George J. Despotis

Factors Associated with Excessive Postoperative Blood Loss and Hemostatic Transfusion Requirements: A Multivariate Analysis in Cardiac Surgical Patients

The purpose of this study was to prospectively evaluate whether heparin and protamine doses administered using a standardized protocol based on body weight and activated clotting time values are associated with either transfusion of hemostatic blood products (HBPs) or excessive postoperative bleeding.Analysis using 10 multiple logistic or linear regression models in 487 cardiac surgical patients included perioperative variables that may have an association with either transfusion of HBP and/or excessive postoperative chest tube drainage (CTD). Prolonged duration of cardiopulmonary bypass (CPB), lower pre-CPB heparin dose, lower core body temperature in the intensive care unit, combined procedures, older age, repeat procedures, a larger volume of salvaged red cells reinfused intraoperatively and abnormal laboratory coagulation results (prothrombin time, activated partial thromboplastin time, and platelet count) after CPB were associated with both transfusion of HBP and increased CTD. Female gender, lower total heparin dose, preoperative aspirin use and the number of HBPs administered intraoperatively were associated only with increased CTD, whereas a larger total protamine dose was associated only with perioperative transfusion of HBPs. Preoperative use of warfarin or heparin was not associated with excessive blood loss of perioperative transfusion of HBPs. In contrast to previous studies using bovine heparin, data from the present study do not support the use of reduced doses of porcine heparin during CPB. (Anesth Analg 1996;82:13-21)

Anticoagulation Monitoring during Cardiac Surgery A Review of Current and Emerging Techniques

The literature does not consistently support the importance of anticoagulation monitoring techniques during CPB. This is best reflected by studies that have evaluated the impact of the ACT method on blood loss and transfusion outcomes. Inconsistent findings from studies that evaluated the impact of ACT monitoring may be related to either suboptimal study design (i.e., retrospective, unblinded, nonrandomized) or possibly the diagnostic inprecision of the ACT method used in these studies. There are a small number of well-controlled studies, some of which suggest that bleeding and transfusion outcomes can be improved by refining heparin monitoring techniques, either by sustaining better anticoagulation during CPB or by optimizing protamine doses (i.e., when empiric protocols result in excessive protamine doses). More well-controlled studies are needed to better define the importance of anticoagulation management during CPB.

Mechanisms and attenuation of hemostatic activation during extracorporeal circulation

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents. Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.

2012 Update to The Society of Thoracic Surgeons Guideline on Use of Antiplatelet Drugs in Patients Having Cardiac and Noncardiac Operations

Division of Cardiovascular and Thoracic Surgery, University of Kentucky, Lexington, Kentucky (VAF and SPS); Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (JHO); Division of Cardiothoracic Surgery, Oregon Health and Science University Medical Center, Portland, Oregon (HKS); State University of New York, Stony Brook School of Medicine, Stony Brook, New York (TR); Department of Cardiothoracic Surgery, University of Colorado Health Sciences Center, Aurora, Colorado (TBR); Department of Anesthesia, St. Michael’s Hospital, University of Toronto, Toronto, Ontario (CDM); Division of Cardiovascular Surgery, Sanger Clinic, Charlotte, North Carolina (CRB); Departments of Anesthesiology, Immunology, and Pathology, Washington University School of Medicine, St. Louis, Missouri (GJD); and The Society of Thoracic Surgeons, Chicago, Illinois (KJ and ERC)

Transfusion medicine service policies for recombinant factor VIIa administration

Recombinant FVIIa (rFVIIa) has been approved for treatment of bleeding in hemophilia patients with inhibitors. It has also been successfully used in nonhemophilia patients with acquired antibodies against FVIII (acquired hemophilia). Pharmacological doses of rFVIIa have been found to enhance the thrombin generation on already activated platelets and, therefore, may also likely be of benefit in providing hemostasis in other situations characterized by profuse bleeding and impaired thrombin generation, 1 such as patients with thrombocytopenia and in those with functional platelet defects. 2,3 Additionally, it has been used successfully in a variety of less well‐characterized bleeding situations, 4–7 as well as in patients with impaired liver function. 8,9

Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomised controlled trial.

BACKGROUND Platelet dysfunction is a major cause of excessive microvascular bleeding after cardiac surgery. A new point-of-care test (hemoSTATUS) can identify patients at risk of excessive bleeding. We aimed to find out whether patients who can benefit from desmopressin during cardiac surgery can be identified by this test. METHODS We enrolled 203 patients scheduled for elective cardiac surgery in a prospective, double-blind, placebo-controlled trial. Patients with abnormal hemoSTATUS clot-ratio results (<60% of maximum in channel 5) after discontinuation of cardiopulmonary bypass were randomly assigned desmopressin (n=50) or placebo (n=51). Patients with normal clot ratios were included in an untreated control group (n=72). FINDINGS Intraoperative platelet counts and clot ratios were significantly higher in the untreated control group than in the study-drug groups. In intensive care, clot ratios in patients who received desmopressin were similar to those in the untreated control group, despite significantly lower platelet counts, but were lower in the placebo group than in the other two groups (p=0.0001). Compared with the placebo group, patients who received desmopressin had less blood loss in 24 h (mean 624 [SD 209] vs 1028 mL [682] p=0.0004) and required less transfusion of red blood cells (1.1 [022] vs 2.2 U [0.32] p=0.009), platelets (0.1 [0.04] vs 1.9 U [4.5] p=0.0001), and fresh-frozen plasma (0.1 [0.07] vs 0.75 U [0.21] p=0.0008), and had less total blood-donor exposures (1.56 [0.31] vs 5.2 [0.8] p=0.0001). Placebo patients also had substantially higher blood loss and transfusion requirements than untreated control patients. INTERPRETATION Patients identified with hemoSTATUS as being at increased risk of excessive bleeding after cardiac surgery can benefit from administration of desmopressin. Further studies are, however, needed to confirm these findings as well as to identify the mechanism of action and safety of desmopressin in the clinical setting.

The efficacy of photopheresis for bronchiolitis obliterans syndrome after lung transplantation

BACKGROUND Extracorporeal photopheresis (ECP) has been used to treat acute and chronic rejection after solid organ transplantation. However, data supporting the use of ECP for bronchiolitis obliterans syndrome (BOS) after lung transplantation are limited. METHODS We retrospectively analyzed the efficacy and safety of ECP for progressive BOS at our institution. Between January 1, 2000, and December 31, 2007, 60 lung allograft recipients were treated with ECP for progressive BOS. RESULTS During the 6-month period before the initiation of ECP, the average rate of decline in forced expiratory volume in 1 second (FEV(1)) was -116.0 ml/month, but the slope decreased to -28.9 ml/month during the 6-month period after the initiation of ECP, and the mean difference in the rate of decline was 87.1 ml/month (95% confidence interval, 57.3-116.9; p < 0.0001). The FEV(1) improved in 25.0% of patients after the initiation of ECP, with a mean increase of 20.1 ml/month. CONCLUSIONS ECP is associated with a reduction in the rate of decline in lung function associated with progressive BOS.

A review of transfusion risks and optimal management of perioperative bleeding with cardiac surgery

A pproximately 10 to 14 million red blood cell (RBC) units and 1.5 million platelet (PLT) transfusions (approx. 85%, single-donor plateletpheresis products; the remainder, pools of six whole-blood-donor PLT concentrates) are administered in the United States each year. Transfusion-related adverse (20% of transfusions) and serious adverse (0.5%) events were estimated by Walker in the 1980s. More recently, serious adverse events have been estimated to occur in 0.1 percent of RBCs and 0.04 percent of PLT transfusions. With early estimates, transfusion-associated adverse events were thought to lead to a short-term (i.e., not including disease transmission–related deaths) mortality of 1 to 1.2 per 100,000 patients, or approximately 35 transfusion-related deaths per year in the United States. With more recent estimates, long-term or total mortality (i.e., including disease transmission–related deaths) is probably higher due to unrecognized or unreported transfusion-related deaths. Perioperative signs and symptoms (e.g., fever, hypotension, tachycardia, hypoxemia, microvascular bleeding, hemoglobinuria, low urine output) can accompany any of several serious transfusion-related complications such as acute hemolytic transfusion reactions (HTRs), bacterial contamination, anaphylaxis, transfusion-related acute lung injury (TRALI), or other events (e.g. hyperkalemia, fluid overload, air embolus). Current risks associated with blood and blood component transfusion can be characterized as immune-mediated versus non–immunemediated, hemolytic versus nonhemolytic, or acute versus delayed transfusion reactions, as well as bloodborne disease transmission. Another approach would involve subdividing transfusion risks into those that are the leading causes of mortality versus those that are uncommon causes of transfusion-related mortality.

A Phase III, Double-blind, Placebo-controlled, Multicenter Study on the Efficacy of Recombinant Human Antithrombin in Heparin-resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

Background:The study evaluated the efficacy of recombinant human antithrombin (rhAT) for restoring heparin responsiveness in heparin resistant patients undergoing cardiac surgery. Methods:This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing cardiac surgery with cardiopulmonary bypass. Heparin resistance was diagnosed when the activated clotting time was less than 480 s after 400 U/kg heparin. Fifty-four heparin-resistant patients were randomized. One cohort received 75 U/kg rhAT, and the other received normal saline. If the activated clotting time remained less than 480 s, this was considered treatment failure, and 2 units fresh frozen plasma was transfused. Patients were monitored for adverse events. Results:Only 19% of patients in the rhAT group received fresh frozen plasma, compared with 81% of patients in the placebo group (P < 0.001). During their hospitalization, 48% of patients in the rhAT group received fresh frozen plasma, compared with 85% of patients in the placebo group (P = 0.009). Patients in the placebo group required higher heparin doses (P < 0.005) for anticoagulation. There was no increase in serious adverse events associated with rhAT. There was increased blood loss 12 h postoperatively (P = 0.05) with a trend toward increased 24-h bleeding in the rhAT group (P = 0.06). There was no difference between the groups in blood and platelet transfusions. Conclusion:Treatment with 75 U/kg rhAT is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation in the majority of heparin-resistant patients. Treating heparin-resistant patients with rhAT may decrease the requirement for heparin and fresh frozen plasma.

A randomized trial comparing acute normovolemic hemodilution and preoperative autologous blood donation in total hip arthroplasty

BACKGROUND: The value of acute normovolemic hemodilution (ANH) as compared to preoperative autologous blood donation (PABD) in orthopedic surgery is unknown. Therefore, a prospective, randomized study was conducted to compare these techniques in patients undergoing primary total hip arthroplasty.