Recommendations From the International Consensus Conference on Anemia Management in Surgical Patients (ICCAMS).

BACKGROUND: Perioperative anemia has been associated with increased risk of red blood cell transfusion and increased morbidity and mortality after surgery. The optimal approach to the diagnosis and management of perioperative anemia is not fully established. OBJECTIVE: To develop consensus recommendations for anemia management in surgical patients. METHODS: An international expert panel reviewed the current evidence and developed recommendations using modified RAND Delphi methodology. RESULTS: The panel recommends that all patients except those undergoing minor procedures be screened for anemia before surgery. Appropriate therapy for anemia should be guided by an accurate diagnosis of the etiology. The need to proceed with surgery in some patients with anemia is expected to persist. However, early identification and effective treatment of anemia has the potential to reduce the risks associated with surgery and improve clinical outcomes. As with preoperative anemia, postoperative anemia should be treated in the perioperative period. CONCLUSIONS: Early identification and effective treatment of anemia has the potential to improve clinical outcomes in surgical patients.

A Global Definition of Patient Blood Management.

While patient blood management (PBM) initiatives are increasingly adopted across the globe as part of standard of care, there is need for a clear and widely accepted definition of PBM. To address this, an expert group representing PBM organizations from the International Foundation for Patient Blood Management (IFPBM), the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA), the Society for the Advancement of Patient Blood Management (SABM), the Western Australia Patient Blood Management (WAPBM) Group, and OnTrac (Ontario Nurse Transfusion Coordinators) convened and developed this definition: "Patient blood management is a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood, while promoting patient safety and empowerment." The definition emphasizes the critical role of informed choice. PBM involves the timely, multidisciplinary application of evidence-based medical and surgical concepts aimed at (1) screening for, diagnosing, and appropriately treating anemia; (2) minimizing surgical, procedural, and iatrogenic blood losses and managing coagulopathic bleeding throughout the care; and (3) supporting the patient while appropriate treatment is initiated. We believe that having a common definition for PBM will assist all those involved including PBM organizations, hospital administrators, individual clinicians, and policy makers to focus on the appropriate issues when discussing and implementing PBM. The proposed definition is expected to continue to evolve, making this endeavor a work in progress.

Anticoagulation Obtained below the Arterial Clamp Using a Single Fixed Bolus of Heparin in Vascular Surgery: A Pilot Study.

BACKGROUND: No clear recommendations exist regarding the optimal dosing of unfractionated heparin (UFH) during vascular surgery. Moreover, little is known about the effect of the UFH bolus downstream of the arterial clamp, where stasis and inflammation can possibly alter the anticoagulation obtained. METHODS: The aim of our prospective observational study was to assess anticoagulation below the arterial clamp and its clinical impact on the quality of revascularization. Thirty-six patients American Society of Anaesthesiologists physical status (ASA) grade I-III undergoing open revascularization surgeries were included. A baseline activated coagulation time (ACT) was obtained. Thirty minutes after a single bolus of 5,000 units of UFH, we measured an upstream ACT via a radial arterial catheter and an ACT below the arterial clamp via surgeon sampling. The quality of revascularization was assessed with preoperative and postoperative ankle-brachial and toe-brachial indexes (TBIs). RESULTS: The upstream postheparin ACT was significantly higher than the downstream postheparin ACT, with a mean difference of 24.3 sec (P < 0.0001). In 7 patients, the downstream ACT was lower than the baseline ACT. The upstream and downstream heparin concentrations were similar. There was no relationship between the downstream ACT and either ankle-brachial index improvement (28 patients, P = 0.51) or TBI improvement (27 patients, P = 0.21). CONCLUSIONS: Our study demonstrates a significant difference between the ACT above and below the arterial clamp without any clinical impact of this possibly insufficient anticoagulation. Further investigations are warranted to determine the optimal dose of UFH in vascular surgery. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02477072.

Major transfusions remain frequent despite the generalized use of tranexamic acid: an audit of 3322 patients undergoing cardiac surgery.

BACKGROUND: Aprotinin has been reapproved for use in Europe and in Canada. We sought to determine if its reintroduction was still pertinent given the widespread administration of tranexamic acid, another antifibrinolytic shown to reduce bleeding and transfusions. STUDY DESIGN AND METHODS: After institutional review board approval, we examined the cardiac surgery database (2012-2015; 3322 patients). Major transfusion was defined as 4 or more red blood cell units. A stratified multivariate logistic regression analysis identified predictors of major transfusion; 1064 patients were matched by propensity score to compare outcomes of patients with or without major transfusion. RESULTS: Cardiopulmonary bypass (CPB) was used in 2342 patients; 98.9% received tranexamic acid versus 15.2% (149/980) in off-pump coronary artery bypass graft patients. Major transfusion was required in 758 patients (23%). Age, low body mass index, low preoperative hemoglobin or platelet count, recent use of P2Y12 receptor blockers, chronic kidney disease, NYHA functional class, left ventricular ejection fraction of less than 30%, prior cardiac surgery, urgency, type of cardiac surgery, and duration of CPB were all independent predictors of major transfusions (all p < 0.05). Major transfusion was associated with a more than threefold increase in mortality (7.1% vs. 2.1%; p < 0.001) and increases in major adverse events (p < 0.001). CONCLUSIONS: Despite the use of tranexamic acid, 23% of cardiac surgery patients require a major transfusion. We identified predictors of major transfusion and showed that major transfusion is associated with important increases in mortality and morbidity. We conclude that there is still a need for an effective and safe blood-sparing drug in cardiac surgery.

Implementation of patient blood management remains extremely variable in Europe and Canada: the NATA benchmark project: An observational study.

BACKGROUND: Preoperative anaemia is associated with increased postoperative morbidity and mortality. Patient blood management (PBM) is advocated to improve patient outcomes. OBJECTIVES: NATA, the 'Network for the advancement of patient blood management, haemostasis and thrombosis', initiated a benchmark project with the aim of providing the basis for educational strategies to implement optimal PBM in participating centres. DESIGN: Prospective, observational study with online data collection in 11 secondary and tertiary care institutions interested in developing PBM. SETTING: Ten European centres (Austria, Spain, England, Denmark, Belgium, Netherlands, Romania, Greece, France, and Germany) and one Canadian centre participated between January 2010 and June 2011. PATIENTS: A total of 2470 patients undergoing total hip (THR) or knee replacement, or coronary artery bypass grafting (CABG), were registered in the study. Data from 2431 records were included in the final analysis. MAIN OUTCOME MEASURES: Primary outcome measures were the incidence and volume of red blood cells (RBC) transfused. Logistic regression analysis identified variables independently associated with RBC transfusions. RESULTS: The incidence of transfusion was significantly different between centres for THR (range 7 to 95%), total knee replacement (range 3 to 100%) and CABG (range 20 to 95%). The volume of RBC transfused was significantly different between centres for THR and CABG. The incidence of preoperative anaemia ranged between 3 and 40% and its treatment between 0 and 40%, the latter not being related to the former. Patient characteristics, evolution of haemoglobin concentrations and blood losses were also different between centres. Variables independently associated with RBC transfusion were preoperative haemoglobin concentration, lost volume of RBC and female sex. CONCLUSION: Implementation of PBM remains extremely variable across centres. The relative importance of factors explaining RBC transfusion differs across institutions, some being patient related whereas others are related to the healthcare process. The results reported confidentially to each centre will allow them to implement tailored measures to improve their PBM strategies.

Postoperative anemia does not impede functional outcome and quality of life early after hip and knee arthroplasties.

BACKGROUND: Clinicians have adopted a restrictive transfusion threshold (75-80 g/L) after major orthopedic surgery. Anemia may be associated with a decrease in postoperative vigor. We hypothesize that, in these patients, a threshold hemoglobin (Hb) concentration exists below which functional recovery and quality of life (QoL) become difficult. STUDY DESIGN AND METHODS: A prospective, observational cohort study in 305 patients 60 years or older undergoing a total hip or knee arthroplasty was conducted. Major outcome variables were distance walked in 6 minutes (6MWT), score on the Borg Scale for perception of effort, maximal dominant hand strength, and Short Form 36 (SF-36) QoL assessment in the preoperative and early postoperative periods. Patients were categorized according to their Hb level the day of the postoperative 6MWT (≤ 80, 81-90, 91-100, and >100 g/L). RESULTS: There was no difference between Hb groups in the decrease of the distance walked preoperatively versus postoperatively. For both moments of observation, the 6MWT was not significantly different between Hb groups (p = 0.190). Similar results were found with perception of effort, maximal dominant hand strength, and SF-36 QoL assessment scores. In a regression model, the decrease in Hb concentration could explain only 1.9% of the total variation observed in the 6MWT (p = 0.008). CONCLUSION: Moderate anemia is not associated with an impaired functional recovery or QoL in the immediate postoperative period after major arthroplasties. Further studies will be required to determine the long-term consequences of a restrictive transfusion strategy in these patients.

Red blood cell transfusion practice in elective orthopedic surgery: a multicenter cohort study.

BACKGROUND: The indications for red blood cell (RBC) transfusions remain unclear despite published guidelines. Our hypothesis was that the transfusion practice varies inside the Centre hospitalier de l'Université de Montréal (CHUM). STUDY DESIGN AND METHODS: A total of 701 charts of patients who underwent a knee or hip arthroplasty or prosthesis revision in three hospitals of the CHUM were reviewed. Demography, hemoglobin (Hb) concentrations, details on transfusions, and postoperative adverse events (AEs) were collected up until discharge. The primary outcome was the presence or absence of RBC transfusion. Secondary outcomes were the nadir Hb, number of units transfused, discharge Hb, blood losses, and postoperative AEs. RESULTS: The rate of postoperative transfusion was 29%. We found no significant difference between odds ratios of each site for sex, coronary artery disease, chronic heart failure, type of procedure, American Society of Anesthesiologists physical status, weight, height, body mass index, body surface area, and estimated blood volume. Overall, patients were transfused at a Hb between 75 and 80g/L. Eighty-five percent of postoperative transfusions could be predicted using only nadir Hb and adding patient characteristics did not substantially improve the model (86.1%). Discharge Hb was below 100g/L in 66% of patients. CONCLUSIONS: There was no difference among hospitals regarding the way RBC transfusions are used. Our data suggest that physicians mainly based their decision to transfuse on a single variable, the Hb concentration, with the use of a restrictive strategy. Future trials should focus on the optimal transfusion trigger to adopt in major orthopedic surgery.

Clopidogrel induces an acute hemostatic deficit and increases intra abdominal bleeding in rabbits.

PURPOSE: Clopidogrel, a potent antiplatelet drug, increases hemorrhagic adverse events when its use is continued up to five days before cardiac surgery but data are lacking in non-cardiac surgery. We sought to determine the dose of clopidogrel which has a maximal antiplatelet and hemorrhagic effect in a rabbit model of non-cardiac surgery. METHODS: Twenty-four rabbits were divided into three groups according to the dose of clopidogrel administered (5, 10 and 20 mg.kg(-1)). Baseline measurement of platelet aggregation induced with ADP, platelet reactivity index (PRI) of the VASP-phosphorylation assay and hematologic variables were obtained the day before the experiment. Two hours after clopidogrel administration, the same variables were measured, along with intra abdominal bleeding following standardized hepato-splenic lesions. RESULTS: Platelet aggregation was inhibited in a dose-dependent manner: 46%+/-16% with 5 mg.kg(-1) and 93%+/-7% with 20 mg.kg(-1) of clopidogrel. PRI was reduced by 61%+/-25% with 5 mg.kg(-1) of clopidogrel and by 92%+/-11% and 94%+/-10% with 10 mg.kg(-1) and 20 mg.kg(-1) respectively (p=0.01). Percentage reduction of platelet aggregation was positively correlated with the percentage reduction of PRI (r=0.69; CI(95), 0.40 to 0.86). Bleeding from hepato-splenic lesions was more important in the 10 and 20 mg.kg(-1) groups compared to the 5 mg.kg(-1) group (p<0.05). CONCLUSION: Higher doses of clopidogrel are associated with a more profound inhibition of platelet aggregation and PRI and increased blood losses following standardized hepato-splenic lesions. We conclude that our animal model demonstrates clopidogrel's propensity to increase intra abdominal bleeding after standardized hepato-splenic lesions and may help develop blood sparing strategies for patients undergoing surgery while on clopidogrel.

Efficacy and safety of activated recombinant factor VII in cardiac surgical patients.

PURPOSE OF REVIEW: Excessive bleeding is a common and morbid problem after cardiac surgery. There is no doubt a need for an effective and safe hemostatic agent in order to minimize transfusions and avoid surgical reintervention for hemostasis. Recombinant activated factor VII (rFVIIa) is being used (off-label) increasingly after cardiac surgery to prevent or to control hemorrhage, but its efficacy and safety remain unclear. RECENT FINDINGS: Several case reports, case series and registries would tend to support the use of activated recombinant factor VII to control excessive bleeding after cardiac operations. On the contrary, two randomized controlled trials have produced negative results whereas a third has not been published yet. Adverse thrombotic events are reported with increasing frequency. SUMMARY: At present, the generalized use of rFVIIa to prevent or to control excessive bleeding after cardiac surgery cannot be recommended. The decision to administer a potent hemostatic such as rFVIIa outside its recognized prescribing indications should be made with caution by well informed physicians and discussed with the patient. Patients should be informed about knowledge gaps and pertinent risks, which are both important in the case of rFVIIa.

Patient blood management in obstetrics: prevention and treatment of postpartum haemorrhage. A NATA consensus statement.

Patient blood management (PBM) is the timely application of evidence-informed medical and surgical concepts designed to maintain haemoglobin concentration, optimise haemostasis, and minimise blood loss in an effort to improve patient outcomes. The aim of this consensus statement is to provide recommendations on the prevention and treatment of postpartum haemorrhage as part of PBM in obstetrics. A multidisciplinary panel of physicians with expertise in obstetrics, anaesthesia, haematology, and transfusion medicine was convened by the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA) in collaboration with the International Federation of Gynaecology and Obstetrics (FIGO), the European Board and College of Obstetrics and Gynaecology (EBCOG), and the European Society of Anaesthesiology (ESA). Members of the task force assessed the quantity, quality and consistency of the published evidence, and formulated recommendations using the system developed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The recommendations in this consensus statement are intended for use by clinical practitioners managing perinatal care of women in all settings, and by policy-makers in charge of decision making for the update of clinical practice in health care establishments.

Recombinant human activated factor VII is thrombogenic in a rabbit model of cyclic flow reduction and does not reduce intra-abdominal bleeding.

Recombinant human activated factor VII (rHuFVIIa) can reduce bleeding but may be associated with arterial thrombosis. We hypothesized that rHuFVIIa would increase the occurrence of cyclic flow reductions (CFR) and reduce intra-abdominal bleeding in an experimental model. An adapted Folts' model of carotid artery lesion and stenosis was used. Twenty four rabbits were randomized to receive rHuFVIIa (group F) or placebo (group P) in a double-blind fashion. A standardized injury to the common carotid artery resulted in CFR and/or thrombosis. Hematological values, coagulation and thromboelastographic (TEG) variables were compared. Intra-abdominal bleeding was evaluated by measuring blood loss from standardized hepatosplenic lesions. The median number (range) of spontaneous CFR [group P: 6 (0-15); group F: 8 (0-16)] was comparable between groups. The number of induced CFR (by "shaking" of the artery) needed to avert thrombosis (group F: 2; group P: 0; p < 0.05) and the incidence of complete carotid artery thrombosis (group F: 3; group P: 0; p < 0.05) were higher in group F. Intra-abdominal bleeding was similar in both groups. TEG analysis demonstrated a hypercoagulable state in both groups but the magnitude of the change was statistically more important in group F. rHuFVIIa increases thrombosis in a rabbit model of carotid artery injury. The bleeding from hepatic and splenic lesions is not reduced by administration of rHuFVIIa despite a hypercoagulable state confirmed by standard TEG analysis.

Current status of transfusion triggers for red blood cell concentrates.

Clinical practice guidelines on red blood cell transfusion (RBC) are based on expert opinion, animal studies and the few human trials available. Twelve randomized controlled trials on the benefits of RBC transfusions in humans have been published. In the absence of definitive outcome studies, numerous theoretical arguments have been put forward in favor or against the classic transfusion threshold of 100 g/l. However, data from randomized controlled trials suggest that overall morbidity (including cardiac) and mortality, hemodynamic, pulmonary and oxygen transport variables are not different between restrictive (transfusion threshold between 70 and 80 g/l) and liberal transfusion strategies and that a restrictive transfusion strategy is not associated with increased adverse outcomes. In fact, a restrictive strategy may be associated with decreased adverse outcomes in younger and less sick critical care patients. The majority of existing guidelines conclude that transfusion is rarely indicated when the hemoglobin concentration is greater than 100 g/l and is almost always indicated when it falls below a threshold of 60 g/l in healthy, stable patients or more in older, sicker patients. In anesthetized patients, this threshold should be modulated by factors related to the dynamic nature of surgery such as uncontrolled hemorrhage, microvascular bleeding, etc. Another important role of RBC relates to primary hemostasis and higher triggers may be appropriate in coagulopathic patients. RBC concentrates are administered to correct inadequate oxygen delivery and/or to sustain primary hemostasis. Reliable monitors of tissue oxygenation and hemostasis will be required to study the benefits (or lack thereof) of RBC transfusions. The quest for a universal transfusion trigger, i.e., one that would be applicable to patients of all ages under all circumstances, must be abandoned. All RBC transfusions must be tailored to the patient's needs, at the moment the need arises. In conclusion published recommendations are commensurate with existing knowledge and, unfortunately, their conclusions are limited. Future research and development should focus on the determination of optimal transfusion strategies in various patient populations and on reliable monitors to guide transfusion therapy.

The indication for perioperative red blood cell transfusions is a predictive risk factor for severe postoperative morbidity and mortality in children undergoing cardiac surgery.

OBJECTIVES: In paediatric cardiac surgery, red blood cell (RBC) transfusions are given to treat haemorrhage or to increase oxygen delivery (therapeutic transfusion). Sometimes, RBCs are added to the prime solution to avoid a too low haematocrit on bypass (CPB-driven transfusion). Our study investigated whether the reason for RBC transfusion might affect severe postoperative morbidity or mortality. METHODS: This retrospective cohort study was conducted in a tertiary care level, children's hospital. The charts of all patients admitted between 2006 and 2009 were reviewed. Among transfused patients, children receiving a therapeutic transfusion were compared with those receiving a CPB-driven transfusion. The primary outcome was severe postoperative morbidity or mortality. Statistically significant variables founded with univariate analysis were incorporated in the multivariable logistic regression analysis to build a model that predicts severe postoperative morbidity or mortality. This model was then adjusted for clinically relevant variables that may interfere with 'indication for transfusion'. RESULTS: One hundred and one (48%) patients in the therapeutic and 92 (26%) patients in the CPB-driven transfusion group developed severe postoperative morbidity or died (P < 0.001). A multivariable logistic regression showed that weight, ASA, calculated blood loss, intraoperative fluid balance, duration of CPB time and the indication group for transfusion [1.64 (1.03-2.62); P = 0.039] were independent risk factors for severe postoperative morbidity or mortality. The indication group for transfusion remained significant [2.0 (1.16-3.45); P = 0.013] after adjustment for significant predictors of indication for transfusion. Number of patients with infections, or neurological deficit, and length of mechanical ventilation, PICU and hospital length of stay, were significantly higher in the therapeutic compared with the CPB-driven transfusion group one. CONCLUSIONS: The indication group for transfusion has an impact on the occurrence of severe postoperative morbidity or mortality in children undergoing cardiac surgery.