Portal de Periódicos da CAPES

Red cell transfusion in elective cardiac surgery patients: where do we go from here?

2009; Elsevier BV; Volume: 102; Issue: 3 Linguagem: Inglês

10.1093/bja/aep001

1471-6771

Robert Slight, Onyekwelu Nzewi, D. B. L. McClelland, Pankaj S. Mankad,

Hemoglobin structure and function

Transfusion of red blood cells (RBCs) is one of the most common interventions carried out upon the cardiac surgery population in the postoperative period. Of late, this practice has received increasing attention in terms of the appropriateness of the decision to transfuse, the deleterious consequences of unnecessary transfusion, and the possibility for viable alternatives.1Madjdpour C Spahn DR Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications.Br J Anaesth. 2005; 95: 33-42Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar We wish to highlight recent developments in these areas and suggest where the future may lie in terms of an evidence-based transfusion practice in cardiac surgery. Since 1942, any decision to administer RBCs has largely been based upon a haemoglobin concentration [Hb] threshold with little consideration for any other patient variables.2Lundy JS Clinical Anesthesia—A Manual of Clinical Anesthesiology. W.B. Saunders Co, Philadelphia1942: 381Google Scholar Largely prompted by the availability of high-quality data from the general intensive care unit population, this situation has gradually changed.3Hebert PC Wells G Martin C et al.A Canadian survey of transfusion practices in critically ill patients. Transfusion Requirements in Critical Care Investigators and the Canadian Critical Care Trials Group.Crit Care Med. 1998; 26: 482-487Crossref PubMed Scopus (152) Google Scholar When considering [Hb] alone, there is considerable debate as to an appropriate threshold for the transfusion of RBCs. Experimental haemodilution studies in healthy volunteers suggest that [Hb] levels as low as 5 g dl−1 may be adequately tolerated in healthy volunteers, albeit with the minor complication of a reversible cognitive deficit.4Weiskopf RB Kramer JH Viele M et al.Acute severe isovolemic anemia impairs cognitive function and memory in humans.Anesthesiology. 2000; 92: 1646-1652Crossref PubMed Scopus (200) Google Scholar Although limited in sample size, several studies have attempted to examine the impact of acute anaemia on the outcome after cardiac surgery. Although it is not possible to extrapolate what an appropriate [Hb] might be, the strong suggestion is that in the absence of hypovolaemia, current levels of RBC transfusion are excessive.5Licker M Ellenberger C Murith N et al.Cardiovascular response to acute normovolaemic haemodilution in patients with severe aortic stenosis: assessment with transoesophageal echocardiography.Anaesthesia. 2004; 59: 1170-1177Crossref PubMed Scopus (15) Google Scholar, 6Spahn DR Schmid ER Seifert B Pasch T Hemodilution tolerance in patients with coronary artery disease who are receiving chronic beta-adrenergic blocker therapy.Anesth Analg. 1996; 82: 687-694PubMed Google Scholar The premise behind any RBC transfusion is that it will improve the oxygen carrying capacity of the blood. Thus, investigators have attempted to identify several variables that may predict when systemic oxygen delivery (DO2) is suboptimal in relation to tissue requirements and additional RBCs may be required. Although these ‘physiological triggers’ are only a suggestion, they provide an additional level of consideration to the transfusion decision-making process.1Madjdpour C Spahn DR Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications.Br J Anaesth. 2005; 95: 33-42Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar Considering such parameters in association with [Hb] is a logically appealing scenario. Unfortunately, however, this can only ever be applied to those patients in whom blood balance is stable. As cardiac surgery patients will lose red cell volume (RCV) to a varying degree, this must also be an important consideration. Our group has examined the relative contribution of haemodilution to postoperative anaemia and incorporated the findings into an RCV-based transfusion algorithm. Provisional findings with this model are favourable, although further investigation is required.7Slight RD O'Donohoe P Fung AK Alonzi C McClelland DB Mankad PS Rationalizing blood transfusion in cardiac surgery: the impact of a red cell volume-based guideline on blood usage and clinical outcome.Vox Sang. 2008; 95: 205-210Crossref PubMed Scopus (7) Google Scholar Any transfusion decision has to be based upon a risk–benefit analysis, that is, the benefits of an increase in oxygen carrying capacity, although itself an area of much debate, outweigh the risks of the RBCs themselves. Newer data are beginning to document that the risks are far greater than previously thought.8Koch CG Li L Duncan AI et al.Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting.Crit Care Med. 2006; 34: 1608-1616Crossref PubMed Scopus (717) Google Scholar The potential infectious risks of transfusion are well established. However, with modern screening techniques, these complications are of negligible significance to current practice. Less well recognized, and altogether more serious to the cardiac surgery population, is the impact of RBCs on lung function, circulatory status, and susceptibility to postoperative infection.9Blumberg N Deleterious clinical effects of transfusion immunomodulation: proven beyond a reasonable doubt.Transfusion. 2005; 45 (9S): 33Crossref PubMed Scopus (7) Google Scholar Although the aetiology of these adverse reactions is unclear, it almost certainly relates, at least in part, to allogenic leucocyte material remaining after universal leuco-reduction.10Blajchman MA The clinical benefits of the leukoreduction of blood products.J Trauma. 2006; 60: S83-S90Crossref PubMed Scopus (82) Google Scholar At present, transfusion-related acute lung injury is a rarely diagnosed condition. It is reasonable to assume that as the clinical diagnostic criteria only describe the most severe forms, milder manifestations go unrecognized and may simply be dismissed as ‘pump lung’. This condition can be distinguished from transfusion-associated circulatory overload, in that the causality of the lung injury is non-hydrostatic.11Despotis GJ Zhang L Lublin DM Transfusion risks and transfusion-related pro-inflammatory responses.Hematol Oncol Clin North Am. 2007; 21: 147-161Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The association between postoperative pneumonia and RBC transfusion is well established.12Vamvakas EC Moore SB Blood transfusion and postoperative septic complications.Transfusion. 1994; 34: 714-727Crossref PubMed Scopus (90) Google Scholar This susceptibility is often referred to as transfusion-related immunomodulation, that is, the host's immune response is down-regulated in response to the aforementioned antigenic leucocyte material.13Blajchman MA Transfusion immunomodulation or TRIM: what does it mean clinically?.Hematology. 2005; 10: 208-214Crossref PubMed Scopus (79) Google Scholar Good quality data have only recently emerged documenting the detrimental impact of RBC transfusion on outcome following cardiac surgery. In the first large prospective study of its kind,8Koch CG Li L Duncan AI et al.Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting.Crit Care Med. 2006; 34: 1608-1616Crossref PubMed Scopus (717) Google Scholar RBC transfusion was identified as the strongest independent predictor of all-cause morbidity, and of more concern was the finding that the impact of each single unit was additive in its detrimental effects. As may be expected, this also has an adverse influence on survival outcomes. Several studies have identified a marked impact in the immediate postoperative phase while longer-term effects have been observed at 5 yr.14Reeves BC Murphy GJ Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery.Curr Opin Anaesthesiol. 2008; 21: 669-673Crossref PubMed Scopus (50) Google Scholar Given the undesirable results discussed above, it is no great surprise that a great deal of effort is going into the development of transfusion alternatives. Broadly speaking, transfusion alternatives include pharmacological intervention, mechanical techniques (namely cell salvage), preoperative autologous donation, and the use of blood substitutes. Pharmacological strategies for blood sparing are relatively well established and include interventions such as preoperative erythropoietin, improved strategies for cardiopulmonary bypass (CPB) anti-coagulation, and the use of anti-fibrinolytics.15Ferraris VA Ferraris SP Saha SP et al.Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.Ann Thorac Surg. 2007; 83: S27-S86Abstract Full Text Full Text PDF PubMed Scopus (766) Google Scholar A recently and particularly exciting development is the use of drag-reducing polymers in animal models. The basic premise of these agents is that by a reduction in myocardial after-load, systemic oxygenation may be improved by an increase in cardiac output rather than an increase in arterial oxygen content.16Cotoia A Kameneva MV Marascalco PJ Fink MP Delude RL Drag-reducing hyaluronic acid increases survival in profoundly hemorrhaged rats.Shock. 2008; (June 27 (Epub ahead of print))Google Scholar This is an appealing prospect in cardiac surgery patients, as any reduction in after-load will also confer protective benefits on the heart.17Licker M Ellenberger C Sierra J et al.Cardioprotective effects of acute normovolemic hemodilution in patients undergoing coronary artery bypass surgery.Chest. 2005; 128: 838-847Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Cell salvage has been proposed as an effective method of reducing allogenic RBC exposure. With this technique, shed RBCs are washed and returned to the patient, thus removing any pro-coagulant mediators. A recent Cochrane review has questioned the evidence base behind this method in terms of effectiveness, safety, and cost, as a result of the poor methodological quality of many studies.18Carless PA Henry DA Moxey AJ et al.Cell salvage for minimising perioperative allogeneic blood transfusion.Cochrane Database Syst Rev. 2006; (CD001888)Crossref PubMed Google Scholar In the authors' experience, cell salvage is a valuable tool in reducing transfusion exposure, provided the perfusate remaining at the termination of CPB is processed.19Slight RD Bappu NJ Nzewi OC et al.Perioperative red cell, plasma, and blood volume change in patients undergoing cardiac surgery.Transfusion. 2006; 46: 392-397Crossref PubMed Scopus (18) Google Scholar An individual's RBCs may also be returned to them after preoperative autologous donation (PAD). Although this is likely beneficial to the patient, PAD has never been widely adopted, again due to concerns over cost-effectiveness.20Birkmeyer JD AuBuchon JP Littenberg B et al.Cost-effectiveness of preoperative autologous donation in coronary artery bypass grafting.Ann Thorac Surg. 1994; 57: 161-168Abstract Full Text PDF PubMed Scopus (147) Google Scholar Artificial oxygen carriers are a relatively recent development, which aim to improve the oxygen carrying capacity of the blood, and thus DO2, independent of RBCs. The primary benefit is the avoidance of transfusion risk. They can be divided broadly into modified [Hb] solutions and perfluorocarbon suspensions.21Mosa MM Cheng DC Oxygen therapeutics (blood substitutes) in cardiac surgery.Curr Opin Anaesthesiol. 2003; 16: 21-26Crossref PubMed Scopus (4) Google Scholar As the latter require a higher inspired oxygen concentration (Fio2) to improve tissue oxygenation, clinical investigation has been largely suspended. Modified [Hb] solutions continue to show promise, although their tendency to increase pulmonary artery pressure through nitric oxide scavenging may cause concern in cardiac surgery patients.22Kocian R Spahn DR Haemoglobin, oxygen carriers and perioperative organ perfusion.Best Pract Res Clin Anaesthesiol. 2008; 22: 63-80Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar In conclusion, current evidence suggests that RBC transfusion in elective cardiac surgery patients is a potentially counter-productive intervention that should only be performed where there is good evidence that systemic oxygenation is compromised, an individual is significantly bleeding, or both.1Madjdpour C Spahn DR Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications.Br J Anaesth. 2005; 95: 33-42Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar 7Slight RD O'Donohoe P Fung AK Alonzi C McClelland DB Mankad PS Rationalizing blood transfusion in cardiac surgery: the impact of a red cell volume-based guideline on blood usage and clinical outcome.Vox Sang. 2008; 95: 205-210Crossref PubMed Scopus (7) Google Scholar 11Despotis GJ Zhang L Lublin DM Transfusion risks and transfusion-related pro-inflammatory responses.Hematol Oncol Clin North Am. 2007; 21: 147-161Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The current development of synthetic oxygen carriers in tandem with compounds that increase tissue oxygenation via flow-mediated changes offers the possible prospect that the requirement for RBCs in this subgroup of patients will be all but removed.16Cotoia A Kameneva MV Marascalco PJ Fink MP Delude RL Drag-reducing hyaluronic acid increases survival in profoundly hemorrhaged rats.Shock. 2008; (June 27 (Epub ahead of print))Google Scholar 22Kocian R Spahn DR Haemoglobin, oxygen carriers and perioperative organ perfusion.Best Pract Res Clin Anaesthesiol. 2008; 22: 63-80Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Download .zip (.0 MB) Help with zip files Download .zip (.0 MB) Help with zip files