Cardiac Surgical Bleeding, Transfusion and Quality Metrics: Joint Consensus Statement by the Enhanced Recovery After Surgery Cardiac Society and Society for the Advancement of Patient Blood Management.

BACKGROUND: Excessive perioperative bleeding is associated with major complications in cardiac surgery, resulting in increased morbidity, mortality and cost. METHODS: An international expert panel was convened to develop consensus statements on the control of bleeding and management of transfusion, and to suggest key quality metrics for cardiac surgical bleeding. The panel reviewed relevant literature from the previous 10 years and used a modified RAND Delphi methodology to achieve consensus. RESULTS: Thirty consensus statements in 8 categories were developed, including prioritizing control of bleeding, pre-chest closure checklists and the need for additional quality indicators beyond re-exploration rate, such as time to re-exploration. Consensus was also reached on the need for a universal definition of excessive bleeding, the use of antifibrinolytics, optimal cessation of antithrombotic agents, and preoperative risk scoring based on patient and procedural factors to identify those at greatest risk of excessive bleeding. Furthermore, there is a need for an objective bleeding scale based on the volume and rapidity of blood loss accompanied by viscoelastic management algorithms and standardized, patient-centered blood management strategies reflecting an interdisciplinary approach to quality improvement. CONCLUSIONS: Prioritizing the timely control and management of bleeding is essential to improving patient outcomes in cardiac surgery. To this end, a cardiac surgical bleeding quality metric that is more comprehensive than re-exploration rate alone is needed. Similarly, interdisciplinary quality initiatives that seek to implement enhanced quality indicators will likely lead to improved patient care and outcomes.

Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper.

Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient's values and target the best outcome possible given the patient's desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes.

Transfusion strategy trials excluding patients transfused outside the trial study period are more likely to report a trend favoring restrictive strategies: a meta-analysis.

OBJECTIVES: Some large, randomized trials investigating red cell transfusion strategies have significant numbers of transfusions administered outside the trial study period. We sought to investigate the potential impact of this methodological issue. STUDY DESIGN AND SETTING: Meta-analysis of randomized controlled trials (RCTs) comparing liberal vs restrictive transfusion strategies in cardiac surgery and acute myocardial infarction patients. The outcome of interest was 30-day or in-hospital mortality. RESULTS: In cardiac surgery, the pooled risk ratio for mortality was 0.83 (95% confidence interval [CI] 0.62-1.12, P = .22) times lower in the restrictive group when compared to the liberal group in trials applying a transfusion strategy throughout the patient's entire perioperative period, and 1.33 (95% CI 0.84-2.11, P = .22) times higher in the restrictive group in trials not applying transfusion strategies throughout the entire perioperative period. When combined, the risk ratio for mortality was 0.98 (95% CI 0.73-1.32, P = .89). In patients with acute myocardial infarction, the risk ratio for mortality was 0.72 (95% CI 0.40-1.28, P = .26) times lower in the restrictive group when compared to the liberal group in 1 trial excluding patients administered the intervention prerandomization and 1.19 (95% CI 0.96-1.47, P = .11) times higher in the restrictive group in 1 trial including patients receiving the intervention prerandomization. When combined the risk ratio for mortality was 1.00 (0.62-1.59, P = .99). CONCLUSION: Though not statistically significant, there was a consistent difference in trends between RCTs administering significant numbers of transfusion outside the trial study period compared to those that did not. The implications of our results may extend to RCTs in other settings that ignore if and how frequently an investigated therapy is administered outside the trial window.

Antithrombin concentrates may benefit cardiopulmonary bypass patients with suspected heparin resistance: A retrospective analysis of real-world data.

Background: Heparin resistance is a common complication of surgical patients requiring anticoagulation, such as those undergoing cardiopulmonary bypass (CPB). Treatments to address heparin resistance include supplementation of antithrombin (AT) or fresh frozen plasma (FFP). This retrospective database analysis compared key outcomes in suspected heparin-resistant patients undergoing CPB treated with AT or FFP. Methods: De-identified United States electronic health records (Cerner Health Facts®) were queried. International Classification of Diseases (ICD-9/10) codes were used to determine CPB procedures and FFP administration. AT administration was identified using medication data, while a combination of lab and medication data examining activated clotting times detected heparin resistance in FFP patients. Adult inpatients (≥18 years old) seen between 2001 and 2018 were included. Differences in mortality, intensive care unit (ICU) length of stay (LOS), and hospital-free days (using a 30-day post-discharge period) were assessed with univariate models as well as adjusted logistic regression models controlling for patient characteristics and Charlson Comorbidity Index (CCI) scores. Results: Of the 502 patients identified, 247 received AT and 255 received FFP. The FFP cohort was associated with a higher CCI compared to the AT cohort (3.3 ± 2.4 vs. 2.3 ± 2.0, P < .001). The AT cohort was associated with a 71% (Odds Ratio [OR]: 0.29, 95% Confidence Interval [CI]: P = .003) and 66% (OR: 0.34, 95% CI: P = .01) reduction in mortality when compared to FFP using univariate and adjusted logistic regression models, respectively. Similarly, use of AT also showed a 22% shorter ICU LOS (P = .02) and 10% more hospital-free days in the 30 days following discharge (P = .004) according to the univariate models, though statistical significance was absent within adjusted models in both ICU LOS (P = .08) and hospital-free days (P = .53). Conclusions: Compared to FFP, AT use suggests a reduction in the odds of mortality in suspected heparin-resistant patients undergoing CPB, though larger prospective studies are necessary to elucidate potential differences in hospital-free days or ICU LOS across treatment modalities.

Penny-wise and pound-foolish: the challenges of preoperative anaemia management.

The timely correction of anaemia before major surgery is important for optimising perioperative patient outcomes. However, multiple barriers have precluded the global expansion of preoperative anaemia treatment programmes, including misconceptions about the true cost/benefit ratio for patient care and health system economics. Institutional investment and buy-in from stakeholders could lead to significant cost savings through avoided complications of anaemia and red blood cell transfusions, and through containment of direct and variable costs of blood bank laboratories. In some health systems, billing for iron infusions could generate revenue and promote growth of treatment programmes. The aim of this work is to galvanise integrated health systems worldwide to diagnose and treat anaemia before major surgery.

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.

Iron metabolism and iron deficiency anemia in women.

Iron deficiency (ID) and iron deficiency anemia (IDA) are highly prevalent among women across their reproductive age. An iron-deficient state has been associated with and causes a number of adverse health consequences, affecting all aspects of the physical and emotional well-being of women. Heavy menstrual bleeding, pregnancy, and the postpartum period are the major causes of ID and IDA. However, despite the high prevalence and the impact on quality of life, ID and IDA among women in their reproductive age is still underdiagnosed and undertreated. In this chapter we summarized the iron metabolism and the diagnosis and treatment of ID and IDA in women.

Management of Perioperative Iron Deficiency in Cardiac Surgery: A Modified RAND Delphi Study.

BACKGROUND: Over the last decade, preoperative anemia has become recognized as a clinical condition in need of management. Although the etiology of preoperative anemia can be multifactorial, two thirds of anemic elective surgical patients have iron deficiency anemia. At the same time, one third of nonanemic elective surgical patients are also iron deficient. METHODS: Modified RAND Delphi methodology was used to identify areas of consensus among an expert panel regarding the management of iron deficiency in patients undergoing cardiac surgery. A list of statements was sent to panel members to respond to using a five-point Likert scale. All panel members subsequently attended a face-to-face meeting. The initial survey was presented and discussed, and panel members responded to each statement on the Likert scale again. Based on the second survey, the panel came to a consensus on recommendations. RESULTS: The panel recommended all patients undergoing cardiac surgery be evaluated for iron deficiency, whether or not anemia is present. Evaluation should include iron studies and reticulocyte hemoglobin content. If iron deficiency is present, with or without anemia, patients should receive parenteral iron. Erythropoietin-stimulating agents may be appropriate for some patients. CONCLUSIONS: Consensus of an expert panel resulted in a standardized approach to diagnosing and managing iron deficiency in patients undergoing cardiac surgery.

How I treat anemia in the perisurgical setting.

Anemia is a common finding in the perioperative setting with significant untoward consequences including worsening of outcomes and diminished quality of life as well as increased risk of allogeneic blood transfusions. Here, we present 3 cases that illustrate how anemia can be perioperatively managed in patients undergoing cardiac, orthopedic, and oncology surgeries. Timely detection of anemia prior to high-blood loss surgeries can allow clinicians to manage it and optimize hemoglobin level, making patients better prepared for the surgery. Treatment of anemia should be guided by the etiology and may include erythropoietic agents, folic acid, B12, and iron preparations. Other blood management strategies geared toward reducing surgical blood loss such as autologous transfusion techniques and agents to optimize hemostasis are used during surgery and in the immediate postoperative period. Patients should be closely monitored following surgery for signs of ongoing bleeding in need of control. Finally, screening for and management of anemia should continue in the postoperative and postdischarge period, as persistence and recurrence of anemia can further undermine patient's outcomes.

A Narrative Review on Hospital-Acquired Anemia: Keeping Blood where It Belongs.

Hospital-acquired anemia (HAA) is a prevalent condition that is independently associated with worse clinical outcomes including prolongation of hospital stay and increased morbidity and mortality. While multifactorial in general, iatrogenic blood loss has been long recognized as one of the key contributing factors to development and worsening of HAA during hospital stay. Patients can be losing over 50 mL of blood per day to diagnostic blood draws. Strategies such as elimination of unnecessary laboratory tests that are not likely to alter the course of management, use of pediatric-size or small-volume tubes for blood collection to reduce phlebotomy volumes and avoid blood wastage, use of closed blood sampling devices, and substituting invasive tests with point-of-care testing alone or bundled together have generally been shown to be effective in reducing the volume of iatrogenic blood loss, hemoglobin decline, and blood transfusions, with no negative impact on the availability of test results for the clinical team. These strategies are important components of Patient Blood Management programs and their adoption can lead to improved clinical outcomes for patients.

Standards and Best Practice for Acute Normovolemic Hemodilution: Evidence-based Consensus Recommendations.

OBJECTIVE: To develop a standardized approach to the implementation and performance of acute normovolemic hemodilution (ANH) in order to reduce the incidence of bleeding and allogeneic blood transfusion in high-risk surgical bleeding-related cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A 2-round modified RAND-Delphi consensus process. PARTICIPANTS: Seven physicians from multiple geographic locations and clinical disciplines including anesthesiology and cardiac surgery and 1 cardiac surgery perfusionist participated in the survey. One registered nurse, specializing in Patient Blood Management, participated in the discussion but did not participate in the survey. METHODS: A modified RAND-Delphi method was utilized that integrated evidence review with a face-to-face expert multidisciplinary panel meeting, followed by repeated scoring using a 9-point Likert scale. Consensus was determined as a result from the second round survey, as follows: median rating of 1-3: ANH acceptable; median rating of 7-9: ANH not acceptable; median rating of 4-6: use clinical judgment. RESULTS: Evidentiary review identified 18 key peer-reviewed manuscripts for discussion. Through the consensus-building process, 39 statements including 26 contraindications to ANH and 10 CPB patient variables were assessed. In total, 22 statements were accepted or modified for the second scoring round. CONCLUSIONS: Consensus was reached on 6 conditions in which ANH would or would not be acceptable, showing that development of a standardized approach for the use of ANH in high-risk surgical bleeding and allogeneic blood transfusion is clearly possible. The recommendations developed by this expert panel may help guide the management and inclusion of ANH as an evidence and consensus-based blood conservation modality.

Perioperative Anemia: Prevention, Diagnosis, and Management Throughout the Spectrum of Perioperative Care.

Anemia is common in the perioperative period and is associated with poor patient outcomes. Remarkably, anemia is frequently ignored until hemoglobin levels drop low enough to warrant a red blood cell transfusion. This simplified transfusion-based approach has unfortunately shifted clinical focus away from strategies to adequately prevent, diagnose, and treat anemia through direct management of the underlying cause(s). While recommendations have been published for the treatment of anemia before elective surgery, information regarding the design and implementation of evidence-based anemia management strategies is sparse. Moreover, anemia is not solely a concern of the preoperative encounter. Rather, anemia must be actively addressed throughout the perioperative spectrum of patient care. This article provides practical information regarding the implementation of anemia management strategies in surgical patients throughout the perioperative period. This includes evidence-based recommendations for the prevention, diagnosis, and treatment of anemia, including the utility of iron supplementation and erythropoiesis-stimulating agents (ESAs).

Tranexamic Acid for Acute Hemorrhage: A Narrative Review of Landmark Studies and a Critical Reappraisal of Its Use Over the Last Decade.

The publication of the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) study and its intense dissemination prompted a renaissance for the use of the antifibrinolytic agent tranexamic acid (TXA) in acute trauma hemorrhage. Subsequent studies led to its widespread use as a therapeutic as well as prophylactic agent across different clinical scenarios involving bleeding, such as trauma, postpartum, and orthopedic surgery. However, results from the existing studies are confounded by methodological and statistical ambiguities and are open to varied interpretations. Substantial knowledge gaps remain on dosing, pharmacokinetics, mechanism of action, and clinical applications for TXA. The risk for potential thromboembolic complications with the use of TXA must be balanced against its clinical benefits. The present article aims to provide a critical reappraisal of TXA use over the last decade and a "thought exercise" in the potential downsides of TXA. A more selective and individualized use of TXA, guided by extended and functional coagulation assays, is advocated in the context of the evolving concept of precision medicine.

Reducing red blood cell transfusion in orthopedic and cardiac surgeries with Antifibrinolytics: A laboratory medicine best practice systematic review and meta-analysis.

OBJECTIVES: To evaluate the effectiveness of antifibrinolytics tranexamic acid (TA), ε-aminocaproic acid (EACA), and aprotinin to decrease overuse of red blood cell transfusions in adult surgical and non-surgical patients. METHODS: This review followed the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best Practice (LMBP™) Systematic Review (A-6) method. Eligible studies were assessed for evidence of effectiveness of TA or EACA in reducing the number of patients transfused or the number of whole blood transfusions. RESULTS: Seventy-two articles met LMBP™ inclusion criteria. Fifty-six studies assessed Topical, Intra-articular Injection, or Intravenous TA, 4 studied EACA, and 12 studied the effectiveness of aprotinin. The overall strength of the body of evidence of effectiveness for each of these practices was rated as high. CONCLUSION: LMBP™ recommends the use of topical, intra-articular injection, or intravenous tranexamic acid and the use of ε-aminocaproic acid for reducing overuse of red blood cell transfusion.

Management of Perioperative Iron Deficiency Anemia.

Preoperative anemia affects 30-40% of patients undergoing major surgery and is an independent risk factor for perioperative blood transfusion, morbidity, and mortality. Absolute or functional iron deficiency is its leading cause. Nonanemic hematinic deficiencies are also prevalent and may hamper preoperative hemoglobin optimization and/or recovery from postoperative anemia. As modifiable risk factors, anemia and hematinic deficiencies should be detected and corrected prior to major surgical procedures. Postoperative anemia is even more common (up to 80-90%) due to surgery-associated blood loss, inflammation-induced blunted erythropoiesis, and/or preexisting anemia. Preoperative oral iron may have a role in mild-to-moderate anemia, provided there is sufficient time (6-8 weeks) and adequate tolerance of oral preparations. Postoperative oral iron is of little value and rife with gastrointestinal adverse events. Intravenous iron should preferentially be used in cases of moderate-to-severe iron deficiency anemia, concomitant use of erythropoiesis-stimulating agents, short time to surgery or nonelective procedures, and for postoperative anemia management. Minor infusion reactions to intravenous iron are rare, the incidence of severe anaphylactic reactions is extremely low, and there is no increase in infections with intravenous iron. Currently available intravenous iron formulations allowing administration of large single doses are preferred.

Proceedings From the Society for Advancement of Blood Management Annual Meeting 2017: Management Dilemmas of the Surgical Patient-When Blood Is Not an Option.

Vigilance is essential in the perioperative period. When blood is not an option for the patient, especially in a procedure/surgery that normally holds a risk for blood transfusion, complexity is added to the management. Current technology and knowledge has made avoidance of blood transfusion a realistic option but it does require a concerted patient-centered effort from the perioperative team. In this article, we provide suggestions for a successful, safe, and bloodless journey for patients. The approaches include preoperative optimization as well as intraoperative and postoperative techniques to reduce blood loss, and also introduces current innovative substitutes for transfusions. This article also assists in considering and maneuvering through the legal and ethical systems to respect patients' beliefs and ensuring their safety.

Prevention and management of acute reactions to intravenous iron in surgical patients.

Absolute or functional iron deficiency is the most prevalent cause of anaemia in surgical patients, and its correction is a fundamental strategy within "Patient Blood Management" programmes. Offering perioperative oral iron for treating iron deficiency anaemia is still recommended, but intravenous iron has been demonstrated to be superior in most cases. However, the long-standing prejudice against intravenous iron administration, which is thought to induce anaphylaxis, hypotension and shock, still persists. With currently available intravenous iron formulations, minor infusion reactions are not common. These self-limited reactions are due to labile iron and not hypersensitivity. Aggressively treating infusion reactions with H1-antihistamines or vasopressors should be avoided. Self-limited hypotension during intravenous iron infusion could be considered to be due to hypersensitivity or vascular reaction to labile iron. Acute hypersensitivity reactions to current intravenous iron formulation are believed to be caused by complement activation-related pseudo-allergy. However, though exceedingly rare (<1:250,000 administrations), they should not be ignored, and intravenous iron should be administered only at facilities where staff is trained to evaluate and manage these reactions. As preventive measures, prior to the infusion, staff should inform all patients about infusion reactions and identify those patients with increased risk of hypersensitivity or contraindications for intravenous iron. Infusion should be started at a low rate for a few minutes. In the event of a reaction, the very first intervention should be the immediate cessation of the infusion, followed by evaluation of severity and treatment. An algorithm to scale the intensity of treatment to the clinical picture and/or response to therapy is presented.