Anesthesiology 2008; 109:1063–76 Copyright © 2008, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Desmopressin Reduces Transfusion Needs after Surgery A Meta-analysis of Randomized Clinical Trials Giuseppe Crescenzi, M.D.,* Giovanni Landoni, M.D.,* Giuseppe Biondi-Zoccai, M.D.,† Federico Pappalardo, M.D.,‡ Massimiliano Nuzzi, M.D.,‡ Elena Bignami, M.D.,‡ Oliviero Fochi, M.D.,§ Giulia Maj, M.D.,§ Maria Grazia Calabro ` , M.D.,‡ Marco Ranucci, M.D., Alberto Zangrillo, M.D.# Background: Perioperative pathologic microvascular bleed- ing is associated with increased morbidity and mortality and could be reduced by hemostatic drugs. At the same time, safety concerns regarding existing hemostatic agents include excess mortality. Numerous trials investigating desmopressin have lacked power to detect a beneficial effect on transfusion of blood products. The authors performed a meta-analysis of 38 randomized, placebo-controlled trials (2,488 patients) investi- gating desmopressin in surgery and indicating at least periop- erative blood loss or transfusion of blood products. Methods: Pertinent studies were searched in BioMed Central, CENTRAL, and PubMed (updated May 1, 2008). Further hand or computerized searches involved recent (2003–2008) conference proceedings. Results: In most of the included studies, 0.3 g/kg desmo- pressin was used prophylactically over a 15- to 30-min pe- riod. In comparison with placebo, desmopressin was associ- ated with reduced requirements of blood product transfusion (standardized mean difference 0.29 [0.52 to 0.06] units per patient; P  0.01), which were more pronounced in the subgroup of noncardiac surgery and were without a statisti- cally significant increase in thromboembolic adverse events (57/1,002  5.7% in the desmopressin group vs. 45/979  4.6% in the placebo group; P  0.3). Conclusions: Desmopressin slightly reduced blood loss (almost 80 ml per patient) and transfusion requirements (almost 0.3 units per patient) in surgical patients, without reduction in the proportion of patients who received transfu- sions. This meta-analysis suggests the importance of further large, randomized controlled studies using desmopressin in patients with or at risk of perioperative pathologic microvascu- lar bleeding. MAJOR bleeding and need for transfusions are common complications of surgical procedures and have been asso- ciated with poor postoperative and long-term outcomes. 1,2 Efforts to minimize the use of limited resources such as blood products are essential, and the most obvious and probably the most effective strategy is to improve surgical techniques and hemostatic management. The most extensively studied hemostatic agents in- clude recombinant activated factor VII, aprotinin, des- mopressin (DDAVP), and the antifibrinolytic lysine ana- logs aminocaproic acid and tranexamic acid. The safety of aprotinin has recently been questioned, 3 and the safety of recombinant activated factor VII in major sur- gery is still under investigation. DDAVP, originally developed and licensed for the treatment of inherited defects of hemostasis, given by slow intravenous infusion at a dose of 0.3 g/kg, acts by releasing ultralarge von Willebrand factor multimers from endothelial cells, leading to an enhancement of primary hemostasis. 4,5 In 1986, Salzman et al. 6 suggested that DDAVP reduces blood loss and transfusion require- ments by approximately 30%, as compared with pla- cebo, during complex cardiac surgery. Subsequent at- tempts to reproduce these findings encountered variable results: Many published trials were not adequately pow- ered to assess clinically relevant outcomes, and several reviews concluded that although DDAVP helps to re- duce perioperative blood loss, its effect is too small to influence other more clinically relevant outcomes, such as the need for blood products. 7–10 A recent review states that there is little evidence that DDAVP is effica- cious in conditions other than mild hemophilia A and von Willebrand disease, 1 and the most recent meta-anal- ysis 10 concluded that, because there is no clear benefi- cial effect of using DDAVP to reduce blood loss or minimize transfusion with allogenic blood, further pla- cebo-controlled trials of DDAVP as an adjunct to surgery in patients who do not have bleeding disorders seem to be unwarranted. Moreover, safety issues have been re- peatedly raised: The main concern is that the use of a procoagulant drug may induce thromboembolic compli- cations, especially in patients at high risk. To address these issues, we conducted a systematic review and meta-analysis of data pooled from existing trials with the purpose of determining the impact of DDAVP on transfusion needs and to evaluate the risk of adverse events, namely thromboembolic complications. Materials and Methods Search Strategy Pertinent studies were independently searched in BioMed Central, CENTRAL, and PubMed (updated May 1, * Assistant Professor, ‡ Staff Anesthesiologist, § Resident in Anesthesiology, # Full Professor, Department of Cardiothoracic Anesthesia and Intensive Care, Universita ` Vita-Salute San Raffaele, Milano, Italia e Istituto Scientifico San Raffaele. † Assistant Professor, Interventional Cardiology, Division of Cardiol- ogy, University of Turin, Turin, Italy.  Head of Department, Department of Cardiothoracic Anesthesia and Intensive Care, IRCCS Policlinico S. Donato, San Donato Milanese, Italy. Received from the Department of Cardiothoracic Anesthesia and Intensive Care, Universita ` Vita-Salute San Raffaele, Milano, Italia e Istituto Scientifico San Raffaele, Milan, Italy. Submitted for publication April 6, 2008. Accepted for publication July 15, 2008. Support was provided solely from institutional and/or departmental sources. Dr. Landoni has received a grant from Kedrion S.p.A. Loc Ai Conti (a drug company producing desmopressin), Lucca, Italy, to perform a review on hemostatic agents in surgery. Address correspondence to Dr. Landoni: Department of Cardiothoracic Anesthesia and Intensive Care, Istituto Scientifico San Raffaele, Via Olgettina 60 Milano, 20132 Italy. landoni.giovanni@hsr.it. This article may be accessed for per- sonal use at no charge through the Journal Web site, www.anesthesiology.org. Anesthesiology, V 109, No 6, Dec 2008 1063