Spahn, D. R.

Zacharowski, K.

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British Journal of Anaesthesia 115 (1): 1–3 (2015)Advance Access publication 15 April 2015 . doi:10.1093/bja/aev099EDITORIALSNon-treatment of preoperative anaemia is substandardclinical practiceD. R. Spahn1,* and K. Zacharowski21 University of Zürich and University Hospital Zürich, Rämistasse 100, CH-8091 Zürich, Switzerland, and2 Department of Anaesthesiology, Intensive Care Medicine & Pain Therapy, University Hospital Frankfurt, Frankfurt,Germany*Corresponding author. E-mail: donat.spahn@usz.chIt is well known that preoperative anaemia is frequent and asso-ciated with increased mortality and morbidity, even if only mildanaemia is present.1 2 In addition, preoperative anaemia is one ofthe most signiﬁcant risk factors in subsequent red blood celltransfusion,3 which in itself has adverse effects on mortalityand morbidity.4 Therefore, unmanaged preoperative anaemia isa contraindication for elective surgery.4In this edition of the British Journal of Anaesthesia, Muñoz andcolleagues5 rightly alerted the medical community, reportingthat preoperative anaemia is often left untreated. The paradoxof known negative consequences of untreated anaemia and cur-rent practice is explained by the presentation of 10 widely heldmisconceptions. Moreover, we identiﬁed two additional reasonswhy physicians are still hesitating to treat preoperative anaemiasystematically. First, the World Health Organization’s deﬁnitionof anaemia with a haemoglobin concentration of <120 g litre−1in women and <130 g litre−1 in men is not sufﬁciently knownby the majority of physicians. Furthermore, the notion thatvery mild forms of anaemia (haemoglobin values between 100–120 and 100–130 g litre−1, respectively) result in adverse clinicaloutcomes, such as increased mortality and a long list of compli-cations,1 2 is also not well known. Second, there may be reluc-tance by some physicians to treat preoperative anaemiaactively, because of the fact that they themselves will be held re-sponsible for any adverse events occurring thereafter. In con-trast, a perioperative transfusion in a patient who is anaemicbefore surgery is considered by most an inevitable event, forwhich medical staff cannot be held responsible. Therefore,some physicians prefer not to be involved in treatingpreoperative anaemia. We hope that the refuting by Muñoz andcolleagues5 of 10 widely held misconceptions helps pave theway to widespread treatment of preoperative anaemia.A consortium of four large German University Hospitals(Frankfurt, Münster, Bonn, and Kiel) is engaged in the conceptof patient blood management (PBM). The Frankfurt group hasshown how to target and implement treatment of preoperativeanaemia (ClinicalTrials.gov Identiﬁers: NCT01820949 andNCT02147795). Their investigation clearly highlights ﬁve key suc-cess factors (Table 1) for implementing a comprehensive pre-operative anaemia treatment programme. The ﬁrst factor,which is clearly themost important, was establishing a dedicatedinterdisciplinary PBM steering committee, with preoperative an-aemia treatment being the ﬁrst pillar of PBM.4 Second, the inclu-sion and support of senior hospital management is of utmostimportance. Only with this support can the necessary reorgan-ization of the preclinical procedures and structures be implemen-ted. Additionally, the understanding of surgical and medicaldisciplines is crucial to the management and treatment of pre-operative anaemia. Last, but not least, focusing our efforts onthe knowledge of how operations are regularly performed in an-aemic patients, who frequently require allogeneic red blood celltransfusions, is also essential (www.patientbloodmanagement.eu). Such favourable hospital conditions and improvements canbe achieved only by continuous education over years and throughthe coordination of a dedicated interdisciplinary PBM steeringcommittee. Should your hospital not yet have the aforemen-tioned structure, then becoming a leader in PBM and establishinga steering committee is the way forwards.© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.For Permissions, please email: journals.permissions@oup.comVolume 115, Number 1, May 2015Other centres have also succeeded in implementing treat-ment of preoperative anaemia. Theusinger and colleagues6 con-tacted the primary physician of each patient found to be anaemicbefore surgery. These patients were to undergomajor orthopaed-ic surgery (n=8871), with suggested treatment of anaemia usingerythropoietin α, i.v. iron, vitamin B12 and folic acid. Despite thefact that not all patients who were anaemic before surgery weretreated, the incidence of anaemia on the day of operation de-creased from 15 to 10% (P<0.01) and total allogeneic transfusionrate reduced from20 to 10% (P<0.01). Short-term treatment of pre-operative anaemiawith erythropoietin and i.v. iron has also beenshown to be successful in orthopaedic7 and cardiac surgery.8Likewise, a group of four Spanish hospitals recently publishedtheir success in short-term preoperative treatment of anaemiawith erythropoietin and i.v. iron in 2547 patients undergoinghip and knee arthroplasty or surgery for hip fracture.9 Theycould decrease the allogeneic transfusion rate from 37 to 24%(P<0.01), the postoperative infection rate from 12 to 8% (P<0.01),and the length of hospital stay from 12 to 11 days (P<0.01). In pa-tients undergoing surgery for hip fracture, the 30 day mortalitywas reduced from 9 to 5% (P<0.01).Through sound scientiﬁc evidence, they disproved 10miscon-ceptions of perioperative anaemia treatment. Moreover, thismedical need can be met with successful treatment options.Therefore, we conclude that there is no reason why treatmentof preoperative anaemia anaemia should not bewidely practised.Untreated preoperative anaemia is indeed a contraindication forelective surgery, and failure to treat preoperative anaemia is sub-standard clinical practice.Declaration of interestD.R.S.’s academic department is receiving grant support from theSwiss National Science Foundation, Berne, Switzerland; the Min-istry of Health (Gesundheitsdirektion) of the Canton of Zurich,Switzerland for Highly Specialized Medicine; the Swiss Societyof Anesthesiology and Reanimation (SGAR), Berne, Switzerland;the Swiss Foundation for Anesthesia Research, Zurich, Switzer-land; Bundesprogramm Chancengleichheit, Berne, Switzerland;CSL Behring, Berne, Switzerland; and Vifor SA, Villars-sur-Glâne, Switzerland.D.R.S. was the chairman of the ABC Faculty and is the co-chairman of the ABC-Trauma Faculty, both of which are mana-ged by Physicians World Europe GmbH, Mannheim, Germanyand sponsored by unrestricted educational grants from NovoNordisk Health Care AG, Zurich, Switzerland; CSL BehringGmbH, Marburg, Germany; and LFB Biomédicaments, Courta-boeuf Cedex, France.In the past 5 years, D.R.S. has received honoraria or travelsupport for consulting or lecturing from the following compan-ies: Abbott AG, Baar, Switzerland; AMGEN GmbH, Munich,Germany; AstraZeneca AG, Zug, Switzerland; Bayer (Schweiz)AG, Zürich, Switzerland; Baxter AG, Volketswil, Switzerland;Baxter S.p.A., Roma, Italy; B. Braun Melsungen AG, Melsungen,Germany; BoehringerIngelheim (Schweiz) GmbH, Basel, Switzer-land; Bristol-Myers-Squibb, Rueil-Malmaison Cedex, Franceand Baar, Switzerland; CSL Behring GmbH, Hattersheim amMain, Germany and Berne, Switzerland; Curacyte AG, Munich,Germany; Ethicon Biosurgery, Sommerville, NJ, USA, FreseniusSE, Bad Homburg v.d.H., Germany; Galenica AG, Bern, Switzer-land (including Vifor SA, Villars-sur-Glâne, Switzerland); GlaxoS-mithKline GmbH & Co. KG, Hamburg, Germany; Janssen-CilagAG, Baar, Switzerland; Janssen-Cilag EMEA, Beerse, Belgium;Merck Sharp & Dohme AG, Luzern, Switzerland; Novo NordiskA/S, Bagsvärd, Denmark; Octapharma AG, Lachen, Switzerland;Organon AG, Pfäfﬁkon/SZ, Switzerland; Oxygen Biotherapeutics,Costa Mesa, CA, USA; Photonics Healthcare GmbH, Munich, Ger-many; ratiopharm Arzneimittel Vertriebs-GmbH, Vienna, Aus-tria; Roche Diagnostics International Ltd, Reinach, Switzerland;Roche Pharma (Schweiz) AG, Reinach, Switzerland; Schering-Plough International, Inc., Kenilworth, NJ, USA; Tem Internation-al GmbH, Munich, Germany; Verum Diagnostica GmbH, Munich,Germany; ViforPharma Deutschland GmbH, Munich, Germany;ViforPharma Österreich GmbH, Vienna, Austria; and Vifor (Inter-national) AG, St Gallen, Switzerland.K.Z.’s department is receiving unrestricted educational grantsfrom B. Braun Melsungen AG, Fresenius Kabi GmbH, CSL BehringGmbH, and ViforPharma GmbH.In the past 3 years, K.Z. has received honoraria or travel sup-port for consulting or lecturing from the following companies:Abbott GmbH & Co. KG, Aesculap Akademie GmbH, AQAIGmbH, Astellas Pharma GmbH, AstraZeneca GmbH, AventisPharma GmbH, B. Braun Melsungen AG, Baxter DeutschlandGmbH, Biosyn GmbH, Biotest AG, Bristol-Myers Squibb GmbH,CSL Behring GmbH, Dr. F. Köhler Chemie GmbH, Dräger MedicalGmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, FreseniusMedical Care, Gambro Hospal GmbH, Gilead, GlaxoSmithKlineGmbH, Grünenthal GmbH, Hamilton Medical AG, HCCMConsult-ing GmbH, Heinen+Löwenstein GmbH, Janssen-Cilag GmbH,med Update GmbH, Medivance EU B.V., MSD Sharp&DohmeGmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH,P. J. Dahlhausen & Co. GmbH, Pﬁzer Pharma GmbH, Pulsion Med-ical Systems S.E., Siemens Healthcare, Teﬂex Medical GmbH,Teva GmbH, TopMed Medizintechnik GmbH, Verathon Medical,and ViforPharma GmbH.References1. Musallam KM, Tamim HM, Richards T, et al. Preoperative an-aemia and postoperative outcomes in non-cardiac surgery: aretrospective cohort study. Lancet 2011; 378: 1396–4072. Baron DM, Hochrieser H, Posch M, et al. Preoperative anaemiais associated with poor clinical outcome in non-cardiac sur-gery patients. Br J Anaesth 2014; 113: 416–233. Gombotz H, Rehak PH, Shander A, Hofmann A. Blood use inelective surgery: the Austrian benchmark study. Transfusion2007; 47: 1468–804. Spahn DR, Goodnough LT. Alternatives to blood transfusion.Lancet 2013; 381: 1855–65Table 1 Key success factors for the large-scale implementationof preoperative anaemia treatment1. Dedicated, interdisciplinary patient blood managementsteering committee2. Support from senior hospital management3. Commitment from surgical and medical disciplines4. Knowledge of patient blood management background(anaemia, transfusion, alternatives to transfusion)5. Knowledge of clinical and preclinical management:• Surgical procedures associatedwith frequentpreoperativeanaemia and considerable blood loss• Structure and processes of preclinical evaluation to bereorganized and optimized2 | Editorials5. MuñozM, Gómez-Ramírez S, Kozek-Langenecker S, et al. ‘Fit toﬂy’: overcoming the barriers to preoperative haemoglobin op-timization in surgical patients. Br J Anaesth 2015; 115: 15–246. Theusinger OM, Kind SL, Seifert B, Borgeat L, Gerber C,Spahn DR. Patient blood management in orthopaedic surgery:a four-year follow-up of transfusion requirements and bloodloss from 2008 to 2011 at the Balgrist University Hospital inZurich, Switzerland. Blood Transfus 2014; 12: 195–2037. Na HS, Shin SY, Hwang JY, Jeon YT, Kim CS, Do SH. Effects ofintravenous iron combined with low-dose recombinanthuman erythropoietin on transfusion requirements in iron-deﬁcient patients undergoing bilateral total knee replacementarthroplasty. Transfusion 2011; 51: 118–248. Yoo YC, Shim JK, Kim JC, Jo YY, Lee JH, KwakYL. Effect of singlerecombinant human erythropoietin injection on transfusionrequirements in preoperatively anemic patients undergoingvalvular heart surgery. Anesthesiology 2011; 115: 929–379. Muñoz M, Gómez-Ramírez S, Cuenca J, et al. Very-short-termperioperative intravenous iron administration and post-operative outcome in major orthopedic surgery: a pooled ana-lysis of observational data from 2547 patients. Transfusion2014; 54: 289–99British Journal of Anaesthesia 115 (1): 3–5 (2015)doi:10.1093/bja/aev155Early cryoprecipitate for trauma patients is feasible,but will it improve outcome?B. S. Sachais and B. H. Shaz*New York Blood Center, 310 East 67th Street, New York, NY 10065, USA*Corresponding author. E-mail: bshaz@nybloodcenter.orgIn this issue of BJA, Curry and colleagues1 demonstrate the feasi-bility of administering cryoprecipitate as a ﬁbrinogen sourcewith-in 90min of admissionof traumapatients. This study is importantbecause cryoprecipitate contains ﬁbrinogen and ﬁbronectin,which are critical to clotting; data are variable on theneed for cryo-precipitate in trauma patients, and no randomized controlledtrials looking at the administration of ﬁbrinogen concentrate orcryoprecipitate in traumapatientshave beenperformed.However,the completion of the randomized clinical trial on the early use ofcryoprecipitate is needed before implementation of this practice.Trauma patients receive plasma, which also contains ﬁbrinogenand ﬁbronectin, but at lower amounts and not in therapeuticdoses. In some countries, prothrombin complex concentrates areused, which contain some but not all of the clotting factors. Also,ﬁbrinogen concentrates are being used in trauma patients and re-quire less volume for administration.Fibrinogen (factor I) is a 340 kDa protein comprised of two setsof disulﬁde-bridged Aα, Bβ and γ chains. Thrombin cleavage of ﬁ-brinopeptide A from the Aα chains creates ﬁbrin, which poly-merizes and forms the proteinaceous structural basis for bloodclots.2 As such, maintaining adequate ﬁbrinogen concentrationsin bleeding patients seems to be a rational objective. However,our understanding of what constitutes an adequate concentra-tion in a bleeding patient, how to determine ﬁbrinogen concen-trations rapidly and meaningfully, and what products to use forreplacement is relatively poor. 3 4 A 2013 review in the CochraneCollaboration examining the use of ﬁbrinogen concentrates inbleeding patients found only six randomized controlled trials(248 subjects), of which two hadmortality data.5 While they con-cluded that there was a suggestion of beneﬁt on reduction of redblood cell (RBC) transfusions, the authors were unable to drawany conclusions onmortality. Interestingly, the studies reviewedshowed no effect on other outcomes, including thrombotic ad-verse events. A systematic review of ﬁbrinogen concentrate intrauma revealed 12 articles, including a single prospectivestudy.6 Again, conclusions by the authors were limited, but sug-gested a reduction in the use of RBC transfusions in this setting.Taken together, these studies suggest that administration of ﬁ-brinogen may result in earlier haemorrhage control.Given that 40% of trauma-relatedmortality is attributable toun-controlled bleeding, a deeper understanding and optimization of ﬁ-brinogen supplementation is of great interest. There has been asubstantialfocusontheearlyadministrationofplasmaandplatelets(plasma:platelet:RBC transfusion ratio); a ratio of 1:1:1 comparedwith 1:1:2 did not demonstrate improved survival, but showed thatmore plasma and platelets help to achieve earlier haemostasis (al-though therewasno decrease in the use of RBC transfusionswithinthetwogroups).7However,cryoprecipitatehasnotbeenaswellstud-ied. Indeed, ﬁbrinogen deﬁciency (as deﬁned by concentrationsbelow 100mg dl−1) develops early in trauma.8 The lower amount ofﬁbrinogen administration via blood products, including wholeblood, plasma, and cryoprecipitate, and deﬁned as ﬁbrinogen:RBCratio hasbeen associatedwithhighermortality inmilitary trauma,9alowercryoprepitate:RBCratiohasbeenassociatedwithhighermor-tality in civilian trauma,10 and data from an observational cohortstudyrelateslowﬁbrinogenatadmissiontohighertraumamortalityat 24 h and 28 days.11 These studies indicate that increasingﬁbrino-gen concentrations in trauma patientsmay be beneﬁcial. However,there are no randomized trials looking speciﬁcally at ﬁbrinogen orcryoprecipitate in trauma patients. It is from this perspective thatthe study by Curry and colleagues,1 published in this issue of theBJA, takes on importance.In their study, Curry and colleagues1 performed a feasibilitystudy to determine whether it is possible to administer cryopre-cipitate as a ﬁbrinogen source within 90 min of admission oftrauma patients. This is operationally complex because cryopre-cipitate must be thawed and then delivered and cannot be storedfor more than 6 h. Secondary objectives included laboratoryEditorials | 3

Non-treatment of preoperative anaemia is substandard clinical practice

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Non-treatment of preoperative anaemia is substandard clinical practice

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