8.1.1 Outcome after the Implementation of First-pillar Measures

In 2010, the WHO adopted PBM as one of the most important aspects of transfusion safety (WHO 2010b). This is important because preoperative anemia is frequent (Kulier and Gombotz 2001, Guralnik et al 2004) and it independently increases the postoperative morbidity and mortality (Musallam et al 2011, Jans et al 2014), increases the 90-day readmission rate (Jans et al 2014), and prolongs hospitalization (Williams et al 2013, Jans et al 2014). This is true even for mild anemia (hemoglobin concentration of 10–13 g/dL in men; hemoglobin concentration of 10–12 g/dL in women) (Musallam et al 2011). In addition, preoperative anemia is a highly significant risk factor for perioperative red blood cell (RBC) transfusion (Gombotz et al 2007, Williams et al 2013, Jans et al 2014). RBC transfusions increase the postoperative mortality and morbidity further (Bernard et al 2009, Ferraris et al 2012) and they are associated with high costs (Shander et al 2010, Ferraris et al 2012).

The treatment of preoperative anemia (first pillar of PBM) (Goodnough and Shander 2012, Spahn and Goodnough 2013) lowers the RBC transfusion rate (Spahn 2010, Yoo et al 2011, Muñoz et al 2014b), the frequencies of acute kidney injury (Yoo et al 2011) and nosocomial infection (Muñoz et al 2014b), and the hospital length of stay (Muñoz et al 2014b). Interestingly, most benefits were also observed after very-short-term administration of intravenous iron and erythropoietin (Yoo et al 2011, Muñoz et al 2014b).

So-Osman et al (2014) assessed the effect of preoperative erythropoietin administration using a highly complex treatment protocol in patients undergoing hip or knee arthroplasty. Despite the fact that 34 % of the patients randomized to the erythropoietin group did not even receive one of the four planned erythropoietin injections, the RBC transfusion rate decreased significantly from 26 % to 16 % in this group; the number of RBC units transfused per patient also decreased, from 0.7 units to 0.5 units, but the difference was not statistically significant. However, when the analysis was restricted to include only patients who had been treated per protocol, the proportion of transfused patients decreased significantly by 70 % and the number of RBC units transfused per patient decreased by 62 % (So-Osman et al 2014). Preoperative anemia treatment is therefore generally recommended prior to surgery (Gombotz 2011, Goodnough et al 2011, Goodnough and Shander 2012, Shander et al 2012b, Spahn and Goodnough 2013).

8.1.2 Outcome after the Implementation of Second-pillar Measures

The avoidance of excessive blood loss (second pillar of PBM) is beneficial since high blood loss in itself—independently of preoperative anemia and allogeneic RBC transfusion—increases the mortality and morbidity. This has been demonstrated in patients undergoing cardiac surgery (Vivacqua et al 2011, Ranucci et al 2013). In the study by Vivacqua et al (2011), patients with high blood loss resulting in reoperation had an approximately threefold increased mortality and a twofold increased rate of major complications. In the study by Ranucci et al (2013), patients with major bleeding had a 3.5-fold increased mortality irrespective of whether they had received RBC transfusions.

In addition to meticulous surgical technique aimed at perfect local hemostasis, an important measure of the second pillar is the avoidance of perioperative coagulopathy by closely monitoring the patient’s coagulation status using viscoelastic techniques and by providing targeted, individualized coagulation therapy (Spahn and Ganter 2010, Weber et al 2012, Bolliger and Tanaka 2013, Haas et al 2014). In a prospective randomized study of cardiac surgery patients with coagulopathy after heparin reversal, Weber and colleagues (2012) demonstrated that an algorithm based on rotational thromboelastometry and treatment with coagulation factor concentrates was effective in reducing the need for allogeneic blood products, with significant declines in the consumption of RBCs (median 5 units versus 3 units), fresh frozen plasma (FFP; median 5 units versus 0 units), and platelets (median 2 units versus 2 units. Postoperative blood loss was also reduced and the 6-month survival improved substantially (Weber et al 2012). Interestingly, the costs of hemotherapy were reduced by approximately 50 %, from €3,109 to €1,658 per patient (Weber et al 2012). Similarly, Haas and colleagues (2014) found in children undergoing surgery for craniosynostosis that the introduction of an algorithm based on rotational thromboelastometry and treatment with coagulation factor concentrates significantly decreased the need for allogeneic blood products while the total costs of hemotherapy were decreased.

8.1.3 Outcome after the Implementation of Third-pillar Measures

The use of a restrictive hemoglobin transfusion threshold (third pillar of PBM) also results in better patient outcomes. In a study of more than 14,000 patients undergoing cardiac surgery, LaPar and colleagues (2013) found that the introduction of a restrictive transfusion regimen resulted in a reduction in RBC transfusions from 24 % to 18 % intraoperatively and from 39 % to 33 % postoperatively; the mortality was reduced from 1.8 % to 1.0 % and the rate of major postoperative complications was reduced from 15 % to 13 %. In addition, the total costs decreased from $30,500 to $26,200 (LaPar et al 2013). Villanueva and colleagues (2013a) showed in a prospective randomized multicenter study in patients with upper gastrointestinal bleeding that a restrictive transfusion regimen improved the survival, decreased the rate of complications, and reduced the hospital length of stay by approximately 2 days. A Cochrane meta-analysis including 19 prospective randomized studies and 6,264 patients indicated that the use of a restrictive transfusion strategy decreased RBC transfusions, in-hospital mortality, and infections (Carson et al 2012a).

Another meta-analysis including 18 prospective randomized studies and 7,593 patients confirmed the reduction in RBC transfusions when using a restrictive hemoglobin transfusion threshold; moreover, the analysis showed that a restrictive strategy resulted in 30 % fewer infections, particularly serious infections, and that this benefit was particularly relevant in orthopaedic surgery (Rohde et al 2014). A very interesting finding of this meta-analysis was that the benefit in lowering the incidence of postoperative infections was fully maintained when the analysis was limited to studies using leukocyte-reduced RBC transfusions.

8.1.4 Outcome after the Implementation of a Full PBM Program

In addition to studies showing the benefit of individual PBM measures, there are also reports on the outcomes after implementing a full PBM program (Moskowitz et al 2010, Kotze et al 2012, Leahy et al 2014, Theusinger et al 2014b). Moskowitz and colleagues (2010) demonstrated that the implementation of a PBM program in cardiac surgery resulted in reductions in the rate of RBC transfusions (from 43 % to 11 %), the rate of complications (from 26 % to 11 %), and the mortality (from 2.5 % to 0.8 %). Subsequently, Kotze and colleagues (2012) reported on the success of implementing PBM in orthopaedic surgery. They were able to reduce the rate of RBC transfusions from 23 % to 7 % in hip arthroplasty and from 7 % to 0 % in knee arthroplasty. In addition, the length of hospitalization decreased from 6 days to 5 days in hip arthroplasty and from 6 days to 4 days in knee arthroplasty, and the overall 90-day readmission rate decreased from 14 % to 8 % (Kotze et al 2012). In 2014, Leahy and colleagues reported on the success of implementing PBM in Western Australia; the mean number of RBC units used per admission declined by 26 %, the use of FFP transfusions decreased by 38 %, and the use of platelet transfusions decreased by 16 %. Finally, Theusinger and colleagues (2014b) reported the results of implementing PBM in orthopaedic surgery; they focused on treating preoperative anemia, improving surgical technique, and lowering the hemoglobin threshold for transfusion to 8 g/dL. In a total of 8,871 patients undergoing major hip, knee, or spine surgery, this program decreased the transfusion rate from 20 % to 10 %.

Despite the great overall success of these PBM programs, it is interesting to note that they all implemented selected PBM measures only, while other measures were not implemented. This clearly indicates that the full potential of PBM has not yet been achieved in any of these centers.

PBM programs are not only beneficial in terms of the outcome of surgical patients; they also reduce the treatment costs substantially (Kotze et al 2012, Spahn et al 2012, Weber et al 2012, Cohn et al 2014, Haas et al 2014). Calculation of the total hospital costs for the population of orthopaedic surgery patients studied by Kotze et al (2012)—accounting for the reductions in RBC transfusion, length of hospitalization, and readmission—revealed that a net cost saving of at least ￡160,000 was achieved (Spahn et al 2012).

8.2.1 Establishment of PBM in the Literature, Teaching, and Continuing Education

A PubMed search for “Patient Blood Management [All Fields]” shows that this phrase was first used in 2007 in a publication by the Australian hematologist and transfusion specialist James Isbister (Isbister 2007). As early as 1988, Isbister advocated a paradigm shift in the use of RBC transfusion in clinical practice (Isbister 1988). In 2005, together with international colleagues and representatives of various medical societies, he coined the term Patient Blood Management during preparations for a symposium. The main intention was to enable a distinction between the new term and Blood Management, a term that mainly refers to activities related to blood banks and transfusion (Farmer et al 2013a). In 2008, the term Patient Blood Management first appeared in the title of a medical publication (Spahn et al 2008). From November 2012 to July 2015, the number of papers listed in PubMed and Embase that addressed the topic of PBM increased to 174. The articles appeared in journals from the fields of anesthesiology, intensive care medicine, general surgery, cardiac surgery, gynecology and obstetrics, internal medicine, hemotherapy, transfusion medicine, and oncology. Moreover, PBM has been featured in some of the major general medical journals. This unusually broad spectrum of journals reflects the fact that PBM is a multidisciplinary approach that has the potential to affect the treatment and outcome of millions of patients in the coming years.

The growing interest in PBM is also borne out by the increasing number of national and international societies that organize lectures on this subject and offer block sessions on PBM at conferences and symposia. Furthermore, several multidisciplinary medical societies exist that deal specifically with PBM and with hemotherapy strategies designed to improve patient outcome by avoiding and preempting the use of allogeneic blood products. Since 2012, the American Association of Blood Banks has also focused on this topic (www.aabb.org/pbm), albeit their definition of PBM does not in all respects concord with the definitions used in the literature or by specialist societies (SABM 2012).

8.2.2 Establishment of PBM as the Standard of Care in Australia

Australia has played a pioneering role in the implementation of PBM as the standard of care (Spahn et al 2008, Hofmann et al 2012, Leahy and Mukhtar 2012). In 2007, the Department of Health in Western Australia launched an initiative that became known as the Western Australia PBM Program. It was the world’s first PBM program to be implemented across the public health system of an entire state or jurisdiction and has won widespread support among local, national, and international experts and clinicians.

▶ Aims of the project. The Western Australia PBM Program was launched to sustainably implement evidence-based PBM as the new standard of care in public hospitals and, with the involvement of general practitioners, in the preoperative management of anemia (www.health.wa.gov.au/blood-management). According to the 2011 Executive Summary, the initiative aims to improve patient outcomes by optimizing blood utilization and reducing inappropriate transfusions while at the same time delivering substantial cost savings. The program has also been described as an initiative focusing on quality, safety, and effectiveness with resource and financial implications (DHWA 2011). This rare combination of achieving improved treatment outcomes while using fewer resources is, of course, attractive and bolsters the implementation of PBM. To promote the implementation of PBM, the Western Australia Department of Health made increasingly more personnel available; it launched postgraduate training courses under the leadership of a multidisciplinary faculty; it ran training courses on surgical hemostasis in cooperation with the University of Western Australia; it helped create an IT infrastructure to support continuous benchmarking of transfusion and outcome; and it produced patient information on PBM.

▶ Favorable structural conditions. Favorable structural conditions continue to have a positive impact on the Western Australia PBM Program and enable the rapid implementation of PBM throughout Australia:

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  The supply of blood and blood products at the national and state/territory level is managed and coordinated by the National Blood Authority (NBA). In 2006, this government agency established a Clinical Advisory Council, which recommended the replacement of the then existing product-focused transfusion guidelines (“Guidelines on the Use of Blood and Blood Products” from 2001) with patient-focused guidelines. PBM was seen as the ideal clinical framework for these new guidelines. Subsequently, the NBA made sufficient funds available for the development of six comprehensive, evidence-based PBM guideline modules. These modules were developed under the direction of a national PBM Steering Committee with the support of an Expert Working Group (a multidisciplinary group of representatives from 14 professional societies in Australia/New Zealand), a Clinical Reference Group (hospital representatives), and a Consumer Reference Group (patient representatives) (NBA 2014; http://www.blood.gov.au). The six modules focus on PBM in the following areas: (1) Critical Bleeding/Massive Transfusion; (2) Peri-operative Setting; (3) Medical; (4) Critical Care; (5) Obstetrics and Maternity; and (6) Pediatrics and Neonatology. At the time of writing, five of the six modules had been published, with publication of the sixth module expected in the near future (www.blood.gov.au/pbm-guidelines). The introduction to each module clearly states that PBM helps to improve outcomes by avoiding unnecessary RBC transfusions. Special emphasis is placed on the three-pillar model, highlighting the role of PBM in treating the potential reasons for transfusion with the implication that transfusion can be avoided in many clinical scenarios and is no longer the default decision.

  
  
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  The national PBM guidelines refer to the Western Australia PBM Program as a model to be emulated at the transnational level.

  
  
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  The Australian Commission on Safety and Quality in Health Care (ACSQHC), which was set up to drive the implementation of safety and quality systems in health care in Australia, considers PBM to be an important contributor to patient safety and treatment quality. The implementation of PBM is therefore an important criterion for the accreditation of hospitals to the blood and blood product standard developed by the ACSQHC (ACSQHC 2012).

  
  
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  The Australian Red Cross Blood Service, which—under the supervision of the NBA—is responsible for the supply of all blood products in Australia, has supported all Australian PBM initiatives from the start through continuing education programs and information materials for clinicians and patients covering PBM, the management of anemia, and related topics (ARCBS 2014a, ARCBS 2014b, Raison 2012).

  
  
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  BloodSafe eLearning Australia—an amalgamation of statutory agencies and other qualified organizations—runs web-based training courses for clinicians that focus on transfusion medicine and PBM. By the middle of 2012, 135,000 clinicians and more than 700 hospitals had registered with this program, which includes training modules on the management of anemia and bleeding (https://bloodsafelearning.org.au).

In the meantime, private hospital organizations in Western Australia have also started to implement PBM on a large scale (Hollywood Private Hospital 2012).

8.2.3 PBM Programs in Other Countries

▶ Austria. The situation in Austria deserves particular mention. A benchmark study funded by the Austrian Federal Ministry of Health investigated the variability in blood transfusion practices before elective procedures at 18 public hospitals. The study revealed that PBM led to a significant reduction in the consumption of blood products while assuring a similar, or even better, outcome (Gombotz et al 2007). These results were confirmed by a second benchmark study, also funded by the Ministry of Health (see Chapter 1.6) (Gombotz et al 2012). In parallel to the first study, process cost analysis of the total expenditure for RBC transfusions was carried out, for example at Linz General Hospital (Austria’s fourth largest hospital) (Shander et al 2010). Following publication of the results of the First Austrian Benchmark Study, Linz General Hospital implemented a comprehensive PBM program. From 2005 to 2011, the number of RBCs transfused per hospital admission dropped from 14,000 to less than 6,000 (see Fig. 1.9, Chapter 1.6). In 2014, the total transfusion index at Linz General Hospital was at 0.16, which represents the lowest figure among the eight largest public hospitals in the country (H. Gombotz, oral communication, July 2015).

▶ European Union and Switzerland. In 2014, the Consumers, Health, Agriculture and Food Executive Agency of the European Commission announced a pilot program for the implementation of PBM in five European teaching hospitals (www.europe-pbm.eu). The main objectives of the project are (AIT 2014):

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  To assess blood use in various medical specialties.

  
  
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  To identify regional and national differences in terms of blood use and PBM strategies.

  
  
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  To identify good practice in the field of PBM.

  
  
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  To develop EU guidance on good practice related to PBM.

In addition, the Joint United Kingdom Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee offers continuing support for the implementation of PBM.

According to Shander et al (2012b), efforts to implement PBM are undertaken in the Netherlands, Spain, Switzerland, and the United Kingdom. The authors also identified a number of obstacles to the widespread implementation of PBM, such as lack of awareness regarding the clinical impact of anemia on patient outcome, limited understanding of transfusion and adverse outcomes, behavioral issues, and misperceptions regarding the cost-effectiveness of transfusion. Shander et al (2012b) also issued recommendations for tackling these obstacles. Similar hurdles were encountered when the Western Australia PBM Program was introduced, but these were successfully overcome in most cases.

▶ Canada. Also noteworthy are the PBM-related initiatives launched in Canada. These include the Transfusion Ontario programs organized by the Ontario Ministry of Health and the Ontario Blood System Reference Group. In addition to providing continuing education and quality control in transfusion medicine, the Transfusion Ontario programs are aimed at promoting the sustainable implementation of treatment modalities to reduce blood consumption in the entire province of Ontario. One of the programs, Ontario Transfusion Coordinators (ONTraC), was initiated with the participation of 25 hospitals (www.ontracprogram.com). During the first 12 months of continuous benchmarking, and also subsequently, marked improvements were noted in most hospitals in terms of both the transfusion rate and the transfusion index. Significant reductions were also seen in the rate of postoperative infections and the hospital length of stay (Freedman et al 2005, Freedman 2005, Freedman et al 2008).

▶ USA. It was in the United States, almost 20 years ago, that the first measures for blood conservation in surgery and internal medicine (the precursors of modern PBM) were introduced, in particular at Englewood Hospital and Medical Center in Englewood, NJ (IPBMBMS 2012). Despite this fact, PBM has to date been implemented in only around 200 hospitals in the United States. However, the Joint Commission, the country’s most important organization for the accreditation and certification of hospitals and health care establishments, has acknowledged PBM as an important quality measure. The Joint Commission’s most recent PBM performance measures to evaluate transfusion practice at U.S. hospitals were published in 2011 (JC 2011).

Furthermore, the U.S. Department of Health and Human Services took the first steps toward the nationwide promotion of PBM in 2011 (see Chapter 8.2.4). The SABM, with members comprising of clinicians from multiple disciplines, focuses with increasing success on matters related to PBM in the United States and abroad (Wald 2014).

8.2.4 Prioritization of PBM by the WHO

▶ WHO resolution. Given that to date no multidisciplinary PBM programs have been set up, apart from the initiative in Australia and isolated projects in a few European countries, Canada, and the United States, it is all the more important that the WHO Executive Board recognized the opportunities for and the significance of PBM, and advocated its implementation. In view of the safety risks associated with blood transfusion and the growing bottlenecks in the supply of blood and blood products, the topic of PBM was placed on the provisional agenda of the 126th Executive Board meeting (WHO 2009). The final agenda was expanded to accommodate a few additional items, two of which again related to PBM. At the 126th Executive Board meeting held at the WHO headquarters in Geneva on January 22, 2010, it was decided to recommend to the World Health Assembly—the highest WHO decision-making body—the adoption of a resolution on the “Availability, Safety and Quality of Blood Products” (WHO 2010a). The resolution contains the following passages:

…patient blood management means that before surgery every reasonable measure should be taken to optimize the patient’s own blood volume, to minimize the patient’s blood loss and to harness and optimize the patient-specific physiological tolerance of anemia following WHO’s guide for optimal clinical use (three pillars of patient blood management).

The Sixty-third World Health Assembly…urges Member States…to establish or strengthen systems for the safe and rational use of blood products and to provide training for all staff involved in clinical transfusion, to implement potential solutions in order to minimize transfusion errors and promote patient safety, to promote the availability of transfusion alternatives including, where appropriate, autologous transfusion and patient blood management.

The Sixty-third World Health Assembly…requests the Director-General…to provide guidance, training and support to Member States on safe and rational use of blood products to support the introduction of transfusion alternatives including, where appropriate, autologous transfusion, safe transfusion practices and patient blood management.

At the 63rd meeting of the World Health Assembly in Geneva in May 2010, the resolution was adopted in all its points, including explicit reference to the three-pillar concept as an important element of modern health care systems (WHO 2010b). This decision brought PBM to the official attention of all 193 WHO Member States.

▶ WHO expert meeting. The following year, the WHO, in collaboration with the Sharjah Blood Transfusion and Research Center and co-sponsored by the government of the United Arab Emirates, organized its first multinational PBM expert meeting entitled “Global Forum for Blood Safety: Patient Blood Management” (WHO 2011b). Below are some of the priorities for action that were identified at the meeting:

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  Benchmark transfusion prescription and practices….

  
  
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  Collect a minimum set of data on patient transfusion outcomes. …

  
  
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  Identify major national clinical needs and, based on these, develop and implement national guidelines on blood use including PBM. …

  
  
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  Conduct multicentric studies on:

  
  
  
  
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    Patient outcomes [using PBM].

    
    
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    Alternatives [to the transfusion of allogeneic blood components].

  
  
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  Conduct benchmarking studies to compare practices in different hospitals and clinicians. …

  
  
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  Focus on outcome research.

  
  
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  Translate – Make available current evidence through desk research – Meta-analysis.

  
  
  
  
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    Move forward on randomized controlled trials (RCTs).

    
    
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    Need more funding for RCTs in PBM.

▶ U.S. Department of Health and Human Services and Advisory Committee on Blood Safety and Availability. Having regard to Resolution WHA63.12, the U.S. Department of Health and Human Services convened its first expert meeting on PBM in 2011. Based on the information presented by the experts, the Advisory Committee on Blood Safety and Availability compiled a document setting out recommendations for the national implementation of PBM (USDHHS 2011). The document includes the following statements:

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  Blood transfusion carries significant risk that may outweigh its benefits in some settings and add unnecessary costs.

  
  
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  Wide variability, in the use of transfusions, indicates that there is both excessive and inappropriate use of blood transfusions.

  
  
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  Medical advances and aging of the population are expected to drive demands for transfusions that could exceed supplies in one to two decades.

  
  
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  Programs of patient-oriented blood management at some hospitals have demonstrated significant reduction in blood use, without increase in patient harm, based on expert decision-making.

Based on these acknowledgements, the Committee recommended that the authorities:

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  Identify mechanisms to obtain data on PBM, utilization of transfusion, and clinical outcomes.

  
  
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  Support development and promulgation of national standards for blood use recognizing the value of patient management, blood conservation, and conservative blood use. …

  
  
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  Establish metrics for good practices of blood use and PBM.

  
  
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  Advise the Office of National Coordination of Healthcare Information Technology (ONC HIT) on the need to integrate PBM and blood utilization into electronic health records.

  
  
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  Promote education of medical students and practitioners on optimizing PBM and use of transfusion and elevate awareness of the essential role of blood management in the quality and cost efficiency of clinical care.

  
  
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  Promote patient education about the risks, benefits, and alternatives of transfusion…

  
  
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  Support demonstration projects on PBM…

8.3.1 Introduction

The ACSQHC has declared the National PBM Collaborative a top national priority (ACSQHC 2015b). The collaborative is being undertaken in consultation with the NBA Australia, states and territories, and public and private health care providers. Its aim is that PBM be the standard of care applied by all clinicians for patients facing a medical or surgical intervention who are at high risk of significant blood loss. The ACSQHC stated that the best and safest blood for patients is their own circulating blood, and that this valuable and unique natural resource should therefore be conserved and managed in the same way as all other body systems. This includes the assessment and management of conditions that might lead to a blood transfusion, so that transfusions are undertaken only when clinically appropriate. The ACSQHC, with its key role in the accreditation of public and private hospitals, sees the following benefits from PBM: improved patient outcomes (including fewer complications, faster recovery, and shorter hospital stay), reduced patient exposure to the potential risks (including allergic and immunologic complications) from receiving allogeneic blood components, reduced risk of infection, and reduced transfusion of incorrect blood (blood meant for someone else).

A national competent authority aiming to implement PBM as a new standard of care across the Australian health care system and declaring it a top national priority marks the latest development in a success story that goes back a quarter of a century and is the result of consistent and considered work on all elements of the Australian health system.