Hofmann, A.

Spahn, D. R.

Theusinger, O. M.

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British Journal of Anaesthesia 108 (6): 889–92 (2012)doi:10.1093/bja/aes166EDITORIALPatient blood management is a win-win: a wake-up callD. R. Spahn1*, O. M. Theusinger2 and A. Hofmann31Institute of Anaesthesiology, Section of Anaesthesiology, Intensive Care Medicine and OR-Management, University Hospital Zurich,Zurich CH-8091, Switzerland2Institute of Anaesthesiology, University Hospital Zurich, Zurich CH-8091, Switzerland3Faculty of Health Sciences, Curtin University, Perth, Australia* Corresponding author. E-mail: donat.spahn@usz.chPreoperative anaemia is frequent in surgical patients andincreases postoperative mortality, major morbidity, andlength of hospital stay.1 Poorly controlled bleeding and surgi-cal blood loss can also contribute to these outcomes.Anaemia, blood loss, and liberal transfusion triggers are themain predictors for red blood cell (RBC) transfusion.2 RBCtransfusion in turn is an additional independent predictorfor adverse outcome and has therefore been referred to asthe ‘second hit’ for the recipient.3 Transfusion outcomesinclude higher mortality, more ischaemic complications,organ dysfunction, infections, delayed wound healing, andincreased length of hospital stay.4 – 8 Transfused patientsmay also be more likely to develop non-Hodgkin lymphoma.9Interestingly, most of these complications are found afteradministration of just a single RBC unit.10 11 Strict applicationof the Bradford-Hill criteria strongly suggests that the linkbetween transfusion and adverse outcomes is causal andnot just associative.6 12A further challenge is the surveillance for newly emergingand re-emerging pathogens. Protozoan parasites in theblood donor pool cause babesiosis and Chagas disease, andtransfusion-transmitted viral infections such as dengueand chikungunya represent real threats to public healthsystems.13 Recently, a transgenic mouse model demonstratedhow human tau protein from injected Alzheimer’s diseasebrain extracts, spreads, and co-aggregates with endogenousmouse tau.14 These findings suggest that tau pathology maydevelop in the brain by a prion-like mechanism.15 Similar tothe pathogenesis of variant Creutzfeldt–Jakob disease (vCJD),transfusion might play a role in one of the infective pathways.16Transfusion of RBCs,8 the treatment of adverse transfusionoutcomes,17 and expanding surveillance systems result inconsiderable financial burdens for all health systems in thedeveloped world.Patient blood management (PBM) has recently beendescribed as a concept pre-empting and significantly redu-cing the resort to transfusions by addressing anaemia,blood loss, and hypoxia as modifiable risk factors that mayresult in transfusion long before transfusion may even beconsidered. The three pillars of PBM—detection and treat-ment of preoperative anaemia, reduction in perioperativeblood loss, and harnessing and optimizing the patient-specific physiological reserve of anaemia (including restrict-ive haemoglobin transfusion triggers)18 (Table 1)—havebeen proposed for years as a new standard of care to avoidthe above described complications and costs.18 PBM wasalso adopted by the World Health Organization (WHA63.12)in 2010 as a principle to improve transfusion safety. Sincethen, the WHO has been urging member states ‘topromote the availability of transfusion alternatives including,where appropriate, autologous transfusion and patient bloodmanagement’.In Europe, however, few PBM programmes have beenstarted so far. Kotze´ and colleagues thus have to be congra-tulated for their study in the British Journal of Anaesthesiadescribing the implementation of such a programme in aYorkshire hospital.19 Their programme was developed inthree stages: first, they analysed the anaemia prevalenceand transfusion rates in their centre and explored the localassociations between preoperative haemoglobin, RBCVolume 108, Number 6, June 2012& The Author [2012]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.For Permissions, please email: journals.permissions@oup.comtransfusion, and hospital outcomes, including the length ofstay and re-admission rate after discharge; secondly, theydesigned their local treatment algorithm; thirdly, they pro-spectively collected post-implementation data includingcosts.With their PBM programme, they succeeded in significant-ly reducing the anaemia prevalence from 26% to 10%, peri-operative RBC loss by 20%, transfusion rate for total hiparthroplasty from 23% to 8%, and in total knee arthroplastyfrom 8% to 0%.19 In addition, they succeeded in reducing thelength of hospital stay from 6 to 5 days in total hip arthro-plasty and from 6 to 4 days in total knee arthroplasty, andto reduce the 90 days re-admission rate from 14% to 8%.These are indeed impressive results.Drug costs were low (£16 695) and largely offset by thecosts of avoided RBC transfusion (£12 625). However, asacknowledged by the authors, they used blood bank acquisi-tion costs for RBC for their calculation and not activity-basedcosts which are three to four times higher.8 It is important tonote that they did not account for 404 fewer days of hospi-talization and that 16 fewer patients were re-admittedwithin 90 days after operation. Using an estimated averagecost of £400 per hospital stay day in the UK and several thou-sand pounds for re-admissions, the PBM team would haveachieved a net saving of over £160 000. Shifting the em-phasis from product centred transfusion practice to PBMrepresents a win-win situation that is extremely rare inmedicine: patients get home sooner, hospitals generatecost savings by using fewer resources per patient, and physi-cians achieve better clinical outcomes.Optimal PBM includes the detection of anaemia sufficient-ly in advance of the planned operation which certainly is alogistical challenge. A very promising approach, as used bythis group,19 is to include the general practitioner in the pre-operative optimization of the patient and to use a simple al-gorithm, based on haemoglobin and ferritin measurements(http://www.nba.gov.au/guidelines/module2/index.html#guidelines/module2/po-v2a.pdf, accessed 11 March 2011),19 20to treat anaemia. In orthopaedic surgery, anaemia treat-ment usually starts 4–8 weeks before the operation; incardiac surgery, this may be more difficult but may not benecessary. Recent studies indicate that a very short-termtreatment with erythropoiesis-stimulating agents and i.v.iron starting only 2–0 days before surgery reduces RBC trans-fusions and improves clinical outcome.21 22 This may be auseful concept in orthopaedic surgery.23For the reduction in perioperative blood loss, a bundle ofmeasures needs to be combined (Table 1). The most import-ant is a meticulous surgical technique aiming at minimizingblood loss. Discussion with surgical colleagues the disadvan-tages of insufficient haemostasis and the advantages ofminimizing blood loss is worthwhile. Along with acute nor-movolaemic haemodilution and cell salvage, an individua-lized, goal-directed coagulation algorithm and the use ofanti-fibrinolytics such as tranexamic acid and, probablysoon again, aprotinin (http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fnews_and_events%2Fnews%2F2012%2F02%2Fnews_detail_001447.jsp&mid=WC0b01ac058004d5c1&jsenabled=true, accessed 24 February 2012), and factor con-centrates are important.24–26 Low haemoglobin transfusiontriggers are another important element to reduce the transfu-sion rate. Low haemoglobin transfusion triggers, such as,70 g litre21 in general surgical patients27 and ,80 g litre21in elderly high-risk patients, are well tolerated.28 In selectedpatients, treatment to maximize oxygenation and minimizemetabolic demand might be required to avoid transfusion.This is a wake-up call for physicians, hospital administra-tors, and regulators. The incidence of preoperative anaemiais known to be high (20–40%),1 4 29 associated with increasedmortality and major morbidity,1 and associated with transfu-sion of RBC that again increases mortality, major morbidity,and hospital length of stay.4 – 7 10 However, too few havechanged from the transfusion-based culture. Therefore, weall should take this study as a model and implement our ownlocal PBM programme—it is time to wake up!Declaration of interestD.R.S.’s academic department is receiving grant support fromthe Swiss National Science Foundation, Berne, Switzerland(grant numbers: 33CM30_124117 and 406440-131268), theSwiss Society of Anesthesiology and Reanimation (SGAR),Berne, Switzerland (no grant numbers are attributed), theSwiss Foundation for Anesthesia Research, Zurich, Switzerland(no grant numbers are attributed), BundesprogrammChancengleichheit, Berne, Switzerland (no grant numbersare attributed), CSL Behring, Berne, Switzerland (no grantnumbers are attributed), and Vifor SA, Villars-sur-Glaˆne,Switzerland (no grant numbers are attributed). D.R.S. wasthe chairman of the ABC Faculty and is a member of theABC Trauma Faculty which both are managed by ThomsonPhysicians World GmbH, Mannheim, Germany, and sponsoredby an unrestricted educational grant from Novo Nordisk A/S,Bagsva¨rd, Denmark, and CSL Behring GmbH, Hattersheim amMain, Germany. In the past 5 yr, D.R.S. has received honorariaTable 1 Patient blood management. ESA,erythropoietin-stimulating agentDetect and correct preoperative anaemia and iron deficiencyIron (i.v.)+ESA perioperativelyReduce perioperative RBC lossMeticulous surgical techniqueAcute normovolaemic haemodilutionCell salvage and re-transfusionAvoidance of coagulopathy with an individualized, goal-directedcoagulation algorithm and the use of anti-fibrinolytics andfactor concentratesLow CVP, no hypertension, normothermiaHarness and optimize physiological reserve of anaemiaTolerate low haemoglobin valuesHigh FIO2Minimizing metabolic demandBJA Editorial890or travel support for consulting or lecturing from the follow-ing companies: Abbott AG, Baar, Switzerland; AstraZenecaAG, Zug, Switzerland; Bayer (Schweiz) AG, Zu¨rich, Switzerland;Baxter S.p.A., Roma, Italy; B. Braun Melsungen AG, Melsungen,Germany; Boehringer Ingelheim (Schweiz) GmbH, Basel,Switzerland; Bristol–Myers–Squibb, Rueil-Malmaison Cedex,France; CSL Behring GmbH, Hattersheim am Main, Germanyand Bern, Switzerland, Curacyte AG, Munich, Germany;Ethicon Biosurgery, Sommerville, NJ, USA; Fresenius SE, BadHomburg v.d.H., Germany; Galenica AG, Bern, Switzer-land (including Vifor SA, Villars-sur-Glaˆne, Switzerland);GlaxoSmithKline GmbH & Co. KG, Hamburg, Germany;Janssen-Cilag AG, Baar, Switzerland; Janssen-Cilag EMEA,Beerse, Belgium; Merck Sharp & Dohme-Chibret AG, Opfikon-Glattbrugg, Switzerland; Novo Nordisk A/S, Bagsva¨rd,Denmark; Octapharma AG, Lachen, Switzerland; OrganonAG, Pfa¨ffikon/SZ, Switzerland, Oxygen Biotherapeutics, CostaMesa, CA, USA; Pentapharm GmbH (now tem InnovationsGmbH), Munich, Germany; ratiopharm ArzneimittelVertriebs-GmbH, Vienna, Austria; Roche Pharma (Schweiz)AG, Reinach, Switzerland; Schering-Plough International,Inc., Kenilworth, NJ, USA; Vifor Pharma Deutschland GmbH,Munich, Germany; Vifor Pharma O¨sterreich GmbH, Vienna,Austria; and Vifor (International) AG, St Gallen, Switzerland.A.H. is currently receiving consulting fees from the WesternAustralian Department of Health. Within the past 5 yr, A.H.has received grant support from the Federal Austrian Ministryof Health, honoraria or travel support for consulting orlecturing from the following companies and legal entities:Amgen GmbH, Switzerland; Australian Red Cross BloodService, Brisbane, Australia; CSL Behring GmbH, Marburg,Deutschland, Dynabyte GmbH, Munich, Germany; FreseniusKabi GmbH, Bad Homburg, Germany; Haemonetics GmbH,Munich, Germany; Janssen-Cilag GmbH, Austria; Johnson &Johnson Ethicon Biosurgery, USA; Novo Nordisk A/S,Bagsva¨rd, Denmark; Pentapharm/TEM GmbH, Germany;United Biosource Corporation, Bethesda, MD, USA; ViforPharma Ltd, Glattbrugg, Switzerland; The Society for theAdvancement of Blood Management, USA; The MedicalSociety for Blood Management, Austria; and The Institutefor Patient Blood Management and Bloodless Medicine andSurgery, Englewood, NJ, USA. In the past 5 yr, O.M.T. hasreceived honoraria or travel support for consulting or lectur-ing from the following companies: CSL Behring Schweiz,Zurich, Switzerland; Vifor SA, Villars-sur-Glaˆne, Switzerland;Roche Pharma (Schweiz) AG, Reinach, Switzerland; Penta-pharm AG, Mu¨nchen, Germany; and TEM International,Mu¨nchen, Germany.References1 Musallam KM, Tamim HM, Richards T, et al. Preoperative anaemiaand postoperative outcomes in non-cardiac surgery: a retrospect-ive cohort study. Lancet 2011; 378: 1396–4072 Gombotz H, Rehak PH, Shander A, Hofmann A. Blood use in elect-ive surgery: the Austrian benchmark study. Transfusion 2007; 47:1468–803 Beattie WS, Karkouti K, Wijeysundera DN, Tait G. Risk associatedwith preoperative anemia in noncardiac surgery: a single-centercohort study. Anesthesiology 2009; 110: 574–814 Karkouti K, Wijeysundera DN, Beattie WS. Risk associated withpreoperative anemia in cardiac surgery: a multicenter cohortstudy. 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