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Desborough MJ, Oakland K, Brierley C, et al. Desmopressin use for minimising perioperative blood transfusion. Cochrane Database Syst Rev. 2017;7(7):CD001884.

Study Population: Patients with normal platelets: 25 trials (1806 patients) of DDAVP versus placebo evaluating red cell transfusion, 22 trials (1631 patients) evaluating mortality, and 29 trials (1984 patients) evaluating thrombotic events

Patients with abnormal platelets: 5 trials (258 patients) of DDAVP versus placebo evaluating red cell transfusion, 7 trials (422 patients) evaluating mortality, and 7 trials (422 patients) evaluating thrombotic events

Efficacy Endpoints

Transfusion requirement and all-cause mortality

Harm Endpoints

Thrombotic events

Narrative

Desmopressin (DDAVP) is a synthetic analogue of vasopressin that stimulates release of von Willebrand factor and promotes platelet adhesion and aggregation, and is therefore typically used for treatment of von Willebrand disease and hemophilia1^, 2^, 3 Some professional societies, however, recommend perioperative DDAVP for the prevention of blood loss and blood product transfusion in patients with bleeding and platelet dysfunction.4^, 5^, 6

The Cochrane Review discussed here included randomized controlled trials (RCTs) evaluating adult and pediatric patients with or without platelet dysfunction who received subcutaneous or intravenous perioperative DDAVP.7 Platelet function was defined as prolonged bleeding time, abnormal Platelet Function Analyzer closure times, or taking antiplatelet medications. Studies including patients with known hemophilia or von Willebrand disease were excluded. Primary outcomes included the number of patients receiving red blood cell transfusion during the procedure or within 30 days, volume transfused, and blood loss in milliliters. Secondary outcomes included all-cause mortality within 30 days, thrombotic events, reoperations due to bleeding, bleeding events during or within 30 days, hypotension within 30 days, and quality of life.

The authors identified 65 RCTs (n = 3874) that met inclusion criteria. For this summary, we focused on studies evaluating DDAVP versus placebo or no treatment in patients with and without platelet dysfunction. Included studies examined DDAVP in one or two doses of 0.2-0.4 micrograms/kilogram, 20 micrograms once, or 15-45 micrograms based on weight. Timing of administration varied, including preoperative, operative, or postoperative. Settings included adult and pediatric cardiac surgery, orthopedic surgery, vascular surgery, plastic surgery, hepatic surgery, kidney biopsy, and maxillofacial surgery.

Overall, there were no significant differences in efficacy endpoints such as transfusion requirements, all-cause mortality, or thrombotic events (quality of evidence: Low). These results remained the same when analysis was repeated in the subgroup of patients with platelet dysfunction.

In addition to thrombotic events, the Cochrane review reports on what the authors term ‘clinically important hypotension’, which was more common in patients receiving DDAVP (RR: 2.9; 95% CI: 1.3 to 6.3; ARD: 5.9%, NNH: 17). Unfortunately, the Cochrane review did not define clinically important hypotension, and definitions were variable and often arbitrary in the original trials. Therefore, we did not list this endpoint in the summary table.

Caveats

There was variable quality of evidence for the included studies, preventing strong conclusions. Evidence quality was moderate for blood transfusion requirement in patients with normal platelet function, but low to very low for all other outcomes and populations. As a result, the authors of the review were unable to pool the data for volume of blood transfused and blood loss. Additionally, mortality and thrombotic events were rare, and studies were therefore underpowered to assess these outcomes. The patient populations were heterogeneous with regard to age, comorbidities, and DDAVP dosing. The most common studied groups were adult cardiac surgery and orthopedic surgery, accounting for 51 trials, with under-representation of other surgeries. The majority of trials were conducted over two decades ago and may not reflect current settings. Less than one third of trials included patients receiving DDAVP preoperatively, and there were no trials evaluating patients with thrombocytopenia or coagulopathy. Finally, most of the included trials did not provide sufficient information for assessment of risk of bias.

When compared to placebo, DDAVP is associated with no clinical difference in patients with normal or abnormal platelet function in red blood cell transfusion, all-cause mortality, or thrombotic complications. Based on this evidence, we have assigned a color recommendation of Red (No benefit). Further data, however, are needed to better evaluate the role of DDAVP in current settings, those with coagulopathies or on antiplatelet medications, and administration based on platelet function or viscoelastic tests.

Author

Brit Long, MD; Michael Gottlieb, MD
Supervising Editors: Shahriar Zehtabchi, MD

Published/Updated

February 3, 2021