Caveh Madjdpour|Donat R. Spahn
Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications
careful assessment risks benefits precede decision allogeneic red blood cell rbc transfusion currently number key issues transfusion medicine highly controversial importantly influence different transfusion thresholds clinical outcome aim article review current evidence blood transfusions highlight hot topics respect efficacy outcome risks provide reader transfusion guidelines addition brief synopsis transfusion alternatives given based uptodate information current evidence together clinical knowledge experience physician able make transfusion decisions bear lowest risk patient careful assessment risks benefits precede decision allogeneic red blood cell rbc transfusion currently number key issues transfusion medicine highly controversial importantly influence different transfusion thresholds clinical outcome aim article review current evidence blood transfusions highlight hot topics respect efficacy outcome risks provide reader transfusion guidelines addition brief synopsis transfusion alternatives given based uptodate information current evidence together clinical knowledge experience physician able make transfusion decisions bear lowest risk patient thorough knowledge oxygen transport physiology anaemia still considered important factor guiding decisions red blood cell rbc transfusions31hbert pc van der linden p biro g hu lq physiologic aspects anemiacrit care clin 2004 20 187212abstract full text full text pdf pubmed scopus 119 google scholar thus emphasize basic principles oxygen supply adequately matched tissue oxygen needs ensure aerobic cell respiration wholebody oxygen delivery do2 product blood flow cardiac output co arterial oxygen content cao2 do2cocao2 do2 expressed ml min1 co l min1 cao2 ml l1 cao2 sum haemoglobinbound oxygen oxygen dissolved plasma cao2sao2k1hbk2pao2 sao2 arterial oxygen saturation k1134 ml g1 oxygencarrying capacity haemoglobin hb g l1 haemoglobin concentration k2023 ml l1 kpa1 plasma oxygen dissolution coefficient body temperature pao2 kpa partial pressure oxygen arterial blood thus complete formula describing oxygen delivery do2cosao2k1hbk2pao2 physiological conditions breathing air oxygen 98 bound haemoglobin amount dissolved plasma 2 relatively minor importance however cases extreme haemodilution ventilation 100 oxygen hyperoxic ventilation changes relationship dramatically since plasma compartment haemodiluted patients significantly augmented hyperoxic ventilation result substantial increase physically dissolved oxygen shown haemoglobin concentrations low 3 g dl1 physically dissolved oxygen contributes 74 oxygen consumption vo228habler op kleen ms hutter jw et alhemodilution intravenous perflubron emulsion alternative blood transfusion effects tissue oxygenation profound hemodilution anesthetized dogstransfusion 1998 38 145155crossref pubmed scopus 76 google scholar reduces mortality significantly51meier j kemming gi kischwedel h wolkhammer habler op hyperoxic ventilation reduces 6hour mortality critical hemoglobin concentrationanesthesiology 2004 100 7076crossref pubmed scopus 91 google scholar therefore hyperoxic ventilation proposed additional method reducing need allogeneic rbc transfusions cases blood loss26habler kleen kemming g zwissler b hyperoxia extreme hemodilutioneur surg res 2002 34 181187crossref pubmed scopus 25 google scholar important note blood flow one key determinants do2 regulated level central circulation represented co formula also regional level blood flow organs microcirculatory level blood flow within organs54morisaki h sibbald wj tissue oxygen delivery microcirculationcrit care clin 2004 20 213223abstract full text full text pdf pubmed scopus 43 google scholar physiological conditions do2 8001200 ml min1 exceeds vo2 200300 ml min1 factor 4 resulting oxygen extraction ratio o2ervo2do2 2030 consequently even marked isolated decrease haemoglobin concentration determinants do2 remaining constant still result sufficient do2 meet tissue oxygen requirements however critical threshold haemoglobin concentration decrease do2 also vo2 relationship vo2 do2 referred concept critical do2 do2crit do2crit tissue oxygenation sufficient represented constant vo2 thus do2 independent contrast do2crit oxygen demands longer met resulting decrease vo2 state characterized vo2do2 dependency development tissue hypoxia40jamnicki kocian r van der linden p zaugg spahn dr acute normovolemic hemodilution physiology limitations clinical usej cardiothorac vasc anesth 2003 17 747754abstract full text full text pdf pubmed scopus 68 google scholar leads important question physiological mechanisms compensate decrease haemoglobin concentration anaemia order maintain do2 do2crit surgical blood loss trauma major reasons blood transfusion82stanworth sj cockburn ha boralessa h contreras groups patients transfused study red cell usage london southeast englandvox sang 2002 83 352357crossref pubmed scopus 64 google scholar one main goals patients blood loss maintain normovolaemia therefore assume hypovolaemia corrected refer situation normovolaemic anaemia adaptative responses decrease haemoglobin concentration include blood flow alterations central regional microcirculatory level shift oxyhaemoglobin dissociation curve resulting key determinants adaptation anaemia increase co redistribution blood flow organs increase o2er54morisaki h sibbald wj tissue oxygen delivery microcirculationcrit care clin 2004 20 213223abstract full text full text pdf pubmed scopus 43 google scholar regulation blood flow level central circulation determined co response anaemia increase co due mainly two mechanisms reduced blood viscosity increased sympathetic stimulation heart decrease blood viscosity due lower haemoglobin concentration leads increased venous return thus increased preload another consequence lower blood viscosity decrease systemic vascular resistance afterload31hbert pc van der linden p biro g hu lq physiologic aspects anemiacrit care clin 2004 20 187212abstract full text full text pdf pubmed scopus 119 google scholar increased sympathetic activity leads increase myocardial contractility contributes significantly increased co27habler kleen podtschaske et althe effect acute normovolemic hemodilution anh myocardial contractility anesthetized dogsanesth analg 1996 83 451458crossref pubmed scopus 70 google scholar increase heart rate response increased sympathetic activity relevant humans receiving medication40jamnicki kocian r van der linden p zaugg spahn dr acute normovolemic hemodilution physiology limitations clinical usej cardiothorac vasc anesth 2003 17 747754abstract full text full text pdf pubmed scopus 68 google scholar95weiskopf rb feiner j hopf h et alheart rate increases linearly response acute isovolemic anemiatransfusion 2003 43 235240crossref pubmed scopus 57 google scholar contrast anaesthetized humans heart rate seem respond anaemia40jamnicki kocian r van der linden p zaugg spahn dr acute normovolemic hemodilution physiology limitations clinical usej cardiothorac vasc anesth 2003 17 747754abstract full text full text pdf pubmed scopus 68 google scholar76spahn dr leone bj reves jg pasch cardiovascular coronary physiology acute isovolemic hemodilution review nonoxygencarrying oxygencarrying solutionsanesth analg 1994 78 10001021crossref pubmed google scholar95weiskopf rb feiner j hopf h et alheart rate increases linearly response acute isovolemic anemiatransfusion 2003 43 235240crossref pubmed scopus 57 google scholar therefore increase co response normovolaemic anaemia anaesthetized patients primarily due augmented stroke volume increase heart rate considered sign hypovolaemia regional adaptation blood flow response anaemia comprises redistribution nonvital vital organs heart brain mediated adrenergic system especially important myocardium physiologically high o2er relatively small oxygen extraction reserve thus do2 heart primarily increased augmenting coronary blood flow contrast brain also able increase o2er significantly addition response elevated blood flow microcirculation homogeneity capillary bed augmented occurs respect changes time temporal heterogeneity differences vessels spatial heterogeneity onethird capillaries perfused normal conditions resulting homogeneity leads increased o2er54morisaki h sibbald wj tissue oxygen delivery microcirculationcrit care clin 2004 20 213223abstract full text full text pdf pubmed scopus 43 google scholar finally owing increased synthesis 23diphosphoglycerate 23dpg red cells oxyhaemoglobin dissociation curve shifts right thus allowing haemoglobinbound oxygen released given oxygen partial pressure31hbert pc van der linden p biro g hu lq physiologic aspects anemiacrit care clin 2004 20 187212abstract full text full text pdf pubmed scopus 119 google scholar view mechanisms adaptation anaemia rationale behind rbc transfusions efficacy proven rationale underlying rbc transfusion aim increasing cao2 thus do2 essentially increasing vo2 thereby restoring adequate tissue oxygenation71spahn dr benefits red blood cell transfusion evidencetatm 1999 1 610google scholar increasing do2 without concomitant increase vo2 would indicate absence vo2do2 dependency thus increase do2 would strictly physiological point view questionable relevance71spahn dr benefits red blood cell transfusion evidencetatm 1999 1 610google scholar hbert colleagues30hbert pc mcdonald bj tinmouth clinical consequences anemia red cell transfusion critically illcrit care clin 2004 20 225235abstract full text full text pdf pubmed scopus 42 google scholar identified 18 studies examining effect rbc transfusions oxygenation variables studies significant increase haemoglobin concentration response blood transfusion four increase do2 furthermore 14 studies increase do2 parallel increase vo2 detected five30hbert pc mcdonald bj tinmouth clinical consequences anemia red cell transfusion critically illcrit care clin 2004 20 225235abstract full text full text pdf pubmed scopus 42 google scholar lack increase vo2 rbc transfusion could explained absence oxygen debt prior infusion indeed evidence experimental studies preexisting vo2do2 dependency thus tissue hypoxia followed increase vo2 rbc transfusion20fitzgerald rd martin cm dietz ge doig gs potter rf sibbald wj transfusing red blood cells stored citrate phosphate dextrose adenine1 28 days fails improve tissue oxygenation ratscrit care med 1997 25 726732crossref pubmed scopus 185 google scholar59nolte steinhauser p pickelmann berger hartl r messmer k effects diaspirincrosslinked hemoglobin dclhb local tissue oxygen tension striated skin muscle efficacy study hamsterj lab clin med 1997 130 328338abstract full text pdf pubmed scopus 37 google scholar prompts us ask whether factors identify patients likely react favourably ie increase vo2 upon rbc transfusion casutt colleagues13casutt seifert b pasch schmid er turina mi spahn dr factors influencing individual effects blood transfusion oxygen delivery oxygen consumptioncrit care med 1999 27 21942200crossref pubmed scopus 88 google scholar examined 67 cardiac surgery patients received total 170 rbc transfusions measurements performed approximately 5 h rbc transfusions found pretransfusion haemoglobin preoperative ejection fraction age unrelated individual responses cardiac index ci do2 vo2 rbc transfusion contrast variables related oxygen delivery oxygen consumption correlated individual responses rbc transfusions allowed better prediction regard increase ci do2 vo2 particular low oxygen consumption index correlated well increase vo2 transfusion similarly another study patients evaluated wholebody o2er parameter guiding transfusion decisions67sehgal lr zebala lp takagi curran rd votapka tv caprini ja evaluation oxygen extraction ratio physiologic transfusion trigger coronary artery bypass graft surgery patientstransfusion 2001 41 591595crossref pubmed scopus 37 google scholar seventy patients undergoing coronary artery bypass graft cabg surgery postoperative hematocrit 25 included o2er monitored without influencing transfusion decisions retrospectively analysed whether o2er 45 transfusion trigger would changed decisionmaking 41 patients received least one allogeneic rbc transfusion seven postoperative o2er 45 three 35 patients transfused reached physiological transfusion trigger thus concluded wholebody o2er might helpful variable transfusion algorithm67sehgal lr zebala lp takagi curran rd votapka tv caprini ja evaluation oxygen extraction ratio physiologic transfusion trigger coronary artery bypass graft surgery patientstransfusion 2001 41 591595crossref pubmed scopus 37 google scholar alternatively one might argue impaired functionality stored rbcs could reason lack increase vo2 rbc transfusion71spahn dr benefits red blood cell transfusion evidencetatm 1999 1 610google scholar storage rbcs undergo variety changes summarized term storage lesions60offner pj age blood make differencecrit care 2004 8 s24s26crossref pubmed scopus 51 google scholar include decrease 23dpg atp depletion release proinflammatory substances results leftward shift oxyhaemoglobin dissociation curve ie increased oxygen affinity impaired rbc deformability inflammatory reactions transfusion recipient57napolitano lm corwin hl efficacy red blood cell transfusion critically illcrit care clin 2004 20 255268abstract full text full text pdf pubmed scopus 97 google scholar60offner pj age blood make differencecrit care 2004 8 s24s26crossref pubmed scopus 51 google scholar particular decrease 23dpg levels rbc deformability suggest decreased efficacy old rbcs thus failure increase vo2 transfusion shown 2 weeks storage priming neutrophils agents released rbc units becomes significant69silliman cc thurman gw ambruso dr stored blood components contain agents prime neutrophil nadph oxidase plateletactivatingfactor receptorvox sang 1992 63 133136crossref pubmed scopus 95 google scholar results study critically ill patients sepsis50marik pe sibbald wj effect storedblood transfusion oxygen delivery patients sepsisjama 1993 269 30243029crossref pubmed scopus 669 google scholar accordance finding measurements made transfusion three units rbcs rbc transfusions result increase systemic vo2 interestingly splanchnic ischaemia occurred patients receiving rbc units 15 days old50marik pe sibbald wj effect storedblood transfusion oxygen delivery patients sepsisjama 1993 269 30243029crossref pubmed scopus 669 google scholar retrospective study purdy colleagues65purdy fr tweeddale mg merrick pm association mortality age blood transfused septic icu patientscan j anaesth 1997 44 12561261crossref pubmed scopus 313 google scholar studied 31 critically ill septic patients found nonsurvivors 19 patients although differing incidence septic shock acute physiology chronic health evaluation ii apache ii score intensive care unit icu length hospital stay los age number rbc units transfused compared survivors transfused significantly older rbcs 24 versus 21 days p00001 analysis medical records cabg surgery patients found age rbcs predictor postoperative infection pneumonia87vamvakas ec carven jh transfusion postoperative pneumonia coronary artery bypass graft surgery effect length storage transfused red cellstransfusion 1999 39 701710crossref pubmed scopus 278 google scholar contrast prospective observational study cardiac surgery patients could identify storage 28 days mean age transfused rbc units predictor pneumonia43lealnoval sr jaralopez garciagarmendia jl et alinfluence erythrocyte concentrate storage time postsurgical morbidity cardiac surgery patientsanesthesiology 2003 98 815822crossref pubmed scopus 179 google scholar however recent reviews concluded current evidence effect storage duration rbcs insufficient additional trials necessary36ho j sibbald wj chinyee ih effects storage efficacy red cell transfusion safecrit care med 2003 31 s687s697crossref pubmed google scholar57napolitano lm corwin hl efficacy red blood cell transfusion critically illcrit care clin 2004 20 255268abstract full text full text pdf pubmed scopus 97 google scholar surprisingly recent prospective randomized study 22 critically ill patients detect difference adverse events transfusion rbcs stored 20 days mean age 28 days compared rbcs stored 5 days mean age 2 days addition study showed lack improvement tissue oxygenation rbc transfusion93walsh ts mcardle f mclellan sa et aldoes storage time transfused red blood cells influence regional global indexes tissue oxygenation anemic critically ill patientscrit care med 2004 32 364371crossref pubmed scopus 207 google scholar owing methodological limitations singlecentre study stated large prospective multicentre clinical trials needed define role rbc age outcome56napolitano lm corwin hl efficacy blood transfusion critically ill age blood make differencecrit care med 2004 32 594595crossref pubmed scopus 14 google scholar although numerous studies addressed effects rbc transfusions one randomized controlled trial rct transfusion requirements critical care tricc trial32hbert pc wells g blajchman et ala multicenter randomized controlled clinical trial transfusion requirements critical caren engl j med 1999 340 409417crossref pubmed scopus 4058 google scholar sufficient power evaluate effect transfusions morbidity mortality12carson jl hill carless p hbert p henry transfusion triggers systematic review literaturetransfus med rev 2002 16 187199abstract full text pdf pubmed scopus 184 google scholar study conducted hbert colleagues32hbert pc wells g blajchman et ala multicenter randomized controlled clinical trial transfusion requirements critical caren engl j med 1999 340 409417crossref pubmed scopus 4058 google scholar enrolled 838 critically ill patients admitted icu initial haemoglobin concentration 9 g dl1 patients randomized either restrictive transfusion strategy transfusion trigger 7 g dl1 target haemoglobin concentration 79 g dl1 liberal transfusion strategy transfusion trigger 10 g dl1 target haemoglobin concentration 1012 g dl1 thirtyday mortality slightly lower restrictive transfusion group 187 versus 233 although statistical significance reached p011 however subgroup analyses patients less acutely ill defined apache ii score aged 55 yr showed significantly lower 30day mortality restrictive transfusion group addition tricc trial carson colleagues12carson jl hill carless p hbert p henry transfusion triggers systematic review literaturetransfus med rev 2002 16 187199abstract full text pdf pubmed scopus 184 google scholar identified nine rcts used clearly defined restrictive liberal transfusion strategy giving total number 1780 patients 10 trials transfusion protocols used studies different resulting overlapping transfusion triggers clinical settings also different may partly explain variability terms effect size clinical outcomes particularly concerning effect restrictive transfusion thresholds use blood transfusions12carson jl hill carless p hbert p henry transfusion triggers systematic review literaturetransfus med rev 2002 16 187199abstract full text pdf pubmed scopus 184 google scholar apart tricc trial two studies comparing different transfusion thresholds included 100 patients8bracey aw radovancevic r riggs sa et allowering hemoglobin threshold transfusion coronary artery bypass procedures effect patient outcometransfusion 1999 39 10701077crossref pubmed scopus 249 google scholar47lotke pa barth p garino jp cook ef predonated autologous blood transfusions total knee arthroplasty immediate versus delayed administrationj arthroplasty 1999 14 647650abstract full text pdf pubmed scopus 59 google scholar however differences postoperative haemoglobin levels significantly different8bracey aw radovancevic r riggs sa et allowering hemoglobin threshold transfusion coronary artery bypass procedures effect patient outcometransfusion 1999 39 10701077crossref pubmed scopus 249 google scholar small47lotke pa barth p garino jp cook ef predonated autologous blood transfusions total knee arthroplasty immediate versus delayed administrationj arthroplasty 1999 14 647650abstract full text pdf pubmed scopus 59 google scholar no47lotke pa barth p garino jp cook ef predonated autologous blood transfusions total knee arthroplasty immediate versus delayed administrationj arthroplasty 1999 14 647650abstract full text pdf pubmed scopus 59 google scholar little mortality significantly different two transfusion strategies8bracey aw radovancevic r riggs sa et allowering hemoglobin threshold transfusion coronary artery bypass procedures effect patient outcometransfusion 1999 39 10701077crossref pubmed scopus 249 google scholar consequently metaanalysis studies dominated tricc trial contributed 80 observed deaths mortality analysis12carson jl hill carless p hbert p henry transfusion triggers systematic review literaturetransfus med rev 2002 16 187199abstract full text pdf pubmed scopus 184 google scholar35hill sr carless 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