State of the art der Bluttransfusion

bei akuter Blutung / perioperativ.

Martin Brüesch / Donat R. Spahn

Conflict-of-Interest

"Die Transfusion ist einer der

sichersten chirurgischen Eingriffe.

Die Sterberate liegt bei einem von

drei Patienten. Damit ist sie noch

niedriger als nach der Behandlung

von Eingeweidebrüchen und

entspricht etwa der Sterberate von

Amputationen. "

1. Transfusion von

Schaf zu Mensch

1667

Denis J. Philos Trans R Soc Lond (1667) 3: 489

Gravitator

Blundell J. Med Chir Trans (1819) 10: 296

Blundell J. Lancet (1829) 1: 431

Hygiene Institut der Universität Wien (um 1900)

Karl Landsteiner

(1868-1943)

Nobel Preis 1930

Why bother about allogeneic blood transfusions ?

Intermittent blood shortages

Adverse effects / risks

High costs

Questionable efficacy

Hemodilution tolerance

Public concern

Spahn D.R. et al. Anesthesiology (2000) 93: 242

Eaton L. BMJ (2004) 329: 308

Stainsby D. et al. Transf Med Rev (2006) 20: 273

Serious hazards of transfusion (SHOT)

SHOT (established 1996)

Data: 1996 – 2004, n = 2630

UK Transfusions: 27 Mio

92

6

28

13

0

93

36

Major Morb

Adverse effectsAcute reactionsMistransfusions 1:14’000-26’000Transmission of infectious diseases HIV, Hepatitis B, C, HTLV I, II Hepatitis E, G, TT virus, HHV8, unknown virus Parasitic and bacterial diseases Prion diseases (February and August 2004) 4 cases

Immunosuppression Increased cancer recurrence Increased postoperative infections

Transfusion related acute lung injury TRALITransfusion related circulatory overload TACO

Spahn D.R. et al. Anesthesiology (2000) 93: 242

Llewelyn, C. A., et al., Lancet (2004) 363: 417 (+ editorial Aguzzi 411)

Peden A.H. et al. Lancet (2004) 364: 527 (+ editorial Wilson 477)

Rana R. et al. Transfusion (2006) 46: 1478

TRALI

Lindgren L. et al. Acta Anaesthesiol Scand (1996) 40: 641

Silliman C.C. et al. Blood (2005) 105: 2266

Crit Care Med (2006) 5 Suppl.

Transfusion Related Acute Lung Injury

« TRALI is the leading cause of transfusion associated mortality »

Incidence 1:5’000 – with 25 mio transfusion per year in the US – 5000 cases

With a mortality of 6% - 300 deaths annually

FDA conference on TRALI in 2004

National Heart Lung and Blood Institute convened a working group to identify areas of research need

First step: Creating a common clinical definition

Toy P. et al. Crit Care Med (2005) 33: 721

Silliman C.C. et al. Blood (2005) 105: 2266

« New » clinical definition of TRALI

Patients without ALI risk factors other

than transfusion

New ALI

non-cardiogenic (PCWP < 18 mmHg)

pulmonary edema (bilateral infiltrates)

Hypoxemia (PaO2/FiO2 < 300 mm Hg)

Onset within 6h after transfusion

Symptoms

Dyspnea, fever, tachycardia, hypotension

Toy P. et al. Crit Care Med (2005) 33: 721

Clinical incidence and relevance

Analysis of 8902 „at risk“ transfusions

in 1352 ICU patients at the Mayo Clinic

Respiratory failure within 6h of

transfusion (new onset of ventilator

support)

Experts: TRALI vs. TACO (circulatory

overload)

94 cases were identified - none was

reported to the local blood bank

Rana R. et al. Transfusion (2006) 46: 1478

Clinical incidence and relevance

Transfusion of:

5044 RBC

2745 FFP

885 Platelet

228 Cryoprecipitate

Incidence of suspected TRALI 1: 1271

Incidence of possible TRALI 1: 534

Incidence of TACO: 1: 356

Mortality: TRALI: 67%, TACO: 20%, Control: 11%

Rana R. et al. Transfusion (2006) 46: 1478

TRALI in a Medical ICU (n=841)

Khan H. et al. Chest (2007) 131: 1308

TRALI: RBC, FFP or platelet transfusion

Khan H. et al. Chest (2007) 131: 1308

TRALI in US: male vs. female donors

550 cases of TRALI reported

201 cases confirmed TRALI

38 fatal confirmed TRALI cases

24 / 38 cases FFP

7 / 38 cases RBC

6 / 38 platelet

1 / 38 case cryoprec.

71% of TRALI cases with female antibody-positive donor

41% of female donors vs. 4% of male donors positive for HLA class I, II or neutrophils AB

Eder A. F. et al. Transfusion (2007) 47: 599

TRALI in US: male vs. female donors

Eder A. F. et al. Transfusion (2007) 47: 599

TRALI in US: male vs. female donors

Eder A. F. et al. Transfusion (2007) 47: 599

TRALI fatalities: 1:200‘000

Underreporting

Stroncek D. F. and Klein H. G. Transfusion (2007) 47: 559

Triulzi D. J. et al. Transfusion (2007) 47: 563

Fresh Frozen Plasma

Indikationen:

Massive Blutung (Blutverlust > 120%), wenn

korrekte Gerinnungstherapie

Faktor V und Faktor XI Mangel

Thrombotisch-thrombozytopenische

Purpura

Leberparenchymerkrankungen mit

Koagulopathie

DIC

RBC transfusion and nosocomial

infection in the ICU

Taylor R. W. et al. (2006) Crit Care Med 34: 2302

Prospective observational study in 2085 ICU patients

Nosocomial infections (NI)

Mortality prediction model (MPM-0) probability of survival (POS)

16

12

8

4

0

7.5

14.3

5.8

Overall157/2,085

Transfused61/428

Nontransfused96/1,657

Efficacy of RBC transfusion

Mortality

Morbidity

Function of the organism

Organ function

Indications for RBC transfusions

Anemia and RBC transfusion in the

critically ill (ABC study - Europe)

Vincent J.L. et al. JAMA (2002) 288: 1499

Pospective observational study (1999) in 146 European ICUs

Blood sampling: 1136 patients

Anemia – transfusion in ICU: 3534 patients

transfused

non-transfused

Anemia and RBC transfusion in the

critically ill (CRIT study - US)

Pospective observational study (2000-2001) in 284 US ICUs, 4892 pat.

ICU and hospital length of stay

Ventilator-associated pneumonia OR 1.89 (1.33-2.68) (>40’000 $)

transfused

non-transfused

Corwin H.L. et al. Crit Care Med (2004) 32: 39

Shorr A.F. et al. Crit Care Med (2004) 32: 666

Are Blood Transfusions Associated

with Greater Mortality Rates?

SOAP (Sepsis Occurrence in Acutely Ill Patients) multicenter

observational study (2002) in 198 EU ICUs, 3147 pat. Substudy

Age, Liver cirrhosis, hem. Cancer, surgical, sepsis

ICU stay, mortality rate, but more severly ill

transfused

non-transfused

Vincent J.L. et al. Anesthesiology (2008) 108: 31

Nuttall G. A. Anesthesiology (2008) 108: 3

„Therefore, the limitations discussed

above suggest that the results

reported by Vincent et al. must be

interpreted with caution.“

RBC transfusion: benefit or harm ?

Transfused patients were

Older

Lower admission hemoglobin

Higher admission lactate

More frequently in shock at admission

SOFA score

APACHE II score

ISS score

Spahn D.R. et al. Critical Care (2004) 8: 89

Hébert P.C. et al.,

New Engl J Med

(1999) 340: 409

Low Hb values in ICU patients

with CV diseases

Subgroup analysis (n=357) of patients with cardiovascular diseases

Hébert P.C. et al., Crit Care Med (2001) 29: 227

All cardiovascular diseases Ischemic heart disease

p = 0.95 p = 0.30

liberal

restrictiverestrictive

liberal

Lacroix J. et al. New Engl J Med (2007) 356: 1609

RBC transfusions in children

637 stable critically ill children (3 days – 14

years) with Hb < 9.5 g/dL

Transfusion trigger: < 7.0 g/dL vs. < 9.5 g/dL

Lowest Hb: 8.7±0.4 vs. 10.8 ± 0.5 g/dL, p< 0.001

Restrictive Group:

44% fewer RBC transfusions

No RBC transfusions: 54% vs. 2%

New or progressive MOF: 38 vs. 39 cases

Mortality: 14 vs. 14 cases

RBC: prestorage leukocyte-reduced

Lacroix J. et al. New Engl J Med (2007) 356: 1609

Perioperative blood conservation

Correction of preoperative anemia

Incidence, type of anemia – treatment options

Minimizing RBC loss during

Optimal surgical technique

Cell salvage

ANH – compensatory mechanisms

Tolerance of minimal Hb levels

Prevention of coagulopathy

Anesthesiological techiques (FiO2, MAP, CVP)

Pharmacologic agents (Fg, antifibrinolytics, rFVIIa)

Optimizing blood transfusion practice

% 30

25

20

15

10

5

0

20-30 31-40 41-50 51-60 61-70 71-80 81-90 >90 Jahre

Incidence of preoperative anemia

Kulier A. et al. Anaesthesist (2001) 50: 73

Frauen

Männer

65’788 patients (1980-2000)

Preoperative evaluation

WHO anemia definition

Preoperative EPO

Preoperative iron deficiency anemia

Treatment with iv iron

Pilot study in orthopedic surgery

20 patients with iron deficiency anemia

Hb < 12 g/dl in women

Hb < 13 g/dl in men

3 x 300 mg iron iv (10 days)

Theusinger O. M. et al. Anesthesiology (2007) 107: 923

21 % of elective orthopedic patients are anemic !

Theusinger O. M. et al.

Anesthesiology

(2007) 107: 923

4804 patients for CABG surgery

72 institutions, 17 countries

28% of male and 36% of female

patients were anemic (WHO)

Prespecified adverse outcomes

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

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

Adverse outcome and preop. Hb

Perioperative blood conservation

Correction of preoperative anemia

Incidence, type of anemia – treatment options

Minimizing RBC loss during

Optimal surgical technique

Cell salvage

ANH – compensatory mechanisms

Tolerance of minimal Hb levels

Prevention of coagulopathy

Anesthesiological techiques (FiO2, MAP, CVP)

Pharmacologic agents (Fg, antifibrinolytics, rFVIIa)

Optimizing blood transfusion practice

Physiologic transfusion triggers

Physiologic signs of insufficient

oxygenation of an organ / organism

Hemoglobin based transfusion trigger

Hemoglobin < (arbitrary) threshold

Spahn D.R. and Madjdpour C. Anesthesiology (2006) 104: 905

Physiologic transfusion triggers

Relative tachycardiaHR > 120-130 % BL, > 110-130 bpm

Relative hypotensionMAP < 70-80% BL, < 60 (55) mmHgMAP < 70-80 mmHg in patients with CAD, cerebrovascular disease or hypertension

ST-segment > 0.1 mV

(ST-segment > 0.2 mV) – MI ?

New wall motion abnormalities in TEE

VO2 > 10%

O2-Extraction > 50%

PvO2 < 32 mmHg (4.3 kPa)

Madjdpour C. et al. Crit Care Med (2006) 5 Suppl: S102

Spahn D.R. Best Pract & Res Anaesth (2004) 18: 661

Hb TT – Evidence and Reality

Evidence Reality in hospital

publ./teaching

OR / ICU Ward

All patients 6 g/dL 6-7 g/dL 7-8 g/dL

> 80 years 7-8 g/dL 8-9 g/dL

Severe CAD 8 g/dL 8-9 g/dL

Signs of CHF 8 g/dL 8-9 g/dL

Cerebro-VD 8 g/dL 8-9 g/dL

> 1 catechol 8 g/dL na

SaO2 < 90% 8-9 g/dL 9 g/dL

Madjdpour C. et al. Crit Care Med (2006) 5 Suppl: S102

Spahn D.R. Best Pract & Res Anaesth (2004) 18: 661