Refractory Hyponatremia in a Patient with Malignancy: A Role for Tolvaptan

Introduction: Tolvaptan may be a valuable adjunct in carefully selected cases of refractory hyponatremia. Recent studies support the safety of using oral tolvaptan in malignant ascites and it suggests that its use be considered more often but its success depends on preserved renal free water clearance. Case Description: A 45-year-old woman with stage IV pancreatic adenocarcinoma and antiphospholipid syndrome presented with lethargy following an outpatient paracentesis. She had decreased oral intake, fatigue, and a transient episode of unresponsiveness after taking her prescribed hydromorphone. On arrival, vital signs were notable for hypothermia (95°F) and hypotension (66/48 mm Hg). Physical examination revealed a cachectic appearance, right lower lobe crackles, a distended abdominal with shifting dullness, and 3+ pitting edema up to the knees. Initial labs showed: serum sodium 125 mmol/L, BUN 38 mg/dL, serum creatine 2.0mg/dL and serum albumin 2.5 g/dL. Urine sodium was < 20 mmol/L and urine osmolality was 598mOsm/kg. CT imaging demonstrated right middle lobe consolidation and significant metastatic disease burden, including IVC compression. She was admitted for sepsis secondary to aspiration pneumonia and upper gastrointestinal bleeding. She received 1.5L of intravenous crystalloids but remained hypotensive. Her serum sodium was low at 124 mmol/L at this time. She was given albumin and droxidopa for persistent low blood pressure and Nephrology was consulted for evaluation of persistent hyponatremia. The patient was started on urea and placed on a 1L/day fluid restriction. Despite these measures, her serum sodium remained unchanged. On hospital day 4, she was initiated on 3% hypertonic saline, repeated over 2 days without significant improvement in serum sodium. At this time, she remained oliguric with creatine rising to 3.6 mg/dL though neurologically intact. With limited therapeutic options and ongoing hyponatremia, the patient was started on tolvaptan 7.5mg. Discussion: This case highlights the complexity of managing hyponatremia in patients with advanced malignancy and multiple comorbidities. The etiology of this patient’s hyponatremia is multifactorial including hypervolemia from hypoalbuminemia, non-osmotic ADH release from hypotension and sepsis, reduced solute intake and possible SIADH from malignancy. Tolvaptan was utilized because conventional management was challenged by contraindications.