Hyponatremia desmopressin

Desmopressin is sometimes used in mild Hemophilia A and Von Willebrand s disease. In December 2007, US drug regulators banned using desmopressin nasal sprays for treating bedwetting after two children died from hyponatremia. 

Desmopressin Activates vasopressin V2 receptors much more than Vi Acts in the kidney to decrease the excretion of water acts on extrarenal V2 receptors Pituitary diabetes insipidus hemophilia A and von Willebrand disease Oral, IV, SC, or intranasal Toxicity Gastrointestinal disturbances, headache, hyponatremia, allergic... 

Hyponatremia has often been reported with desmopressin although significant hyponatremia is rare, provided that guidelines are adhered to (38,39). 

The pharmacokinetics of one dose of desmopressin 400 micrograms have been investigated in 15 men and nine women with nocturia aged over 65 years (40). They then entered a placebo-controlled crossover evaluation period. Peak concentrations occurred at 1-2 hours after administration and gradually fell over 6-7 hours. The women had significantly higher concentrations than the men, even after adjustment for body weight. Four women were withdrawn from the crossover period because of hyponatremia. 

In 224 women aged 20-89 years, desmopressin 0.1—0.4 mg/day was used for treating nocturia (43). There were five adverse events, four of which were reported in the dose-titration period. Of these four events, two were deaths that were not thought to be due to hyponatremia and two were due to serious hyponatremia. The fifth case occurred during the double-blind period in the placebo group. In 27 patients serum sodium concentrations were below the reference range and in 13 they were less than 130 mmol/1 11 of the 13 were aged 65 years or older. 

A 3.5-year-old girl with mild hemophilia A received desmopressin 0.3 micrograms/kg intravenously 30 minutes before adenotonsillectomy. She drank 600 ml of fluid within the first 10 hours and then received 300 ml of intravenous 5% dextrose in 0.45% saline. She developed hyponatremia, headache, nausea, and seizures. 

A potential risk of desmopressin is of water intoxication with resultant hyponatremia (48), and rapid falls in serum sodium concentration can result in seizures. The risk is increased in infants and patients receiving hypotonic intravenous fluids, and such patients need to be carefully monitored. 

An 80-year-old woman with a high baseline fluid intake developed severe hyponatremia, with loss of consciousness and seizures, after a single dose of desmopressin 0.2 mg (49). 

An 89-year-old woman, who had previously been stable on desmopressin, developed severe hyponatremia and became confused and unresponsive after an increase in fluid intake (49). 

A 47-year-old woman with von Willebrand disease, who was given desmopressin and intravenous fluids perioperatively, developed hyponatremia and seizures, which resolved after water restriction (50). 

In a double-blind study of desmopressin, 10 of 224 adult men had serum sodium concentrations below 130 mmol/1 during a 3-week, open, dose-titration period. Men aged 65 years and over were more likely to develop hyponatremia (51). 

In a double-blind, crossover study, 20 men aged 52-80 years were given desmopressin for nocturia. Three of them had symptoms due to fluid retention, particularly bloating, headache, and reversible weight gain, and two of these had a significant fall in plasma sodium (53). In a meta-analysis of 14 studies of serum sodium in 529 patients treated with desmopressin there was mild asymptomatic hyponatremia in up to 10% of patients (54). 

Fluid balance and plasma electrolytes should be monitored to prevent this complication, particularly if repeated doses are required. Children seem to be particularly vulnerable to this complication (55). In a longterm, open study of 245 Swedish children given intranasal desmopressin 20-40 micrograms at night for enuresis, five had an asymptomatic fall in plasma sodium (36). Mild hyponatremia, which did not cause symptoms, was found in five of 399 children in an open, multicenter trial (56). 

In a 12-year-old boy taking desmopressin for nocturnal enuresis, hyponatremia and cerebral edema developed after high fluid intake before a urodynamic procedure... 

There have been several reports of seizures in association with hyponatremia after intravenous administration of desmopressin to cover surgery in young children with congenital bleeding disorders such as mild hemophilia A or von Willebrand s disease (58-60). Hyponatremia and convulsions have occurred in children without congenital bleeding disorders who received desmopressin for urine concentration tests or to treat nocturnal enuresis (54,61,62). 

Carbamazepine increases the release of endogenous antidiuretic hormone and can therefore potentiate the antidiuretic effect of desmopressin. Of 103 children with cranial diabetes insipidus included in a retrospective analysis, 10% became hyponatrcmic (76). The risk of hyponatremia was three-fold higher when desmopressin and carbamazepine were given in combination. 

Weatherall M. The risk of hyponatremia in older adults using desmopressin for nocturia a systematic review and meta-analysis. Neurourol Urodyn 2004 23 302-5. 

Norgaard JP. Hyponatremia in desmopressin treated patients—what is evidence based J Urol Urogynakol 2004 11 7. 

Odeh M, Oliven A. Coma and seizures due to severe hyponatremia and water intoxication in an adult with intranasal desmopressin therapy for nocturnal enuresis. J Clin Pharmacol 2001 41(5) 582-4. 

Shindel A, Tobin G, Klutke C. Hyponatremia associated with desmopressin for the treatment of nocturnal polyuria. Urology 2002 60(2) 344. 

Pruthi RS, Kang J, Vick R. Desmopressin induced hyponatremia and seizures after laparoscopic radical nephrectomy. J Urol 2002 168(1) 187. 

Brodzikowska-Pytel A, Giembicki J. Hyponatremia as a complication of nocturnal enuresis treatment with desmopressin in a child. Pediatr Pol 1999 74 79-83. 

Shepherd LL, Hutchinson RJ, Worden EK, Koopmann CF, Coran A. Hyponatremia and seizures after intravenous administration of desmopressin acetate for surgical hemostasis. J Pediatr 1989 114(3) 470-2. 

In two children with cranial diabetes insipidus, desmopressin requirements fell while they were taking lamotrigine (590). Lamotrigine may act at voltage-sensitive sodium channels and reduce calcium conductance. Both of these mechanisms of action are shared by carbamaze-pine, which can cause hyponatremia secondary to inappropriate secretion of antidiuretic hormone. 

One report described adverse reactions in two pregnant women with von Willebrand disease (59). One went into premature labor after a single dose (attributed to the oxytocic effect of desmopressin) and the other had severe hyponatremia associated with seizures after repeated administration of desmopressin to cover a cesarean section. 

Infrequent adverse effects of desmopressin spray include nasal irritation, epistaxis, rhinitis, and nasal congestion, whereas desmopressin tablets or spray may cause transient headache, chills, dizziness, nausea, and abdominal pain. Rarely, water intoxication, hyponatremia, and subsequent tonic-clonic seizures have been reported, " particularly in children with concurrent physical disorders, intentional overdoses, or excessive fluid intake. When desmopressin is administered, evening fluids should be limited to 8 ounces to prevent hyponatremia or water intoxication. ... 

C. Toxicity In the presence of ADH or desmopressin, a large water load may cause dangerous hyponatremia. Large doses of either peptide may cause hypertension in some individuals. 

Nervous system The safety of desmopressin in children with primary monosjmiptomatic nocturnal enuresis has been reviewed [86 ]. After 61 cases of seizures, including two deaths, the FDA asked that the prescribing information be changed in 2007 to state that desmopressin spray is no longer indicated for monosymptomatic nocturnal enuresis or in patients at risk of hyponatremia. The authors of the review concluded that hyponatremia often resulted from inappropriately high doses of desmopressin and usually occurs in the elderly people they supported continuing the use of desmopressin to treat monosymptomatic nocturnal enuresis imder appropriate medical supervision. Hyponatremia has been reported more commonly with the spray than with the oral formulation this may reflect differences in pharmacokinetics or more extensive evaluation of the spray. 

---