The Next Chapter in Patient Blood Management. Real-Time Clinical Decision Support. Lawrence Tim Goodnough, MD, 1,2 and Neil Shah, MD 1 ABSTRACT

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1 The Next Chapter in Patient Blood Management Real-Time Clinical Decision Support Lawrence Tim Goodnough, MD, 1,2 and Neil Shah, MD 1 From the Departments of 1 Pathology and 2 Medicine, Stanford University, Stanford, CA. Key Words: Blood transfusion; Blood utilization; Clinical decision support; Best practice alert; Physician order entry; Electronic medical records Am J Clin Pathol December 2014;142: ABSTRACT Objectives: Blood transfusion was identified by the American Medical Association as one of the top five most frequently overused therapies. Utilization review has been required by accreditation agencies, but retrospective review has been ineffective due to labor-intense resources applied to only a sampling of transfusion events. Electronic medical records have allowed clinical decision support (CDS) to occur via a best practices alert at the critical decision point concurrently with physician order entry. Methods: We review emerging strategies for improving blood utilization. Results: Implementation of CDS at our institution decreased the percentage of transfusions in patients with a hemoglobin level of more than 8 g/dl from 60% to less than 30%. Annual RBC transfusions were reduced by 24%, despite concurrent increases in patient discharge volumes and case mix complexity. This resulted in acquisition costs savings (direct blood product purchase costs) of $6.4 million over 4 years. Conclusions: We have been able to significantly reduce inappropriate blood transfusions and related costs through an educational initiative coupled with real-time CDS. In deriving increased value out of health care, CDS can be applied to a number of overuse measures in laboratory testing, radiology, and therapy such as antibiotics, as outlined by the American Board of Internal Medicine s Choosing Wisely campaign. In 2009, the Institute of Medicine estimated that 30% of health care spending, approximately $750 billion annually, was wasteful and unnecessary. Deriving value out of health care expenditures is important since reimbursement models are beginning to reward quality over quantity. Blood transfusion was the most frequently performed procedure in 2009, 1 and a significant percentage of transfusions have been identified to be inappropriate. 2-4 Allogeneic blood transfusions carry inherent risk, 5 and studies have increasingly linked transfusions with adverse clinical patient outcomes, including morbidity and mortality. 6-9 A large Cochrane meta-analysis of 19 trials and more than 6,000 patients found that restrictive transfusion strategies were equivalent to liberal transfusion strategies in most patient groups. 10 A more recent study found that restrictive transfusion strategy is actually beneficial for patients with upper gastrointestinal bleeding and was one of the first to show benefits in a hypovolemic patient cohort. 11 To curtail inappropriate and potentially injurious transfusion practices, accreditation agencies such as the AABB and The Joint Commission (TJC) have promoted initiatives in patient blood management (PBM). 12,13 TJC developed seven performance measures in PBM, placing these in their Topic Library to be used by provider institutions as accreditation goals (patient safety activities and/or quality improvement projects), including certification by TJC in PBM. 14 While determining the appropriateness of transfusion or utilization review is a cornerstone of PBM, the comprehensive TJC program also calls for more proactive anemia management and use of pharmacologic alternatives to transfusions. Here we review historic, traditional approaches to utilization review along with some emerging strategies made possible by clinical decision support (CDS) via electronic medical records (EMRs). Am J Clin Pathol 2014;142:

2 Goodnough and Shah / Next Chapter in Patient Blood Management Table 1 Patient Health Care Activity and Patient Outcomes a Characteristic Patient activity RBC transfusions 29,472 30,194 25,304 23,136 23,008 22,991 Discharges 23,146 23,995 24,401 25,105 25,354 25,664 Patient days at risk 156, , , , , ,249 Case mix index Patient outcomes Mortality b day readmissions b LOS, d b Cost savings c NA 0 1,100 1,588 1,612 1,621 LOS, length of stay; NA, not applicable. a All inpatient discharges, Stanford Hospital and Clinics. All values are means, except 30-day readmission and mortality rates, which are per 1,000 discharges. Modified from Goodnough et al. 36 b P <.05. c Net annual savings in dollars (thousands), beginning in 2010, compared with 2009 as the reference year, based on a purchase price of $225/RBC unit. Year Historic Approaches to Blood Utilization Review Process improvements to improve blood transfusion have long been required by accreditation agencies. Traditionally, retrospective review of blood component use is initiated by the transfusion service, and results are reported to an institutional transfusion committee for oversight. Due to the resource- and labor-intensive nature of utilization review, 15,16 along with only a small sampling of cases for evaluation, this traditional model of retrospective peer review has been largely ineffective in improving transfusion practices. 17 Furthermore, appraisal of only a small percentage of cases may not accurately reflect prevailing transfusion practices, and retrospective review does not modify future behavior without continuous follow-up and feedback. 18 Concurrent strategies for review of blood utilization have been described for plasma and platelet products 18,19 as well as for RBC units. 20 Marques et al 20 showed decreased RBC units and percentage transfused per diagnosis-related groups through education and audits. Sarode et al 19 were able to reduce inappropriate plasma usage by 60% and platelet usage by 25% after hospital-wide education and prospective monitoring through transfusion services laboratory staff and pathology house staff and faculty. While concurrent review of each product request can be successful, it is enormously labor intensive, is difficult to maintain long term, and can delay product delivery during ongoing conversation between transfusion and clinical services. In addition to blood utilization review, historic quality indicators have focused on comparing inventory management metrics such as wastage rates and cross-match to transfusion ratio against national benchmarks. 21,22 This focus is on laboratory-based metrics, and it would be prudent for future quality metrics to link blood utilization to clinical patient outcomes. Clinical Decision Support The implementation of EMRs implicitly promised advanced data analytics to further patient care and prevent unnecessary treatment. 23 The use of EMR systems enabled tailored feedback to the provider at the critical time of order entry to promote appropriate use A review of 70 studies of CDS found that 68% of trials significantly improved clinical practice, and in 32 systems that possessed four key features of CDS, 94% significantly improved clinical practices. 24 These four key features can be summarized as computer-based decision support providing recommendations (rather than assessments) at the time of order entry that is automated and integrated into the normal workflow. In optimizing blood transfusions, a computerized, continuous quality improvement method was implemented more than 25 years ago by Gardner et al 23 and shown to be effective in altering transfusion triggers for ordering RBCs. Other groups have used a combination of education and manipulations of computerized provider order entry to reduce inappropriate RBC transfusions. 25,26,28 CDS has also been shown to be effective for improving utilization of other blood components such as plasma, cryoprecipitate, and platelets. 33,34 Some limitations to effective use of CDS systems for improving blood utilization have been defined: teams (not individuals) frequently make transfusion decisions; trainees may overestimate required laboratory tests/interventions, 35 particularly to avoid any possible rounding delay; guidelines and/or level 1 evidence may not be fully developed to support best practice recommendations; patient populations may be too heterogeneous for a one-size-fits-all best practices alert (BPA); and better patient outcomes may not be demonstrably linked to the CDS intervention. 26 To improve transfusion appropriateness at Stanford Hospital and Clinics (SHC), we implemented a CDS system. 36 An alert triggered when a provider ordered RBCs in 742 Am J Clin Pathol 2014;142:

3 Units Transfused/100 Patient Days at Risk RBCs Plasma Platelets 2013 Figure 2 Blood components issued to patients at Stanford Hospital and Clinics. Transfusion of RBCs decreased by 24% from 2008 through Figure 1 Passive guidance as part of the platelet and plasma ordering interface. While indications have to be completed prior to signing the electronic ordering, accuracy of indication is not verified against the patient s current laboratory values or clinical status as for the active clinical decision support for RBCs. The recommended international normalized ratio threshold for patients without bleeding was revised from 1.5 to 1.7 on October 10, a patient with pretransfusion hemoglobin level above a set threshold (7 g/dl for most and 8 g/dl for patients with acute coronary syndrome or postcardiothoracic procedure). Since implementation of the BPA in July 2010, the percentage of transfusions in patients with pretransfusion hemoglobin level greater than 8 g/dl decreased from 60% to 35% in the 6 months after BPA, with a sustained downtrend to below 30% by 2013 (P <.001). In absolute terms, CDS reduced annual RBC transfusions at SHC by 24%, despite concurrent increases in patient discharge volumes and case mix complexity Table In addition to decreased RBC use, hospital-wide patient clinical outcomes after CDS, including mortality and length of stay, have shown statistically significant improvement while 30-day readmission rates remained stable. 36 In addition, while there was no difference in admission hemoglobin levels (P =.11), discharge hemoglobin levels showed a significant (P =.006) downward trend. After CDS, outcomes in a cohort of transfused patients showed even more pronounced improvement than did hospital-wide patients (P <.01 for the three outcomes). Importantly, the mean number of RBC units received by the transfused patients was lower after implementation of the BPA (P =.001). While the improvement in patient outcomes and reduction in RBC transfusion cannot be shown to be causal, it is reassuring that there was not a deleterious effect on patient outcomes at the hospital level or within transfused patients after hospital-wide adoption of restrictive transfusion practices. Additional benefits of a restrictive transfusion strategy included a significant improvement in our laboratory budget, with an estimated annual net savings of $1.6 million and accumulated net savings of $6.4 million over the 4-year period from 2010 to Purchase/acquisition costs represent a fraction of total costs of transfusion blood that also include laboratory testing, reagent costs, nursing time dedicated to transfusion and monitoring, and so on. An activity-based cost summary of blood transfusions estimates that total costs related to transfusion are 3.2 to 4.8 times the purchase costs. 38 Hence, the total hospital transfusion-related savings potentially surpasses $30 million, with the added benefit of stable/ improved patient outcomes from reduced exposure to blood. While there was no activation of a CDA/BPA for platelet and plasma transfusions, we implemented passive guidance for transfusing platelets and plasma Figure 1 as part of the ordering process. Transfusion of RBCs, plasma, and platelets decreased 24%, 10%, and 12%, respectively, from 2008 through 2013 and is summarized in Figure 2. Trends in plasma transfusions relative to most recent pretransfusion international normalized ratio (INR) (within 48 hours) from January 2012 through September 2013 are illustrated in Figure 3. Despite the passive guidance that required clinicians to choose an indication for plasma transfusion, close to half of plasma orders were inappropriate, occurring in patients with a recent INR of less than 1.7. At minimally elevated INR ( ), coagulation factors are at sufficient levels to provide Am J Clin Pathol 2014;142:

4 Goodnough and Shah / Next Chapter in Patient Blood Management 70 INR 1.70 INR INR Percent of Plasma Units Transfused Figure 3 Trends in plasma utilization stratified by pretransfusion international normalized ratio (INR) at Stanford Hospital and Clinics (SHC). Quarterly plasma transfusions were analyzed as the percentage transfused to patients according to INR status within 48 hours prior to plasma therapy for all SHC inpatients. Despite the passive transfusion guidance as part of the order set (Figure 1), a significant amount of plasma (~50%) continues to be transfused at an INR of 1.7 or less. hemostasis, and the odds ratio of bleeding is equivalent to that of patients with a normal INR (within reference range). 39,40 Furthermore, plasma transfusions have not been shown to be effective at correcting minimally elevated INR. 41,42 Passive recommendations such as ours for plasma and platelets seem to be only marginally effective compared with active ones such as CDS for RBCs. At Lucile Packard Children s Hospital (LPCH) at Stanford, a CDS (February 2009) triggered for RBC transfusions for children aged 1 to 18 years with a hemoglobin level of more than 7 g/dl who were normotensive in the last 6 hours. The alert did not trigger in patients from cardiac, hematologyoncology, and neonatal intensive care unit wards. 43 The BPA Figure 4 notified that the RBC order might be unnecessary, with a hyperlink to the supporting reference. 44 This intervention resulted in a decline in RBC transfusions in pediatric patients from to per patient-day over the year interval ending in February Hospital-wide blood components transfused at LPCH from 2006 through 2012 are illustrated in Figure 5. In summary, real-time CDS was effective and efficient at improving RBC utilization at both our pediatric 43 and adult 13,37,45 hospitals at Stanford University Medical Center. This model of a real-time review can be extended to a peer-reviewed process, with further analysis of services/individual providers that continue to transfuse Figure 4 Best practices alert (BPA) screenshots at Stanford University Medical Center. Screenshot from an electronic physician order entry for blood transfusion in adult patients at Stanford Hospital and Clinics illustrates an interruptive alert as a reminder for the merits of a restrictive transfusion practice vs liberal transfusion practice. An acknowledgment/ exception field allows the physician to provide the indication for transfusion (acute bleeding, hemoglobin level <8 g/dl in acute coronary syndrome or postcardiothoracic surgery patient, or other clinical scenario) if such clinical scenarios were not updated in the problem list. The BPA for pediatric patients at Lucile Packard Children s Hospital triggers only for children aged 1 to 18 years with a hemoglobin level more than 7 g/dl who are normotensive in the past 6 hours. The alert does not trigger in patients from cardiac, hematologyoncology, and neonatal intensive care unit wards. outside of recommended guideline. Close to 30% of our RBC transfusions continue to occur in patients with hemoglobin levels greater than 8 g/dl despite CDS, and peer performance executive committees can help reduce variability in clinical practice and/or help modify the CDS to build in clinical exceptions. This later practice serves as continuous education and feedback, which is seen as vital in the success of utilization programs 46 and augments improvements possible through CDS. 744 Am J Clin Pathol 2014;142:

5 Future Directions In 2009, according to the Institute of Medicine, $2.5 trillion were spent on health care and consumed 17.6% of gross domestic product, both of which are predicted to rise. From 1999 to 2009, real income gains in the average US family have been completely wiped out by increasing health care cost. 47 Almost a third, estimated to be 30%, of this expansive health care expenditure is estimated to be wasteful. By reducing this waste, we are not only helping improve patient outcomes by reducing exposure but also addressing real patient concerns with the ability to pay for the high cost of health care. In unnecessary care, blood transfusion was specifically targeted among five key overuse measures by both TJC and the American Medical Association. Strategies to accomplish this have included retrospective review of selected cases 16,17 and more effective yet very resource-intense, prospective, manual audit of individual orders The increased adoption of EMRs and features such as CDS allow the practice of prospective, real-time monitoring of transfusion practice in an automated fashion at the critical time of decision making (order entry). In addition, CDS via EMR allows more algorithm-driven consideration of the composite patient condition rather than just a single laboratory value (hemoglobin) to include underlying factors such as diagnosis/procedure (to reflect acute coronary syndrome or acute bleeding) 37 or vitals (hypotension). 43 The success of our CDS resulted from its design, combined with other important factors, such as executive sponsorship and data. 48 Our SHC CDS working group adheres to intelligent design via the five rights 49 : deliver the right information, to the right person, in the right format, through the right channel, and at the right point in workflow. The education and outreach efforts prior to BPA go-live were paramount in maximizing acceptance and garnering feedback; an electronic solution in a vacuum without concurrent communication can sometimes be ignored. The impact and contributions of the individual elements of the CDS (the alert, link to relevant literature, acknowledgment/exception) will need to be further analyzed to understand components vital to affecting end-user action. While CDS in the form of alerts can help conform actual practice closer to standards, it is not a panacea. Frequent and ill-designed CDS exacerbate alert/click fatigue, where users begin to mechanistically cancel pop-ups without reading the message, particularly when these occur at the time of order signing. Future measures to remedy this will include limiting low-impact CDS 50 and moving the decision making and support downstream to nondirect clinicians such as pharmacy, 51 radiology, 52 or pathology 53 to distribute CDS burden and deliver it to personnel with the highest knowledge base to make a given decision. Displaying recommendations alongside user search items in order entry, instead of at the time of signing, prevents disruptions in workflow and could lead to higher acceptance of Units/1,000 Discharges Figure 5 Blood components (RBC, plasma, and platelets) issued to patients at Lucile Packard Children s Hospital (LPCH). Annual volumes of blood components issued by the transfusion service to patients at LPCH, 2006 to CDS guidance. An additional crucial item missing from many CDS is follow-up of users and groups/services that frequently disregard best practices. Our analysis showed close to a 30% mistransfusion practice (relative to CDS), and others have shown as high as 60%, 26 despite successful CDS. Long term, these groups will have to be engaged for further education or refinement of CDS for continuous quality improvement, an ideal in health care. 54 Looking forward, it would be wise for hospital transfusion and peer performance committees to incorporate quality metrics for appropriate transfusion and clinical outcomes in transfused patients in addition to traditional ones such as cross-match to transfusion ratio. Conclusion RBCs Plasma Platelets 2012 We have been able to significantly reduce inappropriate blood transfusions and related costs through an educational initiative coupled with real-time CDS. Clinical patient outcomes improved after implementation; while this is an association rather than causation (as part of a controlled trial), these observations provide assurance that a restrictive transfusion strategy can be successfully implemented institution-wide without causing patient harm. CDS enables health care systems to effectively implement this strategy in a resource-effective manner. CDS design will require continued maturation to optimize user engagement and end action while minimizing alert fatigue. In deriving increased value out of health care, CDS can be applied to a number of overuse measures in laboratory testing, radiology, and therapy such as antibiotics, as outlined by the American Board of Internal Medicine s Choosing Wisely Campaign. 55 Address reprint requests to Dr Goodnough: Stanford University Medical Center, 300 Pasteur Dr, Room H-1402, 5626, Stanford, CA ; ltgoodno@stanford.edu. Am J Clin Pathol 2014;142:

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