Massive hemorrhage and transfusion in the operating room.

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.

Soil properties, greenhouse gas emissions and crop yield under compost, biochar and co-composted biochar in two tropical agronomic systems.

The addition of organic amendments to agricultural soils has the potential to increase crop yields, reduce dependence on inorganic fertilizers and improve soil condition and resilience. We evaluated the effect of biochar (B), compost (C) and co-composted biochar (COMBI) on the soil properties, crop yield and greenhouse gas emissions from a banana and a papaya plantation in tropical Australia in the first harvest cycle. Biochar, compost and COMBI organic amendments improved soil properties, including significant increases in soil water content, CEC, K, Ca, NO3, NH4 and soil carbon content. However, increases in soil nutrient content and improvements in physical properties did not translate to improved fruit yield. Counter to our expectations, banana crop yield (weight per bunch) was reduced by 18%, 12% and 24% by B, C and COMBI additions respectively, and no significant effect was observed on the papaya crop yield. Soil efflux of CO2 was elevated by addition of C and COMBI amendments, likely due to an increase in labile carbon for microbial processing. Our data indicate a reduction in N2O flux in treatments containing biochar. The application of B, C and COMBI amendments had a generally positive effect on soil properties, but this did not translate into a crop productivity increase in this study. The benefits to soil nutrient content, soil carbon storage and N2O emission reduction need to be carefully weighed against potentially deleterious effects on crop yield, at least in the short-term.

Off-label use of recombinant activated factor VII in surgical and non-surgical patients at 16 Canadian hospitals from 2007 to 2010 (Canadian Registry Report).

PURPOSE: 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. METHODS: For this historical cohort study, data were collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at 16 Canadian centres, and the pattern of use was examined. Logistic regression was used to determine the prognostic importance of severity of bleeding and the presence of an rFVIIa dose-effect relationship with major adverse events. RESULTS: One thousand three hundred seventy-eight patients received rFVIIa off-label, and 987 (72%) of these patients underwent cardiac surgery. The median [interquartile range] dose was 57 [36-85] µg·kg(-1). Usage increased from 2007 to 2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and 307, respectively). Dose of rFVIIa and bleeding severity were associated with measured adverse events (P < 0.05). After adjusting for bleeding severity, dose was not associated with any of the adverse events. CONCLUSIONS: The off-label use of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically important, the benefits of rapidly gaining control of bleeding that is non-responsive to conventional therapies may at times warrant the use of potent hemostatic drugs with established risk profiles, such as rFVIIa.

Clinical review: Canadian National Advisory Committee on Blood and Blood Products--Massive transfusion consensus conference 2011: report of the panel.

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.

Comprehensive Canadian review of the off-label use of recombinant activated factor VII in cardiac surgery.

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.

Thoracic epidural analgesia improves pulmonary function in patients undergoing cardiac surgery.

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.

The role of recombinant factor VIIa in on-pump cardiac surgery: proceedings of the Canadian Consensus Conference.

PURPOSE: 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. METHODS: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendations were based on evidence from the literature and derived by consensus following recognized grading procedures. RESULTS: The panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35-70 microg.kg(-1)) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication. CONCLUSIONS: In cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its riskbenefit profile in cardiac surgery patients.

Aortic dissection and hypothermic arrest in a Jehovah's Witness patient: a case for recombinant factor VIIa?

PURPOSE: To present a case of survival of a cognitively intact Jehovah's Witness patient with an aortic dissection who underwent hypothermic arrest. Recombinant factor VIIa, but no blood products were administered. CLINICAL FEATURES: An 83-yr-old female with an acute type A aortic dissection underwent emergent surgical repair. Proximal extension of the dissection necessitated prolonged cardiopulmonary bypass (CPB) and hypothermic circulatory arrest. Despite this, perioperative hemostatis was adequate. Recombinant factor VIIa 90 microg x kg(-1) i.v. was administered post-CPB. The patient had an uneventful postoperative course, and was discharged home neurologically intact. CONCLUSIONS: Patients who conscientiously object to the transfusion of blood products may present a considerable anesthetic challenge, especially those at risk from coagulopathy associated with CPB and hypothermic circulatory arrest. Recombinant factor VIIa may play a role in hemostasis management of these individuals, however, well-designed randomized controlled trials need to be undertaken to establish the efficacy and risks related to this potential indication.