TECHNIKI POSTĘPOWANIA

UMOŻLIWIAJĄCE

OSZCZĘDZANIE KRWI

BLOOD SAVING STRATEGIES

Risks concerning blood transfsusion

Risks concerning blood transfsusion

Current Opinion in

Current Opinion in

Anaesthesiology 2007

Anaesthesiology 2007

• Transmission of infection

• Prolonged wound healing

• Reactions connected with transfusion

• TRALI (Transfusion-related acute lung injury)

• Immunomodulation

• Potential risk of cancer regression

• Human mistaces

Complications

Complications

(Best practice & Research

(Best practice & Research

Clinical Anaesthesiology 2007;21:221-239)

Clinical Anaesthesiology 2007;21:221-239)

mistake acute haemolytic reaction 1:6000-1:33000
delayed haemolytic reaction 1:2000-

1:11000

viral infection HIV 1:20 millions
hepatits A 1:1 millions

hepatits B 1:63000-1:320000
hepatits C 1:1.2-1:11 millions
CMV 1:10-1:30
EBV 1:200

Bacterial infection Yersinia enterocolica 1:200000-1:4.8

millions

Serratia marcescens, Pseudomonas
enterobacterie

immunologic TRALI 1:4000
immunisation 1:16000
immunosuppression 1:1
allergic reactions 1:2000

Possible ways to decrease the risk

Possible ways to decrease the risk

of complications

of complications

•

Improvement of procedures that decrease
the risk of infectious agents transmission

•

Guidelines for blood transfusion

•

Methods and techniques leading to reduce
frequency of allogenic blood transfusion



Techniques concerning the use of patient’s own

blood

1. acute normovolemic hemodilution

2. preoperative blood deposit

3. intra- and postoperative reclaim of morphotic
elements



blood substitutes instead of allogenic blood



the use of pharmacologic methods dereasing

blood loss in the

perioperative period

ACUTE, NORMOVOLEMIC

ACUTE, NORMOVOLEMIC

HEMODILUTION

HEMODILUTION



moderate

( Ht 26-30% )



extreme

( Ht 15-20% )

Blood is collected in the OR.

Blood volume is counted according to a

rule

GROSS’ RULE:

V = EBV x [ (Ht

0

– Ht

t

) / Ht

0

]

EBV~70ml/kg

MECHANISMS THAT COMPENSATE

MECHANISMS THAT COMPENSATE

OXYGEN DELIVERY TO THE TISSUES

OXYGEN DELIVERY TO THE TISSUES

•  cardiac output
•  stroke volume
•  preload ( blood viscosity)
•  afterload

KEEPING NORMOVOLEMIA IS

CRUCIAL

ACUTE, NORMOVOLEMIC

ACUTE, NORMOVOLEMIC

HEMODILUTION

HEMODILUTION

THE EFFECT DEPENDS ON:



initial hematocrit



hematocrit at the moment of collected

blood transfusion



volume of collected blood



intraoperative blood loss

ADVANTAGES OF ACUTE,

ADVANTAGES OF ACUTE,

NORMOVOLEMIC HEMODILUTION

NORMOVOLEMIC HEMODILUTION



no need for laboratory tests



minimising the risk of human errors

(blood

doesn’t leave OR)



safety (continuous monitoring of
patient’s condition)



no need for the patient to spend additional
time for blood testing etc.

RISKS

RISKS

OF ACUTE, NORMOVOLEMIC

OF ACUTE, NORMOVOLEMIC

HEMODILUTION

HEMODILUTION



possibility of tissue ischemia if

compensation is not adequate



coagulation pathology as an effect of

blood dilution



increased blood loss as a result of

increased tissue perfusion (clinically

not important)

„

AUGMENTED” - ANH

Combination of normovolemic

hemodilution with preoperative

supplementation of

erythropoiethin

or

artificial oxygen carriers

Advantages of preoperative blood

Advantages of preoperative blood

deposit

deposit

1.

Potentially excludes possibility of viral

infection and the risk of post-transfusional

reaction

[but 1:100 000 –HIV; 5% - fever ]

2.

It may decrease the risk of postoperative

infections and neoplasmatic regression

(elimination of immunosuppression)

Disadvantages of preoperative

Disadvantages of preoperative

blood deposit

blood deposit

1.

Doesn’t eliminate the risk of bacterial

contamination or fluid overload of

cardiovascular system

2.

Doesn’t eliminate the risk of human error

concerning incompatibility of blood ABO

system

3.

Higher costs than those of allogenic

deposit?

4.

Blood is not always transfused.

5.

Results in preoperative anaemia and

creates possibility if allogenic transfusion.

Criterions for patient’s qualification for

Criterions for patient’s qualification for

preoperative blood deposit.

preoperative blood deposit.



Sufficient circulatory system



Infection - excluded



Hematocrit > 30% and Hb > 11g/dl
before each blood collection



No age limit



Visible veins, easy to puncture

Criterions for patient’s qualification for

Criterions for patient’s qualification for

preoperative blood deposit.

preoperative blood deposit.

Maximum 2 units per one donation-

about 10% of circulating blood volume

Usually 1 unit/week, 2-4 weeks before

planned surgical procedure.

No later than 72 hrs before surgical

procedure

Reclaim of morphotic elements

Reclaim of morphotic elements

Cell Salvage

Cell Salvage

•

Lost blood is suctioned, lavaged in a special

Lost blood is suctioned, lavaged in a special

centrifuge and given back to patient

centrifuge and given back to patient



Washed blood containes only erythrocytes, Ht>50%

Washed blood containes only erythrocytes, Ht>50%



Plasma and washing fluid are separated and

Plasma and washing fluid are separated and

thrown away

thrown away



Quality of

Quality of

intraoperatively

intraoperatively

reclaimed erythrocytes

reclaimed erythrocytes

is good

is good



Quality of blood

Quality of blood

postoperatively

postoperatively

reclaimed

reclaimed

erythrocytes is poor

erythrocytes is poor



infected surgical field

infected surgical field



operation on cancer tumor

operation on cancer tumor



sepsis

sepsis

Cell Salvage

Cell Salvage

„

„

machine autotransfusion”

Contraindications

Machine autotransfusion

Side effects



dilutional coagulopathy ( lack of

plasma)



free hemoglobin is delivered

(checking its concentration is
neccessary)

„BLOOD

SUBSTITUTES”:

ARTIFICIAL OXYGEN

CARRIERS

Perfluorocarbons

Free hemoglobin solutions

Ideal blood substitute

Ideal blood substitute

• no antigen character

• Similar to blood concerning O

2

i CO

2

transport and

delivery

• Doesn’t result in ↑ arterial and pulmonary BP

• Long enough T1/2

• NO: metHb production, activation of immuologic

reaction, ↑ WBC, reaction with plasma and plateletes
substitutes

Ideal blood substitute

Ideal blood substitute

• No nephrotxicity

• Stable at room temperature

• Immediate availability

• Easy to administer

• Do not block reticuloendothelial system

• Easy to store

• Do not produce free radicals

Free hemoglobin solutions

HBOC

SOURCES

• human hemoglobin
• bovine hemoglobin
• recombinated
hemoglobin

• transgenic
hemoglobin

Free hemoglobin solutions

• allogenic, ksenogenic i recombinant
• sources of Hb:

human (lysis of RBC)

animal: bovine, transgenic pig

biotechnology: Escherichia coli and

Sarcomyces cerevisiae

Modification of Hb:

cross -linked

closing in
microcapsules

polimerisation

Free hemoglobin solutions

Free hemoglobin solutions

• Experiments on animals – 1934
•
• Use in human - 1949

• I generation didn’t pass clinical phase (worsening of cells

oxygenation, increase of morbidity and mortality)

• 1980s ,,second generation”

• Nowadays 2 products are in the final phase of research

-Hemopure (HBOC-201 – polimeric bovine Hb)
well tolerated in surgical patients (Extracorporeal circuit

and

aortic reconstruction - late

metHb)

april 2001 in South Afric Republic in surgical patients with

anemia

HBOC-200 – vetrinary drug. FDA – for use in dogs with

- Poly-Heme (polimeric human B - trauma patients)

Hemospan ( Hb linked with poliethylene glycol) – research has

began

Free hemoglobin solutions

Free hemoglobin solutions

FREE HEMOGLOBIN SOLUTIONS

FREE HEMOGLOBIN SOLUTIONS

Non-polimeric

half-life in circultory system - 6-8 hrs

polimers

half-life may be prolonged, but still is
relatively short vs erythrocytes life
time

FREE HEMOGLOBIN

FREE HEMOGLOBIN

SOLUTIONS

SOLUTIONS

Controversions:

•

high affinity to NO - vasoconstrictive effect

high affinity to NO - vasoconstrictive effect

(inreased resistance)

(inreased resistance)

•

pro-coagulation effect

pro-coagulation effect

•

vasoconstriction more expressed than

vasoconstriction more expressed than

advantageous effect of improved oxygenation

advantageous effect of improved oxygenation

•

price: 400-800$ /unit vs 100-150$ /RBC unit

price: 400-800$ /unit vs 100-150$ /RBC unit

•

quantity of sources

quantity of sources

FREE HEMOGLOBIN SOLUTIONS

FREE HEMOGLOBIN SOLUTIONS

Advantages

• no serology problems
• do not contain leucocythes
• minimal risk of contamination
• powder – may be stored for

several years

NEW

NEW

LOOK AT HEMOGLOBIN

LOOK AT HEMOGLOBIN

SOLUTIONS

SOLUTIONS



Solutions of free hemoglobine may penetrate to all organs

(low viscosity, transported by plasma)



Act in microcirculatory system in adifferent way than

erythrocytes



Precapillary sphincters regulate erythrocytes transport, but not

the plasma’s – free hemoglobine may pass thru contracted

vessels – local oxygenatin increases even if vasoconstriction

exists

PERFLUOROCARBONS

PERFLUOROCARBONS



high affinity to O

2

i CO

2



chemically and biologically neutral, water
soluble



as O

2

carriers they must be in a form of

emulsion

PERFLUOROCARBONS

PERFLUOROCARBONS

Advantages



stored up to 2 years



no serology required



no risk of transmission of infectious disease



oxygen is not binded, but dissolved



1 unit ( 100ml) ~ 300-600 ml RBC



most of molecules stay in bloood for several

hrs

PERFLUOROCARBONS

PERFLUOROCARBONS

Disadvantages



Small paricles- foreign bodies



muscle pains, fever, nausea – flu-like

syndroms



Spleno, hepatomegaly



decreased number of platelets



Some molecules „survive” for about
2 years

(PFC are not metabolised)

PERFLUOROCARBONS

PERFLUOROCARBONS



Ability to carry oxygen is proportional to O

Ability to carry oxygen is proportional to O

2

2

partial

partial

pressure in blood

pressure in blood



Mechanical ventilation is neccessary

Mechanical ventilation is neccessary



Use may be combined with ANH

Use may be combined with ANH

• Perftoran (Moscow, Rosja) used in Russia

Pharmacological ways to decrease bleeding

Pharmacological ways to decrease bleeding



Desmopressin



Aprotinin



Lysine analogues:

 aminocaproic acid
 tranexamic acid



recombinant factor VIIa

DESMOPRESSIN

DESMOPRESSIN

(synthetic analogue of vasopressin)

(synthetic analogue of vasopressin)

Intravenously or intranasally



Stimulates endothelium to release
vonWillebrand’s factor



Increases 2-20 times factor VIII concentration



Benefits for patients with



hemophilia,



platelets disfunction in the course of uremia,



hepatic insufficiency – when used during surgical
procedures

APROTININ

APROTININ

Inhibits



formation of XIIa



intrinsic pathway of coagulation



fibrinolysis

├ proteases, esp. trypsin, chymotrypsin,

kalikrein and

plasmin

Lysine analogues

Lysine analogues

Inhibitors of fibrinolysis

Plasminogen plasmin

rFVIIa

rFVIIa

NovoSeven

NovoSeven

®

®



Product of genetic recombination of DNA



Inactive beyond the limits of injury



Well tolerated



No reports in the literature about

thrombotic complications

Mechanism of action

Mechanism of action

Concentration in plasma

Concentration in plasma





25 nmol/L:

25 nmol/L:

interaction with TF – (tissue factor)

interaction with TF – (tissue factor)

at the site of

at the site of

injury or with phospholipids of activeted platelets

injury or with phospholipids of activeted platelets

and direct activation of factor IX i X

and direct activation of factor IX i X





↑

↑

of thrombin concentration and acceleration of local

of thrombin concentration and acceleration of local

hemostasis

hemostasis

Result depends on pH

Result depends on pH

- lower effectiveness in acidosis

- lower effectiveness in acidosis



rFVIIa cannot be cosidered as an universal

solution in

case of „coagulation problems” or
insted of surgery

when there is „surgical” bleeding



it’s use has to be limited



it’s expensive



there are no rational reasons for using

rVIIa instead of „normal therapy”



when all alternative possibilities had been

used, rVIIa

may be used as an attent to
„rescue therapy”

rFVIIa has been registrated for treatment

of bleeding and preservation of

hemostasis in perioperative period

for patient suffering from hemophilia

with lack of factor VIII (type A) i IX (type

B)

DOSING OF rFVIIa

DOSING OF rFVIIa



only iv rute



Large range of dosing:

from the lowest effecive- 20 g/kg up to 120 g/kg



200 g/kg in open trauma (class B

recommendation)



not recommended in penetrating trauma (class B)



doses repeated after 1-4 hrs