title: Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients.
abstract: BACKGROUND
  Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables.
  
  
  METHODS
  This randomized, double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery. Patients received sugammadex 4 mg/kg or usual care (neostigmine or spontaneous recovery) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. The Cochran-Mantel-Haenszel method, stratified by thromboprophylaxis and renal status, was used to estimate relative risk and 95% confidence interval (CI) of bleeding events with sugammadex versus usual care. Safety was further evaluated by prespecified endpoints and adverse event reporting.
  
  
  RESULTS
  Of 1,198 patients randomized, 1,184 were treated (sugammadex n = 596, usual care n = 588). Bleeding events within 24 h (classified by an independent, blinded Adjudication Committee) were reported in 17 (2.9%) sugammadex and 24 (4.1%) usual care patients (relative risk [95% CI], 0.70 [0.38 to 1.29]). Compared with usual care, increases of 5.5% in activated partial thromboplastin time (P < 0.001) and 3.0% in prothrombin time (P < 0.001) from baseline with sugammadex occurred 10 min after administration and resolved within 60 min. There were no significant differences between sugammadex and usual care for other blood loss measures (transfusion, 24-h drain volume, drop in hemoglobin, and anemia), or risk of venous thromboembolism, and no cases of anaphylaxis.
  
  
  CONCLUSIONS
  Sugammadex produced limited, transient (<1 h) increases in activated partial thromboplastin time and prothrombin time but was not associated with increased risk of bleeding versus usual care.
authors.affiliation: From the Department for Anaesthesiology and Critical Care Medicine, Franziskus Hospital Bielefeld and Hannover Medical School, Hannover, Germany (N.R.-M.); Biostatistics, MSD-Oss, Oss, The Netherlands (H.F., M.S.); Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada (S.S.); Anesthesiology and Intensive Care, Medical Research Society, Danube Hospital, Vienna, Austria (W.K.); Department of Anesthesia and Intensive Care, Annastift, Hannover, Germany (M.P.); Klinik für Anästhesiologie der Technischen Universität München, Munich, Germany (M.B.); Klinik für Anästhesie und Intensivtherapie, Universitätsklinikum, Marburg, Germany (H.W.); Global Scientific and Medical Publications, Merck & Co., Inc., Whitehouse Station, New Jersey (C.M.S.); and Clinical Research, Merck & Co., Inc., Whitehouse Station, New Jersey (D.W.-H., T.W., A.S.).
authors.forename: Niels
authors.initials: N
authors.lastname: Rahe-Meyer
authors.forename: Hein
authors.initials: H
authors.lastname: Fennema
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.forename: Walter
authors.initials: W
authors.lastname: Klimscha
authors.forename: Michael
authors.initials: M
authors.lastname: Przemeck
authors.forename: Manfred
authors.initials: M
authors.lastname: Blobner
authors.forename: Hinnerk
authors.initials: H
authors.lastname: Wulf
authors.forename: Marcel
authors.initials: M
authors.lastname: Speek
authors.forename: Christine
authors.initials: C
authors.lastname: McCrary Sisk
authors.forename: Debora
authors.initials: D
authors.lastname: Williams-Herman
authors.forename: Tiffany
authors.initials: T
authors.lastname: Woo
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000762:Anesthesia Recovery Period; D001777:Blood Coagulation / Q000187:drug effects; D016063:Blood Loss, Surgical / Q000401:mortality; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade; D000077122:Sugammadex; D013927:Thrombosis / Q000517:prevention & control; D055815:Young Adult; D047408:gamma-Cyclodextrins / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D005343:Fibrinolytic Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex