Outcome of Transfusion The urgend need to implement ... · RBC transfusion survival Study in a rural hospital in Kenya on the effect of RBC transfusion in children with malaria induced

Outcome of Transfusion

The urgend need to implement

Patient Blood Management

Donat R. Spahn

Conflict-of-Interest

Consulting for B. Braun, CSL Behring, Vifor International

ABC / ABC trauma faculty, managed by Thomson Physicians World GmbH (unrestricted educational grant - Novo Nordisk and CSL Behring)

In the past 5 years I received honoraria / travel support for occasional consulting / lecturing:

Abbott AMGEN

Astra-Zeneca Baxter

Bayer B. Braun

Boehringer Ingelheim Bristol-Myers Squibb/Pfizer

CSL Behring Ethicon Biosurgery

Essex Fresenius Kabi

Galenica (Vifor AU, CH, G) GlaxoSmithKline

Janssen-Cilag Merck Sharp & Dohme

Octapharma Organon

Oxygen Biotherapeutics TEM Innovations (Pentapharm)

ratiopharm Roche

What is

Patient Blood Management ?

Donat R. Spahn

Gombotz H. et al. Anästhesist (2013) 62: 519

Gombotz H. et al. Anästhesist (2013) 62: 519

Axel Hofmann Vifor Zurich 07-2012

„[PBM] goes beyond the concept of appropriate use of blood products, because it preempts and significantly reduces the resort to transfusions by addressing modifiable risk factors that may result in transfusion long before a transfusion may even be considered.“

PBM – Preempting Transfusion by Addressing Modifiable

Risk Factors

Hofmann A, Shander A, Farmer S. Five Drivers Shifting the Paradigm from Product Focused Transfusion Practice to Patient Blood Management. Oncologist. 2011;16. (suppl3):3-11

Courtesy of Dr. A. Hofmann

The problems ?

Incidence of anemia is high (30%) and per se

Mortality + Major Morbidity

Predisposes for RBC transfusions

Incidence of iron deficiency is high (25%) and

Morbidity

Predisposes for RBC transfusions

RBC transfusion per se

Mortality + Major Morbidity

Short term preoperative EPO and iv iron

RBC transfusion

Acute renal failure

LOS () Musallam K. M. et al. Lancet (2011) 378: 1396

Piednoir P. et al. Europ J Anaesth (2011) 28: 796

Spahn D. R. et al. Lancet (2013) 381: 1855

Yoo Y-C. et al. Anesthesiology (2011) 115: 926

Triad of

Independent

Risk Factors

for

Adverse Outcomes


Anaemia

Blood loss

&

bleeding

Transfusion


Optimise

red cell

mass

Minimise

Blood loss

& bleeding

Harness &

optimise

physio-

logical

reserve of

anaemia

Multidisciplinary team approach


Anaemia

Blood loss

&

bleeding Transfusion




RBC transfusion survival

Study in a rural hospital in Kenya on the effect

of RBC transfusion in children with malaria

induced anemia

RBC transfusion within the first 2 days

reduced mortality:

In children with a Hb < 3.9 g/dL

In children with a Hb < 4.7 g/dL and respiratory

distress

Lackritz, E. M. et al. Lancet (1992) 340: 524

English M. et al. Lancet (2002) 359: 494

Holzer B. R. et al. Acta Trop (1993) 55:47

Bojang K. A. Trans R Soc Trop Med Hyg (1997) 91:557

Meremikwu M. et al. Cochrane Database Syst Rev 2000:CD001475

RBC transfusion can be life-saving

Severe malaria induced anemia in children

Major trauma with exsanguination

Major surgery in severely anemic patients

without possibility of preoperative anemia

correction

Very severe intra- / postoperative anemia with

signs of cardiovascular insufficiency Lackritz, E. M. et al. Lancet (1992) 340: 524

English M. et al. Lancet (2002) 359: 494

Meremikwu M. et al. Cochrane Database Syst Rev 2000:CD001475

Spahn D. R. et al. Crit Care (2013) 17:R76


Wu W. C. et al. Ann Surg (2010) 252: 11

RBC transfusions result in

Mortality

Length of hospital stay

Organ dysfunction

Lung injury (TRALI, TACO)

Renal impairment

Stroke

Myocardial infarction

Infection

Transfusion reactions

Tumor growth promotion

Costs

Non-Hodgkin lymphoma


Correct preoperative anemia Iron (iv) + EPO

Reduce perioperative RBC loss Surgical technique

Cell salvage and re-transfusion

Acute normovolemic hemodilution

Coagulopathy (anti-fibrinolyt., fibrinogen, F XIII, PCC)

Low CVP, no hypertension, normothermia,

Optimize anemia management Tolerate low hemoglobin values (restrictive TT)

Iron (iv) + EPO postoperatively

FiO2


Spahn D. R. et al. Anesthesiology (2008) 109: 951

Williamson L. M. Lancet (2013) 381: 1866


WHO urges member states to „promote the

availability of transfusion alternatives including,

where appropriate, autologous transfusion and

patient blood management“

http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_R12-en.pdf,

accessed, 2012-02-24

http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_R12-en.pdf



Musallam K. M. et al. Lancet (2011) 378: 1396

ACS NSQIP surgery 2008

N = 227’425 patients

No anemia vs.

Mild anemia (HCT 30-39% / 30-36%)

Moderate-severe anemia (HCT < 29%)

Outcome:

Mortality and 7 types of major morbidity

Preoperative anemia: 30.4%

Mild anemia OR mortality : 1.4 (1.3 – 1.5)

Mild anemia OR morbidity : 1.3 (1.3 – 1.4)

RBC trans. OR mortality : 2.0 (1.8 – 2.2)

RBC trans. OR morbidity : 1.8 (1.7 – 1.9)

Musallam K. M. et al. Lancet (2011) 378: 1396

RBC transfusion and outcome

N Anemia Anemia RBC

Transfusion

Kulier 4‘804 28% / 36% (+) ++

Murphy 8‘598 not eval. ++

Karkouti 3‘500 26% + +

Kulier A. et al. Circulation (2007) 116: 471

Murphy G. J. et al. Circulation (2007) 116: 2544

Karkouti K. et al. Circulation (2008) 117: 478

Mortality

Major morbidity (ischemia)

Loor G. et al. J Thorac Cardiovasc Surg (2013) Epub

9’144 patients undergoing cardiac surgery

with CPB

Period: 2004 - 2009

Patients without RBC perioperatively (7’942)

Patients with only intraoperative RBC (1’202)

Patients with postoperative RBC excluded (!)

Outcome in relation nadir HCT< 25% / RBC:

Mortality, eGFR, troponin, ventilator time, LOS



Call for Patient Blood Management

Do not operate anemic patients

Ensure minimal operative blood loss

Then you avoid low HCTs and RBC transfusions

Ferraris V. A. et al. Arch Surg (2012) 147: 49

ACS-NSQIP

Surgery 2005 – 2009

N = 941‘496

48’291 patients received RBCs

15’186 patients received 1 single RBC unit

Propensity score matching 2 x 11’855 p.



D n Cost

Wound problems (500$) 201 100’500$

Pulmonary complications

(1’500$)

426 639’000$

Renal problems (1000$) 154 154’000$

Sepsis (5’000$) 284 1’420’000$

Length of stay (500$) 17’782 8’891’250$

Total 11’204’500$

Extra costs per transfused

patient (1 single unit RBC)

945$

Cost of a RBC transfusion

Shander A. et al. COBCON I Transfus Med Rev (2005) 19: 66

Shander A. et al. Best Pract Res Clin Anaesthesiol (2007) 21:271

Acquisition cost

1unit of RBC = 230 CHF

Process cost analysis

Process cost analysis (PCA)

Shander A. et al. Transfusion (2010) 50:753

1’000 $

450 €

945 $

“unknown” costs for

donation and RBC

production, and the treatment

of adverse effects such as

postoperative infections,

TRALI, tumor growth

promotion, hemovigilance

programs, litigation and

(mortality)

True costs of 1 u of RBC in surgery

+

Shander A. et al. Transfusion (2010) 50:753


Carson J. L. et al. New Engl J Med (2011) 365: 2453

RBC transfusion and outcome in elderly

high-risk patients in hip surgery

PRT in 2016 patients with hip fracture and CAD and a postop. Hb < 10 g / dL

Hb transfusion triggers: Hb < 10 g/dL vs.

Symptoms of anemia (angina, signs of cardiac failure, HR, MAP) or Hb < 8 g/dL

Exclusion criteria: Inability to walk, MI (30 d) and symptoms of anemia

Primary Outcome: Mortality and inability to walk 4 m at 60 days


RBC transfusion and outcome in elderly

high-risk patients in hip surgery

Liberal Restrictive

RBC Transfusion (%) 100% 41%

RBC Transfusion (u) 2 0

Mortality 7.6% 6.6%

Inability to walk 27.6% 28.1%


Carson J. L. et al. Cochrane Database of Systematic Reviews (2012) 4:

DOI: 10.1002/14651858.CD002042.pub3

Transfusion triggers and outcome

19 PRT with 6264 patients, Restr. vs. liberal

Restrictive transfusion triggers

RBC transfusions -39% (RR 0.61 (0.52-0.73)

No adverse outcomes

Hospital mortality -23% (RR 0.77 (0.62-0.95)

30 day mortality -15% (RR 0.85 (0.70-1.03)

Infections -19% (RR 0.81 (0.66-1.00)

For most patients Hb TT of 7.0 – 8.0 g/dL

Carson J. L. et al. Cochrane Database of Systematic Reviews (2012) 4:

DOI: 10.1002/14651858.CD002042.pub3

Villanueva C. et al. New Engl J Med (2013) 368: 11

Laine L. New Engl J Med (2013) 368: 75

RBC transfusion and outcome in

patients with acute upper GI bleeding

PRT in 912 patients with acute upper GI bleeding

Randomization was stratified by liver cirrhosis

Hb transfusion triggers – 1 unit transfusion: Hb < 9 g/dL vs.

Hb < 7 g/dL

Primary Outcome: Mortality at 45 days

Secondary Outcomes: Secondary bleeding

In-Hospital complications




Mechanisms of

RBC toxicity Immunomodulation

Immunosuppression

– T cell activity

–Macrophage activity

–Natural killer cell activity

Inflammatory potential

Storage lesion

Stiffness tissue oxygenation

Hemolysis liberation of Hb, growth factors

Microvesiculation coagulation

2,3 DPG , ATP

RBC adhesiveness

Baek J. H. et al. J Clin Invest (2012) 122:1444

Gladwin M. T. et al. J Clin Invest (2012) 122:1205

Baek J. H. et al. J Clin Invest (2012) 122:1444

Gladwin M. T. et al. J Clin Invest (2012) 122:1205

Transfusion of stored RBC in guinea pigs

Hypothesis: Storage RBC stiff and hemolysis ,

free hemoglobin organ damage

80% BV exchange, “old” RBC = 28 days GP

Ba

ek

J. H

. e

t a

l. J

Cli

n In

ve

st

(20

12

) 1

22

:14

44

Histology of aortic

arch at 24h / 48h

Ba

ek

J. H

. e

t a

l. J

Cli

n In

ve

st

(20

12

) 1

22

:14

44

Correct preoperative anemia Iron (iv) + EPO

Reduce perioperative RBC loss Surgical technique

Cell salvage and re-transfusion

Acute normovolemic hemodilution

Coagulopathy (anti-fibrinolyt., fibrinogen, F XIII, PCC)

Low CVP, no hypertension, normothermia,

Optimize anemia management Tolerate low hemoglobin values (restrictive TT)

Iron (iv) + EPO postoperatively

FiO2


Spahn D. R. et al. Anesthesiology (2008) 109: 951

Farrugia A. Transfusion (2011) 51: 216

Spahn et al. Lancet (2013) 381: 1855

http://www.nba.gov.au/guidelines/review.html

Time !

Intra- and postop. iv Iron + EPO

Na H. S. et al. Transfusion (2011) 51: 118

Transfusion rate : 20 vs. 54%, p< 0.01

PRS in patients with iron deficiency undergoing bilateral TKA

Iv iron (200 mg) and sc rHU-EPO-b (3000u) intraoperatively

and up to 2 times postop if Hb = 7 - 8 g/dL

RBC transfusions at Hb < 7 g/dL



Fox A. A. et al. Anesthesiology (2011) 115: 912

Anemic patients (WHO), n=74

EPO 500 U/kg + 200 mg iv iron; 1 day bOP

Hb-TT: < 7 g/dL at CPB, < 8 g/dL post CPB

Transfusion-rate: 86% vs. 59% (p=0.009)

RBC-POD4: 3.3±2.2 vs. 1.0±1.1 (p=0.001)

Postop. AKI: 54% vs. 24% (p=0.017)

LOS: 13.5±8.0 vs. 11.3±4.1 days (p=0.113)

Munoz M. et al., Transfusion (2013) epub

All patients

Iv iron / EPO Control p

Transfusion rate 24.2% 36.9% 0.001

Nosocomial infection

rate

7.9% 12.0% 0.001

LOS 10.7 d 11.7 d <0.001


RBC transfusion

Elective arthroplasty / hip fracture


Elective arthroplasty Hip fracture

Leahy M. F. et al., Transfusion (2013) epub

PBM programs

Highly efficacious overall

However, in all publications it

becomes clear that the PBM programs

were successful only in a few of all

components

Despite being highly efficacious, the

full potential has not been realized at

all in any of the programs

Patient Blood Management – 1. Pillar


Patient Blood Management – 1. Pillar


Conclusion

Preoperative anemia is associated with

serious adverse outcome

Perioperative RBC transfusions cause

serious adverse outcome

Unmanaged anemia (Hb < 120 g/L in

women; Hb < 130 g/L in men) is a

contraindication for elective surgery

Patient Blood Management is the way to

go and needs to be implemented now

Spahn D.R. et al. Anesthesiology (2011) 114: 283


Documents

Outcome of Transfusion The urgend need to implement ... · RBC transfusion survival Study in a rural hospital in Kenya on the effect of RBC transfusion in children with malaria induced