Patient blood management: an update of its effects on patient safety (Meybohm, Zacharowski)
Patient blood management (PBM) is an interdisciplinary diagnostic, behavioural and therapeutic concept, which reduces and avoids unnecessary blood loss and focuses on the rational handling of blood components. Based on the possibility of increasing and maintaining a patients’ own blood resources and to enable safe handling of donor blood, the World Health Assembly endorsed PBM in 2010 (WHA63.12).625 The use of PBM in clinical practice follows the three main pillars: first, comprehensive pre-operative anaemia management; second, minimisation of iatrogenic (unnecessary) blood loss; third, harness and optimise the patient-specific physiological tolerance of anaemia (Fig. 17).626
Comprehensive pre-operative anaemia management
In 18 large observational studies encompassing more than 650 000 surgical patients, the prevalence of pre-operative anaemia varied between 10 and 48%.627 Pre-operative screening should include evaluation and management of anaemia. From a practical point of view, patients scheduled for surgical procedures with expected blood loss (>500 ml) or a at least 10% probability of red blood cell (RBC) transfusion should be identified and assessed at the earliest opportunity, and be screened for iron-deficiency and other likely causes of anaemia.628–630 The availability of an easy-to-follow, diagnostic algorithm is desirable.631 Intravenous iron is efficacious, safe and should be used in patients in whom oral iron is not tolerated, or if surgery is planned in less than 4 to 6 weeks after the diagnosis of iron deficiency.632–634 It is notable that most effective increments of haemoglobin (Hb) levels could be reached when intravenous iron was administered between 2 and 4 weeks before surgery.633,635 If possible, elective surgery should be postponed until pre-operative anaemia has been appropriately classified and treated. Treatment of anaemia a few days before surgery has also been shown to effectively increase Hb level postoperatively, and to reduce transfusion rate.636 Spahn et al.637 recently demonstrated the clinical benefits of an ultra-short-term combination treatment consisting of a slow infusion of 20 mg kg−1 ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid in patients undergoing elective cardiac surgery with anaemia or isolated iron deficiency. The combination treatment increased Hb levels and reduced RBC transfusions from a median of one unit in the placebo group to a median of zero units in the treatment group.637
Minimisation of iatrogenic (unnecessary) blood loss
Surgical procedures may be associated with a higher risk of bleeding and transfusion. For example, total knee or hip arthroplasty are associated with extensive blood loss up to 1500 ml.638 The average cardiac surgery patient loses between 500 and 1200 ml of blood peri-operatively, and about 5% of all cardiac surgery patients are re-explored due to excessive bleeding.639 In this respect, intra-operative RBC recovery and autologous transfusion is highly effective to minimise allogeneic RBC transfusion. A recent meta-analysis showed that the use of cell salvage reduced the number of patients exposed to allogeneic RBCs by 39%.640
Blood loss associated with invasive laboratory testing can either cause or aggravate hospital-acquired anaemia. Reduction of blood drawn for laboratory analyses can be achieved by avoiding unnecessary laboratory tests and a lower frequency of sampling and using the smallest collection tube size that is feasible for the required analysis.641 Further reduction of phlebotomy associated blood loss can be achieved by using closed in-line flush blood sampling devices for arterial (and central) lines.642 Advanced peri-operative coagulation monitoring and management are crucial for avoiding unnecessary blood loss and should be a precondition before RBC transfusion is considered. In this respect, the use of a coagulation algorithm is recommended, encompassing pre-operative assessment, ensuring basic conditions for haemostasis (e.g. temperature, calcium, pH), reversal of anticoagulants, point-of-care diagnostics in bleeding (e.g. coagulopathic) patients and optimised coagulation management with the use of clotting factor concentrates.643–645 To reduce surgical blood loss, tranexamic acid should be used unless contraindicated (e.g. history of venous thromboembolic events).646
Harness and optimise the patient-specific physiological tolerance of anaemia
Several trials have been conducted to compare outcomes in patients undergoing either a restrictive or a liberal transfusion strategy. Significantly, outcome measures (e.g. mortality, length of hospital stay, acute kidney failure) were similar in critical care patients, patients undergoing cardiac surgery, patients with hip fracture or acute upper gastro-intestinal haemorrhage either assigned to a pretransfusion Hb trigger of below 7 to 8 g dl−1 or 9 to 10 g dl−1, respectively.647–650 At this point, it remains unclear whether cardiovascular risk patients, geriatric or oncological patients will benefit more from a higher transfusion trigger than from the one currently recommended.630 A clinical corridor for making medical discretionary decisions is still needed in this context. To optimise utilisation of allogeneic blood products, a physician order entry with a clinical decision support based on electronic medical records has been suggested.651 Thereby, indication for transfusion considering patient-specific factors (e.g. age, diagnosis, comorbidities, surgical or nonsurgical setting), signs/symptoms of acute anaemia, laboratory values (e.g. Hb) and presence or absence of bleeding can be confirmed with required checkboxes.652 If a RBC transfusion is indicated in case of patients not actively bleeding, only a single RBC should be administered (Single-Unit Policy).
Multimodal patient blood management programme
Significantly, a multidisciplinary, multimodal PBM programme might have the highest potential in reducing RBC utilisation and improving postoperative outcomes. The overall clinical efficacy of PBM has been confirmed by many recent large studies encompassing several hundred thousands of patients.653–660 Overall, implementation of PBM is associated with a reduced transfusion rate of allogeneic blood products by about 40%, improved clinical outcomes, a reduced complication rate, reduced length of hospital stay and reduced costs. Meybohm et al. conducted a prospective, multicentre study with a total of 129 719 patients discharged between July 2012 and June 2015 from four German University Hospitals and analysed patients before (pre-PBM) and after the implementation of PBM. The PBM programme included multiple measures, for example, pre-operative optimisation of Hb levels, blood-sparing techniques, and standardisation of transfusion practice. While the mean number of RBCs transfused per patient was reduced by 17%, the primary safety composite endpoint was comparable between both cohorts.661 Based on a retrospective analysis of 836 patients undergoing visceral surgery for cancer treatment, Keding et al.662 demonstrated PBM as a quality improvement tool with a significant improved 2-year overall survival (80.1 vs. 67.0% of patients). Leahy et al. published a retrospective study of 605 046 patients admitted to four major adult tertiary-care hospitals between July 2008 and June 2014 in Western Australia. Comparing final year with baseline measurements, units of RBC, fresh frozen plasma and platelets transfused per admission decreased by 41%, representing a direct saving of AU$18 507 092, and between AU$80 million and AU$100 million estimated activity-based savings. This PBM programme was even associated with risk-adjusted reductions in hospital mortality, length of stay and hospital-acquired infections.653 A PBM monitoring and feedback programme at the University Hospital of Zurich/Switzerland resulted in a reduction of allogeneic blood transfusions of 27% with savings of direct transfusion costs of 84 USD per inpatient which yielded more than 2000 000 USD per year.657 The beneficial effects of PBM were also demonstrated in a recent systematic meta-analysis including seventeen studies addressing each of the three PBM pillars with at least one measure per pillar, comprising 235 779 surgical patients.663 Implementation of PBM significantly reduced transfusion rates (−39%), hospital length of stay (−0.5 day), total number of complications (−20%) and mortality rate (−11%). Significantly, PBM had the highest impact on patients undergoing orthopaedic and cardiac surgical procedures: the relative risk for RBC transfusion decreased by 55% and 50% in these patients, respectively.
Different characteristics of published studies may contribute to clinical heterogeneity and persistent lack of clinical PBM implementation. Only a minority of hospitals have yet adopted measures for all three pillars. Therefore, implementation strategies should target complementary measures for all three PBM pillars to specifically minimise risk factors associated with anaemia and transfusion. So far, more than 100 individual PBM measures addressing the three main pillars have been defined based on the broad interdisciplinary fields (e.g. anaesthesia, surgery and central laboratory) and temporal application (pre-operative, intra-operative to postoperative).664 The great advantage of this PBM bundle concept is that the selection can be dynamically adapted to the individual local, financial and personal resources as well as the respective focus of each hospital. Many important factors, such as infrastructure, staff, equipment and economic resources differ between hospitals. Individualisation is vitally important for the social acceptance of any new standard. For this reason, PBM programmes need to be specifically designed for each site using the bigger frame of the recommended concept.
Moreover, implementation of PBM needs to include practical and strategic components aimed at increasing knowledge. This can be achieved by stressing the clinical implications of anaemia and the need for alternatives to allogeneic transfusion. The focus should be placed upon clinical outcomes and the inappropriateness of transfusion practice variability. The learning materials can be provided by a website (www.patientbloodmanagement.eu), a comprehensive e-learning programme (www.patientbloodmanager.com), a central virtual room for documents/guidelines/posters/education materials, and numerous media reports. In addition, quantification and validation of successful training should be measured by a local online certification course for anaemia management, PBM and general transfusion practice.
The huge evidence base should motivate all executives and healthcare providers to support further PBM activities. Up to the present, only a few regulatory authorities support the implementation of PBM. For example, the European Commission previously released an EU PBM implementation and dissemination guide; however, PBM measures are not an obligatory part of clinical routine yet.665,666 The National Blood Authority supported the first worldwide implementation of PBM in Western Australia in 2008 and the National Institute for Health and Care Excellence guidelines in the United Kingdom postulate treatment with iron in iron-deficiency anaemic patients 2 weeks prior to surgery.667,668
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