PURPOSE:In this Continuing Professional Development module, we review the pathophysiology and clinical manifestations associated with massive hemorrhage as well as laboratory investigations and appropriate therapeutic measures. In addition to reviewing the available blood/plasma products and adjunct therapy, we also explore the role of the anesthesiologist in a massive transfusion protocol scenario.PRINCIPAL FINDINGS:Massive hemorrhage can be either anticipated or unexpected. The coinciding presence of acidosis, hypothermia, and hypotension contribute greatly to a poor outcome. Red blood cells not only increase oxygen carrying capacity, but they also play a role in providing hemostasis. While timely laboratory results, including point-of-care testing, are important, transfusion remains a clinical decision. Adjunct therapies other than blood components have contributed to improved outcomes. The pathophysiology of massive obstetric hemorrhage is unique when compared with the non-obstetric population. The approach to massive hemorrhage and its treatment vary considerably from institution to institution.CONCLUSIONS:Massive hemorrhage is a multidisciplinary challenge that requires immediate response and communication between clinicians, nurses, other healthcare providers, laboratory testing, and blood banks. Basic knowledge and utilization of available products and therapies are inconsistent. A massive transfusion protocol can be used effectively to reduce chaos and ensure that correct treatments and proper dosing occur in a timely manner.

Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that is approved for treatment of bleeding in hemophilia patients, but it is frequently used off-label in non-hemophiliacs. The purpose of this study was to determine if the off-label use of rFVIIa is expanding and whether this poses a net harm to patients.

In June 2011 the Canadian National Advisory Committee on Blood and Blood Products sponsored an international consensus conference on transfusion and trauma. A panel of 10 experts and two external advisors reviewed the current medical literature and information presented at the conference by invited international speakers and attendees. The Consensus Panel addressed six specific questions on the topic of blood transfusion in trauma. The questions focused on: ratio-based blood resuscitation in trauma patients; the impact of survivorship bias in current research conclusions; the value of nonplasma coagulation products; the role of protocols for delivery of urgent transfusion; the merits of traditional laboratory monitoring compared with measures of clot viscoelasticity; and opportunities for future research. Key findings include a lack of evidence to support the use of 1:1:1 blood component ratios as the standard of care, the importance of early use of tranexamic acid, the expected value of an organized response plan, and the recommendation for an integrated approach that includes antifibrinolytics, rapid release of red blood cells, and a foundation ratio of blood components adjusted by results from either traditional coagulation tests or clot viscoelasticity or both. The present report is intended to provide guidance to practitioners, hospitals, and policy-makers.

BACKGROUND:This observational study sought to identify the off-label use pattern of recombinant activated factor VII (rFVIIa) in cardiac surgery and to identify predictors of its effectiveness and risk. METHODS AND RESULTS:At 18 Canadian centers, 522 nonhemophiliac cardiac surgical patients received rFVIIa during the period 2003 through 2006; data were available, and retrospectively collected, on 503 patients. The median (quartile 1, quartile 3) units of red blood cells transfused from surgery to therapy and in the 24 hours after therapy were 8 (5, 12) and 2 (1, 5), respectively (P<0.0001). Mortality rate was 32%, and mortality or major morbidity rate was 44%. These rates were within expected ranges (mortality, 27% to 35%; mortality or morbidity, 39% to 48%), which were calculated with a separate cohort of cardiac surgical patients who did not receive rFVIIa used as reference. Independent predictors of complications included instability before therapy (multiple inotropes or intra-aortic balloon pump) and increasing red blood cell units transfused before and after therapy. Variables independently associated with nonresponse included abnormal coagulation parameters and >15 red blood cell units transfused before therapy. CONCLUSIONS:In Canada, rFVIIa is used primarily when standard interventions have failed to control bleeding. In this setting, rFVIIa is associated with reduced blood product transfusions and, after risk adjustment, does not appear to be associated with increased or decreased complication rates. The effectiveness of the drug may be enhanced if it is given early in the course of refractory blood loss in the setting of adequate amounts of circulating coagulation factors.

Introduction: Recombinant Factor VIIa (rFVIIa) has been in use for several years in Canada(1).While it has been shown to be of benefit in hemophiliacs with inhibitors to Factors VIII and IX (2-3), the literature on its use in massive bleeding is limited to several randomized controlled studies(4-6), or anecdotal clinical experience in local settings(7-9).There are currently no guidelines for its administration in massive bleeding, and the dosage employed has varied greatly among its users (6,(10)(11)(12).The Physicians and Nurses for Blood Conservation (PNBC) is a non-profit national organization that has an interest in promoting blood conservation.Utilizing the PNBC network allows information to be collected from a large number of hospitals in Canada; with this in mind, the PNBC undertook a review of the use of rFVIIa in Canada.Methods: PNBC contacted 52 hospitals from across Canada through regional coordinators.All provinces except P.E.I. were included.Data collection sheets were sent to the coordinators who contacted the individual hospitals to provide the information.Not all hospitals were able to contribute due to Ethics Review processes or resource issues.The data was based on a 12 month 'snapshot' in [2005][2006].Most of the information came from hospital Blood Banks, and patient demographics were excluded.The requested information included: Hemophilia use and Non-hemophilia use and dosage Results: Of the 52 hospitals contacted, 29 provided the requested data.Of a total of 715 records reported, 546 (76.4%) were for non-hemophilia use.The average dose for nonhemophilia use per treatment episode varied by institution (range 1.9 -16 mg per patient), with the overall mean being 5.3 mg.Because of exclusion of patient demographics, a dose in mcg/kg was not available.Discussion: This audit provides a general representation of rFVIIa use across Canada, with all provinces except Alberta, Saskatchewan, and P.E.I. reporting.There appears to be uncertainty in what dose of rFVIIa should be used in the non-hemophilia population.In the absence of specific Guidelines, this variable practice will probably continue until further studies are conducted or Guidelines developed.In addition to having consensus Guidelines, there would be a benefit in establishing a national registry for rFVIIa use.

PURPOSE:Pulmonary dysfunction commonly occurs following coronary artery bypass graft (CABG) surgery, increasing morbidity and mortality. We hypothesized that thoracic epidural anesthesia (TEA) would improve pulmonary function and would decrease complications in patients undergoing CABG surgery.METHODS:This prospective, randomized, controlled trial was conducted with Ethics Board approval. Fifty patients, undergoing CABG surgery, were randomized to the epidural group or to the patient-controlled analgesia morphine group. Patients in the epidural group received a high, thoracic epidural, preoperatively. Intraoperatively, 0.75% ropivacaine was infused, followed postoperatively, by 0.2% ropivacaine for 48 hr. Outcome measurements included: visual analogue pain scores; spirometry; atelectasis scores on chest radiographs; and the incidence of atrial fibrillation.RESULTS:Twenty-five patients were enrolled in each group. Patients in the epidural group had significantly less pain on the operative day, and for the subsequent two days. Compared to baseline, the forced expiratory volume in one second was significantly higher in the epidural group, on the first and second postoperative days (43.7 +/- 12.2% vs 36.4 +/- 12.0%, p < 0.002, and 43.3 +/- 12.5% vs 38.4 +/- 11.0%, p <0.05). There was significantly more atelectasis in the control group, four hours postoperatively (p < 0.04); however, on the third, postoperative day, the groups were similar with regards to this outcome. The incidence of atrial fibrillation was similar in both groups, and there were no complications related to the epidural.CONCLUSIONS:High TEA decreases postoperative pain and atelectasis and improves pulmonary function in patients undergoing CABG surgery. Our results support the use of TEA in this group of patients.

Introduction:The potassium load of a unit of red blood cells (RBCs) is estimated at 5.5 mEq per unit after 35 days of storage (1).In the operating room, RBCs are often infused centrally, through a fluid warmer, and under pressure.The actual infused postassium concentration of RBCs in this setting was determined.Methods: Local REB approval was obtained for this study.Twenty-five randomly selected units of blood transfused in the operating room were studied.All units were undiluted and given through a filter and fluid warmer.The age of the blood and use of a pressure bag were recorded.A sample was taken from the intravenous line, distal to the fluid warmer, and analyzed for potassium concentration by blood gas analysis.Results: Potassium concentration of transfused blood varied considerably and was related to the age of the blood.The use of a pressure bag does not convincingly increase the potassium load of banked blood.Discussion: Transfusion of RBCs in the operating room may be associated with a large, rapidly infused potassium load, particularly as the age of the RBCs increases.For patients who require rapid transfusion and are at risk for hyperkalemia, washing of RBCs prior to transfusion can minimize the risk of acute hyperkalemia and the associated complications (2).

Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used “off-label” for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery.

Présenter le cas ďun Témoin de Jéhovah qui a subi un asystolie sous hypothermie lors ďune dissection aortique et qui a survécu avec des fonctions cognitives intactes. Le facteur VIIa recombinant a été administré, non des produits sanguins.

Résumé Objectif Présenter le cas ďun Témoin de Jéhovah qui a subi un asystolie sous hypothermie lors ďune dissection aortique et qui a survécu avec des fonctions cognitives intactes. Le facteur VIIa recombinant a été administré, non des produits sanguins. Éléments cliniques Une femme de 83 ans a été opérée ďurgence pour la réparation ďune dissection aortique aiguë de type A. Ľextension proximale de la dissection a nécessité une circulation extracorporelle (CEC) prolongée et un arrêt hypothermique. Malgré cela, ľhémostase périopératoire a été adéquate. Le facteur VIIa recombinant, 90 μg·kg -1 iv, a été administré après la CEC. La patiente n’a subi aucun déficit neurologique. Conclusion Les patients qui refusent volontairement la transfusion de produits sanguins peuvent représenter un défi anesthésique considérable, surtout s’ils sont à risque de coagulopathie associée à la CEC et à ľasystolie hypothermique. Dans ces cas, le facteur VIIa recombinant peut jouer un rôle dans ľatteinte ďhémostase, mais des études randomisées et contrôlées devront déterminer ľefficacité et les risques reliés à cette utilisation possible.

THE TRAGEDY OF the 1980s and 1990s caused by viral transmission in blood products has been responsible for efforts to reduce the amount of allogeneic blood products used in both surgical and medical patients. In his final report on the Blood System in Canada, Krever1 recommended appropriate use of, and alternatives to, blood components and blood products. Over the last 2 decades, there have been institutional, regional, and national attempts to prevent allogeneic transfusions. Cardiac surgery is responsible for approximately 20% of allogeneic transfusions; in the last 20 years, the transfusion rate in cardiac surgery has dropped from nearly 100% to 27% to 92% depending on the institution.2 Contributing factors to this decrease include shorter bypass times, improved surgical techniques, bone marrow stimulation, antifibrinolytics, lowering of the transfusion trigger, and the use of autologous blood products. Autologous practices include recovery of shed blood, acute normovolemic hemodilution (ANH), and preoperative autologous donation (PAD). Although some of these techniques have been effective, many, including PAD, remain controversial.