Science Evidence Cost

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1 Anemia, Evidence, and Anemic Evidence: Is there a rational approach to perioperative transfusion? Elizabeth L Whitlock, MD, MSc Resident physician, Anesthesia & Perioperative Care University of California, San Francisco Examining our transfusion practices Science Evidence Cost 1

2 Choosing (transfusion) Wisely ASA: Don t administer packed red blood cells in a young healthy patient without ongoing blood loss and hemoglobin of 6 unless symptomatic or hemodynamically unstable. (10/12/2013) Critical Care Societies Collaborative: Don t transfuse red blood cells in hemodynamically stable, non-bleeding ICU patients with a hemoglobin concentration greater than 7g/dL. (1/28/2014) AABB: Don t transfuse more units of blood than absolutely necessary. (4/24/2014) Everyone agrees there (is/might be) a problem. Is there? Demographics of perioperative RBCs units 10% >1 unit 69% 1 unit 31% 3 units 7% 2 units 52% 1 unit 31% Ferraris et al, Arch Surg 2012 Jan: 147(1),49-55 Whitlock et al, BMJ 2015 Jun: h3037 2

3 But the blood system is safe! Does this really matter? The science of stored blood Science Evidence Cost Stored blood: pathologic changes Stored RBCs: less flexible, more adherent to vascular endothelium, and more aggregable Supernatant: inflammatory cytokines, dysregulated NO Microvascular ischemia, impaired autoregulation, atherosclerotic plaque rupture Healthy volunteers, ICU patients: infusion of stored blood reduces tissue oxygenation x 24 hours Images: Relevy et al, Transfusion 2008 Jan; 48(1): Roberson & Bennett-Guerrero, Mt Sinai J Med 2012 Jan-Feb; 79(1):66-74 Reynolds et al, PNAS 2013 Jul 9; 110(28):

4 Stored blood: pathologic changes Stored RBCs: less flexible, more adherent to vascular endothelium, and more aggregable Supernatant: inflammatory Should we be looking for cytokines, dysregulated ischemic NO harms related to Microvascular ischemia, transfusion? impaired autoregulation, atherosclerotic plaque rupture Healthy volunteers, ICU patients: infusion of stored blood reduces tissue oxygenation x 24 hours Images: Relevy et al, Transfusion 2008 Jan; 48(1): Roberson & Bennett-Guerrero, Mt Sinai J Med 2012 Jan-Feb; 79(1):66-74 Reynolds et al, PNAS 2013 Jul 9; 110(28): What is the evidence in humans? Cohort studies, and RCTs of transfusion thresholds Science Evidence Cost 4

5 Evolution of cohort evidence Hemorrhage 4 units or more: OR 2.5 [ ] for stroke 4 units or more: OR 2.7 [ ] for MI 700,000 patients Low-volume transfusion But can you ever escape the specter of residual confounding? 1-2 units: OR 2.33 [ ] for stroke/mi 3 units: OR 3.13 [ ] for stroke/mi 1.6 million patients PCI: no blood loss OR 8.49 [ ] for stroke OR 2.38 [ ] for MI 2.3 million patients 9 Kamel et al, Circulation 2012 June; 126: Whitlock et al, BMJ 2015 Jun: h3037 Sherwood et al, JAMA 2014; 311: /21/2015 Briefly: definitions Liberal: 9-10 g/dl Restrictive: 7-8 g/dl Typical exceptions: Active hemorrhage, hemodynamic instability, symptomatic anemia 10 9/21/2015 5

6 Meta-analysis of transfusion RCTs Trial sequential analysis: trials with low risk of bias 11 Holst et al, BMJ 2015; 350:h1354 9/21/2015 Perioperative trials: mortality zcv Restrictive Surg onc Vascular Hip fx Hip fx Pedi cardiac Hip fx THA/TKA Adult cardiac Hip fx Adult cardiac THA/TKA UGIB Liver txplt Liberal Favors restrictive Favors liberal CI crosses 1 (0.76 to 1.49): No difference in mortality Holst et al, BMJ 2015; 350:h1354 6

7 Perioperative trials: Infection asdf Cardiac Orthopedic Possible reduction in infection 13 Rohde et al, JAMA 2014 Apr; 311(13): /21/2015 An opportunity for cost savings while improving patient care Science Evidence Cost 7

8 Transfusion: How much? Most recent data is from 2011: 13,785,000 units of RBCs transfused Adverse reactions reported for 1:414 units Average Medicare reimbursement: $ Average cost of 1 unit: $ Average process cost to provide 1 unit transfusion: $760 Dollars Medicare Blood Total costs 2011 Nat l Blood Collection & Utilization Survey Report, US Dept of Health & Human Services Shander et al, Transfusion 2010 Apr;50(4): Cost savings of restrictive periop transfusion Single-center (Johns Hopkins) transfusion practice review Major abdominal surgery (3027 patients) Intraop 122 units at Hb 10 Postop 79 units at Hb 8 Costs incurred by liberal transfusion: $100k/yr (abdominal surgery alone) Liberal surgeons (90 th %ile) Ejaz et al, JAMA Surg 2015 Jul 1; 150(7):

9 UCSF try one unit first initiative Orthopedic surgery, neurosurgery, medicine Encouraged: Lower (evidence-based) transfusion thresholds Symptom assessment One unit first Used 711 fewer units in 2.5 quarters (1,140/y) $866,400/yr ( societal costs) $644,260/yr (accounting for Medicare reimbursement: hospital costs) Gonzales R et al, Caring Wisely: A Program to Support Frontline Providers and Staff in Improving Health Care and Reducing Costs. UCSF. Patient blood management: next frontier The Ontario Health System ONTraC intervention Targeted CABG, prostatectomy, TKA/THA 20.0% TKA RBC use Blood conservation measures: Erythropoietin Topical hemostatics IV iron Controlled hypotension Antifibrinolytics Acute normovolemic Cell salvage hemodilution Savings ($CAD) in 2011 C$10,521,450: unit purchase alone C$39,467,900: unit purchase + ancillary costs 15.0% 10.0% 5.0% 0.0% None One Two 3 or more Number of conservation measures (C$3,257,000: program cost) Freedman et al, Transfus Apher Sci 2014 Feb; 50(1):32-6. Autologous units: Etchason et al, NEJM 1995 Mar; 332(11);

10 Conclusions The biochemistry of stored blood suggests we should worry about more than infectious complications High-level evidence suggests restrictive transfusion policy is no worse than liberal, though less evidence from perioperative setting Best cost reduction is with large-scale patient blood management programs but may require substantial investment Small-scale single-center initiatives can work, too Science Evidence Cost 10