Desmopressin Acetate (DDAVP) And Hyponatremia: Foe or Friend?
Juan Carlos Ayus, MD, FACP, FASN Director, Renal Consultants of Houston
Case Presentation
27 year old white female admitted to a university teaching hospital for elective cholecystectomy.
Past medical history unremarkable except for a history of central diabetes insipidus on intra-nasal DDAVP therapy.
Physical examination was non revealing. Electrolytes, serum creatinine, urinalysis, complete blood cell count, chest x-ray, EKG were within normal limits.
She was placed on intranasal DDAVP at a dose of 10 mcg twice daily which is her chronically prescribe outpatient dose.
Post operative period
Patient underwent cholecystectomy, immediate post-operative course was unremarkable.
The patient started on D51/2 NS with 10mEq KCI at 120 ml per hour, dilaudid 1 mg IV every four hours was ordered as needed for pain, and phenergan 25 mg IV as needed for nausea.
Twelve hours post operatively she was awake and alert, but complained of nausea. She vomited once and was treated with intravenous phenergan.
Twenty-four hours post operatively she complained of severe prefrontal headache, continued to have nausea and vomiting. Was treated with additional doses of dilaudid and phenergan.
Forty eight hours post operatively the patient was found in respiratory distress. Physical examination also revealed temperature 100, blood pressure 165/85 mmHg, heart rate 66 beats/min and significant physical findings.
Post operative period
Laboratory examination revealed Serum Na+ 111 mEq/l, K+ 3.8 mEq/l, Cl– 86 mEq/l, C02– 24 mEq/l, BUN 4 mg/dl, creatinine 0.4 mg/dl, glucose 90 mg/dl, uric acid 2.3 mg/dl. Serum osmolality 238 mOsm/l. Urine Osm 610 mOsm/l. Arterial blood gasses: pH 7.32, PO2,44 mmHg, PCO2, 48 mmHg. Hgb 11.2 g/l, hct 35%. Chest x-ray showed evidence of pulmonary edema. Pulmonary capillary wedge pressure is 8 mm Hg.
Clinical course summary
In summary, this patient has noncardiogenic pulmonary edema, respiratory distress and hyponatremic encephalopathy.
Why did hyponatremia develop in this patient?
Mechanism of action DDAVP
DDAVP (Desmopressin) acts on the collecting tubule to enhance water reabsorption by increasing AQ-2 channels in the collecting duct and thereby inhibiting water excretion
Why did hyponatremia develop in this patient? The simultaneous administration of DDAVP and hypotonic IV fluids.
How would you treat this patient?
Discontinue DDAVP and give 3% hypertonic saline?
Give tolvaptam?
Discontinue DDAVP and give tolvaptam?
This patient was given 3% hypertonic saline and DDAVP was withheld
Subsequent events
The patient made clinical improvement within a few hours.
Eight hours later the urine output increased to 300 cc/hour, and the urine osmolality fell to 60 mOsm/l. Serum sodium rose to 144 mEq/l within 48 hours.
Serum sodium remained in this range and on the 6th hospital day the patient deteriorated neurologically and ultimately survived with permanent brain damage.
Why did this patient develop brain damage?
Discontinuing DDAVP allowed for a free water diuresis and therefore “autocorrection” of the serum sodium occurred. Additionally, hypertonic saline was given to the patient producing significant overcorrection of the serum sodium.
Giving Tolvaptam would have made the situation worse.
Desmopressin Acetate (DDAVP) Associated Hyponatremia and Brain Damage: A Case Series
Study design was a case series of 15 cases involving patient s treated with DDAVP either for central diabetes insipidus (77%) or von Willebrand’s disease (23%).
All patients developed clinically significant hyponatremia associated with DDAVP use.
All patients were treated by withholding DDAVP and providing intravenous saline. The mean change in serum sodium in the first 1-2 days was 37.1 mEq/L.
Consequences of discontinuing DDAVP therapy and giving hypertonic saline
Achinger SG, Arieff AI, Kalantar-Zadeh K, Ayus JC. Nephrol Dial Transplant 29(12): 2310-5, 2014
Consequences of discontinuing DDAVP therapy and giving hypertonic saline
Achinger SG, Arieff AI, Kalantar-Zadeh K, Ayus JC. Desmopressin acetate (DDAVP) - associated hyponatremia and brain damage: a case series. Nephrol Dial Transplant 29(12): 2310-5, 2014
Treatment of DDAVP associated hyponatremia while continuing the medication
Achinger SG, Arieff AI, Kalantar-Zadeh K, Ayus JC. Desmopressin acetate (DDAVP) - associated hyponatremia and brain damage: a case series. Nephrol Dial Transplant 29(12): 2310-5, 2014
Use of DDAVP to slow correction of hyponatremia during water diuresis
Approach to the management of DDAVP associated hyponatremia
Achinger SG, Arieff AI, Kalantar-Zadeh K, Ayus JC. Nephrol Dial Transplant 29(12): 2310-5, 2014
Achinger SG. Disorders of plasma sodium. N Engl J Med 372(13):1267-8, 2015
Key points
DDAVP should never be stopped when treating DDAVP associated hyponatremia and neurological symptoms are present
Give hypertonic saline to treat the hyponatremia while continuing DDAVP therapy
Hypotonic fluids should never be given to a patient receiving DDAVP in the hospital
