B L O O D C O N S E RVAT I O N A N D T R A N S F U S I O N A LT E R N AT I V E S

Experience of a network of transfusion coordinators for blood conservation (Ontario Transfusion Coordinators [ONTraC])
John Freedman, Katherine Luke, Michael Escobar, Lee Vernich, and Jo Anne Chiavetta

BACKGROUND: The experiences of the development of a provincial program to promote blood conservation are herein reported. STUDY DESIGN AND METHODS: Transfusion coordinators were placed in 23 Ontario hospitals. Anonymized laboratory and clinical information was collected in a dened number of all consecutive patients admitted for three designated procedures: knee arthroplasty, abdominal aortic aneurysm (AAA), and coronary artery bypass graft (CABG) surgery (n 1100, 300, and 300 at each time period, respectively). RESULTS: Considerable interinstitutional variation was observed in the proportion of patients who received transfusions. At 12 months, and over the 24-month period of the project, most hospitals demonstrated decreased use of allogeneic blood; at 12 months an approximate 24 percent reduction in patients undergoing knee surgery, 14 percent in AAA, and 23 percent in CABG was obtained. In addition, patients who received transfusions received less allogeneic blood. Patients who did not receive allogeneic transfusions had lower postoperative infection rates (p < 0.05) and length of stay (p < 0.0001); allogeneic transfusion was an independent predictor of increased length of stay. The main blood conservation measures employed during this time were education, preoperative autologous donation, erythropoietin, and cell salvage. CONCLUSION: The implementation of a provincial network of transfusion coordinators was feasible and allogeneic transfusion rates declined over the period the program has been in place.

lood transfusion may be potentially life-saving and health-promoting. It has, however, become increasingly apparent that the benecial effects of transfusion need to be balanced against the potential hazards and mishaps that can result from transfusion. The paradigm shift in transfusion medicine over recent years, from emphasizing transfusion benets to avoidance of allogeneic transfusion (called blood conservation, bloodless medicine, or blood management), has resulted in many well-known blood conservation methods and alternatives to allogeneic red cell (RBC) transfusion. There is an expanding body of literature demonstrating the effectiveness of these approaches, particularly in the setting of elective surgical procedures, and their relative merits continue to be evaluated. Although guidelines for blood transfusion in the form of algorithms and maximum blood ordering schedules have been developed, as well as physician and staff educational materials and programs, reports of blood use suggest that available blood conservation measures are underutilized.1 Blood

ABBREVIATIONS: AAA = abdominal aortic aneurysm; CABG = coronary artery bypass graft; LOS = length of stay; MOHLTC = Ministry of Health and Long-term Care; ONTraC = Ontario Transfusion Coordinators; PAD = preoperative autologous donation. From the St Michaels Hospital, Toronto Platelet Immunobiology Group (TPIG), Department of Public Health Sciences, EPI-STAT Research, Inc., University of Toronto, Toronto, Ontario, Canada. Address reprint requests to: Dr John Freedman, Blood Transfusion Service, St Michaels Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8; e-mail: freedman@ smh.toronto.on.ca. Source of support: Ministry of Health and Long-term Care, Province of Ontario. Received for publication March 6, 2007; revision received May 31, 2007, and accepted July 18, 2007. doi: 10.1111/j.1537-2995.2007.01515.x. TRANSFUSION 2008;48:237-250. Volume 48, February 2008 TRANSFUSION 237

FREEDMAN ET AL.

shortages occur and the cost and complexity of the collection of volunteer blood continues to escalate.2,3 Wide variation in RBC use for similar conditions and procedures is reported both in descriptive studies4,5 and in institutional comparisons for specic procedures.6,7 In Canada each province contributes to one of two blood collection agencies: Hma-Qubec, which collects and supplies blood to the province of Qubec, and the Canadian Blood Services, which is responsible for all blood supply in the rest of Canada. In Ontario, as in the rest of Canada, there is minimal cost to the patient for transfusion or transfusion alternatives as these are supported by the Canadian health care system. Therefore, the patients (or physicians) decision regarding transfusion options is not directly affected by cost concerns. Nonetheless, although blood conservation methods may be available and their benets recognized, use of these options are often not a routine part of patient care. This program was designed to enhance awareness of, and access to, blood conservation measures for both the patient and the medical staff. This was done by creating a network of transfusion nurse coordinators, called Ontario Transfusion Coordinators (ONTraC), trained in relevant transfusion issues and dedicated to facilitating the availability and use of blood conservation options in the program hospitals through dissemination of information, education, monitoring, and evaluation of transfusion practice. In mid-2002, with support from the Ministry of Health and Long-term Care (MOHLTC) of Ontario, as part of an initiative aimed at enhancing blood management in the province, transfusion coordinators were emplaced in 23 hospitals throughout Ontario. The intent was to 1) enhance transfusion practice outside of the blood bank by acting as a clinical bridge between the blood transfusion service and the rest of the hospital and 2) interact with physicians, nurses, and patients to promote blood conservation and alternatives to transfusion. The intention was not to promote a specic method or technique, but to educate about the various options available, recognizing that different approaches would be more or less suitable in the different hospital settings. Although individual hospitals have, since the 1980s, instituted comprehensive, and not so comprehensive, blood conservation programs in their hospitals, we speculated that this approach could be applied as a network of hospitals, each able to assist one another, deriving mutual benet from individual experiences. The hypothesis was that the emplacement of educated and motivated transfusion coordinators within the hospitals would enhance blood conservation, in the presurgical setting in particular, and would result in a reduction in allogeneic transfusion. The initial expectation was that this would result in a 5 to 10 percent reduction in allogeneic RBC transfusion. We report here on the rst phases of this program.
238 TRANSFUSION Volume 48, February 2008

MATERIALS AND METHODS

Twenty-three hospital corporations were selected based on high blood use patterns over the preceding 2 years, in decreasing order of blood use, to include at least three hospitals from all areas of the province (east, west, north, south, and central regions). Letters of agreement to participate in this project were signed by the hospitals chief operating ofcers; medical staff were not directly consulted at this point. The hospitals included teaching and community hospitals, large and small, and each needed to have a critical mass of patients admitted for the selected targeted procedures. The hospitals involved were: Guelph General Hospital (Guelph), Hamilton Health Sciences Center (Hamilton), Hospital for Sick Children (Toronto), Kingston General Hospital (Kingston), Lakeridge Health (Oshawa), London Health Sciences Center (London), Mt Sinai Hospital (Toronto), Niagara Health System (Niagara Falls/St Catharines), North Bay General Hospital (North Bay), Peterborough Regional Health Center (Peterborough), Sault Area Hospitals (Sault Ste Marie), Scarborough General Hospital (Toronto), St Josephs Health Center (Toronto), St Marys General Hospital (Kitchener/ Waterloo), St Michaels Hospital (Toronto), Sudbury Regional Hospital (Sudbury), Sunnybrook & Womens College Health Sciences Center (Toronto), The Ottawa Hospital (Ottawa), Toronto East General Hospital (Toronto), Trillium Health Center (Mississauga), University Health Network (Toronto), William Osler Health Corporation (Brampton), and Windsor Regional Hospital (Windsor). RBC usage in these 23 hospitals (of the 129 hospital corporations in the province that transfuse blood) accounts for approximately 65 percent of allogeneic RBC transfusions in the province. Funds were made available to each institution for the transfusion coordinator salary and a small amount to cover costs for computer, printer, phone, and supplies. Each institution hired its own coordinator, who was usually responsible to the medical director of transfusion at the hospital and to a nursing administrator. In all hospitals, approval for anonymized data collection, data transfer to a central site, and analysis was obtained from the local ethics review board. The project was coordinated through St Michaels Hospital by a project administrator and the project lead, a medical director of transfusion medicine. Targeted procedures were 1) total knee arthroplasty in 19 hospitals, 2) abdominal aortic aneurysm (AAA) surgery in 17 hospitals, and 3) elective coronary artery bypass graft (CABG) surgery in 4 hospitals. Baseline or retrospective cases were identied through surgical schedules and information was obtained through chart review. Once the program was implemented, prospective cases were identied again through surgical schedules. The Canadian Classication of Diagnostic, Therapeutic and Surgical Procedures codes and number of cases at

ONTraC TRANSFUSION COORDINATORS

TABLE 1. Targeted procedures and number of patients evaluated in each time period (see Materials and Methods)
Time CCP code 93.41 48.11-48.19 50.34 Procedure Knee arthroplasty CABG AAA 1 (baseline) 1088 274 287 2 (12 months) 1137 271 292 3 (18 months) 1078 294 236 4 (24 months) 1127 275 232

CCP = Canadian Classication of Diagnostic, Therapeutic and Surgical Procedures.

each time point are shown in Table 1. At TABLE 2. Summary of role prole of ONTraC Transfusion Coordinator the designated time points (12, 18, and Use advanced knowledge and skills to provide optimal care to patients and/or families 24 months) data was prospectively colanticipating possible transfusion, through the development of a blood conservation lected by the transfusion coordinator at program. The transfusion coordinators major areas of responsibility are: each hospital on a designated number 1. Management of a blood conservation program (50% of time) Provide ongoing support for the mission of the Provincial Blood Conservation (the same for each institution) of all Program within the hospital, by performing a variety of activities that will contribute consecutive patients having the tarto establishing a blood conservation program in the hospital. geted procedure, whether or not the Liaise with appropriate personnel in relevant departments (e.g., anesthesia, preadmission facility, perioperative services, blood transfusion services). patient was seen by the coordinator. Enroll qualied patients in the appropriate programs. Extensive information was collected for Liaise with appropriate staff to follow-up on blood conservation strategy employed. this cohort on demographics, blood uti Liaise with blood transfusion laboratory to collect appropriate data and troubleshoot problems relevant to blood conservation, particularly those external to the laboratory lization, blood conservation measures, itself. hemoglobin (Hb) levels at different Contact patients by phone, mail, or in person, to provide pertinent information once times, and clinical variables such as they are accepted for a surgical procedure that may require a transfusion (focus will be on the targeted surgical procedures). infection rate, comorbidities, and length Facilitate referrals to appropriate services as required, for example, CBS Autologous of stay (LOS). The data have been colProgram, host institution autologous program, EPREX assistance line. lected manually, but plans are under Ensure appropriate reporting on blood conservation to the transfusion review committee. way to use direct entry into a personal Monitor transfusion informed consent. digital assistant. The anonymized data 2. Patient, family, and staff education (25% of time) forms are sent to a central site, where, Ensure that patient and/or family focused support and educational information is provided to those patients who may require a blood transfusion. Ensure that all following a check for accuracy, the data relevant staff at institution are made aware of, and have access to, this information. are coded, sent for data entry into a Provide a forum on a regular basis to deliver educational initiatives related to blood computer, and then extensively anaconservation and transfusion safety to hospital staff (nurses and physicians) and patients. lyzed with computer software. In addi Ensure appropriate reporting on blood conservation to the transfusion review tion, the project administrator makes committee. site visits twice a year; included in this Relate procedural information as per institutional requirement. Inform patients and their families of available options, to facilitate patients having visit is random checking of the data procedures completed within recommended waiting time guidelines. forms with original patient chart 3. Data management and analysis (20% of time) information; there was greater than Ensure maintenance of a current, complete, and accurate database for all patients enrolled in the blood conservation program. 95 percent agreement between the two Forward monthly activity reports to the ONTraC office. data sources. Provide local institution reports as required. At the beginning of the project in Ensure data accuracy through ongoing quality assurance. 4. Institutional and regional activities (5% of time) mid-2002, all coordinators attended an [No more than 5% to 10% of time to be spent on independent research projects] intensive week-long education program of approximately 30 hours of seminars and interactive sessions in which they to accept these functions, although it was recognized that were exposed to the principles of blood transfusion and there would be some differences depending on individual safety, blood conservation, and methods that could be hospital structure, practice, and resources. The general employed to implement and enhance transfusion pracapproach employed is shown in Table 3. With the aim of tice, and promote alternatives to transfusion. The coordireducing allogeneic RBC use, the transfusion coordinanators were instructed in data collection and a precise tors main purpose was to increase awareness and access eld manual was used for training and thereafter, which to transfusion alternatives. This was to be done through: 1) specied exactly what and how procedures were to be monitoring of blood orders and Hb levels and assessing done. The role prole of the transfusion coordinators was patients for anemia and need for treatment; 2) facilitating dened (summarized in Table 2) and all hospitals agreed
Volume 48, February 2008 TRANSFUSION 239

FREEDMAN ET AL.

vancement of Transfusion Alternatives (NATA) conference in San Francisco (2003), the annual meetings of the Identify patients at risk of transfusion ahead of surgery Society for Advancement of Blood Discuss informed consent and transfusion alternatives Management (SABM) in Phoenix (2005) Assess patient at preadmission clinic (3-5 weeks before surgery) Investigate, diagnose, and treat anemia (e.g., by family doctor, surgeon, and Jersey City (2006), and annual anesthesiologist, hematologist) meetings of the AABB. In addition, EPO and/or iron subscriptions are provided for all coor Predonation of autologous blood (with hematinics EPO) Use of cell salvage dinators to the CSTM, AABB and Stop anticoagulants/anti-platelet drugs if safe to do so TRANSFUSION, SABM, and to selected Minimize blood taken for lab testing journals on OVID. An Internet network has been developed allowing for interchange of ideas and problem solving, as well as dissemithe development of blood conservation committees; 3) nation of literature information, etc. educating and promoting transfusion alternatives to patients, physicians, and staff; 4) developing a network of staff involved in transfusions across all hospitals; 5) Statistical analysis serving as a link between the transfusion service and other departments; and 6) assessing patients for suitability The primary measure in this initiative was whether or not and facilitating the opportunity for blood conservation allogeneic blood transfusion was reduced after the estaboptions such as autologous donations, including for hoslishment of the ONTraC coordinators. In addition, we pitals without hematology departments or autologous examined 1) the use of blood conservation procedures programs. Within each institution, the transfusion coordiduring this time and 2) the possible relationship of allogenator identied departments and individuals who could neic transfusion on clinical variables such as postoperaplay a key role in promoting and implementing blood contive infection, hospital LOS, and where applicable, servation. Information from the program training, as well discharge status (death). For each specic procedure, the as current information on relevant transfusion issues, was patients were compared as a group at each time point in used to orient and educate others in the participating terms of patient characteristics, clinical factors, Hb levels, institution. Educational material and instruction included the use of blood conservation methods, and outcome preoperative assessment, patient informed consent, algovariables. When examining the relationship over time of rithms for transfusion, use of alternatives such as erythropatient group characteristics and outcome variables, the poietin (EPO) and autologous donation, and overall risks group variable and a binary variable (such as sex or the use and benets of transfusion. Eligible patients were conof blood conservation methods) were evaluated by examtacted through preadmission visits usually 3 to 4 weeks ining differences in the percentages and the odds ratio before surgery. At that time, preadmission Hb was mea(OR) statistics; condence intervals (CIs) were computed sured, and transfusion options and consent for transfuand chi-square statistics were calculated. When examinsion were reviewed. As determined appropriate, options ing the relationship of the group to a continuous variable were discussed or implemented including the opportunity (such as Hb level or age), means, standard errors, and CIs for autologous donation, the administration of hematinwere calculated with an F test for signicant difference ics, pharmacologic interventions such as EPO, or other between the means. Logistic regression was used to evaluoptions designed to reduce the need for allogeneic transate the effect on the group of binary outcomes such as fusion upon surgery. Analyzed aggregate data are sent to the use of an allogeneic transfusion or the presence of the MOHLTC and, for benchmarking, each hospital infection; this relationship was also examined to deterreceives the aggregate data as well as its own site data. mine if any of the other independent variables were interDetailed progress and nancial reports are sent quarterly mediate or confounding variables of this relationship. A to the MOHLTC. possible interaction effect of the group time variable The project has also funded attendance of the coorcrossed with each of the independent variables was deterdinators at 1) 1-day meetings of the network in Toronto mined. Since the LOS is a continuous variable, analyses three times a year to review progress, discuss problems, of LOS employed a procedure similar to that described and highlight new information and 2) major relevant above, but instead of a logistic regression an ordinary blood transfusion meetings, for example, the Internalinear regression was used. Because the LOS outcome tional Society of Transfusion (ISBT) conference in Vanvariable may be highly skewed, in all relevant analyses the couver (2002); the Canadian Society of Transfusion LOS variable was logarithmically transformed and usual Medicine (CSTM)/Canadian Blood Services (CBS)/ linear regression methods used; when reporting these HemaQuebec annual conferences in Halifax (2003), Banff results, back-transformation was done and when back(2005), and Montreal (2006); the Network for Adtransforming the mean of the logged variable, the geometTABLE 3. General approach considered by ONTraC transfusion coordinators
240 TRANSFUSION Volume 48, February 2008

ONTraC TRANSFUSION COORDINATORS

ric mean was obtained, which is what is reported in the basic demographics. A parallel set series of analyses was performed with a rank transformation, but these results are not reported because they were very similar. Final models included only those factors that remained signicant in association of the outcome. A statistical software program8 (SAS, Version 9.0, SAS Institute, Cary, NC) was used. A p value of not more than 0.05 was considered signicant.

RESULTS
Transfusion practice was observed over time with the information collected from patient charts before ONTraC and at three intervals afterward. The data gathered did not identify specic patients or whether a particular aspect of the program directly affected the patients transfusion outcome. Rather, overall patterns of transfusion practice in the specic targeted procedures were assessed. The information that follows summarizes these observations.

Fig. 1. Data from individual sites of allogeneic RBC use in one-knee surgery. (A) The proportion of patients who received transfusion with allogeneic RBCs at each site; and (B) mean number of allogeneic units of RBCs per patient who received transfusions at each site. Note that Sites 4, 7, and 23 did not collect data for knee surgery patients. The black bars represent the means for all sites.

General results
The possible impact of ONTraC on transfusion practice in the participating hospitals could be assessed in general terms 1) indirectly from the increase in formal blood conservation and/or transfusion practice interventions introduced since initiation of the program, such as the addition of informed consent for transfusion, or the establishment of blood conservation committees; 2) directly from the observation of an increase in the use of alternatives to allogeneic blood transfusion; and 3) by a decrease in allogeneic transfusion over time as monitored by tracking blood use in the targeted procedures. Over the time of the establishment of this network of transfusion coordinators: 1) hospital transfusion committees increased from 52 to 100 percent over the rst 6 months of the program; 2) specic blood conservation committees in hospitals increased from 18 to 86 percent over the 24 months; and 3) although practiced in only 18 percent of institutions at baseline, at 24 months, informed consent was implemented in 87 percent of the hospitals. In addition, the number of transfusion education sessions held at all institutions combined increased from less than 20 per 6 months to more than 250 per 6 months.

Allogeneic blood use

For this report, the term blood refers to units of RBCs, and all blood was leukoreduced. As shown in Fig. 1, at baseline, for single-knee arthroplasty there was considerable interinstitutional variability in the proportion of patients transfused with allogeneic blood (Fig. 1A) and in the amount of blood received per transfused patient (Fig. 1B). The same was true for AAA and CABG surgeries (data not shown). Whereas 24.5 percent of single-knee arthroplasty patients received allogeneic blood, 44.9 percent of revision knee surgeries and 62.1 percent of bilateral knee arthroplasty patients received transfusion with allogeneic blood (data not shown). By 12 months, most (68.4%), although not all, hospitals demonstrated a decrease in allogeneic transfusion rate; the ndings were similar with AAA and CABG surgery. As seen in Fig. 2A, showing the aggregate data (mean, 95 percent CI) for baseline and the three subsequent data collection time points (12, 18, and 24 months), there was an overall decrease in the proportion of patients who received allogeneic blood for all three patient groups. There was also a reduction in the number of units of allogeneic RBCs transfused per transfused patient in CABG
Volume 48, February 2008 TRANSFUSION 241

FREEDMAN ET AL.

Fig. 3. The proportions of patients who donated autologous blood over the four periods of data collection (baseline and at 12, 18, and 24 months); means 95 percent CI (**p < 0.001; *p < 0.05; NS = not signicant; chi-square). ( ) Knee surgery; ( ) AAA surgery; ( ) CABG surgery.

Fig. 2. Mean 95 percent CI over the four periods of data collection (baseline [Time 1] and 12, 18, and 24 months) of (A) the proportion of patients who received transfusion with allogeneic RBCs, (B) the number of units of allogeneic blood per patient who received transfusion, and (C) per patient overall, in patients undergoing knee ( ), AAA ( ), and CABG ( ) surgery (***p < 0.0001; **p < 0.001; *p < 0.05; NS = not signicant; chi-square for A, Kruskal-Wallis for B and C).

patients (Fig. 2B) and, for knee and CABG surgery patients, per patient overall (Fig. 2C).

Impact of preoperative autologous donation

Through the time period reported in this program, preoperative autologous donation (PAD) was (other than education) the main blood conservation measure employed. The proportion of patients who underwent PAD is indicated in Fig. 3. Although there was an increase in CABG patients overall over time (p = 0.0112), there was a reduction in knee surgery patients (p = 0.0064). There was concurrently a reduction in the proportion of autologous patients transfused with their autologous blood, for example, from 73 to 52 percent for knee surgery and 70 to 55 percent for CABG surgery, but an increase from 68 percent to 84 percent in AAA surgery. There was also, over time, a decrease in the proportion of collected autologous units that were transfused: from 37 to 28 percent in knee surgery, from 64 to 54 percent in CABG, and 52 to 48 percent in AAA surgery. Figure 4 shows the proportion of patients having knee and CABG surgery who received allogeneic RBCs in rela242 TRANSFUSION Volume 48, February 2008 Fig. 4. Comparison over time of allogeneic RBC transfusion rates in knee ( ) and CABG ( ) surgery patients who entered the autologous donation program, that is, PAD (B) versus those who did not (A); means 95 percent CI (***p < 0.0001; NS = not signicant; chi-square).

tion to whether they donated autologous blood (Fig. 4B) or not (Fig. 4A). It is evident that in the nonautologous patients, there was a progressive reduction in patients receiving allogeneic blood (p < 0.0001). Patients who had donated autologous blood were, however, much less likely to receive allogeneic blood, for example, at baseline, the allogeneic transfusion rate was 25 percent for knee surgery patients who had not donated autologous blood versus 7 percent for those who had and, in CABG patients, 62 percent for nonautologous patients versus 18 percent for autologous patients (p < 0.0001); this lower allogeneic

ONTraC TRANSFUSION COORDINATORS

Fig. 5. Nadir Hb levels (transfusion trigger) over time for allogeneic or autologous blood transfusion in knee ( , allogeneic; , autologous) and CABG ( , allogeneic; , autologous) surgery patients; means 95 percent CI (***p < 0.0001; **p < 0.001; *p < 0.05; NS = not signicant; ANOVA).

transfusion rate in patients who had donated their own blood before surgery was true for all time periods analyzed.

Fig. 6. Comparison of Hb levels (initial, preoperative, nadir, and postoperative) in knee surgery (A) and in CABG patients (B) between men and women who received transfusion only with autologous blood ( , men; , women), those who received transfusion with allogeneic RBCs ( , men; , women), and those who did not receive transfusion ( , men; , women); means 95 percent CI (***p < 0.0001; **p < 0.001; *p < 0.05; NS = not signicant; ANOVA).

Impact of Hb levels
The mean SD nadir Hb levels are presented in Fig. 5; the nadir Hb was considered to be a surrogate for the transfusion trigger. As shown in Fig. 5, there was a progressive reduction in mean nadir Hb levels over time in knee surgery patients receiving allogeneic transfusion. The transfusion trigger was higher in autologous patients than nonautologous patients, however, and was, interestingly, higher in knee surgery than in CABG patients. The reduction in transfusion trigger in the autologous patients observed at 12 and 18 months was not sustained (baseline vs. 24 months, p = 0.2523 and p = 0.6704 for knee and CABG patients, respectively; t test). Figure 6 further shows the mean CI Hb levels grouped by sex according to whether the patients donated autologous blood (autologous) or not (transfused with allogeneic blood or were not transfused), when the patients were rst seen by the transfusion coordinator (initial), within 1 week of surgery (preoperative), and at discharge. Initial and preoperative Hb levels were lower in women than in men. Patients who did not receive transfusions had higher initial, preoperative, and nadir Hb levels than did those receiving allogeneic blood. Autologous patients generally had similar initial Hb levels to those who received allogeneic blood (non-PAD patients) and did not have signicantly lower preoperative Hb levels than patients who received allogeneic blood. Discharge Hb levels were similar in all groups.

Figure 7A shows the signicant correlation (p < 0.0001) between the preoperative Hb levels (at baseline) and the number of allogeneic units transfused. The ORs (likelihood) of receiving allogeneic blood in relation to a preoperative Hb level of 130 g per L are shown in Fig. 7B.

Association of allogeneic transfusion and infections and LOS

As seen in Table 4, infection rates decreased with p values that approached signicance (p = 0.073 and p = 0.062 for knee and CABG surgery, respectively); infections were rigorously dened by relevant symptoms and required a positive culture. Similarly, there was a downward trend in LOS over time (p = 0.0888 and p = 0.0576 for knee and AAA surgery and p < 0.0001 for CABG surgery patients). Although there was over time a decrease in proportion of deaths in the CABG and AAA cohorts, this did not achieve signicance in any of the patient groups. Figure 8, however, describes the differences in these variables for patients who received allogeneic blood versus those who did not. The signicantly lower infection
Volume 48, February 2008 TRANSFUSION 243

FREEDMAN ET AL.

Fig. 7. Relationship of preoperative Hb levels and the likelihood of receiving an allogeneic transfusion in knee surgery patients at baseline (n = 1081): (A) Relative to the preoperative Hb level in 5 g per L increments, the percentage of patients who received no transfusion ( ), 1 unit of RBCs ( ), 2 units ( ), 3 to 5 units ( ), or at least 6 units ( ). Mean SD Hb levels were 134.60 13.88 (n = 817) for patients who did not receive transfusion, 126.72 12.12 (n = 68) for patients who received 1 unit, 123.90 14.99 (n = 154) for patients who receive 2 units, 117.64 16.88 (n = 36) for patients who received 3 to 5 units, and 108.67 18.45 (n = 6) for patients who received transfusion with 6 or more units (p < 0.0001; Wilcoxon nonparametric test). N = the number of patients in each group in each set of Hb levels. (B) ORs (and 95% CI) of transfusion relative to a preoperative Hb level of 130 g per L.

TABLE 4. Number of patients with adverse clinical outcome*

Time Surgery Knee arthroplasty Total number Infection LOS (days) Death CABG Total number Infection LOS (days) Death AAA Total number Infection LOS (days) Death 1 (baseline) 1089 41 (3.76%) 7.16 (6.54-7.47) 1 (0.09%) 274 30 (10.95%) 10.78 (9.80-11.76) 6 (2.19%) 287 28 (9.76%) 12.91 (10.56-15.26) 7 (2.44%) 2 1138 27 (2.37%) 6.71 (6.10-7.32) 5 (0.44%) 271 17 (6.27%) 9.04 (8.05-10.03) 1 (0.37%) 292 30 (10.27%) 10.90 (8.57-13.24) 13 (4.45%) 3 1078 30 (2.78%) 6.15 (5.53-6.78) 1 (0.09%) 294 18 (6.12%) 7.88 (6.93-8.83) 3 (1.02%) 236 27 (11.44%) 11.52 (8.92-14.11) 6 (2.54%) 4 1127 23 (2.04%) 6.25 (5.64-6.86) 2 (0.18%) 275 16 (5.82%) 7.81 (6.83-8.79) 2 (0.73%) 232 27 (11.64%) 8.07 (5.45-10.69) 3 (1.29%) p Value

0.0730 0.0888 0.2142

0.0620 <0.0001 0.1888

0.8797 0.0576 0.1640

* Numbers in parentheses represent percentage or 95 percent CIs.

rates in patients who did not receive transfusions versus those who received allogeneic transfusion are shown in Fig. 8A. Figure 8B shows that the LOS was also lower in patients who did not receive transfusions than in those who received allogeneic blood. Patients who received only autologous blood had similar reductions in LOS and infection rates to those of patients who did not receive transfusions. In multivariate analysis, allogeneic transfusion was an independent predictor for LOS. Figures 8C and 8D show the ORs of increased risk of infection and of increased LOS per number of allogeneic units transfused, compared to having no allogeneic blood transfused.
244 TRANSFUSION Volume 48, February 2008

Patient groups over time

In Table 5 various variables are provided that indicate that there was reasonable consistency of the patient groups for all targeted procedures over the analysis periods. In the CABG patients, for all time periods, there was a similar distribution of subjects with one- to three- versus fourvessel surgery (approx. 60 and 40%, respectively) and with American Society of Anesthesiology scores of less than 4 or greater than 4 (25% vs. 75%, respectively). Other than a slight but signicant increase in males in the CABG cohort over time, the groups for each procedure were similar over

ONTraC TRANSFUSION COORDINATORS

Anesthesiology score); LOS also decreased over time (Time 3 vs. Time 1). Although a number of factors were associated with all three outcomes, an increased number of allogeneic units transfused appeared to be the predominant predictor of postoperative infection and longer LOS. The bivariate analyses strongly suggested the value of autologous donation in decreasing the likelihood of allogeneic transfusion with an OR of 0.20 (CI, 0.14-0.29) and, in knee surgery at least, of EPO (OR, 0.45; CI, 0.20-0.99), but few patients received EPO.

Blood conservation measures employed

In addition to PAD, as described above, other measures used are shown in Table 7. Some of these were employed only in small numbers of patients and signicance of increased or decreased use over time needs to be interpreted with caution. EPO was little used in the presurgical setting initially (5 patients at baseline), but there has been progressive use over time (60 patients in the 24-month cohort), and this has continued to increase.

Fig. 8. Infection rates and LOS in patients who did not receive transfusion versus those who received allogeneic RBCs. (A) Higher infection rates in patients who received allogeneic blood; (B) these patients also had longer LOS (**p < 0.01; ***p < 0.001; chi-square). ( ) Allogeneic transfusion; ( ) autologous transfusion; ( ) no transfusion. The effect of the number of allogeneic RBCs transfused (C) on the infection rate and (D) on the LOS; means 95 percent CI. ( ) Knee surgery; ( ) AAA surgery; ( ) CABG surgery.

time in terms of sex, age, and body surface area. In knee and CABG patients there was a small but signicant increase in the preoperative Hb levels.

Costs
An estimate of cost savings was performed taking into account 1) the reduction in costs for units of allogeneic blood avoided (considering the decrease in patients who received transfusions and fewer units per patient who received transfusion), 2) the reduction in LOS, and 3) reduced work in hospital blood transfusion laboratories and on nursing units. An arbitrary cost of CAD$400 per unit of RBCs was used. Costs potentially associated with adverse events to transfusions were not included in the analysis. Prorated for the number of each procedure done in Ontario annually (estimated 12,000 knee arthroplasties, 15,000 CABG surgeries, and 1,200 AAA surgeries), at the 12-month period, the estimated annual cost savings in RBC product based on the demonstrated reduction in proportion of patients who received transfusions and the reduction in units per patient who received transfusion was $8,640,000. Recognizing differences in costs of hospitalization per day, for example, for intensive care beds for the CABG and AAA surgeries for several days postoperatively versus ward beds for the remainder of their stay and for orthopedic patients, a mean cost per day of $1,000 was
Volume 48, February 2008 TRANSFUSION 245

Association of allogeneic transfusion and clinical outcomes (infection, LOS, death)

Initially, single factors were assessed as possible predictors of chance of allogeneic transfusion, postoperative infection, and LOS. A number of multivariate logistic models were then employed to determine which of many possible factors could lead to the outcomes of interest. The relevant multivariate analyses are shown in Table 6. In multivariate analysis, the likelihood of allogeneic transfusion increased for every 10 years of age, female sex, for every 10 g per L decrease in preoperative Hb level, and in CABG patients, in nadir Hb level. In AAA surgery, use of cell salvage reduced likelihood of allogeneic transfusion, as did controlled hypotension in knee surgery. An increased LOS was associated with increasing age, lower nadir Hb level, and presence of infection and, in CABG patients, a higher severity (American Society of

FREEDMAN ET AL.

TABLE 5. Comparability of patient groups over time (mean

Time Surgery Knee arthroplasty Patient characteristics Sex: % male Age BSA Hb Preoperative Nadir Discharge CABG Patient characteristics Sex: % male Age BSA Hb Preoperative Nadir Discharge AAA Patient characteristics Sex: % male Age BSA Hb Preoperative Nadir Discharge BSA = body surface area. 1 (baseline) 2 3

SD)
4 p Value

38.84 69 12 1.96 0.25 132 93 100 15 13 12

38.31 69 10 1.97 0.25 134 94 99 14 14 12

38.22 69 9 1.97 0.25 135 94 100 13 14 12

37.18 69 10 1.97 0.25 136 93 99 14 15 14

0.8763 0.9661 0.9442 <0.0001 0.6654 0.106

74.45 67 9 1.95 0.24 133 78 100 16 12 12

82.29 65 10 1.96 0.22 135 79 101 15 12 12

81.97 65 10 1.96 0.22 139 81 101 13 12 12

86.18 65 10 1.96 0.21 139 83 101 14 12 13

0.0047 0.036 0.8235 <0.0001 <0.0001 0.3788

85.37 71 8 1.98 0.25 137 92 106 17 15 12

79.79 72 8 1.96 0.24 137 93 109 16 15 13

81.78 72 8 1.96 0.23 137 91 107 17 15 14

81.90 71 8 1.95 0.22 138 94 109 14 16 13

0.3665 0.4753 0.7409 0.7763 0.1304 0.0086

arbitrarily used, representing a potential reduction in costs for reduced LOS of $5,300,000. A workload savings of $650,000 was estimated, with the time in minutes (682,000) and salaries of technologists and nurses (at $28.2/hour) not needing to perform serologic testing pretransfusion (and of decreased reagents) nor of logging products in and out of inventory, not needing to identify patients and blood products, administer transfusion, and monitor the patient, for the calculated reduction of 21,600 units transfused in the three procedures. The total estimated savings were $14,950,000; the annual cost of running the program was $1,800,000.

DISCUSSION
In 1997, the Krever Commission Report9 stated that blood components and blood products will never be without risk. The best way to reduce that risk is to reduce their use. Despite important advances to reduce transfusion risks, this statement remains true today. The ONTraC program was developed to facilitate transfusion avoidance and blood management in the province of Ontario, Canadas second largest province (1,076,395 km2) with its highest population (12,599,364). The intent, and the primary assessment in this initiative, was whether or not allogeneic blood transfusion was reduced after the institution of the ONTraC coordinators. It is recognized that
246 TRANSFUSION Volume 48, February 2008

the observations reported do not represent contemporaneously controlled data. Possible inuences on transfusion practice may have included specic interactions the coordinators had with the physicians and the system as a whole, which occurred during a period when there was increasing attention to blood conservation and safety. Nonetheless, this observational report describes the experiences in setting up a large blood conservation network, observations on blood utilization, and the possible relationship of blood transfusion with clinical outcomes seen over the time the program has been in place. Although the transfusion coordinators themselves were actively instrumental in these transfusion practice initiatives, the development of institution-based cadres of blood conservation advocates among physicians, nurses, and others involved in transfusion choices was an important factor. Response by physicians to implementation of the transfusion coordinators varied. Although generally perceived as useful and important additions to enhanced presurgical care, promoting quality decision making regarding transfusion and improving patient access to transfusion alternatives, in a few institutions some physicians were reluctant to work with the coordinators to alter practice. A cardinal feature enabling success of the program was the development of a local champion, a well-respected physician prepared to work closely with the coordinator in developing new procedures and proto-

ONTraC TRANSFUSION COORDINATORS

TABLE 6. Predictors of allogeneic transfusion, LOS, and infection in multivariate analysis: adjusted ORs (95% CI)*
Outcome Allogeneic transfusion Characteristics Age (+10 years) Sex: female Hb (-10 g/L) Preoperative Nadir Conservation Cell salvage Controlled hypotension Desmopressin Infection Characteristics Nadir Transfusion Number of allogeneic units LOS Characteristics Age (+10 years) Severity scores ASA NYHA Hb (-10 g/L) Nadir Transfusion Number of allogeneic units Time 3 vs. 1 Conservation EPO Endpoint Infection Knee CABG AAA

1.36 (1.2-1.52)c 1.34 (1.06-1.70)a 1.20 (1.10-1.31)c NS NS 0.08 (0.03-0.21)c NA

1.38 (1.14-1.67)a 3.03 (1.79-5.13)c 1.30 (0.67-1.49)b 3.98 (3.15-5.02)c NS NS 4.76 (1.7-13.27)b

1.74 (1.39, 2.17)c NS 1.15 (1.03-1.28)a NS 0.60 (0.43-0.84)b NS NA

1.27 (1.05-1.53)a 1.43 (1.07-1.67)a

NS 1.52 (1.28-1.82)c

1.30 (1.08-1.57)b 1.31 (1.09-1.57)b

1.04 (1.03-1.05)c NA NA 1.05 (1.03-1.06)c 1.10 (1.09-1.12)c 0.94 (0.91-0.97)c 1.11 (1.02-1.21)a 1.33 (1.26-1.4)c

1.05 (1.02-1.08)c 1.12 (1.05-1.19)b NS NS 1.11 (1.09-1.13)c 0.88 (0.81-0.95)c NA 1.85 (1.75-1.96)c
a

NA NA NA 1.04 (1.01-1.07)a 1.07 (1.05-1.10)c NS NA 1.77 (1.65-1.88)c p 0.05,

b

* The data shown represent only those factors that demonstrated signicance in multivariate analysis. NS, p > 0.05. For every change of one category. NA = cell sizes too small to be computed. ASA = American Society of Anesthesiology; NYHA = New York Heart Association.

0.01,

0.001.

cols and presenting them to the staff. Most often, the champion was an anesthesiologist, working closely with the medical transfusionist, hematologist, or hematopathologist. Together with the champion and other appropriate staff, the coordinators developed blood conservation algorithms relevant for their institution. Because early contact between the transfusion coordinator and patient is critical, allowing sufcient time before surgery for the Hb to be optimized and an appropriate blood conservation strategy to be developed and carried out, interaction with the surgeons secretaries was particularly useful, because the latter would often best know the scheduling arrangements. Other difculties encountered in the establishment of this program were the costs of, and patient accessibility to, some blood conservation measures; for example, some centers had on-site access to PAD, others did not; in some cell salvage equipment was not available. Additionally, recent increasing emphasis on reducing wait times for surgery poses new issues in permitting sufcient time to address preoperative anemia and plan

blood conservation approaches. Buy-in by physicians and hospital administrators was variable, but is essential. It was difcult to avoid the desire at some hospitals to co-opt the transfusion coordinators to other functions, such as general data collection or research projects, and the role prole, as indicated in Table 2, needed constant reinforcement. Despite the difculties, the program has proven to be feasible and successful. The recognized interinstitutional variability in transfusion practice for the same procedure6,7 is demonstrated in Fig. 1. Nonetheless, as shown in Fig. 2, there was, over the initial 2 years of this program, a relative reduction in allogeneic transfusion rate of 28 percent in knee arthroplasty and CABG surgery, exceeding the anticipated 5 to 10 percent decrease. Although the 23 hospitals included in this program account for approximately 65 to 70 percent of blood use in Ontario, the decrease in utilization for the province overall is reected in data on RBC issues in Canada (Fig. 9); in contrast to other provinces, Ontario has had a decreasing annual increment in RBC transfusions (vs. the previous
Volume 48, February 2008 TRANSFUSION 247

FREEDMAN ET AL.

TABLE 7. Blood conservation measures used

Time Methods used Knee Total number in cohort Donated autologous blood (PAD) Received autologous blood only EPO Controlled hypotension ANH Cell salvage Antibrinolytics Desmopressin CABG Total number in cohort Donated autologous blood (PAD) Received autologous blood only EPO Controlled hypotension ANH Cell salvage Antibrinolytics Desmopressin AAA Total number in cohort Donated autologous blood (PAD) Received autologous blood only EPO Controlled hypotension ANH Cell salvage Antibrinolytics Desmopressin * Cell too small for reliable computation. ANH = acute normovolemic hemodilution. 1 (baseline) 1089 18.4% 11.8% 0.1% 7.7% 0 5.1% 0 0.1% 274 6.2% 3.3% 1.5% 0 2.2% 2.6% 63.5% 5.8% 287 2.1% 1.4% 0 9.1% 0 44.3% 0.4% 0 2 1138 19.2% 8.6% 2.4% 2.3% 0.1% 5.4% 0.6% 0 271 14.6% 5.2% 1.1% 5.9% 0 4.4% 63.0% 3.4% 292 4.1% 2.4% 0.3% 5.5% 0 61.3% 0.3% 0 3 1078 15.0% 5.0% 3.9% 0.8% 0 5.6% 0.1% 0 294 12.3% 4.1% 0.3% 5.1% 0.3% 3.1% 75.5% 2.7% 236 4.7% 0.9% 1.7% 1.7% 0 64.8% 0 0 4 1127 14.7% 6.3% 4.5% 4.2% 0 6.8% 0.7% 0 275 13.5% 6.6% 1.5% 9.1% 0.4% 2.9% 79.6% 0.7% 232 3.5% 2.2% 2.2% 3.5% 0 72.0% 0.9% 0.4% p Value

0.0064 <0.0001 <0.0001 0.0001 0.4083* 0.3115 0.0075* 0.3812*

0.0112 0.3021 0.5308* <0.0001 0.0100* 0.6174 <0.0001 0.0074

0.3960 0.5131* 0.0317* 0.0010 <0.0001 0.5067* 0.3187

Fig. 9. Comparison of RBC use over time in Ontario ( ) versus the rest of Canada (excluding Quebec; ); data from the Blood Program Coordinating Ofce of the MOHLTC of Ontario.

annual increase, as continues to be seen with the other provinces). There are undoubtedly a number of contributing factors and we are unable to isolate the specic impact of the ONTraC program on this phenomenon. It should be noted that the data presented under Results relate to cohorts of all consecutive patients with the specied diagnoses over that time period. In limited analysis, however, when the patients within the cohort were evaluated based on whether they were or were not seen by the
248 TRANSFUSION Volume 48, February 2008

transfusion coordinator, there was a marked difference. For example, for CABG patients at the 12-month period, there was an overall 21.6 percent decrease in patients who received transfusions with allogeneic blood. In patients not seen by the coordinator there was, however, only a 12 percent reduction, but in those who were seen preoperatively by a coordinator, there was a 50.2 percent reduction in transfusion rate. In part, at least, the difference might be attributable to differences in clinical and logistic factors between patients; for example, some of those not seen may not have had sufcient lead time or had medical conditions precluding some blood conservation measures and were therefore not referred to the coordinator. It has not been possible to isolate the differences, but these observations support the benet of early interaction with the transfusion coordinator. It is of interest that the extent of reduction in blood utilization differed between the different procedures; the reasons for this are not known, but likely include such factors as individual physician preferences and practices, new concepts in blood management, and literature focus on blood management in specic disciplines, for example, orthopedics and cardiac surgery, lead time for preoperative anemia management, and extent of surgery.

ONTraC TRANSFUSION COORDINATORS

The patient groups were relatively comparable over the four time periods. The small but signicant increase in preoperative Hb levels observed over time, as shown in Table 5, likely reects the improved management of preoperative anemia resulting from this program. Table 7 shows the increasing use of several measures of Hb enhancement and avoidance of allogeneic transfusion; others decreased in use, likely reecting individual preferences and recent literature.10,11 The use of some measures, particularly EPO, has continued to increase. It is not, however, the intent of this article to discuss the relative merits of these measures; there is considerable literature addressing this. It should be noted that PAD was a frequently used approach in this program, but its use has been recently decreasing (Fig. 3). Nonetheless, despite the recognized pros and cons of this maneuver,12-14 the data from Figs. 4 and 7 support the effectiveness of PAD in avoiding allogeneic transfusion. Often, blood conservation measures are prescribed for a given set of circumstances, the preoperative Hb level being an important consideration. Too little attention is given, however, to the distinction between normal or acceptable Hb levels in women versus men.15,16 It is evident, for example, from Table 6, that women are more likely to receive allogeneic transfusion, and their generally lower Hb levels (Fig. 6) need further consideration in the developing of algorithms for blood conservation. The transfusion trigger is an important determinant of allogeneic transfusion and the predictive value of the Hb levels for likelihood of transfusion is shown in Table 6 and Fig. 7. The fact that a higher transfusion trigger is used for autologous transfusion than for allogeneic transfusion (Fig. 5) is well known17 and is regarded as inappropriate. The higher trigger for allogeneic transfusion in knee surgery than in CABG was surprising, but is being lowered; it may reect the desire to mobilize orthopedic patients more quickly after surgery. This report conrms the literature indicating the benets of avoidance of allogeneic transfusion and demonstrates the exponential dose relationship of allogeneic transfusion to important determinants of patient safety (Fig. 8). Whether the adverse relationship between leukoreduced allogeneic transfusion and postoperative morbidity is causal or due to confounding factors cannot be answered by this observational study, but it is of interest that even with leukoreduced transfusions allogeneic transfusion was still a signicant dose-dependent predictor of morbidity. We have recently expanded this program to 25 hospitals, increased the number of centers performing CABG surgery from 4 to 10, and added two new procedures for focus, that is, hip surgery and radical prostatectomy. Patient enrollment and program evaluation continues in its efforts to achieve optimal patient care by reducing patient exposure to allogeneic blood, with its consequent potential benets in health-care costs and safety.

ACKNOWLEDGMENTS The authors thank the MOHLTC of Ontario, particularly Kathryn Pagonis, for their administrative and nancial support of this program. We are indebted to the many transfusion coordinators involved, without whose very considerable efforts this project could not have been done. The voluntary participation of all hospitals involved and their staff is also appreciated.

REFERENCES
1. Tinmouth A, MacDougall L, Fergusson D, Amin M, Graham I, Hebert P, Wilson K. Reducing the amount of blood transfused: a systematic review of behavioral interventions to change physicians transfusion practices. Arch Intern Med 2005;165:845-52. 2. Amin M, Fergusson D, Wilson K, Tinmouth A, Aziz A, Coyle D. The societal unit cost of allogeneic red blood cells and red blood cell transfusion in Canada. Transfusion 2004;44: 1479-86. 3. Custer B. Economic analyses of blood safety and transfusion medicine interventions: a systematic review. Transfus Med Rev 2004;18:127-43. 4. Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy AM, Abraham E, MacIntyre NR, Shabot M, Dun MS, Shapiro MJ. The CRIT Study: anemia and blood transfusion in the critically illcurrent clinical practice in the United States. Crit Care Med 2004;32:39-52. 5. Sullivan MT, McCullough J, Schreiber GB, Wallace EL. Blood collection and transfusion in the United States in 1997. Transfusion 2002;42:1253-60. 6. Stover EP, Siegel LC, Parks R, Levin J, Body SC, Maddi R, DAmbra MN, Mangano DT. Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24-institution study. Anesthesiology 1998;88:327-33. 7. Hutton B, Fergusson D, Tinmouth A, McIntyre L, Kmetic A, Herbert P. Transfusion rates vary signicantly amongst Canadian medical centres. Can J Anaesth 2005;52:581-90. 8. SAS/STAT Software. Release 9.1. Cary (NC): SAS Institute Inc.; 2003. 9. Krever H. Commission of inquiry on the blood system in Canada: nal report. Cat. No. CP32-62-3-1997E, Vol. 3. Ottawa: Canadian Government Publishing, Public Works and Government Services; 1997. p. 1052. 10. Graham ID, Alvarez G, Tetroe J, McAuley L, Laupacis A. Factors inuencing the adoption of blood alternatives to minimize allogeneic transfusion: the perspective of eight Ontario hospitals. Can J Surg 2002;45:132-40. 11. Leal-Noval R, Muoz M, Paramo JA, Garcia-Erce JA. Spanish consensus statement on alternatives to allogeneic transfusions: the Seville document. Transfus Altern Transfus Med 2006;8:178-202. 12. Forgie MA, Wells PS, Laupacis A, Fergusson D. Preoperative autologous donation decreases allogeneic transfusion but Volume 48, February 2008 TRANSFUSION 249

FREEDMAN ET AL.

increases exposure to all red blood cell transfusion. Arch Intern Med 1998;158:610-6. 13. Brecher ME, Goodnough LT. The rise and fall of preoperative autologous blood donation. Transfusion 2001;41:145962. 14. Rosencher N, Shander A. Preoperative autologous blood donation. Transfus Altern Transfus Med 2006;8:29-34. 15. Beutler E, Waalen J. The denition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood 2006;107:1747-50.

16. Cheng CK, Chan J, Cembrowski GS, van Assendelft OW. Complete blood count reference interval diagrams derived from NHANES III: stratication by age, sex, and race. Lab Hematol 2004;10:42-53. 17. Kanter MH, van Maanen D, Anders KH, Castro F, Win Mya W, Clark K. Preoperative autologous blood donations before elective hysterectomy. JAMA 1996;276:798-201.

250 TRANSFUSION

Volume 48, February 2008