title: Point-of-Care Hemostatic Testing in Cardiac Surgery: A Stepped-Wedge Clustered Randomized Controlled Trial.
abstract: Cardiac surgery is frequently complicated by coagulopathic bleeding that is difficult to optimally manage using standard hemostatic testing. We hypothesized that point-of-care hemostatic testing within the context of an integrated transfusion algorithm would improve the management of coagulopathy in cardiac surgery and thereby reduce blood transfusions.
  
  
  
  We conducted a pragmatic multicenter stepped-wedge cluster randomized controlled trial of a point-of-care-based transfusion algorithm in consecutive patients undergoing cardiac surgery with cardiopulmonary bypass at 12 hospitals from October 6, 2014, to May 1, 2015. Following a 1-month data collection at all participating hospitals, a transfusion algorithm incorporating point-of-care hemostatic testing was sequentially implemented at 2 hospitals at a time in 1-month intervals, with the implementation order randomly assigned. No other aspects of care were modified. The primary outcome was red blood cell transfusion from surgery to postoperative day 7. Other outcomes included transfusion of other blood products, major bleeding, and major complications. The analysis adjusted for secular time trends, within-hospital clustering, and patient-level risk factors. All outcomes and analyses were prespecified before study initiation.
  
  
  
  Among the 7402 patients studied, 3555 underwent surgery during the control phase and 3847 during the intervention phase. Overall, 3329 (45.0%) received red blood cells, 1863 (25.2%) received platelets, 1645 (22.2%) received plasma, and 394 (5.3%) received cryoprecipitate. Major bleeding occurred in 1773 (24.1%) patients, and major complications occurred in 740 (10.2%) patients. The trial intervention reduced rates of red blood cell transfusion (adjusted relative risk, 0.91; 95% confidence interval, 0.85-0.98; P=0.02; number needed to treat, 24.7), platelet transfusion (relative risk, 0.77; 95% confidence interval, 0.68-0.87; P<0.001; number needed to treat, 16.7), and major bleeding (relative risk, 0.83; 95% confidence interval, 0.72-0.94; P=0.004; number needed to treat, 22.6), but had no effect on other blood product transfusions or major complications.
  
  
  
  Implementation of point-of-care hemostatic testing within the context of an integrated transfusion algorithm reduces red blood cell transfusions, platelet transfusions, and major bleeding following cardiac surgery. Our findings support the broader adoption of point-of-care hemostatic testing into clinical practice.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02200419.
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.). keyvan.karkouti@uhn.ca.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Karkouti
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.).
authors.forename: Jeannie
authors.initials: J
authors.lastname: Callum
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.).
authors.forename: Duminda N
authors.initials: DN
authors.lastname: Wijeysundera
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.).
authors.forename: Vivek
authors.initials: V
authors.lastname: Rao
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.).
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.).
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Grocott
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.).
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Pinto
authors.affiliation: From Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Canada (K.K.); Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.C.); Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Canada (D.N.W.); Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada (V.R.); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (M.C.); Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada (H.P.G.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (R.P.); Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Canada (D.C.S.); and the Peter Munk Cardiac Centre, University Health Network, Toronto, Canada (K.K., D.N.W., V.R.).
authors.forename: Damon C
authors.initials: DC
authors.lastname: Scales
mesh_terms: D000368:Aged; D000465:Algorithms; D001778:Blood Coagulation Disorders / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D001780:Blood Coagulation Tests / Q000379:methods*; D001803:Blood Transfusion / Q000379:methods; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D019468:Disease Management; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D019095:Point-of-Care Systems; D065227:Transfusion Reaction; D016896:Treatment Outcome
keywords: cardiopulmonary bypass; clinical trial; coagulation; hemorrhage; hemostasis