U014
Severe
refractory hyponatraemia secondary to syndrome of
inappropriate antidiuretic hormone secretion treated with Tolvaptan
M Kostoula, V Bravis, S Robinson, J Cox
Introduction: Syndrome of inappropriate antidiuretic
hormone secretion (SIADH) accounts for approximately 30% hyponatraemia
cases. Therapeutic modalities include nonspecific measures (fluid restriction,
hypertonic saline, demeclocycline). Recently,
vasopressin receptor antagonists have been introduced as specific, direct
therapy of SIADH.
Case: A 53-year-old female with a history of
non-small cell lung cancer and multiple brain metastases was admitted
unresponsive with [Na+] 114 mmol/L.
Clinical and biochemical assessment led to a diagnosis of SIADH and she was
treated with a combination of fluid restriction, hypertonic saline and demeclocycline. She was discharged with [Na+]
129 mmol/L, on demeclocycline
therapy. She subsequently represented with impaired level of consciousness (GCS
9/15) and [Na+] 110 mmol/L. The diagnosis
was again SIADH. After 24-hour treatment with hypertonic saline and 1L/day
fluid restriction, she improved to GCS 11/15 and [Na+] 113 mmol/L. The trial of demeclocycline
was deemed unsuccessful and the drug was stopped, whilst hypertonic saline with
fluid restriction were continued. 48 hours later [Na+] was 115 mmol/L, so the fluid
restriction changed to 500mls/day. By day 8 of admission [Na+]
reached 130 mmol/L. In view
of the background of metastatic malignancy, the recurrent severe hyponatraemia and the severity of the clinical
presentations, the decision was made to initiate low dose Tolvaptan
therapy, in order to facilitate her discharge and decrease the risk of
recurrence. 8 hours after the first 15mg dose, the patient developed a
headache, complained of thirst and became polyuric.
Her [Na+] had increased to 142 mmol/L and
her urinary [Na+]
had dropped to <20 mmol/L, with urine osmolality
of 81 mOsm/kg, in the context of clinical
hypovolaemia. The Tolvaptan-induced aquaresis was reversed with oral and intravenous
rehydration and the drug was withheld for 24 hours. A further 24 hours later,
the patient was euvolaemic with [Na+] 137 mmol/L. A 7.5mg dose of Tolvaptan
was re-trialled and 24 hours later the [Na+] was 131
mmol/L. She was discharged on that dose with
close and frequent metabolic day ward reviews and strict instructions for home
fluid balance monitoring. She currently remains normonatraemic
and undergoing palliative chemotherapy.
Discussion: Tolvaptan is a competitive vasopressin receptor antagonist
and has some evidence-base for the treatment of refractory SIADH.
Hypersensitivity to Tolvaptan leading to excessive aquaresis is rare, but can occur. Vaptans can be considered in patients with refractory
SIADH-induced hyponatraemia, in the context of
chronic illness, to facilitate outpatient management, particularly
when other drug therapies have failed and unsustainable fluid restriction
remains unrealistic in the community setting.