Economics and Quality Care:

The Case for Patient Blood Management

Why We Should Avoid Transfusions

Irwin Gross, M.D., Medical Director Transfusion Services, Eastern Maine Medical Center

Disclosures

• Medical Advisory Board – Strategic Healthcare Group

A little about Eastern Maine Medical Center

• • • • • • • • • 370 bed community and tertiary care hospital in rural Maine Large hospitalist service High risk obstetrics Trauma center, Level 2 Dialysis center Family Practice residency Cardiac surgery program – Approx. 450 cases/yr.

Active heme/onc service – 10 oncologists No transplant surgery

Patient Blood Management (PBM)

The timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss in an effort to improve patient outcome.

What is Patient Blood Management: The Three Pillars

Optimize erythro poieis Minimize bleeding & blood loss Harness & optimize physiologic tolerance of anemia

© Axel Hofmann/Shannon Farmer – SHEF Meeting Perth August 2010

Can Patient Blood Management Reduce the Need for Transfusions?

Red Cell Units Transfused

FY 1994 – FY 2010 9470

Patients Transfused: FY 1994 - 2011

Patients Transfused

3000 2500 2000 1550 1686 1846 1815 1998 1500 2157 2422 2393 2468 2474 2684 2773 2843 2263 1737 1608 1534 1606 1000 500 0 FY 94 FY 95 FY 96 FY 97 FY 98 FY 99 FY 00 FY 01 FY 02 FY 03 FY 04 FY 05 FY 06 FY 07 FY 08 FY 09 FY 10 FY 11

Transfusion Rates All Cases: CABG, Valve, CABG/Valve April 2008 – March 2011

23% Transfusion rate in 2006: 48% 14%

Cardiac Surgery and Transfusions

• With reduction in transfusion rate from 48% to approximately 20% , there was a reduction in: – Perioperative AMI – New onset renal failure – Perioperative infection – Stroke – Length of stay – No change in mortality

Transfusion Rate: Orthopedics

Blood Transfusion: A Growth Industry

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Our Demographic Challenge

• Rapidly increasing percentage of population over the age of 65 and decreasing percentage of population between 17 and 65 – – Decrease in eligible donors Increase in population that are transfusion recipients – Demand may exceed supply in the near future

Transfusion is expensive!

Between $832 and $1284 per unit in the EMHS System

Blood and Blood Components: Cost Savings – All Components (EMMC) • • Total blood acquisition costs in FY ‘06 were $3,200,000 Cost savings compared to base year, FY ’06* – FY ’07 $ 850,000 – FY ’08 $ 1,400,000 – FY ’09 $ 1,600,000 – FY ’10 $ 1,550,000 – –

Total (Acquisition) $ 5,400,000 Total (ABC) $ 17,280,000 **

* No change in per unit cost from blood supplier from 2007 – 2010 * Using ABC 3.2 times acquisition cost

The Macroeconomic Burden of Transfusion

• • • • • Retrospective cohort study by American College of Medical Quality Evaluated all 38.7 million hospitalizations in U.S. in 2004 Adjusted for age, gender, comorbidities, admission type and DRG Charges per transfused patient were $17,194 more than charges for non transfused, matched patient Total excess financial burden: $40 billion Am J Med Qual 2010;25:289-296

Is Blood Utilization in the U.S. Optimal?

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Observed Variation in Hospital-Specific Transfusion Rates for Primary Isolated CABG Surgery With Cardiopulmonary Bypass During 2008 (N = 798 Sites)

Bennett-Guerrero, E. et al. JAMA 2010;304:1568-1575.

Are Transfusions Safe: Risk vs. Benefit

• • • The risks of transfusion are increasingly well defined and extend far beyond concerns about disease transmission (e.g. HIV, hepatitis) The benefits of red cell transfusion, except in severe hemorrhage, have never been proven While anemia is associated with poorer outcomes,

red cell transfusion to treat anemia does not appear to improve outcomes

Impact of Transfusion on Patient Outcomes

Author (year)

Leal-Novel et al (2001) Wu et al (2001) Engoren et al (2002) Vincent et al (2002) Malone et al (2003) Corwin et al (2004) Dunne et al (2004) Koch et al (2006)

Population

Cardiac surgery Elderly with MI Cardiac surgery Critically ill Trauma Critically ill Trauma Innerhofer et al (2005) Weber et al (2005) Orthopedic surgery Orthopedic surgery Cardiac surgery

n Impact of Blood Transfusion

738 78,974 1,915 3,534 15,534 4,892 9,539 308 695 5,841

- Higher mortality rate - Longer ICU stay - Lower 30-day mortality (if admission Hct<33*) - Higher 30-day mortality (if admission Hct>36) - Higher 5-year mortality rate - Higher 14- and 28-day mortality rate

- Higher mortality rate

- More ICU admission - Longer ICU/hospital stay - Higher mortality rate - Longer length of stay - More number of complications - Higher mortality rate - More ICU admission - More SIRS - More infections - Longer time to ambulation - Longer length of stay - More AF

Impact of Transfusion on Patient Outcomes

Author (year)

Koch et al (2005) Murphy et al (2007) Surgenor et al (2009) Pedersen et al (2009) Nikolsky et al (2009) van Straten et al (2010) D’Ayala et al (2010) O’Keeffe et al (2010) Veenith et al (2010)

Population

Cardiac surgery Cardiac surgery Cardiac surgery Total hip replacement PCI after MI Cardiac surgery Lower extremity amputation Lower extremity revascularization Elderly undergoing cardiac surgery

n Impact of Blood Transfusion

11,963 8,598 3,254 4,508 2,060 10,435 300 8,799 874

- Higher postop mortality rate - Higher postop morbidity rate (RF, prolonged ventilatory support, serious infection, cardiac complications, & neurologic events) - Higher mortality rate - More ischemic complications - More infectious complications - Decreased survival after cardiac surgery - Higher mortality rate - More pneumonia - Higher 30-day and 1-year mortality rate - Worse early survival - More postop adverse events - Longer ICU/hospital stay - Higher mortality rate - More pulmonary complications - More infectious complications - Higher mortality rate - Longer ICU/hospital stay

Transfusion and Outcomes

• Following transfusion: – In all of the studies, Hb increased – Is this a useful metric of clinical efficacy?

– – In 79% of the studies, DO2 increased In 16% of the studies, VO2 increased – In none of the studies, did ischemia (as measured by lactate) improve – In all of the studies, transfused patients had poorer outcomes

Efficacy of RBC Transfusion in the Critically Ill

• • • • Meta-analysis - 45 observational studies of 272,596 patients Included surgical (trauma, general, ortho, neuro, and cardiac) and general ICU patients 42 of 45 studies: risks outweighed benefits of transfusion; risk neutral in 2 studies Transfusion an independent risk factor for increased: • Mortality • • Infection Multi-organ dysfunction • ARDS Marik, et al CCM 2008;36:2667-2675

Adverse Effects of Allogeneic Blood

• • • • • • • •

Storage Lesion TRIM

TRALI: 1 in 2,000 transfusions; primarily plasma rich products; up to 20% mortality Hemolytic transfusion rxns: (1:4,000) Bacterial contamination (Plts.-1:75,000) HIV, HCV, HBV Febrile and allergic reactions: 1-2% Other: ARDS, TA-GVH, SIRS, TACO, TAHA, unknown viruses

Adverse effects of RBC transfusion contrasted with other risks.Risk is depicted on a logarithmic scale.

Relative risk of: Storage lesion, TRIM, SIRS, etc?

Carson J L et al. Ann Intern Med doi:10.1059/0003-4819 156-12-201206190-00429

©2012 by American College of Physicians

Storage Lesion: Tissue Oxygenation and Red Cell Transfusions

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Phase Contrast Video – Single file RBCs Click to play

Cytoscan – Pre & Post Transfusion Click to play

RCTs to Evaluate Red Cell Storage

• • • • Age of Blood Evaluation (ABLE): comparing 8 day old blood vs. standard issue (2-42 days) in ICU patients – Outcome: 90 day all-cause mortality Age of Red Blood Cells in Premature Infants (ARIPI): 8 day old blood vs. standard issue – Outcome: 90 day all-cause mortality and organ dysfunction

Red Cell Storage and Duration and Outcomes in Cardiac

Surgery: < 14 day vs. > 20 day old blood – Outcome: Post-op mortality Red Cell Storage Duration Study (RECESS): Cardiac surgery patients randomized to < 10 days vs. > 21 day old blood – Outcome: Change in Composite Multi-organ Dysfunction Score (MODS)

Adverse Effects of Allogeneic Blood

• • • “Stored RBCs resulted in significantly malperfused and underoxygenated microvasculature “ – Decreased functional capillary density May contribute to multi-organ failure Applies to stored autologous blood Tsai, A.G. et al. Transfusion 2004;44:1626-34

Transfusion Related Immunomodulation (TRIM)

Transfusion and Cadaver Renal Allograft Survival

Transfusion Related Immunomodulation (TRIM)

•

Improved renal allograft survival

• • • Increase in nosocomial infection rates leading to increased LOS, resource consumption, total hospital costs Increased cancer recurrence rates in transfused patients

Increased long-term mortality in CABG

•

A linear dose-response curve of adverse clinical effects is well documented in large studies using multivariate analysis

Nosocomial Infections And Transfusion

Nosocomial Infection Rates in Critically Ill Patients

• • • • Prospective cohort study Patients stratified by probability of survival into quartiles Lowest quartile for survival: transfusion had no impact on infections Highest quartile for survival: transfusion resulted in significant increase on infections

16 12 8 4 0 7.5

157/2,085 P < .0001

14.3

61/428

All Patients Transfused Patients Non-transfused Patients 5.8

96/1,657 Taylor RW, et al. Crit Care Med . 2006;34:2302-08.

Small Amounts of Intraoperative Blood Loss Heralds Worse Postoperative Outcome • • • • Database study of NSQIP data with propensity–score matching 8728 nonvascular thoracic operations 6.6 % received one or two units during surgery After propensity adjustment – – Increased pulmonary complications and LOS Increased systemic sepsis and wound infections – Composite morbidity 43% vs.32% Ferraris, et al. Ann Thorac Surg 2011

S. aureus and Iron Surface Determinant (IsdB)

.

Lowy FD. N Engl J Med 2011;364:1987-1990.

Transfusion and Mortality

Association Between Blood Transfusion and Risk of Death

Marik, et al CCM 2008;36:2667-2675

Transfusion and Mortality in CABG

• Retrospective study of long-term outcome in 1,915 patients after primary CABG • Excluded patients who died within 30 days of surgery • Transfused patients (546) were matched by propensity score (age, gender, size, LOS, perfusion time and STS risk) with pts. not transfused and 5-year mortality compared •

Adjusted 5-year mortality 70% higher in transfused

group (p<0.001)

Engoren et al, Ann Thorac Surg 2002;74:1180-6

Mortality and Transfusion-Cardiac Surgery

Fig 3. Kaplan-Meier estimates of survival based on equal propensity scores of any transfusion (XFN) versus no transfusion (No XFN). (CABG = coronary artery bypass grafting

Engoren et al, Ann Thorac Surg 74:1180-6, 2002

Transfusion and ARDS

Association Between ARDS and Transfusion

Marik, et al CCM 2008;36:2667-2675

Transfusions in Acute Coronary Syndrome

Blood Transfusion and Clinical Outcomes in Patients with ACS • • • • Retrospective analysis of 24,112 patients from GUSTO IIb, PURSUIT, and PARAGON B trials Main outcome: 30 day mortality Data adjusted for baseline characteristics: bleeding, transfusion propensity, nadir hematocrit

Transfusion was associated with a hazard ratio for death of 3.94 (3.26 – 4.25)

Rao, et al. JAMA, Oct. 6, 2004, Vol 292, No. 13. pp. 1555 -1562

Transfusion and Cancer Survival

Influence of Transfusion on Outcome in Pancreatic Cancer • • • • 67 patients underwent pancreaticoduodenectomy for cure 25 patients received > 3 units No difference in tumor size, stage, histology compared to group receiving < 2 units Median and cumulative 3 year and 5 year survival worse with > 3 units – 5 year survival 68.9% vs. 30.2% World J Surg, 2008

Influence of Transfusion on Colorectal Cancer Recurrence

• • • Cochrane meta-analysis involving 12,127 patients Evaluated role of transfusion in colorectal cancer recurrence Overall OR for recurrence was 1.41 (95% CI 1.20-1.67) in transfused patients Amato, A, et al. Cochrane Database System Rev 2006;(1): CD005033

Lymphoma and Transfusion

• • • Meta-analysis of 14 studies – – Case control and cohort studies Outcome reported as relative risk (RR) Previous RBC transfusion associated with later development of non Hodgkin lymphoma, RR 1.2 (95%CI 1.07-1.35, P< .01) In subset analysis, risk greatest for development of chronic lymphocytic leukemia/small lymphocytic lymphoma Castillo, JJ, et al. Blood. 2010;116(16):2897-2907)

Radiation Therapy, Transfusion and Outcomes: DAHANCA 7 Study • • • Evaluated effect of transfusion on disease specific and overall survival in head/neck SCCa Low hemoglobin group had poorer survival than high hemoglobin group Low hgb group with transfusion showed trend toward poorer survival than low hgb group without transfusion Acta Oncologica, 2011; 50:1006-1014

Risk vs. Benefit

“The issue (no longer) is whether or not blood transfusion is harmful, but the inflection point at which it is associated with more harm than benefit.” -Rao et al, JAMA 2005;292(13)

Blood Product Transfusions

•

The Traditional Concept

Blood products are an effective therapeutic intervention •

The New Concept

Transfusion of blood products is an undesirable outcome to be avoided Goodnough L.T.

“Primum non nocere” (

First, Do No Harm) The accumulating evidence suggests that, when we fail to prevent an avoidable transfusion, we are harming patients.

When to Transfused Red Cells: The Transfusion Threshold

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Survival in Patients with Profound Anemia in the Absence of Transfusion Ford, et al, Blood 2005 106: Abstract 949

Hb Level (gm/dL)

2.5-3.0

3.1-4.0

4.1-5.0

5.1-6.0

6.1-7.0

Overall

Survival

6/7 (85.7%) 9/11 (81.8%) 29/32 (90.6%) 30/30 (100%) 48/48 (100%) 122/128 (95.3%)

Transfusion in Critical Care: TRICC Trial

A prospective, randomized trial comparing a restrictive red cell transfusion strategy vs. a liberal transfusion strategy Copyright 2006 – 2011 Strategic Healthcare Group LLC. All Rights Reserved

Transfusion in Critical Care

• 838 critically ill patients randomized to a restrictive (7-9 g/dl) or liberal (10-12 g/dl) transfusion strategy • Overall 30 day mortality similar (no

transfusion benefit in liberal transfusion

group) • Mortality rates significantly lower in restrictive transfusion group for those with APACHE score < 20 and those < age 55 • No difference in patients with clinically significant heart disease Hebert. NEJM 1999;340:409-17

Liberal or Restrictive Transfusion in High-Risk Patients after Hip Surgery • Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) – RCT of 2016 patients with hip fracture requiring surgery – > age 50 (mean age 81.6 years) with cardiovascular disease (62.9%) or risk factors for CVD (37.1%) – Randomized to liberal (single unit if Hgb < 10 g/dL) vs. restrictive (single unit for Hgb < 8 g/dl or symptomatic from anemia Carson , JL et al. NEJM. December, 2011

Liberal or Restrictive Transfusion in High-Risk Patients after Hip Surgery • Results – Primary outcome: death or inability to walk 10 feet without assistance at 60 days – No difference between liberal and restrictive transfusion group – Low rate of cardiovascular adverse events in both groups –

65% fewer units transfused in restrictive group and half received no transfusion

Carson , JL et al. NEJM. December, 2011

The “10/30 Rule” Should be Banished

(also the 9/27 rule and 8/24 rule)

No single hemoglobin threshold should be used to make a transfusion decision No rigid “transfusion trigger” based on hemoglobin alone

But… for most patients, consideration of red cell transfusion should begin at hemoglobin of 7 gm/dl (hematocrit of 21%)

Distribution of Pretransfusion Hematocrits

2006 Mean 24.3 % SD 4.28

2010 Mean 20.9 % SD 3.27

Red Cells Should Not be Ordered in “Pairs”

For Red Cells: • In the absence of acute hemorrhage RBC’s should be given as single units • Each unit should be an independent clinical decision • Each unit represents an incremental increase in adverse consequences • Remember: transfusion of red cells may NOT increase oxygen delivery at a tissue level Napolitano - Crit Care Med 2009 Vol. 37, No. 12

Reduce Phlebotomy and Procedure-related Blood Losses

• • • Meticulous surgical hemostasis Meticulous hemostasis with “bedside” procedures Minimize phlebotomy blood loss – Only necessary labs – Smallest sample practical

Role of Intravenous Iron in Inpatients

• • • Most inpatients have inflammation and functional iron deficiency (FID) – – – – Chronic inflammatory diseases Malignancy Perioperative Trauma Oral iron is poorly tolerated, poorly absorbed, and not bioavailable Intravenous iron may play a role in improving erythropoiesis – There may also be a limited role for ESAs in inpatients

Conclusions

• • Red cell transfusions in patients who are not bleeding and have hemoglobin levels greater than 6-7 g/dL are generally associated with worse outcomes The best way to optimize oxygen delivery to the tissues is not by transfusing stored RBCs; instead: – – Optimize oxygenation Optimize hemodynamics

Conclusions

• • • Even mild anemia contributes to all cause morbidity and mortality and should be evaluated and treated, when possible – Anemia management before elective surgery helps decrease transfusion rates Intravenous iron replacement may be effective at increasing hemoglobin in patients with anemia of chronic inflammation and in patients with an acute inflammatory process Limited role for ESAs in inpatients

Anemia independently associated with increased: • morbidity • hospital length of stay • • likelihood of transfusion mortality Anemia Spahn DR. Anesthesiology 2010; 113(2) 1-14 Beattie WS, et al Anesthesiology 2009; 110(3) 574-81 Dunne JR, et al J Surg Res 2002; 102: 237-44 Shander A. Am J Med 2004; 116(7A) 58S-69S

Bleeding associated with increased

• Morbidity • ICU and hospital length of stay • • • Mortality Elective : ~0.1% Blood loss • • • Vascular 5–8% & Up to 20% with severe bleeding bleeding Triad of Independent Risk Factors for •

dose-dependent relationship with increased:

• Morbidity Outcomes ICU and hospital length of stay • Mortality Transfusion •

Causes

On average 75 – 90% local surgical interruption or Beattie WA, et al Anesthesiology 2009 Murphy GJ, et al Circulation 2007 Salim A, et al J Am Coll Surg 2008 Bernard AC, et al J Am Coll Surg 2008 vessel interruption • 10–25% acquired or congenital coagulopathy Shander A. Surgery 2007 © Axel Hofmann/Shannon Farmer – SHEF Meeting Perth August 2010 Hearnshaw SA, et al Aliment Pharmacol Ther 2010 Blair SD, et al Br J Surg 1986

So Why Practice Patient Blood Management?

• • Higher quality and safety: better patient care Lower costs • “Stewardship” of the blood supply – Optimal use of blood – Efficient use of resources

Patient Blood Management: The Three Pillars

• • • • • Pre-op anemia screening Refer for further

Optimize

necessary

erythro poieis

contraindication for elective surgery • • Identify and manage bleeding risk and • anticoagulants • • • • • • ANH

Minimize

DDAVP

bleeding &

Topical hemostatics

blood loss

hemostasis Avoid secondary hemorrhage Minimize phlebotomy © Axel Hofmann/Shannon Farmer – SHEF Meeting Perth August 2010 • Optimize hemodynamics • • • •

Harness & optimize

Low hemoglobin

physiologic

transfusion

tolerance of anemia

infections promptly

Before I go, a topic for another time

• • There is a substantial LACK of evidence that an increased PT/INR (at least < 2.0) can or should be used to make clinical decisions re: benefit of pre procedure frozen plasma Avoid prophylactic plasma transfusions – No proven clinical benefit – Substantial risk of acute pulmonary reactions