Özet

Successful implementation of a patient blood management program necessitates the collaboration of a strong organization and a multidisciplinary approach. We organized a meeting with broad participation in our center to establish a consensus for implementation of a specific patient blood management program. International and domestic experiences were shared, the importance of coordination and execution of different pillars in patient blood management were discussed, and the problems about the blood transfusion system were also investigated with the proposal for solutions. The data obtained from this meeting are presented to be a guide for similar large-volume tertiary hospitals for integration of a patient blood management protocol.

The World Health Organization (WHO) described the patient blood management (PBM) in the early 2000s, which was made effective in the Netherlands for the first time. In 2008, Australia was the first country which made it compulsory nationwide.[1-3] The United States, in 2007, published a guideline on bleeding and blood management before and after cardiac surgery.[4] The criticism and suggestions were considered for four years and were used to reform the guideline in 2011.[5] The European PBM guideline was published in 2017,[6] and the Turkish guideline was published in 2019.[7] Numerous studies conducted in these countries endorsed 30 to 40% reduction in the number of blood transfusions, significant resource savings, and a significant reduction in morbidity and mortality of patients.

The PBM is a three-pillar strategy to cure preoperative anemia and iron deficiency (intravenous [IV] iron + erythropoietin [EPO] + vitamin B12 + folic acid), reduce preoperative red blood cell (RBC) loss by an improved surgical technique, cell salvage, and re-transfusion, acute normovolemic hemodilution, coagulopathy management (anti-fibrinolytics, fibrinogen, Factor XIII, prothrombin complex concentrate [PCC], low central venous pressure, no hypertension, normothermia), and optimize anemia management (tolerate low hemoglobin values, IV iron + EPO postoperatively, increased fraction of inspired oxygen [FiO₂]).[8-13]

In this review, we aimed to share previous experiences and indicate current problems with solutions which would ensure the implementation of a PBM protocol in our hospital that can be also a guide for similar large-volume tertiary hospitals.

SUCCESSFUL IMPLEMENTATION STORIES: INTERNATIONAL
University Hospital of Zurich PBM Program
The University Hospital of Zurich (USZ) aimed to achieve the best possible surgical patient outcome (lowest mortality, no organ dysfunction, no lung injury, no renal impairment, no stroke, no myocardial infarction, minimal infection rate, minimal thromboembolic adverse events, minimal length of hospital stay, least amount of blood product transfusions, minimal costs) and adopted the strategies of PBM to attain this target.

Key steps in the implementation of PBM included the development of hospital-wide guidelines, creating a commission for the responsible use of blood products, achieving general ownership at all disciplines, monitoring guideline adherence, and collecting data to evaluate the success rate. Firstly, the anesthesiology department, in collaboration with the hematology department, developed evidencebased transfusion and anemia management guidelines (Tables 1 and 2). Eight specialties were defined to use these guidelines: cardiac surgery, trauma, transplantation, obstetrics, neurosurgery, burn unit, intensive care unit (ICU), and plastic surgery. Patients with an RBC transfusion rate of >10% and an expected blood loss of >500 mL were included as the focus group identified by the workgroup of USZ. The PBM program organization is listed in Table 3.

The PBM was put into practice in USZ about 10 years ago, and its success was demonstrated in many studies.[14,15]

SUCCESSFUL IMPLEMENTATION STORIES: NATIONAL
Numune Training and Research Hospital
The cardiovascular surgery clinic of Ankara Numune Training and Research Hospital in 2016 was one of the pioneers in launching the first applications of PBM in Turkey (Table 4). Thus, a two-step project was implemented: firstly, initiating a PBM program in the cardiovascular surgery clinic and subsequently, spreading out the program to the entire hospital after accomplishing successful outcomes.

Table 1: University Hospital of Zurich Guideline-Hemoglobin thresholds for transfusion

Table 2: University Hospital of Zurich Guideline-Preoperative treatment of anemia

Table 3: University Hospital of Zurich-Patient blood management program organization

Table 4: 2016 data of Ankara Numune Training and Research Hospital

Staff training, transfusion monitoring, IV fluid restriction, preoperative anemia treatment (IV iron carboxymaltose), revision and adaptation of international guidelines, and cooperation with cardiology were the parts of the preoperative phase.[16] The preoperative phase included goal-directed coagulation (impaired platelet function, surgical bleeding, etc.), goal-directed perfusion (low blood pressure or anemia may not be indicative of blood transfusion every time, what is important is the oxygen that penetrates the tissues), minimally invasive surgery, routine tranexamic acid administration, cerebral/somatic oximetry, minimally invasive extracorporeal circulation circuits, microplegia, retrograde autologous priming, vacuum-assisted venous drainage, ultrafiltration, cytokine adsorption, and recirculation of waste blood. The postoperative phase comprised of transfusion monitoring, IV fluid restriction, fibrinogen concentrate administration, and goal-directed coagulation tests.

remarkable reduction in the use of blood and blood products after this PBM program was evident in the cardiovascular surgery clinic (Figure 1). A significant cost reduction was also achieved by implementing the PBM program. To accurately determine the cost of blood in this population, the activity-based costing (ABC) model was used as described by Shander et al.[17] The cost of approximately 42 triple coronary artery bypass surgeries was saved. Hospital records documented early extubation of patients accompanied by reduction of bleeding rates, shortening of the length of stay in hospital and ICU, and reduced mortality rate. Therefore, PBM was also successful in improving clinical outcomes. In the light of these data, Numune Hospital was entitled to 2018: JCI Patient Blood Management Certification.

Figure 1: Ankara Numune Training and Research Hospital-the usage of blood and blood products in the cardiovascular surgery clinic by years (2015-2017 data).
FFP: Fresh frozen plasma.

Successful consequences obtained in the first step motivated the dissemination of the project in all surgical clinics. Objectives of the program included determining the current situation, determining the problems in blood use, constituting a team of surgical branches, and holding meetings to form a strategic plan with the purpose of reducing blood use in the hospital by 50% in the 2018 to 2021 period. Approximately 35,000 units of total blood and blood products were utilized for about 55,000 operations at Numune Hospital in 2017. Figure 2 illustrates the distribution in some prominent branches.

Figure 2: Ankara Numune Training and Research Hospital-the usage of blood products by branches (2017 data).
FFP: Fresh frozen plasma.

The in-depth investigation highlighted the wastage of many of the unused blood products, which incurred a high cost equivalent to 16 triple coronary artery bypass surgeries (Table 5). As depicted in Table 6, the reasons for the destruction of blood and blood products were quite striking.

Table 5: Ankara Numune Training and Research Hospital - Used and destroyed blood products

Table 6: Ankara Numune Training and Research Hospital-Reasons for the destruction of blood products

In 2018, hospital-wide blood and blood product usage dropped to 29,500 units, approximately. Therefore, a reduction in blood and blood product usage by 3% could be achieved in one year by conducting multidisciplinary scientific meetings and initiatives in surgical clinics of Numune Training and Research Hospital (Figure 3).

Figure 3: Ankara Numune Training and Research Hospital-reduction in blood products usage in one year (2018 data).
FFP: Fresh frozen plasma.

The data obtained from the Numune Hospital were published in various journals and presented at international congresses.[18-22] Subsequently, international training programs were launched in Turkey. The EuroAsia Heart Foundation decided to organize PBM Schools in Turkey, and the first meeting entitled Interdisciplinary Meeting on Bleeding Management in (Cardiac) Surgery and Obstetrics was held with 55 participants from 11 countries in Izmir in April 2019.

Consensus Meeting on PBM
The second stage of Numune Hospital's PBM program was decided to be continued in a larger scale hospital, which was established by the transportation of Ankara's largest state hospitals and put into service in December 2018. The city hospital comprises of 3,804 hospital beds, 735 outpatient clinics, and 128 operating theaters. The PBM has become one of the most important targets in the city hospital. The main objective of PBM implementation is to portray a good example for other hospitals in Turkey. The data gathered from the City Hospital on blood product usage and destruction are detailed in Tables 7 and 8.

Table 7: Ankara City Hospital Transfusion Center-used and destroyed blood products (February 2019-July 2019)

Table 8: Ankara City Hospital Transfusion Center-reasons for the destruction of blood products (February 2019- July 2019)

A strong organization, coupled with a multidisciplinary approach, is a prerequisite to cope with similar challenges during the implementation of PBM program in City Hospital.

Aiming at kick-off building a multidisciplinary PBM program in this extremely large hospital setting, a consensus meeting was organized to provide a platform where all components may come together to fix problems, discuss, and propose solutions. Over 150 participants in the meeting included members from the departments of anesthesiology, surgery, transplantation, ICU, perfusion, blood bank, nursing, pharmacy, and Ministry of Health. Professor Donat Spahn from the University Hospital of Zurich, being one of the leaders in the implementation of the PBM program, was invited and acted as a consultant.

In this multidisciplinary meeting, international and domestic experiences were shared, the importance of coordination and execution of different pillars in PBM was discussed, and the problems of the blood transfusion system were also explored with a proposal for solutions. Based on these data, it was aimed to develop a standard protocol for PBM which could be used as a guide by similar large-volume tertiary hospitals.[23,24]

There is not any purpose of comparison of any previous data with each other and/or with current situation. The geographic and background conditions of each instant are completely different. The main idea is to present different PBM protocols in various hospital settings.

Synopsis of Problems/Solutions
The following problems and proposals for the solutions were documented, discussed with managers, and a final consensus report was submitted for the hospital directorate.

1) Anesthesiology and Reanimation
2) Blood Transfusion Center
3) Nursing Services
The blood transfusion procedures of our hospital are prepared following the national guidelines, National Blood and Blood Components Preparation, Use and Quality Assurance Guideline-2016,[25] and National Hemovigilance Guideline-2016.[26] According to these blood transfusion procedures, monitoring, educating, reporting, analysis, and documentation of blood transfusion applications are the responsibilities of our hemovigilance nurses.

4) Intensive care unit
5) Transplantation Services
6) Perfusion Services

Sonuçlar

The liberal RBC transfusion approaches can effectively achieve restoration of hemoglobin concentrations toward non-anemic values; however, transfusion of stored allogeneic RBCs does not correct the primary metabolic deficiencies associated with anemia, nor does it restore iron homeostasis. On the other hand, it has become a common practice to transfuse stable patients with low hemoglobin without symptoms of anemia.[27]

Despite the demonstrated benefits of PBM, several challenges limit the application of PBM guidelines into clinical practice worldwide, particularly due to the lack of knowledge, lack of interdisciplinary commitment, lack of resources, and general concerns. It should enable PBM's patient-centered approach to be delivered in a way that is also hospital centered and, therefore, compatible with each institution. The initial success achieved from the institution should impart further motivation and activities in the field of PBM.[28,29]

Pillars need to be adapted with respect to characteristics of the region and legislations available. For instance, there are specific reimbursement policies for IV iron therapy in Turkey. Also, limitations of the use of EPO and vitamin B12/folic acid by nephrologists may become a burden for cardiac surgeons to implement perioperative anemia correction. Successful PBM implementation involves structural changes, logistic reorganizations and leadership with psychological skills, a monitoring, and feedback program, and persistence. An individualized program must be established by the hospitals with the consensus of participants.

The Ankara City Hospital is the largest hospital in Turkey. Current practice with the use of more than 60,000 units of blood and blood products in one year necessitates the need for a PBM program.

We believe that this consensus report would accelerate the cooperation within disciplines and provoke more optimal results in the short-term. Furthermore, it is valuable as it represents a guide for similar large-volume hospital settings.

Acknowledgement
We thank to Figen Yavuz, MD (Turkiye Klinikleri) for her valuable assistance in the writing process of this review.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

Kaynaklar

1) What is patient blood management (PBM)? Available at: http://www.sabm.org/ [Accessed: March 03, 2019].

2) Implementing the PBM guidelines. Available at: https://www. blood.gov.au/implementing-pbm [Accessed: March 03, 2019].

3) Patient blood management guidelines. Available at: https:// www.blood.gov.au/pbm-guidelines [Accessed: March 03, 2019].

4) Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, et al. Perioperative blood transfusion and blood conservation in cardiac surgery: The Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg 2007;83:S27-86.

5) Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011;91:944-82.

6) Pagano D, Milojevic M, Meesters MI, Benedetto U, Bolliger D, von Heymann C, et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. Eur J Cardiothorac Surg 2018;53:79-111.

7) Ertugay S, Kudsioğlu T, Şen T; Patient Blood Management Study Group Members. Consensus Report on Patient Blood Management in Cardiac Surgery by Turkish Society of Cardiovascular Surgery (TSCVS), Turkish Society of Cardiology (TSC), and Society of Cardio-Vascular-Thoracic Anaesthesia and Intensive Care (SCTAIC). Turk Gogus Kalp Dama 2019;27:429-50.

8) Spahn DR, Moch H, Hofmann A, Isbister JP. Patient blood management: the pragmatic solution for the problems with blood transfusions. Anesthesiology 2008;109:951-3.

9) Farrugia A. Falsification or paradigm shift? Toward a revision of the common sense of transfusion. Transfusion 2011;51:216-24.

10) Spahn DR, Goodnough LT. Alternatives to blood transfusion. Lancet 2013;381:1855-65.

11) Muñoz M, Acheson AG, Auerbach M, Besser M, Habler O, Kehlet H, et al. International consensus statement on the peri-operative management of anaemia and iron deficiency. Anaesthesia 2017;72:233-47.

12) Althoff FC, Neb H, Herrmann E, Trentino KM, Vernich L, Füllenbach C, et al. Multimodal Patient Blood Management Program Based on a Three-pillar Strategy: A Systematic Review and Meta-analysis. Ann Surg 2019;269:794-804.

13) Arıtürk C, Ozgen ZS, Kilercik M, Ulugöl H, Ökten EM, Aksu U, et al. Comparative effects of hemodilutional anemia and transfusion during cardiopulmonary bypass on acute kidney injury: a prospective randomized study. Heart Surg Forum 2015;18:E154-60.

14) Stein P, Kaserer A, Sprengel K, Wanner GA, Seifert B, Theusinger OM, et al. Change of transfusion and treatment paradigm in major trauma patients. Anaesthesia 2017;72:1317-26.

15) Kaserer A, Rössler J, Braun J, Farokhzad F, Pape HC, Dutkowski P, et al. Impact of a Patient Blood Management monitoring and feedback programme on allogeneic blood transfusions and related costs. Anaesthesia 2019;74:1534-41.

16) Senay S, Toraman F, Karabulut H, Alhan C. Is it the patient or the physician who cannot tolerate anemia? A prospective analysis in 1854 non-transfused coronary artery surgery patients. Perfusion 2009;24:373-80.

17) Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion 2010;50:753-65.

18) Budak AB, McCusker K, Gunaydin S. A structured blood conservation program in pediatric cardiac surgery. Eur Rev Med Pharmacol Sci 2017;21:1074-9.

19) Budak AB, McCusker K, Gunaydin S. A Cardiopulmonary Bypass Based Blood Management Strategy in Adult Cardiac Surgery. Heart Surg Forum 2017;20:E195-8.

20) Lafçı A , Gökçınar D , Dağ O , Günertem E , Günaydın S. The effect of "patient blood management" training on the number of red blood cell transfusions in patients undergoing cardiac surgery: a 5-year retrospective study. Turkish Journal of Clinics and Laboratory 2019;10:98-103.

21) Gunaydin S. The evolution of patient blood management programs in cardiac surgery: what is the ultimate frontier? Presented at the 57th AmSECT International Conference; March 8-10, 2019; Nashville, TN, USA.

22) Gunaydin S, McCusker K. Protective efficacy of minimally invasive techniques on patient blood management programs in aortic valve surgery. Presented at the 19th ISMICS Annual Scientific Meeting; May 29-Jun 1, 2019; New York, USA.

23) Spahn DR, Schoenrath F, Spahn GH, Seifert B, Stein P, Theusinger OM, et al. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet 2019;393:2201-12.

24) Vlot EA, Verwijmeren L, van de Garde EMW, Kloppenburg GTL, van Dongen EPA, Noordzij PG. Intra-operative red blood cell transfusion and mortality after cardiac surgery. BMC Anesthesiol 2019;19:65.

25) National blood and blood components preparation, use and quality assurance guideline-2016. Available at: https:// www.kanver.org/Upload/Dosya/ulusal_kan_rehberi.pdf [Accessed: March 03, 2019].

26) National hemovigilance guideline-2016. Available at: https:// sbu.saglik.gov.tr/Ekutuphane/Yayin/528 [Accessed: March 03, 2019].

27) Froessler B, Olsen K, Parker B, Robinson KL. Room for improvement: audit results of perioperative red cell transfusion practice at an Australian university teaching hospital. Anaesth Intensive Care 2009;37:852.

28) Meybohm P, Richards T, Isbister J, Hofmann A, Shander A, Goodnough LT, et al. Patient Blood Management Bundles to Facilitate Implementation. Transfus Med Rev 2017;31:62-71.

29) Spahn DR, Muñoz M, Klein AA, Levy JH, Zacharowski K. Patient Blood Management: Effectiveness and Future Potential. Anesthesiology 2020;133:212-22.