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Pharmacological Methods to Reduce Blood Loss in Surgery PowerPoint PPT Presentation


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Pharmacological Methods to Reduce Blood Loss in Surgery. George Despotis, MD Associate Professor of Anesthesiology, Pathology and Immunology Department of Anesthesiology and Blood Bank Washington University School of Medicine St. Louis, Missouri.

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Pharmacological Methods to Reduce Blood Loss in Surgery

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Pharmacological Methods to Reduce Blood Loss in Surgery

George Despotis, MDAssociate Professor of Anesthesiology, Pathology and Immunology Department of Anesthesiology and Blood Bank Washington University School of Medicine St. Louis, Missouri


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Reexploration for Bleeding: Risk Factors and Outcomes

Unsworth et al

(n=2221)

Moulton et al

(n=6015)

Dacey et al

(n=8586)

Reexploration for bleeding

4.2%

3.6%

3.8%

CPB time

 time

 time

Procedure

Non-coronary OP

 # grafts

Valve/Repeat

Other factors

 Age,  Cr

 Age,  BSA

 x4

Mortality

 x4

 x3

Renal Failure

 x18

Mech vent support / ALI

 x5

Sepsis / arrhythmias / IABP

 x2

 x6

Hospitalization interval

 x2

Dacey LJ et al, Arch Surg 1998; 133: 442-7

Moulton MJ et al, J Thorac Cardiovasc Surg 1996; 111: 1037-46

Unsworth-White et al, Ann Thorac Surg 1995; 59: 664-7

Risk Factors

Adverse Outcomes


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Pathophysiology of CPB-Related Hemostatic Abnormalities

HEMODILUTION

ACTIVATION

CONSUMPTION

Contact activation • XIIa, KallikreinTissue Factor activation •Tissue Injury• Monocyte-related• Pericardial bloodActivation of fibrinolysis • Increased tPA via: -endothelial cells -pericardial cavity• Intrinsic activation • Heparin or Protamine

Thrombin-mediated Plasmin-mediatedInflammation-mediated:• Elastase• Complement• Leukocyte-platelet complexes Mechanical (ECC): oxygenator, cardiotomy suction, roller/centrifugal pump, filter

CPB prime (crystalloid/colloid) Cardioplegia volumeExtensive use of cell salvage systems (loss of platelets/ coagulation factors)

Despotis GJ et al, Anesthesiology 1999; 91: 1122-51


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Non-Bleeders (n=31)

Bleeders (n=42)

*

CPB Time

121 min

200 min

*

CTD 24 hrs

1051±509 mL

1594±1440 mL

*

Postop TDE

1.9±4.2 U

8.2±11.1 U

0

FIX 122

*

p < 0.05

FVIII 137

FIX 98

-20

% Decrease

FVII 58

FXII 53

FVII 48

FIB 196

-40

FVIII 90

FX 53

FXII 40

*

PLT 118

FX 36

*

FV 42

*

FIB 170

-60

PLT 83

*

FV 26

*

pre-CPB

post-CPB

*

-80

Despotis GJ et al, J Thorac Cardiovasc Surg 1994;107:271-79


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OPERATIVE PREDICTORS OF MICROVASCULAR BLEEDING

Single

Combined

37/248 (0.15)

25/61 (0.41)

[0.14]

[0.44]

[0.44]

1.0

PrimaryOperation

0.5

Incidence of MVB

0

12/42 (0.29)

9/10 (0.9)

[0.33]

[0.71]

1.0

Reoperation

0.5

0

Despotis GJ et al, J Thorac Cardiovasc Surg 1994;107:271-79

Single vs Combined Procedures

Operative History


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PHARMACOLOGIC PRESERVATION OF THE HEMOSTATIC SYSTEM

  • Platelet inhibition: - Dipyridamole - Prostacyclin (PGI2), PGE1 - IIb/IIIa receptor inhibition: Abxcimab, integrelin

  • Broad-spectrum inhibition: Aprotinin

  • Plasmin inhibition: Tranexamic Acid, EACA

  • Thrombin and Factor Xa inhibition: - Heparin: LMWH (Xa) vs UFH (Xa/IIa) - Heparin Adjuncts: AT III, HCF II (Dermatan Sulfate) - Warfarin - Direct Thrombin Inhibitors


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Reduction in Blood Loss and Transfusion by Aprotinin

Alderman 1998 n=870

Lemmer 1996 n=317 (704)

Levy 1995n=126 (278)

Lemmer 1994 n=216

Primary

Primary

Repeat

Both

15

2000

5%

3%

3%

4%

12

1600

9

1200

Mean Total Donor Exposures (U)

Blood Loss: CTD (mL)

0

1%

0

1.6%

6

800

3

400

0

0

P

A

P

A

P

A

P

A


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Efficacy of Aprotinin Based on Dose and Operative Risk

Lemmer 1996n=704 primary

Levy 1995n=278 repeat

12

1600

9

1200

Blood Loss: CTD (mL)

Mean Total Donor Exposures (U)

6

800

3

400

ASA

No ASA

0

0

P PO LD HD

P PO LD HD


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Reduction in Blood Loss & Transfusion: Aprotinin vs EACA

EACA: 9 studies (n = 932)

Aprotinin: 4 studies (n = 1529)

15

15

2000

4.0%

12

12

1600

p=0.006

9

9

1200

Mean Total Donor Exposures (U)

Blood Loss: CTD (mL)

27% in PRBC Tx

1.6%%

6

6

800

3

3

400

0

0

0

P

P

A

E


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Mechanisms of Action: Aprotinin vs Antifibrinolytic Agents

Aprotinin

EACA / TA

Yes

Yes

Preservation of Fibrinogen, Factors V, VIII

Yes

Yes

Preservation of Platelet GP 1b receptors

Yes

Yes

Reduced Platelet Inhibition via FDPs

Yes*

No

Inhibition of Contact Activation

Probable*

No

Inhibition of Tissue Factor Activation

Yes*

No

Inhibition of Platelet Activation / Consumption

Yes*

No

Antiinflammatory Properties

Yes**

No

Inhibition of Protein C Activity

Antifibrinolytic Actions:

Effect on Hemostatic System Activation:

*200 KIU/mL** > 250-300 KIU/mL


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CHALLENGES TO HEMOSTATIC SYSTEM BALANCE DURING CPB

GOAL: EFFECTIVE HEMOSTASIS

HEMORRHAGE

THROMBOSIS

ADEQUATE AND REVERSIBLE ANTICOAGULATION

Pre-existing HYPERCOAGULABILITY:ATIII/Protein C/S, FV Leiden, LA/ACLAbs,

 homocysteine, HIT, h/o thromboembolism,

h/o CHF, hypoperfusion

INHIBITION OF FIBRINOLYSIS (e.g. EACA) or PROTEIN C (e.g. >300 KIU/mL Aprotinin)

INCREASED PROCOAGULANTS DDAVP (e.g. vWF), Tx (e.g. platelets, FEIBA)

 INADEQUATE SUPPRESSION OF

HEMOSTATIC ACTIVATION DURING CPB

 DECREASED PROCOAGULANTS

CPB hemodilution, consumption INHIBITION OF HEMOSTASIS

- Antibodies to platelets, coag proteins

- Xa/IIa inhibitors (e.g. LMWH, r-hirudin)

- Platelet inhibitors (e.g Plavix, ? Reopro)

- Heparin rebound, FFP Tx (i.e., ATIII)


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Summary for Bleeding Complications

Perioperative Bleeding Complications:

Can lead to adverse outcomes related to complications

associated with reexploration, transfusion and CNS injury

Patients at high-risk include those: with congenital defects,

on long-acting anti-thrombotic agents, with trauma, or

patients who require complex cardiac procedures (CPB)

Prevention

 When compared to EACA/TA, aprotinin (full-dose regimen):

- is probably more effective in reducing bleeding,

transfusion and reexploration in high-risk patients

- and has an extensive safety record

Optimal Anticoagulation results in preservation of the hemostatic

system especially with prolonged CPB which leads to reduced

blood loss / transfusion and possibly thrombotic complications


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Summary for Bleeding Complications

Optimal Management of excessive bleeding:

Although laboratory-based tests may be helpful, the history

and physical exam should preoperatively identify patients

at risk who require further laboratory evaluation

 Use of POC diagnostic tests along with a standardized

transfusion approach (e.g. algorithm) can optimize

perioperative transfusion/pharmacologic (e.g. DDAVP)

management

 Although factor concentrates used as a rescue therapy can

be life-saving, thrombotic risk and cost preclude routine use


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