Anemia In Cardiac Surgery Research Articles

Randomised open-label trial comparing intravenous iron and an erythropoiesis-stimulating agent versus oral iron to treat preoperative anaemia in cardiac surgery (INITIATE trial)

BackgroundPreoperative anaemia is a risk factor for adverse postoperative outcomes after cardiac surgery. Iron deficiency is a frequent cause of low preoperative haemoglobin. An effective treatment for preoperative anaemia associated with iron deficiency has not been determined. MethodsWe conducted a single-centre, open-label, pragmatic randomised trial, enrolling 156 elective cardiac surgery patients who had low preoperative haemoglobin (100–130 g L−1) with iron deficiency (serum ferritin <100 μg L−1 or transferrin saturation <30%) to compare intravenous ferric derisomaltose 1000 mg and darbepoetin 200 μg subcutaneously (intervention group) with oral ferrous sulphate 600 mg daily (control group). The primary outcome was transfusion of at least one unit of allogeneic red cells during surgery and within the following 5 days. Secondary outcomes included the change in haemoglobin concentration between randomisation and surgery, red cell transfusion volume, postoperative blood loss, pre-specified postoperative complications, length of hospital stay, and in-hospital death. ResultsThe odds of red cell transfusion were lower in the intervention group compared with the control group (adjusted odds ratio=0.33; 95% confidence interval [CI], 0.15–0.75; P=0.008). Of the secondary outcomes, the only significant difference was the increase in haemoglobin between randomisation and surgery, intervention vs control 9.5 g L−1 (95% CI, 6.8–12.2; P<0.001). ConclusionsIn patients with a low preoperative haemoglobin and iron deficiency, preoperative treatment with a single dose of ferric derisomaltose and darbepoetin decreased the proportion of participants who received a perioperative blood transfusion as a consequence of a greater increase in haemoglobin compared with treatment with oral ferrous sulphate. Clinical trial registrationISRCTN Number: 41421863; EUDRACT number: 2011-003695-36.

Preoperative Anemia is Associated with Increased Intraoperative Mortality in Patients Undergoing Cardiac Surgery.

ObjectivesWe sought to investigate the incidence of preoperative anemia in cardiac surgery and its association with outcomes.MethodsA retrospective review of clinical, laboratory, and transfusion data for all patients who underwent cardiac surgery at Sultan Qaboos University Hospital between 2008 and 2014 was performed. Patients were divided into two groups, anemic and non-anemic, with anemia defined as hemoglobin levels < 13 g/dL (males) and < 12 g/dL (females). Clinical variables were compared using chi-square and independent t-test. Factors influencing preoperative mortality were analyzed using multivariate binary logistics regression.ResultsA total of 599 patients (69.9% males and 30.1% females) were included in the study; 69.3% underwent coronary artery bypass surgery. Preoperative anemia was found in 76.1% of females and 26.7% of male patients. Rates of intraoperative red blood cell transfusions were higher among anemic patients (75.9% vs. 52.3%, p < 0.001). Anemic patients had a worse risk profile with higher incidence of diabetes mellitus (53.8% vs. 38.9%, p < 0.001), congestive heart failure (51.4% vs. 28.3%, p < 0.001), arrhythmia (16.5% vs. 8.6%, p = 0.004), and cerebrovascular disease (10.0% vs. 4.9%, p = 0.015). In addition, they had a higher risk of overall mortality (6.4% vs. 2.6%, p = 0.023). Preoperative anemia remained a risk factor for intraoperative mortality after logistic regression (odds ratio = 4.08, 95% confidence interval: 1.43–11.66; p = 0.009).ConclusionsPreoperative anemia in cardiac surgery is independently associated with increased intraoperative mortality and early readmission rates post-surgery.

Anemia in Cardiac Surgery — Can Something Bad Get Worse?

IntroductionAnemia and blood transfusion are risk factors for morbidity/mortality in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The objective of this study is to analyze the association of blood transfusion with morbidity/mortality in patients undergoing coronary artery bypass grafting (CABG) under CPB in the state of São Paulo, Brazil.MethodsThis is a retrospective analysis using the State of São Paulo Registry of Cardiovascular Surgery from November 2013 to August 2014. Blood transfusion was only considered during surgery or within six hours after surgery. Anemia was defined as hematocrit ≤ 37.5%. Patients < 18 years old were excluded. The sample was divided in four groups - Group I (851, no anemia), Group II (200, anemia without blood transfusion), Group III (181, no anemia and transfusion), and Group IV (258, anemia and transfusion).ResultsA total of 1,490 patients were included; 639 (42.9%) were anemic and 439 (29.5%) underwent blood transfusion. Group II showed lower composite morbidity (odds ratio [OR] −0.05; confidence interval [CI] −0.27-0.17; P=0.81) than Group III (OR 0.41; CI 0.23-0.59; P=0.018) or Group IV (OR 0.54; CI 0.31-0.77; P=0.016). Group III was at greater risk of mortality (OR 0.73; CI 0.43-1.03; P=0.02) than Group II, which was exposed only to anemia (OR −0.13; CI −0.55-0.29; P=0.75), or Group IV (OR 0.29; CI −0.13-0.71; P=0.539).ConclusionAnemia in patients undergoing CABG with CPB is bad, but blood transfusion can be worse, increasing at least 50% the risk for mortality and/or morbidity.

Anaemia in cardiac surgery - a retrospective review of a centre's experience with a pre-operative intravenous ironclinic.

Pre-operative anaemia is associated with higher rates of transfusion and worse outcomes, including prolonged hospital stay, morbidity and mortality. Iron deficiency is associated with significantly lower haemoglobin levels throughout the peri-operative period and more frequent blood transfusion. Correction of iron stores before surgery forms part of the first pillar of patient blood management. We established a pre-operative anaemia clinic to aid identification and treatment of patients with iron deficiency anaemia scheduled for elective cardiac surgery. We present a retrospective observational review of our experience from January 2017 to December 2019. One-hundred and ninety patients received treatment with intravenous iron, a median of 21days before cardiac surgery. Of these, 179 had a formal laboratory haemoglobin level measured before surgery, demonstrating a median rise in haemoglobin of 8.0g.l-1 . Patients treated with i.v. iron demonstrated a significantly higher incidence of transfusion (60%) compared with the non-anaemic cohort (22%) during the same time period, p<0.001. Significantly higher rates of new requirement for renal replacement therapy (6.7% vs. 0.6%, p<0.001) and of stroke (3.7% vs. 1.2%, p=0.010) were also seen in this group compared with those without anaemia, although there was no significant difference in in-hospital mortality (1.6% vs. 0.8%, p=0.230). In patients where the presenting haemoglobin was less than 130g.l-1 , but there was no intervention or treatment, there was no difference in rates of transfusion or of complications compared with the anaemic group treated with iron. In patients with proven iron deficiency anaemia, supplementation with intravenous iron showed only a modest effect on haemoglobin and this group still had a significantly higher transfusion requirement than the non-anaemic cohort. Supplementation with intravenous iron did not improve outcomes compared with patients with anaemia who did not receive intravenous iron and did not reduce peri-operative risk to non-anaemic levels. Questions remain regarding identification of patients who will receive most benefit, the use of concomitant treatment with other agents, and the optimum time frames for treatment in order to produce benefit in the real-world setting.

DELIRE: Impact of perioperative anaemia in cardiac surgery: a retrospective observational study comparing different levels of haemoglobin

Introduction anaemia around cardiac surgery (CS) is an independent risk factor for adverse outcomes but transfusion is also associated with morbidity and mortality. However, evidences are still scarce to recommend a transfusion trigger, as in many studies, haemoglobin values in both restrictive and liberal groups were often higher than the planned thresholds. Objective to assess which nadir haemoglobin threshold is linked to morbidity and mortality within the 4 first days after cardiac surgery. Methods retrospective observational study from data collected between May 2013 and January 2018 in the cardiac surgery ICU (CS ICU) of Grenoble Alps University Hospital. 3 groups were compared based on the lowest haemoglobin measurements within the 4 first days after surgery: group 1 under 80g/L, group 2 between 80 and 95 g/L, group 3 no values under 95g/L. Main outcome measured: a composite index including 30-day all-cause mortality, and morbidity: myocardial infarction, low cardiac output syndrome, and renal failure. Results Files from 2220 patients how underwent CS were analysed, 263 in group 1, 575 in group 2 and 1382 in group 3. The demographic analysis showed that patients in group 1 had the worst preoperative renal function and, higher Euroscore 2 (3.9 (sd 3.8) vs group 2, 2.7 (sd 2.9) vs group 3, 1.9 (sd 1.8) p Discussion This large retrospective observational study comparing the impact of different haemoglobin nadir within 4 days after cardiac surgery on morbidity and mortality showed a worsening in outcomes for haemoglobin values under 80g/L.

Intravenous iron does not effectively correct preoperative anaemia in cardiac surgery: a pilot randomized controlled trial.

Preoperative anaemia is a strong predictor of blood transfusion requirements and must be assessed for appropriate optimization before elective surgery. Iron therapy is a transfusion-sparing approach effective for increasing haemoglobin concentrations. However, its role in elective cardiac surgery and the optimal route of administration remain unknown. This single-centre, non-blinded, randomized, controlled trial compared the effectiveness of intravenous ferric carboxymaltose therapy with oral iron for anaemic patients undergoing elective cardiac surgery. Fifty anaemic patients scheduled for elective cardiac surgery were randomized to receive either oral or intravenous iron therapy 3-8 weeks preoperatively. Changes in haemoglobin concentration were measured. Blood transfusion and postoperative outcome data were collected. Preoperative median increases in haemoglobin were 1.0 g/l (interquartile range -3.25 to 7.25 g/l) and 3.0 g/l (interquartile range -1.25 to 6.25 g/l) for patients receiving intravenous and oral iron, respectively (P = 0.42). The median first 12-h blood loss was significantly higher in the intravenous group (655 ml; interquartile range 162-1540 ml) compared to the oral group (313 ml; interquartile range 150-1750 ml; P < 0.007). Median increments in serum ferritin were superior for the intravenous group (median difference 313 µg/l; interquartile range 228-496) compared to the oral group (median difference 5.5 µg/l; interquartile range -1.4 to 19.4; P < 0.001). Increases in ferritin after intravenous iron administration were significantly greater than those after oral iron administration. There was no significant difference in haemoglobin increments between groups. Despite significantly higher intraoperative blood loss in the group receiving intravenous iron, blood transfusion requirements for both groups were not statistically different. ISRCTN22158788.

Potential biomarkers of tissue hypoxia during acute hemodilutional anemia in cardiac surgery: A prospective study to assess tissue hypoxia as a mechanism of organ injury

Hemodilutional anemia is associated with acute kidney injury (AKI) and mortality in patients undergoing cardiac surgery by mechanisms that may include tissue hypoxia. Our hypothesis was to assess if changes in the potential hypoxic biomarkers, including methemoglobin and erythropoietin, correlated with a decrease in hemoglobin (Hb) concentration following hemodilution on cardiopulmonary bypass (CPB). Arterial blood samples were taken from patients (n = 64) undergoing heart surgery and CPB at baseline, during CPB, following CPB, and in the intensive care unit (ICU). Potential hypoxic biomarkers were measured, including methemoglobin, plasma Hb, and erythropoietin. Data were analyzed by repeated measures one-way analysis of variance on ranks and linear regression. Hemoglobin levels decreased following CPB and methemoglobin increased in the ICU (P < 0.001 for both). No correlation was observed between the change in Hb and methemoglobin (P = 0.23). By contrast, reduced Hb on CPB correlated with increased lactate, reduced pH, and increased erythropoietin levels following CPB (P ≤ 0.004 for all). Increased plasma Hb (P < 0.001) also correlated with plasma erythropoietin levels (P < 0.001). These data support the hypothesis that erythropoietin rather than methemoglobin is a potential biomarker of anemia-induced tissue hypoxia. The observed relationships between decreased Hb during CPB and the increase in lactate, reduced pH, and increase in erythropoietin levels suggest that early changes in plasma erythropoietin may be a pragmatic early biomarker of anemia-induced renal hypoxia. Further study is required to determine if anemia-induced increases in erythropoietin may predict AKI in patients undergoing cardiac surgery. www.clinicaltrials.gov (NCT01883713). Registered 21 June 2013.

Reducing RBC Transfusion in Cardiac Surgery: A Single Centre's Experience in a Multicentre Quality Improvement Initiative of The Australian and New Zealand Collaborative Perfusion Registry (ANZCPR)

Purpose: To reduce RBC transfusion within a multicentre project of the Australian and New Zealand Collaborative Perfusion Registry (ANZCPR) through implementation of industry guidelines and avoidance of anaemia. Methodology: This multicentre project was modelled on a single centre 3 phase study, where current processes were identified (phase I) then new protocols implemented (phase II) and follow-up monitoring of progress was undertaken (phase III) [[1]Likosky D.S. Surgenor S.D. Dacey L.J. et al.Rationalizing the treatment of anaemia in cardiac surgery: short and mid-term results from a local quality improvement initiative.Qual Saf Health Care. 2010; 19: 392-398Crossref PubMed Scopus (12) Google Scholar]. Local sites formed a local multi-disciplinary quality improvement team to review current practice and incidence of transfusion for their site (phase 1). Our team included cardiac surgery, anaesthetics, CICU, haematology, blood bank and perfusion. This team would then review current literature and guidelines and select initiatives and changes in practice they considered worthwhile (phase II). These were then relayed to staff and introduced. Then a 3- and 6-month follow-up reporting changes in incidence of RBC transfusion fed back to team members and their staff was undertaken (phase III). Concurrently, indications for each transfusion were also recorded in line with the project model. Results: At our centre, each discipline was involved in introducing a variety of simple wide-reaching evidence-based strategies with very small costs with spectacular results. Our centre has had a 57% reduction in the number of RBC units transfused for our open heart, RBC transfusion rate per 6 months has fallen 20%, and of those transfused, patients receiving more than 2 units has dropped 13%. Also, a 34% reduction in units of platelets given, 50% reduction in cryoprecipitate units and 49% reduction in units of FFP transfused. These changes in practice continue to improve transfusion rates. Conclusion: A multidisciplinary team approach to RBC conservation using well established evidence-based guidelines can effectively optimise the use of blood products in a cardiac surgical setting and in a cost effective manner.

Anemia in cardiac surgery: next target for mortality and morbidity improvement?

To assess the effects of preoperative anemia on outcomes of cardiac surgery and to explore the trend in mortality over an 8-year period. During the study period (2005-2012), all 1170 patients undergoing elective or urgent cardiac surgery and classed as anemic were included. A matched group of non-anemic 1170 patients was used as a control group. Postoperative outcomes were compared between the 2 groups. The association between preoperative anemia and postoperative outcomes was analyzed using a logistic regression model. Compared with patients without anemia, the need for airway support (15% vs. 12%, p = 0.05), renal replacement therapy (13% vs. 8%, p < 0.01) and the rate of in-hospital surgical site infection (9% vs. 7%, p = 0.05) were higher in the anemic group. Anemia was associated with greater need for renal replacement therapy (odds ratio = 1.76, confidence interval: 1.21-2.37, p = 0.002) and prolonged (> 7 days) hospital stay (odds ratio = 1.21, confidence interval: 0.97-1.51, p = 0.08). The blood transfusion rate (54% vs. 33%, p < 0.01) and hospital mortality (5.6% vs. 3.5%, p = 0.02) were higher in the anemic group. Over the 8-year period, there was a significant improvement in mortality in the non-anemic group (from 6.5% to 1.6%) but less so in the anemic group (from 6.7% to 4.7%). Anemia impacts significantly on morbidity and mortality after cardiac surgery, with less improvement over time compared to patients without anemia. Preoperative correction of anemia, when feasible, could potentially help to improve cardiac surgery outcomes.

Invited Commentary

Invited Commentary

Effects of Preoperative Intravenous Erythropoietin Plus Iron on Outcome in Anemic Patients After Cardiac Valve Replacement

Preoperative anemia is a risk factor for postoperative morbidity and in-hospital mortality in cardiac surgery. However, it is not known whether treatment of anemia before cardiac surgery by administering recombinant human erythropoietin (rhEPO) plus iron improves postoperative outcomes and decreases red blood cell transfusions in these patients. In 1998 a collection of consecutive data for patients who underwent valve replacement was initiated and the inclusion criterion was anemia. Treatment with rhEPO was given at a dose of 500 IU/kg/day every week for 4 weeks and the fifth dose 48 hours before valve replacement. During each rhEPO session, patients received intravenous iron sucrose supplementation. The intervention cohort (2006 to 2011) included 75 patients and the observation cohort was composed of 59 patients who did not receive any treatment (1998 to 2005). Multivariable logistic regression analysis showed that administration of combined therapy was independently associated with decreased postoperative morbidity (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.03 to 0.59 p = 0.008) and in-hospital mortality (OR 0.16, 95% CI 0.28 to 0.95 p = 0.04) after adjusting for logistic European System for Cardiac Operative Risk Evaluation score, type of intervention, time of cardiopulmonary bypass, and year of surgery. Individually, this treatment also decreased postoperative renal failure (OR 0.23, 95% CI 0.06 to 0.88, p = 0.03). Rate of red blood cell transfusion decreased from 93% in the observation cohort to 67% in the intervention cohort as did days of hospitalization (median, 15 days, 10 to 27, versus 10 days, 8 to 14, respectively, p = 0.01 for all comparisons). In conclusion, administration of intravenous rhEPO plus iron in anemic patients before valve replacement improves postoperative survival, decreases blood transfusions, and shortens hospitalization.

Implications and management of anemia in cardiac surgery: Current state of knowledge

Decreasing oxygen delivery during and after cardiopulmonary bypass (CPB) can adversely affect patient outcomes. Balancing morbidities associated with anemia, red blood cell (RBC) transfusion, pharmaceuticals to prevent fibrinolysis, and reoperations for bleeding poses a dilemma. One would optimally balance these factors to minimize patient risk. Uncertainty in defining an optimal transfusion threshold, a trigger for reoperation, and a strategy for use of pharmaceuticals is evidenced by the considerable variability in clinical practice worldwide. 1,2 Therefore, to gain insight to inform surgical practice, we have brought together current knowledge of the association of preoperative anemia, intraoperative anemia, blood transfusion, and measures to address blood loss with adverse outcomes after cardiac surgery. PREOPERATIVE ANEMIA AND OUTCOMES The World Health Organization defines anemia as a hemoglobin level less than 13 g/dL in men and less than 12 g/dL in women. By that measure, prevalence of preoperative anemia in patients undergoing cardiac surgery ranges from 16% to 54%, with severe anemia (hemoglobin < 10 g/dL) in 5.5%. 3-5 Patients presenting with low hemoglobin are more susceptible to end-organ ischemia; however, oxygen demands on CPB vary, and it is unclear what hemoglobin level is adequate. Nonetheless, several large observational studies suggest that preoperative anemia is associated with increased noncardiac morbidity and mortality after CPB (Table 1). Zindrou and colleagues 6 performed an observational study of 2059 patients undergoing isolated coronary artery bypassgrafting(CABG)thatshowedthatpatientswithapreoperative hemoglobin of 10 g/dL or less had a 5-fold higher in-hospital mortality than those with a greater hemoglobin concentration.Thiswasconfirmedbymultivariableanalysis. However, this study may have been confounded by RBC transfusion, which was not considered in the analysis. Likewise, van Straten and colleagues 5 from the Dutch Central Bureau for Statistics performed an observational study of 10,626 patients who underwent CABG. Preoperative anemia, as defined by the World Health Organization, was an independent risk factor for increased early (<30 days) mortality and higher degree of preoperative anemia for higher late mortality. Preoperative hemoglobin of 14.5 g/dL or greater in men and 13.5 g/dL in women was associated with an 88% survival at 8 years, whereas a value less than 12 g/dL in men and less than 11 g/dL in women was associated with a 55% survival at 8 years. This study did not factor intraoperative anemia or use of RBC transfusion into the analysis. To account for transfusion as a potential confounder, Ranucci and colleagues 7 reviewed 3003 consecutive patients undergoing isolated CABG without perioperative RBC transfusion and found no association between preoperative anemia and postoperative mortality. However, they reported a 5-fold greater unadjusted occurrence of major morbidity in patients with a preoperative hematocrit (HCT) of 33% or less versus 42% or greater. After risk adjustment, preoperative HCT and lowest HCT on CPB were associated with an increased postoperative occurrence of prolonged ventilation, renal insufficiency, stroke, and reoperation. Several additional studies have identified an association between preoperative anemia and postoperative morbidity. A multicenter observational study by Kulier and colleagues 4 demonstrated that preoperative anemia (hemoglobin <13 g/dL) was associated with increased neurologic, renal, and gastrointestinal complications. Anemia was not associated with more cardiac complications, although these events were related to perioperative RBC transfusion. De Santo and colleagues 8 studied a co

Rationalising the treatment of anaemia in cardiac surgery: short and mid-term results from a local quality improvement initiative

BackgroundTransfusion of red blood cells, while often used for treating blood loss or haemodilution, is also associated with higher infection rates and mortality. The authors implemented an initiative to reduce...

Perioperative Implications of Hereditary Spherocytosis in Coronary Artery Surgery

HEREDITARY SPHEROCYTOSIS (HS) is the most common inherited hemolytic anemia in Europe and North America, affecting between 0.02% and 0.05% of the population.1 Despite the prevalence of HS, few reports addressing the perioperative implications of this hemolytic anemia in cardiac surgery have appeared in the literature.2-9 In the current report, the authors describe their management of a man with HS undergoing coronary artery bypass graft (CABG) surgery and discuss the potential ramifications of the disease during the perioperative period.

The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery

The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery

Influence of Intraoperative Fluid Volume on Cardiopulmonary Bypass Hematocrit and Blood Transfusions in Coronary Artery Bypass Surgery

A hematocrit (Hct) of less than 25% during cardiopulmonary bypass (CPB) and transfusion of homologous packed red blood cells (PRBC) are each associated with an increased probability of adverse events in cardiac surgery. Although the CPB circuit is a major contributor to hemodilution intravenous (IV) fluid volume may also significantly influence the level of hemodilution. The objective of this study was to explore the influence of asanguinous IV fluid volume on CPB Hct and intraoperative PRBC transfusion. After Institutional Review Board approval, a retrospective chart review of 90 adult patients that had undergone an elective, isolated CABG with CPB was conducted. Regression analysis was used to determine if pre-CPB fluid volume was associated with the lowest CPB Hct and the incidence of an intraoperative PRBC transfusion. In separate multivariate analyses, higher pre-CPB fluid volume was associated with lower minimum CPB Hct (p&lt; .0001), and higher minimum CPB Hct was associated with a decreased probability of PRBC transfusion (p&lt; .0001). Compared to patients that received &lt;1600 mL (n= 55) of pre-CPB fluid, those that received &gt;1600 mL (n= 35) had a decreased mean low CPB Hct (22.4% vs 25.6%,p&lt; .0001), an increased incidence of a CPB Hct &lt;25% (74% vs. 38%,p= .0008) and PRBC transfusion (60% vs. 16%,p&lt; .0001), and increased median PRBC units transfused (2.0 vs 1.0,p= .1446) despite no significant difference in gender, age, patient size, baseline Hct, or CPB prime volume. Patients that received a PRBC transfusion (n= 30) received a significantly higher volume of pre-CPB fluid than nontransfused patients (1800 vs. 1350 mL,p= .0039). These findings suggest that pre-CPB fluid volume can significantly contribute to hemodilutional anemia in cardiac surgery. Optimizing pre-CPB volume may preserve baseline Hct and help limit intraoperative hemodilution.

The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery

Current red blood cell (RBC) transfusion guidelines assume that most acutely anemic patients can tolerate hemoglobin (Hb) concentrations as low as 6.0 to 7.0 g per dL and recommend that range as the transfusion threshold in patients who have no overt signs of organ dysfunction. Nonetheless, "normal" Hb concentrations vary widely in the population, and this variability may influence patients' tolerance of acute anemia. This retrospective cohort study was carried out to test this hypothesis. Data were analyzed on 10,179 consecutive patients who had normal Hb concentrations (12.0-16.0 g/dL in women and 13.0-18.0 g/dL in men) and underwent on-pump cardiac surgery from 1999 to 2006 at an academic hospital. The relationships of lowest intraoperative Hb concentration and maximum decrease in Hb concentration (from baseline) with the composite outcome of in-hospital death, stroke, or kidney failure were determined in various patient subgroups. The relationship between lowest Hb concentration and adverse outcomes was not independently associated with increased risk. In contrast, the relationship between maximum decrease in Hb concentration and adverse outcomes was independently associated with increased risk, with a 50 percent decrease being the threshold beyond which risk was increased (adjusted odds ratio, 1.53; 95% confidence interval, 1.12-2.08; p = 0.007). The degree of acute anemia that patients can safely tolerate during cardiac surgery is inversely related to their baseline Hb concentration. Current transfusion guidelines do not account for this relationship.

Risk Associated With Preoperative Anemia in Cardiac Surgery

Preoperative anemia is an important risk factor for perioperative red blood cell transfusions, which are associated with postoperative morbidity and mortality. Whether preoperative anemia also is an independent risk factor for adverse outcomes after cardiac surgery, however, has not been fully elucidated. In this multicenter cohort study, data were collected on 3500 consecutive patients who underwent cardiac surgery during 2004 at 7 academic hospitals. The prevalence of preoperative anemia, defined as hemoglobin <12.5 g/dL, and its unadjusted and adjusted relationships with the composite outcome of in-hospital death, stroke, or acute kidney injury were obtained. The overall prevalence of preoperative anemia was 26%, with values ranging from 22% to 30% at the participating hospitals. After the exclusion of patients who had severe preoperative anemia (hemoglobin <9.5 g/dL) or preoperative kidney failure and those who underwent emergency surgery, the composite outcome was observed in 7.5% of patients (247 of 3286). The unadjusted odds ratio for the composite outcome in anemic versus nonanemic patients was 3.6 (95% confidence interval, 2.7 to 4.7). The risk-adjusted odds ratios, obtained by multivariable logistic regression and propensity-score matching to control for important confounders (including comorbidities, institution, surgical factors, and blood transfusion), were 2.0 (95% confidence interval, 1.4 to 2.8) and 1.8 (95% confidence interval, 1.2 to 2.7), respectively. Preoperative anemia is independently associated with adverse outcomes after cardiac surgery. Future studies should determine whether therapies aimed at treating preoperative anemia would improve the outcomes of patients undergoing cardiac surgery.

Risk Associated With Preoperative Anemia in Cardiac Surgery: A Multicenter Cohort Study

Risk Associated With Preoperative Anemia in Cardiac Surgery: A Multicenter Cohort Study

Transfusion of S-303 Treated RBCs To Treat Acute Anemia during or Following Cardiac Surgery: Results of a Phase III Trial.

Background : The FRALE compound, S-303, effectively inactivates contaminating pathogens in RBC concentrates. Phase I trials in healthy subjects showed recovery of S-303-treated RBCs (SRBC) stored for 35 days (d) to be comparable to conventional RBCs (CRBC). Phase III trials were initiated to evaluate SRBC for transfusion (tx) support of acute anemia in cardiac surgery and of chronic anemia for sickle cell anemia or thalassemia.Methods : A randomized, controlled, double-blind, parallel group, non-inferiority design trial of SRBC vs. CRBC tx for support of acute anemia in cardiac surgery patients (pts) was conducted at 5 study sites. RBCs were txed during and for up to 6 d post surgery; pts were followed to d 13 for adverse events (AEs), and to d 27 for serious AEs (SAEs). The primary endpoint was selected to measure adverse sequelae associated with inadequate tissue oxygenation by RBCs: a composite endpoint of myocardial infarction (MI), acute renal failure (ARF), and death. The trial had 80% power with 200 pts to show non-inferiority with an absolute difference of 15% in the primary endpoint compared to CRBC. Secondary endpoints were: RBC and other blood product use, change in hemoglobin (Hb), and AEs.Results : While this trial was enrolling, 2 asymptomatic pts in the chronic trial developed antibodies to SRBC, leading to early termination of both trials. At time of termination, 148 pts in the acute anemia trial had been txed. Despite the reduced sample size, the trial still has >70% power to show non-inferiority at the 0.05 significance level, assuming a common primary endpoint incidence of 20% for both groups. The 2 groups were balanced for demographics (mean age 68 yrs; 62% male; 95% Caucasian), type of surgery (68% intermediate risk group: repeat surgery or multiple procedures) and baseline characteristics. The primary endpoint was achieved: SRBC were not inferior to CRBC, with 1-sided 95% CI for treatment difference (SRBC-CRBC) of 12%. Results were similar by surgery and study site. Study RBCs only were received by 91% of pts; 41% of RBCs were txed during surgery. Other blood product use (see table) and AEs were similar in both groups. Tx reactions were uncommon. No antibodies to SRBC were detected in the acute trial.EndpointSRBCCRBCp-Value*(n=74)(n=74)Composite endpoint (%)22211.00MI (%)02.70.25ARF (%)22190.84Death (%)01.40.50Mean change in Hb (g/dL)Pre vs. post-tx1.41.50.74Pre-surgery up to d 6−2.6−2.20.17Mean no. RBC tx/units2.1/4.41.9/3.80.49/0.20Other blood product tx (% pts/mean no. units)FFP47/2.145/2.50.87/0.55Platelets45/1.740/1.40.62/0.59Cryo6.8/0.511/0.50.40/0.94*2-sided p-value, testing for treatment difference.Conclusions : Although enrollment was not completed, efficacy endpoints for S-303-treated RBCs were comparable to conventional RBCs in this trial for support of acute anemia in cardiac surgery; no antibodies to S-303 RBC were detected; and the safety profile for S-303 RBCs was comparable to conventional RBCs. Processing improvements are being evaluated to reduce the immunogenicity potential associated with chronic exposure to S-303-treated RBCs.