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Thromb Haemost 1995; 74(04): 1064-1070
DOI: 10.1055/s-0038-1649883
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

Marco Cattaneo
1   The A. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, University of Milano, Italy
,
Alan S Harris
2   The Biomedicum, University of Uppsala, Sweden
,
Ulf Strömberg
3   The Dept. of Mathematical Statistics, Lund University, Sweden
,
Pier Mannuccio Mannucci
1   The A. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, University of Milano, Italy
› Author Affiliations
Further Information

Publication History

Received 10 May 1995

Accepted 28 June 1995

Publication Date:
09 July 2018 (online)

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Summary

The effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

 

  • References

  • 1 Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood 1990; 76: 1680-1697
    PubMedGoogle Scholar
  • 2 Kucuk O, Kwaan HC, Frederikson J, Wade L, Green D. Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation. Am J Hematol 1986; 23: 223-239
    CrossrefPubMedGoogle Scholar
  • 3 Harker LA, Malpass TW, Branson HE, Hessel EA, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction with selective-granule release. Blood 1980; 56: 824-834
    PubMedGoogle Scholar
  • 4 Páramo JA, Rifón J, Llorens R, Casares J, Paloma MJ, Rocha E. Intra- and postoperative fibrinolysis in patients undergoing cardiopulmonary bypass surgery. Haemostasis 1991; 21: 58-64
    PubMedGoogle Scholar
  • 5 Khuri SF, Michelson AD, Valeri CR. Effects of cardiopulmonary bypass on hemostasis. In: Thrombosis and Haemorrhage. Loscalzo J, Schafer AI. eds. New York: Blackwell Scientific Publications; 1993. pp 1051-1073
    Google Scholar
  • 6 Bick RL, Schmalhorst WR, Arbegast NR. Alterations of hemostasis associated with cardiopulmonary bypass. Am J Clin Pathol 1975; 63: 588
    PubMedGoogle Scholar
  • 7 Bick RL. Hemostasis defects associated with cardiac surgery, prosthetic devices, and other extracorporeal circuits. Semin Thromb Haemost 1985; 11: 249-280
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Edmunds LH, Ellison N, Colman RW, Niewiarowski S, Rao AK, Addonizio Jr VP, Stephenson LW, Edie RN. Platelet function during cardiac operation. Comparison of membrane and bubble oxygenators J Thorac Cardiovasc Surg 1982; 83: 805-812
    PubMedGoogle Scholar
  • 9 Mannucci PM, Canciani MT, Rota L, Donovan BS. Response of factor VUI/von Willebrand factor to DDAVP in healthy subjects and patients with haemophilia A and von Willebrand’s disease. Br J Haematol 1981; 47: 283-293
    CrossrefPubMedGoogle Scholar
  • 10 Mannucci PM, Remuzzi G, Pusineri F, Lombardi R, Valsecchi C, Mecca G, Zimmerman TS. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med 1983; 308: 8-12
    CrossrefPubMedGoogle Scholar
  • 11 Kobrinsky NL, Israels ED, Gerrard JM, Walson CM, Bishop AJ, Schroeder ML. Shortening of bleeding time by I -deamino-8-D-arginine vasopressin in various bleeding disorders. Lancet 1984; 1: 1145-1148
    PubMedGoogle Scholar
  • 12 Mannucci PM. Desmopressin: A nontransl’usional form of treatment for congenital and aquired bleeding disorders. Blood 1988; 72: 1449-1455
    PubMedGoogle Scholar
  • 13 Czer LS C, Bateman TM, Grau RJ, Raymond M, Stewart ME, Lee S, Goldfinger D, C’haux A, Matloll JM. Treatment of severe platelet dysfunction and hemorrhage after cardiopulmonary bypass: Reduction in blood product usage with desmopressin. J Am Coll Cardiol 1987; 9: 1139-1147
    CrossrefPubMedGoogle Scholar
  • 14 Salzman EW, Weinstein MJ, Weintraub RM, Ware JA, Tluirer RL, Robertson L, Donovan A, Gaffney T, Bertel V, Troll J, Smith M, Chute LE. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery. N Engl J Med 1986; 314: 1402-1406
    CrossrefPubMedGoogle Scholar
  • 15 Sacks HS, Berrier J, Rcitman D, Ancona-Berk VA, Chalmers TC. Metaanalyses of randomized controlled trials. N Engl J Med 1987; 316: 450-455
    CrossrefPubMedGoogle Scholar
  • 16 Seear MD, Wadsworth ED, Rogers PC, Sheps S, Ashmore PG. The effect of desmopressin acetate (DDAVP) on postoperative blood loss after cardiac operations in children. J Thorac Cardiovasc Surg 1989; 98: 217-219
    PubMedGoogle Scholar
  • 17 Lazcnby WD, Russo I, Zadek BJ, Zelano JA, Ko W, Lynch CC, Isom OW, Krieger KH. Treatment with desmopressin acetate in routine coronary bypass surgery to improve postoperative hemostasis. Circulation 1990; 82 (Suppl. 05) Suppl 4: 413-419
    PubMedGoogle Scholar
  • 18 Jahr JS, Marquez J, Cottington E, Cook R. Hemodynamic performance and histamine levels after desmopressin acetate administration following cardiopulmonary bypass in adult patients. J Cardiothorac Vase Anesth 1991; 5: 139-141
    CrossrefPubMedGoogle Scholar
  • 19 Lo Cicero III J, Massad M, Matano J. Effect of desmopressin acetate on hemorrhage without identifiable cause in coronary bypass patients. The American Surgeon 1991; 57: 165-168
    PubMedGoogle Scholar
  • 20 Chuang H-I, Horng Y-J, Li Y, Chern F-C, Shieh D-Y, Chiou I-S, ShuhShiun J. Clinical assessment of desmopressin to reduce blood loss in patients after cardiopulmonary bypass. Acta Anaesthesiol Sin 1993; 31: 35-42
    PubMedGoogle Scholar
  • 21 de Prost D, Barbier-Boehm G, Hazebroucq J, Ibrahim H, Bielsky MC, Hvass U, Lacombe C, Fransais JL, Desmonths JM. Desmopressin has no beneficial effect in excessive postoperative bleeding or blood product requirements associated with cardiopulmonary bypass. Thromb Haemost 1992; 68: 106-110
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Salmenpera M, Kuitunen A, Hynynen M, Heinonen J. Hemodynamic responses to desmopressin acetate after CABG: A double-blind trial. J Cardiothoracic Vase Anesth 1991; 5: 146-149
    PubMedGoogle Scholar
  • 23 Kuitunen AH. Haemostatic responses to desmopressin acetate after primary coronary artery bypass surgery. Ann Chirurg Gynaecol 1992; 81: 11-18
    PubMedGoogle Scholar
  • 24 Mongan PD, Hosking MP. The role of desmopressin acetate in patients undergoing coronary artery bypass surgery. A controlled clinical trial with thromboelastographic risk stratification Anesthesiology 1992; 77: 38-46
    CrossrefPubMedGoogle Scholar
  • 25 Gratz I, Koehler J, Olsen D, Afshar M, DeCastro N, Spagna PM, Ablaza SG, Larijani GE. The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations. J Thorac Cardiovasc Surg 1992; 104: 1417-1422
    PubMedGoogle Scholar
  • 26 Marquez J, Koehler S, Strelec SR, Benckart DH, Spero JA, Cottington EM, Torpey DJ. Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: A prospective, blinded, randomized study. J Cardiothorac Vase Anesth 1992; 6: 674-676
    CrossrefPubMedGoogle Scholar
  • 27 Andersson TL G, Solem JO, Tengborn L, Vinge E. Effects of desmopressin acetate on platelet aggregation, von Willebrand factor, and blood loss after cardiac surgery with extracorporeal circulation. Circulation 1990; 81: 872-878
    CrossrefPubMedGoogle Scholar
  • 28 Hedderich GS, Petsikas DJ, Cooper BA, Leznoff M, Guerraty AJ, Poirier NL, Symes JF, Morin JE. Desmopressin acetate in uncomplicated coronary artery bypass surgery: a prospective randomized clinical trial. Can J Surg 1991; 33: 33-36
    PubMedGoogle Scholar
  • 29 Reich DL, Hammerschlag BC, Rand JH, Weiss-Bloom L, Perucho H, Galla J, Thys DM. Desmopressin acetate is a mild vasodilator that does not reduce blood loss in uncomplicated cardiac surgical procedures. J Cardiothorac Vase Anesth 1991; 5: 142-145
    CrossrefPubMedGoogle Scholar
  • 30 Horrow JC, van Riper DF, Strong MD, Brodsky I, Parmet JL. Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery. Circulation 1991; 84: 2063-2070
    CrossrefPubMedGoogle Scholar
  • 31 Brown MR, Swygert TH, Whitten CW, Hebeler R. Desmopressin acetate following cardiopulmonary bypass: Evaluation of coagulation parameters. J Cardiothorac Anesth 1989; 3: 726-729
    CrossrefPubMedGoogle Scholar
  • 32 Spyt TJ, Weerasena NA, Bain WH, Lowe GD O, Rumley A. The effects of desmopressin acetate (DDAVP) on haemostasis and blood loss in routine coronary artery bypass surgery. A randomized double-blind trial Perfusion 1990; 5 Suppl 57-61
    PubMedGoogle Scholar
  • 33 Frankville DD, Harper GB, Lake GL, Johns RA. Hemodynamic consequences of desmopressin administration after cardio-pulmonary bypass. Anesthesiology 1991; 74: 988-996
    CrossrefPubMedGoogle Scholar
  • 34 Joucken K, Collard E, Mayne A, Simon M, Randour PH. Is the bleeding post coronary-artery bypass grafting reduced after prophylactic administration of desmopressin. European Association of Cardiothoracic Anaesthesiologists Lyon-Villeurbanne; France: 08.06.1988
    Google Scholar
  • 35 Ansell J, Klassen V, Lew R, Ball S, Weinstein M, VanderSalm T, Okike N, Gratz I, Leslie J, Roberts A, Fleming N, Salzman P. Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations. J Thoracic Cardiovasc Surg 1992; 104: 117-123
    PubMedGoogle Scholar
  • 36 Dilthey G, Dietrich W, Spannagl M, Richter JA. Influence of desmopressin acetate (DDAVP) on homologous blood requirement in cardiac surgical patients pretreated with platelet-inhibiting drugs. J Cardiothorac Anesth 1990; 6: 32
    PubMedGoogle Scholar
  • 37 Rocha E, Llorens R, Paramo JA, Areas R, Cuesta B, Trenor AM. Does desmopressin acetate reduce blood loss after surgery in patients on cardiopulmonary bypass. Circulation 1988; 1319-1323
    PubMedGoogle Scholar
  • 38 Hackmann T, Gascoyne RD, Naiman SC, Growe GH, Burchill LD, Jamieson E, Sheps SB, Schechter MT, Townsend GE. A trial of desmopressin (l-deamino-8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery. N Engl J Med 1989; 321: 1437-1443
    CrossrefPubMedGoogle Scholar
  • 39 Zuzu-Jausoro I, Oliver A, Casas L, Caralps JM, Aris A, Sanz M, Fontcuberta J. Aprotinin or desmopressin, which is the best one to control bleeding associated to cardiopulmonary bypass (CBP). A prospective randomized double blind trial Thromb Haemost 1993; 69: 1289 (A)
    PubMedGoogle Scholar
  • 40 Altman DG. Practical statistics for medical research. London: Chapman and Hall; 1991
    Google Scholar
  • 41 Kendall M, Stuart A. The advanced theory of statistics. London: Charles Griffin; 1977. pp 246-247
    Google Scholar
  • 42 Salzman EW, Weinstein MJ, Reilly D, Ware A. Desmopressin in cardiac surgery. Arch Surg 1993; 128: 212-217
    CrossrefPubMedGoogle Scholar
  • 43 Goodnough LT, Johnston MF, Toy PT. The variability of transfusion practice in coronary artery bypass surgery. J Am Med Ass 1991; 265: 86-90
    CrossrefPubMedGoogle Scholar
  • 44 Weinstein M, Ware JA, Troll J, Salzman E. Changes in von Willebrand factor during cardiac surgery: Effect of desmopressin acetate. Blood 1988; 71: 1648-1655
    PubMedGoogle Scholar
  • 45 Sakariassen KS, Cattaneo M, van den Berg A, Ruggeri ZM, Mannucci PM, Sixma JJ. DDAVP enhances platelet adhesion and platelet aggregate growth on human artery subendothelium. Blood 1984; 64: 229-236
    PubMedGoogle Scholar
  • 46 Cattaneo M, Lombardi R, Bettega D, Lecchi A, Mannucci PM. Shear- induced platelet aggregation is potentiated by desmopressin and inhibited by ticlopidine. Art Thromb 1993; 13: 393-397
    PubMedGoogle Scholar
  • 47 Cattaneo M, Moia M, Della Valle P, Castellana P, Mannucci PM. DDAVP shortens the prolonged bleeding times of patients with severe von Willebrand disease treated with cryoprecipitate. Evidence for a mechanism of action independent of released von Willebrand factor Blood 1989; 74: 1972-1975
    PubMedGoogle Scholar
  • 48 Ferraris VA, Ferraris SP, Lough FC, Berry W. Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass grafting. Ann Thorac Surg 1988; 45: 71-74
    CrossrefPubMedGoogle Scholar
  • 49 Goldman S, Copeland J, Moritz T, Henderson W, Zadina K, Ovitt T, Doherty J, Read R, Chesler E, Sako Y, Lancaster L, Emery R, Sharma G, Josa M, Pacold I, Montoya A, Parikh D, Sethi G, Holt J, Kirklin J, Shabetai R, Moores W, Aldrige J, Masud Z, DeMots H, Floten S, Haakenson C, Harker LA. Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy. Circulation 1988; 77: 1324-1332
    CrossrefPubMedGoogle Scholar
  • 50 Spiess BD, Tuman KJ, McCarthy RJ, DeLaria GA, Schillo R, Ivankovich AD. Thromboelastography as an indicator of postcardiopulmonary bypass coagulopathies. J Clin Monit 1987; 3: 25-30
    CrossrefPubMedGoogle Scholar
  • 51 Royston D, Bidstrup B, Taylor KM, Sapsford RN. Effect of aprotinin or need for blood transfusion after repeat open heart surgery. Lancet 1987; 2: 1289-1291
    PubMedGoogle Scholar
  • 52 Bidstrup BP, Royston D, Sapsford RN, Taylor KM. Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin (Trasylol). J Thorac Cardiovasc Surg 1989; 97: 364-372
    PubMedGoogle Scholar
  • 53 Rocha E, Hidalgo F, Llorens R, Melero JM, Arroyo JL, Paramo JA. Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery. Circulation 1994; 90: 921-927
    CrossrefPubMedGoogle Scholar
  • 54 de Smet AA E A, Joen MC N, van Oeveren W, Roozendaal KJ, Harder MP, Eijsman L, Wildevuur CR H. Increased anticoagulation during cardiopulmonary bypass by aprotinin. J Thorac Cardiovasc Surg 1990; 100: 520-527
    PubMedGoogle Scholar
  • 55 van der Meer J, Hillege HL, Terres W, Ascoop CA P L, Dunselman PH J M, Mulder BJ M, Pfisterer M, Lie KI. Aprotinin in coronary bypass surgery reduces blood loss but is associated with an increased risk of vein graft occlusion and clinical thrombotic events. Br J Haematol 1994; 87 Suppl (Suppl. 01) 189 A
    CrossrefPubMedGoogle Scholar
  • 56 Mannucci PM, Lusher JM. Desmopressin and thrombosis. Lancet 1989; 2: 675-676
    PubMedGoogle Scholar
  • 57 Mannucci PM, Carlsson S, Harris AS. Desmopressin, surgery and thrombosis. Thromb Haemost 1994; 71: 154-161
    PubMedGoogle Scholar