Transfusion practice in coronary artery bypass surgery in Denmark: a multicenter audit,

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1 doi: /icvts Interactive CardioVascular and Thoracic Surgery 6 (2007) Institutional report - Cardiac general Transfusion practice in coronary artery bypass surgery in Denmark: a multicenter audit, a,e, b c d e Jan J. Andreasen *, Mikkel Westen, Peter A. Pallesen, Søren Jensen, Anders Gorst-Rasmussen, Søren P. Johnsen e,f a Department of Cardiothoracic Surgery, Aalborg Hospital, Aarhus University Hospital, Hobrovej, Postboks 365, DK-9100 Aalborg, Denmark b Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark c Department of Cardiothoracic Surgery, Odense University Hospital, Odense, Denmark d Department of Cardiothoracic Surgery, Gentofte Hospital, University of Copenhagen Hellerup, Denmark e Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Denmark f Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Received 17 February 2007; received in revised form 4 July 2007; accepted 6 July 2007 Abstract Transfusion rates in coronary artery bypass grafting (CABG) continue to vary substantially, although guidelines for allogeneic transfusion have been developed. In order to evaluate ongoing transfusion practices, we performed a multicenter audit in four Danish hospitals regarding the use of allogeneic blood products among patients undergoing first-time CABG. Data on patient characteristics, peri- and postoperative factors were retrieved from 600 patient records (150 records per hospital). Substantial differences were seen regarding preoperative intake of antiplatelet drugs, perioperative use of antifibrinolytic drugs, use of cardiopulmonary bypass (CPB), cross-clamp time, time on CPB, lowest hemoglobin during CPB, and number of distal anastomoses. The percentage of patients transfused with allogeneic red blood cells ranged from 30.0% to 64.2%. Several patients ( %) transfused with red blood cells were discharged with a hemoglobin concentration )7 mmolyl, indicating inappropriate transfusions. The relative risk of receiving an allogeneic blood transfusion was 2.1 (95% CI: ) in the hospital with the highest transfusion rate, after adjustment for patient-, drug-, and procedure-related factors. Interesting differences in transfusion rates exists in Danish hospitals and these differences may reflect true variations in transfusion practices. Audits create a basis for educational efforts among surgeons and anesthesiologists to standardize transfusion practices Published by European Association for Cardio-Thoracic Surgery. All rights reserved. Keywords: Transfusion; Coronary artery bypass grafting; Blood loss 1. Introduction Although operative and anesthesiological techniques, as well as postoperative management, continue to evolve, peri-operative bleeding leading to transfusion of allogeneic blood components in patients undergoing coronary artery bypass grafting (CABG) remains an important clinical problem. Transfusion of blood products in cardiac surgery is associated with increased mortality and morbidity w1, 2x, including the risk of incompatibility reactions, increased risk of perioperative infection, renal failure, transfusionrelated immunomodulation, and transmission of microorganisms. Allogeneic transfusion rates vary considerably, and transfusion rates between 9% and 99% among patients undergoing CABG have been published during the last decade w3 5x, despite the existence of guidelines for transfusion w6x. The manuscript has been presented as a poster presentation at NATA (Network for Advancement of Transfusion Alternatives), the 8th Annual Symposium, April 20 21, 2007, Budapest, Hungary. This study was supported by a grant from Vestdansk Sundhedsvidenskabeligt Forskningsforums konsulenttjeneste. *Corresponding author. Tel.: q ; fax: q address: jan.jesper.andreasen@stofanet.dk (J.J. Andreasen) Published by European Association for Cardio-Thoracic Surgery These variations may to some extent be explained by differences in patient-related risk factors, drug-related risk factors, and procedure-related factors. However, a lack of consensus regarding the most optimal transfusion practice for allogeneic blood components, and differences in institutional traditions, may also play a role. Regular audits have been suggested as a way to assess and improve institutional transfusion practices w7x. The objective of the present study was to audit the use of allogeneic blood products among patients undergoing first-time CABG, in order to compare transfusion practices among hospitals in Denmark. 2. Material and methods 2.1. Study population and design CABG is performed in five public, university-affiliated hospitals and in one private hospital in Denmark. Between January and December 2004, a total of 2340 patients underwent CABG without other concomitant cardiac surgery (

2 624 J.J. Andreasen et al. / Interactive CardioVascular and Thoracic Surgery 6 (2007) We intended to perform out a retrospective review of consecutive medical records from patients who underwent first-time CABG during 2004 in all public, university-affiliated hospitals, because these hospitals were comparable regarding staff and resources. One hospital was unable to participate due to other tasks and the study was therefore carried out in four hospitals. These hospitals performed 77% of all CABG operations in Denmark during At each hospital, 150 medical records were reviewed. Patients were identified through the local hospital discharge registers. In case of missing patient records, the record for the next patient in line was obtained Data collection The following baseline patient characteristics were collected: sex, age, height, previous history of chronic obstructive lung disease, left ventricular ejection fraction, and additive EuroSCORE w8x. Place of surgery was also recorded. Baseline laboratory characteristics were hemoglobin, creatinine, platelet count, and international normalized ratio (INR). Further, treatment with antiplatelet drugs such as acetylsalicylic acid, clopidogrel, and nonsteroidal anti-inflammatory drugs (NSAID) was recorded. Recorded perioperative data included use of antifibrinolytic drugs (aprotinin and tranexamic acid), use of extracorporeal circulation, number of distal anastomoses, aortic crossclamp time, cardiopulmonary bypass (CPB) time, and lowest hemoglobin during CPB. Recorded postoperative data included chest tube drainage at 6 h postoperatively and, in total, use of autotransfusion, use of allogeneic blood products during the entire hospitalization, and hemoglobin concentration at discharge. The hemoglobin concentration at discharge was defined as the last measurement of hemoglobin before discharge. We also recorded postoperative complications as reoperation due to bleeding or surgery for other major complications, such as mediastinitis and gastrointestinal complications. Transfusion at any time during the entire hospitalization was registered. In order to restrict the audit to patients who were transfused for reasons directly related to the CABG operation alone, we excluded patients who later underwent surgery due to major complications or gastrointestinal bleeding, as transfusions in these patients were not directly related to peri- and postoperative treatment of the microvascular bleeding following CABG. Jehovah s witnesses were not included in the study Clinical procedures and indications for allogeneic transfusions In general, surgical routines, anesthetic procedures, and standard normothermic cardiopulmonary bypass procedures were comparable among all included hospitals. On-pump and off-pump surgery were carried out according to the preferences of the surgeons, who were senior surgeons, as well as trainees in all centers. In hospital 2, a cell saver was used perioperatively during off-pump coronary artery bypass (OPCAB) procedures. The left internal thoracic artery was used as a standard whenever the anterior descending artery was to be grafted. The right internal thoracic artery, saphenous veins, and radial arteries were used as additional grafts according to the preferences of the surgeons. During surgery, blood from the operative field was returned to the CPB circuit. At the end of the operation, residual blood volume remaining in the CPB circuit was returned unprocessed to the patients as a routine in all centers. Postoperative autotransfusion of unwashed mediastinal blood was used as a routine. Transfusions of allogeneic blood components (packed red cells, fresh frozen plasma and platelet concentrates) were given at the discretion of the attending anesthesiologist andyor surgeon. Apheresis products were not used. Indications for allogeneic transfusion were based on routine laboratory measurements of INR, ACT, platelet counts, fibrinogen levels, hemoglobin, and hematocrit values, in addition to measurements of hemodynamic and physiologic data, the rate of blood loss, and the existence of concomitant diseases. Specific transfusion algorithms were not used in any of the centers postoperatively. Preoperative autologous blood donation, acute normovolemic hemodilution, hemofiltration, and prophylactic transfusions of plasma and platelets were not used in any of the hospitals Statistical analysis Descriptive statistics included mean, standard deviation, median, interquartile range, and percentage of patients when appropriate. Differences between hospitals were tested for statistical significance by using chi-square analysis, analysis of variance, and Kruskal-Wallis tests in the case of non-normality. Missing data were excluded from the analysis. We used Poisson regression with robust variance estimation to compare the use of allogeneic blood transfusion between the hospitals. Specifically, we computed relative risks (RR) with 95% confidence intervals (95% CI) for requirement of G1 allogeneic blood transfusion. Poisson regression was used because, in contrast to logistic regression, it may provide more accurate estimates of adjusted RRs in cohorts with common outcomes. RRs were adjusted for EuroSCORE, preoperative hemoglobin, preoperative platelet count, INR, preoperative use of antiplatelet drugs, use of antifibrinolytic drugs, use of CPB, CPB time, cross-clamp time, and number of distal anastomoses. All analyses were carried out using Stata version Results The proportion of patients reoperated due to bleeding or other major complications varied between 2.0% and 6.7% among the hospitals. Reoperated patients (ns29) were excluded from further audit, leaving 141, 147, 143, and 140 patients from hospital 1, 2, 3, and 4, respectively, to be included in the analyses. Baseline characteristics of the included patients undergoing isolated first-time CABG in the four hospitals are shown in Table 1. We identified a number of statistically significant differences between the hospitals regarding operative characteristics, as shown in Table 2. The percentage of patients transfused with allogeneic red blood cells in the four hospitals varied from 30.0% to 64.2%, as shown in Table 3. However, we found no institutional differences regarding

3 J.J. Andreasen et al. / Interactive CardioVascular and Thoracic Surgery 6 (2007) Table 1 Baseline characteristics of patients undergoing first-time coronary artery bypass surgery Variable Hospital 1 Hospital 2 Hospital 3 Hospital 4 P-value (ns141) (ns147) (ns143) (ns140) Male gender (%) NS Age (years) 65.2" " " "9.2 NS Height (cm) 171.8" " " " Weight (kg) 80.1" " " "15.1 NS Body mass index (kgym ) 27.0" " " "4.2 NS Hemoglobin (mmolyl) 8.5" " " " Creatinine (mmolyl) 99.9" " " " Platelet count (10 yl) 254.2" " " "76.6 NS INR 1.0" " " "0.1 NS Ejection fraction (%) 56.4" " " "12.3 NS Additive EuroSCORE 3.5" " " "2.4 NS COPD 1.95" " " "0.2 NS Preoperative use of acetylsalicylic acid (%)* Preoperative use of clopidogrel (%)* Patients without preoperative usage of antiplatelet drugs (%) Data are presented as mean"s.d. or percentage of patients. NS, not significant; INR, international normalized ratio; EuroSCORE w8x; COPD, chronic obstructive pulmonary disease; *Acetylsalicylic acid andyor clopidogrel within seven days prior to surgery. Table 2 Operative characteristics of patients undergoing first-time coronary artery bypass surgery Variable Hospital 1 (ns141) Hospital 2 (ns147) Hospital 3 (ns143) Hospital 4 (ns140) P-value Percentage of patients operated with the use of CPB Percentage of patients undergoing OPCAB Percentage of patients treated with antifibrinolytic drugs CPB time (min) 102.6" " " " Cross-clamp time (min) 55.3" " " " Number of distal anastomoses 3.3" " " " Lowest perioperative hemoglobin 4.9" " " " on CPB (mmolyl) Data are presented as mean"s.d. or as percentage. CPB, cardiopulmonary bypass; OPCAB, off-pump coronary bypass; NS, not significant. the number of units per transfused patient, including both packed red blood cells, fresh frozen plasma, and platelets. Unadjusted and adjusted RRs with 95% CIs for receiving G1 allogeneic blood transfusion according to hospital are shown in Table 4. The risk of receiving allogeneic blood transfusion was more than twofold higher in hospital 1 (RR: 2.1; 95% CI: ) when compared with hospital 4. Postoperative chest tube drainage at 6 h postoperatively and in total differed significantly between the hospitals (Table 3), but we found no association between the amount Table 3 Postoperative blood loss and transfusion requirements Variable Hospital 1 (ns141) Hospital 2 (ns147) Hospital 3 (ns143) Hospital 4 (ns140) P-value Chest tube drainage (ml) 6 h 560 ( ) 350 ( ) 410 ( ) 510 ( ) Total chest tube drainage (ml) 950 ( ) 575 ( ) 600 ( ) 808 ( ) Percentage of patients receiving allogeneic transfusion Packed red blood cells (Uypatient) 2 (2 3) 2 (2 4) 2 (1 3) 2 (2 3) NS Fresh frozen plasma (Uypatient) 3 ( ) 2 ( ) 2 ( ) 2 ( ) NS Platelets (Uypatient) 1 (1 2) 1.5 (1 2) 1 (1 2) 1 (1 1) NS Percentage of patients autotransfused postoperatively Percentage of transfused patients (red blood cells) discharged with a hemoglobin concentration of )7 mmolyl Data are presented as median (interquartile range) or as percentage. NS, not significant.

4 626 J.J. Andreasen et al. / Interactive CardioVascular and Thoracic Surgery 6 (2007) Table 4 Unadjusted and adjusted relative risk (RR) with 95% confidence interval (CI) for allogeneic blood transfusion according to institution among patients undergoing first-time coronary artery bypass grafting Hospital Unadjusted RR (95% CI) Adjusted RR (95% CI) ( ) 2.1 ( ) ( ) 1.1 ( ) ( ) 1.7 ( ) (reference) (reference) RRs were adjusted for EuroSCORE w8x, preoperative hemoglobin, preoperative platelet count, INR (International normalized ratio), preoperative use of antiplatelet drugs, use of antifibrinolytic drugs, use of cardiopulmonary bypass (CPB), CPB time, cross-clamp time, and number of distal anastomoses. of chest tube drainage and requirements for allogeneic blood transfusion in any of the hospitals. The percentage of transfused patients discharged with a hemoglobin concentration of )7 mmolyl varied between 12.1% and 42.7% among the four hospitals (Table 3). 4. Discussion This study demonstrates that transfusion rates in patients undergoing isolated first-time CABG varies considerably among hospitals in Denmark even after adjusting for a wide range of patient-, drug-, and procedure-related risk factors. These differences may reflect true differences in institutional transfusion practices. Our findings are in accordance with a few existing studies, where institution was also found to be an independent determinant of use of blood products in patients undergoing CABG w5x. The transfusion rates found in the present study are within the range reported in other recent studies w3 5x, but the large differences in comparable patient populations within a small country are notable. Further, the fact that patients transfused with red blood cells were regularly discharged with a hemoglobin concentration of more than 7 mmolyl, indicating transfusion of at least one unnecessary portion of blood, underlines the need for standardization in transfusion practices and the use of transfusion algorithms that can facilitate a more optimal administration of blood products. During the last decade, the risk profile of CABG patients regarding peri- and postoperative bleeding has changed. In particular, a high proportion of patients come to surgery while they are taking oral antiplatelet agents such as clopidogrel andyor acetylsalicylic acid which increases the risk of postoperative bleeding and transfusion w9, 10x. Larger studies w11 13x found only a modest perioperative hemorrhagic risk, indicating that these antiplatelet drugs may be used with relative safety in the perioperative period. In the present study chest tube drainage and transfusion rates were highest in the hospital where antiplatelet drugs were most often discontinued. It is interesting to note that both the postoperative chest drainage and transfusion rate were highest in the hospital that carried out the most OPCAB procedures. OPCAB has been shown to reduce bleeding and allogeneic blood transfusion requirements compared to on-pump surgery w14x, but the benefits of OPCAB with regard to postoperative bleeding appeared not to be present in hospital 1. These findings may reflect the fact that postoperative bleeding has multiple causes. Educational efforts among surgeons and anesthesiologists have previously proved their value w7x as intervention in physicians transfusion behavior can improve transfusion therapy in patients undergoing elective CABG. Results from audits of transfusion practice such as the present study may lead to a better understanding among the staff in regard to the need for further educational efforts and provide a basis for standardization of transfusion practices. The strengths of our study included the population-based design, the detailed data, and the relatively large sample size. Study limitations include missing data for some of the study variables. This is partly due to the fact that our study was a historical cohort study and we thus had no influence on the data that were registered at the time of admission and surgery of the patients. Whether surgery was carried out emergently or electively was not registered. This is a limitation of the study as bleeding may be more prominent in emergent surgery. However, we have no reason to believe that the proportion of patients requiring emergent surgery differed substantially between the hospitals. It would have been interesting to see if there was any differences between hospitals regarding outcomes such as death, renal failure, length of stay, infections to see if these outcomes correlate with transfusions, however, the number of patients included in this audit are too small to make a meaningful evaluation regarding these outcomes. In conclusion, substantial differences in transfusion rates exist among Danish hospitals regarding patients undergoing first-time CABG, and these differences appear not to be explained by differences in patient-related risk factors, drug-related risk factors, and procedure-related factors. These differences may therefore reflect true variations in transfusion practices. An audit of transfusion practice creates a basis for educational efforts among surgeons and anesthesiologists to standardize transfusion practices. Reassessment of institutional transfusion practices should be coupled with increased focus on optimizing blood-conserving strategies. Acknowledgments The authors gratefully acknowledge biostatistical assistance from Claus Dethlefsen, PhD, Center for Cardiovascular Research, Aalborg Hospital, as well as fruitful discussions with Dr. Daniel Steinbrüchel, Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen, and Dr. Lars I. Andersen, Department of Cardiothoracic Surgery, Odense University Hospital, Odense, Denmark. References w1x Spiess BD. Transfusion of blood products affects outcome in cardiac surgery. Seminars in Cardiothoracic and Vascular Anesthesia 2004; 8: w2x Kuduvalli M, Oo AY, Newall N, Grayson AD, Jackson M, Desmond MJ, Fabri BM, Rashid A. Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery. Eur J Cardiothorac Surg 2005;27:

5 J.J. Andreasen et al. / Interactive CardioVascular and Thoracic Surgery 6 (2007) w3x Légaré J-F, Buth KJ, King S, Wood J, Sullivan JA, Friesen CH, Lee J, Stewart K, Hirsch GM. Coronary bypass surgery performed off-pump does not result in lower in-hospital morbidity than coronary artery grafting performed on pump. Circulation 2004;109: w4x Kytölä L, Nuutinen L, Myllylä G. Transfusion policies in coronary artery bypass a nationwide survey in Finland. Acta Anaesthesiol Scand 1998;42: w5x Stover EP, Siegel LC, Parks R, Parks R, Levin J, Body SC, Maddi R, D Ambra MN, Mangano DT, Spiess BD, the Institutions of the Multicenter Study of Perioperative Ischemia Research Group. Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines. A 24-institution study. Anesthesiology 1998;88: w6x Goodnough LT, Johnston MFM, Ramsey G, Sayers MH, Eisenstadt RS, Anderson KC, Rutman RC, Silberstein LE. Guidelines for transfusion support in patients undergoing coronary artery bypass grafting. Ann Thorac Surg 1990;50: w7x Toy PTCY. Effectiveness of transfusion audits and practice guidelines. Arch Pathol Lab Med 1994;118: w8x Nashef SAM, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R, the EuroSCORE study group. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9 13. w9x Hongo RH, Ley J, Dick SE, Yee RR. The effects of clopidogrel in combination with aspirin when given before coronary artery bypass grafting. J Am Coll Cardiol 2002;40: w10x Engelberger L, Faeh B, Berdat PA, Eberli F, Meier B, Carrel T. Impact of clopidogrel in coronary artery bypass grafting. Eur J Cardiothorac Surg 2004;26: w11x Fox KAA, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ, Yusuf S. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-st-elevation acute coronary syndrome. The Clopidogrel in Unstable angina to Prevent Recurrent ischemic Events (CURE) trial. Circulation 2004;110: w12x Kapetanakis EI, Medlam DA, Boyce SW, Haile E, Hill PC, Dullum MKC, Bafi AS, Petro KR, Corso PJ. Clopidogrel administration prior to coronary artery bypass grafting surgery: the cardiologist s panacea or the surgeon s headache? Eur Heart J 2005;26: w13x Cannon CP, Mehta SR, Aranki SF. Balancing the benefit and risk of oral antiplatelet agents in coronary artery bypass surgery. Ann Thorac Surg 2005;80: w14x Raja SG, Dreyfus GD. Impact of off-pump coronary artery bypass surgery on postoperative bleeding: current best available evidence. J Card Surg 2006;21:35 41.