6 weeks. In February 2012, he was admitted after a seizure. Laboratory tests showed sodium 118 mmol/L, urea 5.2 mmol/L, and creatinine 62 μmol/L. Despite strict fluid restriction, his sodium did not improve, and he remained confused and disoriented. He was started on tolvaptan 15 mg on alternate days to avoid rapid correction. He had profuse diuresis, and by Day 4 (just after two doses), his sodium had increased to 133 mmol/L and his urea from 5 to 16 mmol/L, and his symptoms had improved dramatically. To avoid overcorrection and renal failure, tolvaptan was stopped, and fluid restriction was restarted, but his sodium fell to 119 mmol/L, and his symptoms returned within 2 days, so it was decided to try tolvaptan once a week. To avoid wide fluctuations in his sodium, he was advised to drink until thirst is eliminated for 4 days after taking tolvaptan and to restrict his fluids 3 days before the next dose. His sodium increased by 2 to 3 mmol/L per day for 3 days after tolvaptan and fell by 1 to 2 mmol/L per day after Day 3, and he remained symptom free. After discharge, he took tolvaptan 15 mg once a week for 12 months and then 15 mg every 6 days because of tiredness and lethargy returning 5 days after taking tolvaptan. During this period, his sodium fluctuated around 125 mmol/L (range 122–133 mmol/L; Figure 1). Despite the fluctuation in his sodium, he remained asymptomatic and had not been admitted to the hospital. In February 2014, he was admitted with sepsis and died of multiorgan failure nearly 2 years after taking tolvaptan. Hyponatremia is the most frequent electrolyte imbalance in elderly adults, and severe hyponatremia (sodium < 125 mmol/L) is found in up to 6% of hospitalized older adults.1 Hyponatremia due to SIADH is often chronic and asymptomatic, but sodium levels of less than 125 mmol/L can cause unsteadiness, falls, attention deficit, and fractures in elderly adults.2, 3 Even though fluid restriction is effective, it is difficult to sustain over the long term. Tolvaptan is a vasopressin receptor antagonist and is effective in the treatment of hyponatremia due to SIADH by promoting free water excretion.4-6 Adverse effects include thirst, dehydration, and too-rapid correction of sodium (which can lead to complications). In clinical trials, 7% of participants had an increase in serum sodium of 8 mmol/L at 8 hours, and 2% had an increase of more than 12 mmol/L at 24 hours.6 The major constraints in using this drug are its cost, rapid correction with the risk of osmotic demyelination syndrome, rebound hyponatremia after stopping the drug, and uncertainty regarding long-term use. Concerns have also been raised in using this drug over the long term because it could cause liver injury, and the Food and Drug Administration has warned that tolvaptan should not be used for longer than 30 days,7 although this advice stems from a study in autosomal-dominant polycystic kidney disease in which tolvaptan was used at much higher doses (average dose 95 mg/d) for longer periods (total duration of the trial was 36 months).8 So whether the risk is similar when used intermittently in lower doses is unclear. The man in the current study was made aware of this complication and was happy to continue with the current regime with close monitoring. To summarize, chronic hyponatremia due to SIADH is common and mostly asymptomatic and could be managed by fluid restriction, but in individuals with significant morbidity and recurrent hospitalizations due to hyponatremia not responding to fluid restriction, intermittent tolvaptan combined with fluid restriction should be considered. When used appropriately, it is still cheaper than recurrent hospital admissions and the morbidity and mortality associated with hyponatremia. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors had an active role in management of the patient. All contributed to the article. Sponsor's Role: None." @default.
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• W1964485917 date "2014-07-01" @default.
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• W1964485917 title "Once-Weekly Tolvaptan for Chronic Symptomatic Hyponatremia Due to Syndrome of Inappropriate Secretion of Anti-Diuretic Hormone" @default.
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• W1964485917 doi "https://doi.org/10.1111/jgs.12917" @default.
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