Uncontrolled uremic bleeding? – Reach for the Desmopressin.
Patients with end stage renal disease frequently present to the emergency department with bleeding that can be difficult to control. Desmopressin (DDAVP), one of the medications on the World Health Organization’s list of essential medicines [1], is a synthetic octapeptide that has a variety of uses, from reversing anti-platelet effects in intracranial hemorrhage, to reducing renal colic pain, to preventing bed-wetting in children. Its main ED indications are to help stop bleeding in uremic patients, and to manage bleeding in select patients with von Willebrand disease, though the management is much more complicated.
How It Works
Desmopressin is a synthetic analog of endogenous vasopressin (Anti-Diuretic Hormone). Vasopressin is synthesized in the hypothalamus and released by the posterior pituitary in response to dehydration, and functions by increasing water reabsorption in the renal distal convoluted tubules and collecting ducts. It also increases sodium absorption in the loop of Henle, which allows greater concentration of the urine through countercurrent multiplication. At high concentrations, usually in a shock state, it causes peripheral vasoconstriction which increases blood pressure. Vasopressin also triggers release of factor VIII and von Willebrand factor from endothelial cells. The half-life of vasopressin is about 20 minutes. Desmopressin has similar actions, except it lacks the vasopressor activity, and it has a longer half-life of 2-4 hours.
Major Indications
Desmopressin is approved for use in patients with diabetes insipidus, nocturia, nocturnal enuresis, type 1 von Willebrand disease (VWD), and hemophilia A. The treatment of patients with VWD with desmopressin is complex [2-4]. Bleeding patients with type 1 VWD are likely to respond to desmopressin administration. However, some patients with severe type 1, type 2, or with acquired VWD will not respond. Patients with type 3 VWD will not respond, and some patients with type 2B may actually worsen. Therefore it is important to ascertain whether the patient has been tested with desmopressin in the past, or discuss management with their hematologist if possible before ad- ministration. In the ED desmopressin is most often used off-label for the treatment of uremic bleeding in patients with acute or chronic renal failure. Uremia causes platelet dysfunction and increases bleeding through a number of mechanisms [5]. In the ED, patients with chronic renal failure may present with prolonged bleeding, including epistaxis, bleeding from dialysis catheter access or other venipuncture sites, or GI bleeding. After treatment, bleeding time is shortened for up to 24 hours [5].
Recently In The News For
Recent studies of the effect of desmopressin and platelet administration on rates of progression of traumatic intracranial hemorrhage showed no effect on early radiographic hemorrhage progression [6]. Desmopressin has also been studies in combination with morphine for treatment of renal colic, and no added benefit of desmopressin was found [7]. However, a similar study looking at ketorolac with or without desmopressin did show a small improvement in pain with the added desmopressin [8].
Adverse Events
Side effects are non-specific and generally self-limited. Patients may experience headaches or dizziness, nausea, or abdominal pain. With the intranasal desmopressin they may develop rhinitis or local irritation. Because desmopressin increases water reabsorption, it can cause hyponatremia with multiple dose treatment, in which case water restriction may be necessary.
Cautions
Single dose treatments in the ED are unlikely to have significant side effects. Rare side effects related to thrombotic events include CVA and myocardial infarction [9]. Desmopressin is pregnancy class B. It has been used in breast-feeding women, and is destroyed by proteases in infant’s GI tract, so is unlikely to have a significant absorption by the infant [10].
Dosing Adjustments
For uremic bleeding, treatment is with 0.4mcg/kg IV over 10 minutes. The manufacturer’s instructions advise against use if CrCl <50. However, it is frequently used off-label in hemodialysis patients. It is excreted primarily in the urine, so the half-life, normally 2-4 hours, may increase up to 9 hours in patients with renal impairment. There are no hepatic or geriatric dosing adjustments. Administration for other indications can be PO or intranasal. However, only 10-20% is absorbed through the intranasal route.
Cost
The IV solution of 4mcg/mL (1mL) costs around $85 [9]. A 100kg individual would require 40mcg IV for uremic bleeding.
REFERENCES
- World Health Organization. WHO model lists of essential medicines – 19th edition. http://www.who.int/medicines/publications/essentialmedicines/en/. Published 04/2015. Updated 2015. Accessed 02/29, 2016.
- Federici AB. The use of desmopressin in von willebrand disease: The experience of the first 30 years (1977-2007). Haemophilia. 2008;14 Suppl 1:5-14.
- Rick ME. Treatment of von willebrand disease. In: Leung LL, Tirnauer JS, eds. UpToDate. ; 2015. uptodate.com. Accessed 02/29/2016.
- Livesey K, Yealy DM, Li J, Moore CG, Ragni MV. Von willebrand disease in the emergency department. Haemophilia. 2015.
- Hedges SJ, Dehoney SB, Hooper JS, Amanzadeh J, Busti AJ. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol. 2007;3(3):138-153.
- Kim DY, O’Leary M, Nguyen A, et al. The effect of platelet and desmopressin administration on early radiographic progression of traumatic intracranial hemorrhage. J Neurotrauma. 2015;32(22):1815-1821.
- Keshvari Shirvani M, Darabi Mahboub M, Ghazi M, Delijani A. A comparison of the effects of morphine and sublingual desmopressin combination therapy with morphine alone in treatment of renal colic: A controlled clinical trial. Urol J. 2015;12(1):2001-2004.
- Masoumi K, Asgari Darian A, Forouzan A, et al. The efficacy of intranasal desmopressin as an adjuvant in the acute renal colic pain management. Pain Res Treat. 2014;2014:320327.
- Lexicomp. Desmopressin: Drug information. UptoDate.
- Hale TW. Medications and mothers’ milk: A manual of lactational pharmacology. 12th ed. Amarillo, TX: Hale Publishing L.P.; 2012:1331.
