Editorial article
Transfusion thresholds and red blood cells transfusion focused on tissue oxygenation
Umbrales transfusionales y transfusión de hematíes enfocada a la microcirculación
a Servicio de Anestesiología y Reanimación, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain
b Grupo Español de Rehabilitación Multimodal (GERM), Zaragoza, Spain
c Banco de Sangre y Tejidos de Navarra, Servicio Navarro de Salud-Osasunbidea, Pamplona, Spain
d Grupo de Trabajo de la Sociedad Española de Transfusión Sanguínea «Hemoterapia basada en sentido común», Spain
e Grupo Multidisciplinar para el Estudio y Manejo de la Anemia del Paciente Quirúrgico (www.awge.org), Spain
f Grupo idiPAZ de «Investigación en PBM», Madrid, Spain
g Department of Intensive Care, Erasme University Hospital (Université Libre de Bruxelles), Brussels, Belgium
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Ripollés-Melchor, J.A. García-Erce, V.J.L. Vincent" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Ripollés-Melchor" "email" => array:1 [ 0 => "ripo542@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.A." "apellidos" => "García-Erce" "referencia" => array:5 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 4 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 2 => array:3 [ "nombre" => "V.J.L." "apellidos" => "Vincent" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Servicio de Anestesiología y Reanimación, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Grupo Español de Rehabilitación Multimodal (GERM), Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Banco de Sangre y Tejidos de Navarra, Servicio Navarro de Salud-Osasunbidea, Pamplona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Grupo de Trabajo de la Sociedad Española de Transfusión Sanguínea «Hemoterapia basada en sentido común», Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Grupo Multidisciplinar para el Estudio y Manejo de la Anemia del Paciente Quirúrgico (www.awge.org), Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Grupo idiPAZ de «Investigación en PBM», Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Department of Intensive Care, Erasme University Hospital (Université Libre de Bruxelles), Brussels, Belgium" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Umbrales transfusionales y transfusión de hematíes enfocada a la microcirculación" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Red blood cells transfusion (RBC) is a much-debated topic in medicine. One the one hand, reasonable RBC transfusion can save lives, but on the other it is associated with risks that can contribute to adverse patient outcomes in some situations. The challenge is to balance the risk of anaemia against the risk of transfusion,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> but many clinicians have insufficient training, information, or both to make this decision,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> and find it easier to simply administer transfusion according to protocols.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> This underscores the need to optimize not only haemoglobin (Hb) levels, but also to improve tolerance to anaemia in any clinical setting.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a> The relationship between RBC transfusion and outcome is much more than a simple binary; in addition to the volume of transfused blood products, the underlying condition that leads to transfusion (for example, anaemia and/or haemorrhage) and the patient's characteristics influence outcome. While treatment of anaemia by transfusion of limited volumes of RBC may be clearly beneficial under some circumstances, there is a large grey area where some patients will benefit from transfusion while in others equal amounts blood products will be detrimental.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Ferraris et al. illustrated this in a retrospective analysis of almost half a million postoperative patients, showing that in contrast to high-risk patients, low-risk patients had an 8- to 10-fold risk of adverse outcomes when they received an RBC transfusion.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> Similarly, Nielsen et al. showed that in patients with abnormal tissue oxygenation or microcirculatory indices prior to transfusion, these values improved after transfusion.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Transfusion thresholds are determined by the Hb value at which the benefit of RBC transfusion is expected to outweigh the risk. Otherwise, the tolerance of a patient to anaemia depends on the clinical condition and the presence of co-morbidities.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> There are two scenarios is which transfusion is less restrictive: the presence of coronary artery disease,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">7</span></a> and severe disease.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a> This is frequent in both cardiac and non-cardiac surgery, as well as in patients admitted to the intensive care unit (ICU), especially with sepsis or neurological problems.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The comparison of predefined transfusion thresholds in cardiac surgery has been studied extensively in recent years, after evidence that RBC transfusion in these patients was associated with increased length of stay, and higher morbidity and mortality rates and care costs.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">9</span></a> Although it is reasonable to assume that the rate of RBC transfusion should be higher in the sickest patients with the worst prognosis, the Transfusion Requirements in Cardiac Surgery (TRICS) III trial showed that a <span class="elsevierStyleItalic">restrictive</span> RBC transfusion strategy (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>7.5<span class="elsevierStyleHsp" style=""></span>g/dL intra-operatively or post-operatively) was not inferior to a <span class="elsevierStyleItalic">liberal</span> strategy (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>9.5<span class="elsevierStyleHsp" style=""></span>g/dL intra-operatively or post-operatively or <8.5<span class="elsevierStyleHsp" style=""></span>g/dL in non-ICU patients) in terms of mortality and major morbidity including myocardial infarction, stroke, or new onset of renal failure with dialysis in moderate-to-high-risk patients undergoing cardiac surgery.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a> Interestingly, a subgroup analysis based on age showed the restrictive-threshold group to be associated with a lower risk of the composite primary outcome than the liberal-threshold group in elderly patients (>75 years) (OR 0.70; 95% CI 0.54–0.89; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> This contrasts directly with the results of a substudy<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> of the Transfusion Requirements After Cardiac Surgery Trial (TRACS),<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> where a <span class="elsevierStyleItalic">restrictive</span> RBC transfusion strategy was independently associated with a 2.5-fold higher rate of cardiogenic shock in patients aged >60 years; these patients presented Hb values at the end of the surgery of less than 10<span class="elsevierStyleHsp" style=""></span>g/dL (9.9<span class="elsevierStyleHsp" style=""></span>+−<span class="elsevierStyleHsp" style=""></span>1.2),<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> which were probably insufficient to meet the physiological demands of cardiac pathology in elderly patients due to anaemia-induced tissue hypoxia.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> The TRICS III results also contrast to those published by Murphy et al. in 2011, in which it was found that a <span class="elsevierStyleItalic">restrictive</span> transfusion threshold (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>7.5<span class="elsevierStyleHsp" style=""></span>g/dL) compared with a more <span class="elsevierStyleItalic">liberal</span> transfusion threshold (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>9.5<span class="elsevierStyleHsp" style=""></span>g/dL) was associated with higher 90-day all-cause mortality (4.2% vs 2.6%; HR 1.64, CI 1.00–2.67; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.045) in the postoperative period of non-urgent cardiac surgery, despite the lack of significant differences in the number of global complications.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The Functional Outcomes in Cardiovascular patients Undergoing Surgical repair of hip fracture (FOCUS) trial<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">16</span></a> was designed to compare a <span class="elsevierStyleItalic">restrictive</span> vs <span class="elsevierStyleItalic">liberal</span> RBC transfusion strategy among anaemic (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g/dL at recruitment), relatively old (>50 years) patients with a history of or risk factors for ischaemic heart disease who underwent surgical repair of a fractured hip; In the <span class="elsevierStyleItalic">liberal</span>-strategy group, <span class="elsevierStyleItalic">single-unit</span> RBC transfusions were given to restore and maintain an Hb level of over 10<span class="elsevierStyleHsp" style=""></span>g/dL. In the <span class="elsevierStyleItalic">restrictive</span>-strategy group, transfusions were given when Hb was <8<span class="elsevierStyleHsp" style=""></span>g/dL. Transfusion for symptoms of anaemia (chest pain deemed to be cardiac in origin, congestive heart failure, and unexplained tachycardia or hypotension unresponsive to fluids) was permitted in both groups, which meant that transfusions were usually indicated by these symptoms in the <span class="elsevierStyleItalic">restrictive</span> group (14% vs 5%). There were no significant inter-group differences in 30-day and 60-day mortality rates. In the <span class="elsevierStyleItalic">restrictive</span> group, 59% of patients did not receive a transfusion vs 97% of the patients in the liberal group. This FOCUS trial suggests that it is reasonable to withhold transfusion in the absence of symptoms of anaemia or a decline in Hb level below 8<span class="elsevierStyleHsp" style=""></span>g/dL in an otherwise health patient population.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Docherty et al. conducted a systematic review to compare clinical outcomes of restrictive (<8<span class="elsevierStyleHsp" style=""></span>g/dL) or liberal transfusion strategies in patients with cardiovascular disease undergoing non-cardiac surgery. The restrictive transfusion group showed a trend towards increased 30-day mortality (RR 0.96 (95% CI 0.58–1.59, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.87), as well as a higher incidence of acute coronary syndrome (RR 1.78, 95% CI 1.18–2.70, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01), compared to the more liberal transfusion group.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a> Similarly, Almeida et al. found that in the postoperative period of major cancer surgery, a restrictive transfusion threshold was associated with an increase in mortality and severe complications compared to a more liberal transfusion threshold (19.6 vs 35.6%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0012),<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">16</span></a> supporting the notion that in this group of patients, a restrictive transfusion threshold is not the best option.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6,8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Despite the multiple clinical trials and meta-analyses<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7,15</span></a> comparing two predefined transfusion thresholds, it would seem preferable to individualize the decision to transfuse by factoring in physiological and individual clinical factors with Hb levels, and thus avoiding the use of a simple laboratory value as an indication for transfusion.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Advances in the development and validation of physiological, accessible, practical and reliable markers to guide RBC transfusions are expected. Near-infrared spectroscopy (NIRS) is a non-invasive technique that uses the differential absorption properties of oxyhaemoglobin and deoxyhaemoglobin to measure the tissue oxygenation status, and has been used to evaluate the effect of the duration of RBC storage on tissue oxygenation response.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">18</span></a> In 2017, Leal-Noval et al. performed the first randomized controlled trial<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> to explore the utility of regional cerebral oxygen saturation (rSO<span class="elsevierStyleInf">2</span>) measured by NIRS compared with predefined Hb thresholds to guide RBC transfusion in adult neurocritical patients with moderate anaemia (Hb values between 7 and 10<span class="elsevierStyleHsp" style=""></span>g/dL). Patients were randomly assigned to Hb-guided (to maintain Hb levels between 8.5 and 10<span class="elsevierStyleHsp" style=""></span>g/dL) or rSO<span class="elsevierStyleInf">2</span>-guided (to maintain forehead rSO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>60%) RBC transfusion. The introduction of an rSO<span class="elsevierStyleInf">2</span> cut-off into the RBC transfusion protocol reduced the number of transfused RBC units per patient (mean difference, 0.51<span class="elsevierStyleHsp" style=""></span>U [95%CI −1.008–0.002]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04), but did not reduce RBC transfusion rates. In the rSO<span class="elsevierStyleInf">2</span> group, RBC transfusion was associated with an increase in Hb (77<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 to 88.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>g/dL) in parallel with an increase in rSO<span class="elsevierStyleInf">2</span> values (55<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 to 58<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4%), suggesting a direct relationship between RBC transfusion and rSO<span class="elsevierStyleInf">2</span>, though not in the same proportion. It would have been interesting to know if this increase occurred in all patients, if it was homogeneous in all patients, if it was maintained over time, and if it was influenced by the storage age and volume of the transfused RBC.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Inclusion of patients with widely varying Hb levels (from 7.1 to 9.9<span class="elsevierStyleHsp" style=""></span>g/dL) makes comparison between cases impossible, since patients with Hb close to 10<span class="elsevierStyleHsp" style=""></span>g/dL have almost 40% more erythrocyte mass. Presumably, the low number of patients included prevented a subgroup analysis based on Hb level at inclusion. It would also have been interesting to report the rSO<span class="elsevierStyleInf">2</span> values in the Hb-guided group, which would have shown whether RBC transfusion in patients with rSO<span class="elsevierStyleInf">2</span> values greater than that set in the intervention group were associated with increases in rSO<span class="elsevierStyleInf">2</span>.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Although there were no differences in mortality or hospital stay between the two transfusion strategies (the study was underpowered for this outcome), and despite the many limitations, Leal-Noval et al.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> single out tissue oxygenation as the ultimate threshold for RBC transfusion, and present physiological alternatives that could complement or replace arbitrary Hb thresholds to guide RBC transfusions.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ripollés-Melchor J, García-Erce JA, Vincent VJL. Umbrales transfusionales y transfusión de hematíes enfocada a la microcirculación. Rev Esp Anestesiol Reanim. 2018;65:363–365.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0100" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood transfusion and adverse surgical outcomes: the good and the bad" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "V.A. Ferraris" 1 => "M. Hochstetler" 2 => "J.T. Martin" 3 => "A. Mahan" 4 => "S.P. 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