Cardiopulmonary Bypass in infants and childreninfants and children

The impact of priming solutions and volumes

Helen Holtby MB BS FRCPCHelen Holtby MB, BS FRCPCHospital for Sick Children Toronto

The Ideal Cardiopulmonary Bypass Prime …

Would be physiologic mild hypocalcemia

Would not trigger:inflammationimmune response

Would prevent macro or microthrombosisWould protect end organ function Would protect end-organ function

Prime volumes in Pediatric Patients

S b 200 300 l ll Start at about 200-300ml generally

Circulating volume of neonates is 80ml/kg (240ml)

Dilution of RBC, platelets, coagulation factors

Dilution of plasma proteins, drug levelsp p , g

Significant electrolyte changes

R li ti P i S l tiRealistic Prime Solutions At least physiologic:

Blood Prime: Age of blood

I t f R d C ll t f i Impact of Red Cell transfusions Hematocrit values

Cr stalloid/colloid Sol tions: Crystalloid/colloid Solutions: Colloid osmotic pressure and outcomes Small volume circuits

Blood Products and C di l BCardiopulmonary Bypass

A f RBC d t Age of RBCs and outcomes

Use of whole blood vs component products

Target hematocrit

Dil ti l C l th Dilutional Coagulopathy

Metabolic Consequences

Age of RBCs and Clinical Effects i P di t i P ti tin Pediatric Patients

Keidan I,et al . The metabolic effects of fresh versus old stored blood in the priming of cardiopulmonary bypass solution for pediatric patients. J Thorac Cardiovasc Surg. 2004 Apr;127(4):949-52.

Schroeder TH, Hansen M. Effects of fresh versus old stored blood in the priming solution on whole blood lactate levels during paediatriccardiac surgery. Perfusion. 2005 Jan;20(1):17-9.

Gruenwald CE et al Reconstituted fresh whole blood improves Gruenwald CE,et al. Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: a randomized controlled trial. J Thorac Cardiovasc Surg. 2008 Dec;136(6):1442-9.

Ranucci M, et al. Duration of red blood cell storage and outcomes in pediatric cardiac surgery: an association found for pump prime blood. Crit Care. 2009;13(6):R207. Epub 2009 Dec 21.

Studies of Blood Products,Bleeding and Outcomes Are Confounded By:

S S l i Storage Solutions

Leucocyte Depletion

Legislation

Transfusion Protocols and adherence

Surrogate end points and relevant findings Lactate during CPB?g Definition of old vs new

Reconstituted Fresh Whole Blood vs Stored Bl d C Th f NBlood Component Therapy for Neonates Undergoing Cardiac SurgeryS d D iStudy Design

♥ single center, prospective RCT

♥Entrance criteria : neonates less than one month of age undergoing CPB for elective open

heart surgery

♥Exclusion criteria: emergency surgery

known pre-existing coagulopathy

St d P t lStudy ProtocolTreatment Group Control GroupReconstituted Fresh Whole Blood (RFWB)

Component Blood Therapy

CPB Prime • RFWB to achieve

HCT 22-24% on CPB

• RBC to achieve

HCT 22-24% on CPB

During CPB • RFWB to achieve

HCT >28% i i i

• 1 unit FFP prior to cross clamp removalHCT >28% prior to termination

of CPB

clamp removal

• RBC to achieve

HCT >28% prior to termination of CPBtermination of CPB

ConclusionsRFWB is associated with improved clinical outcomes:

d d h t t b l t 24 h i CCCUreduced chest tube loss at 24 hours in CCCUreduced markers of systemic inflammationreduced ventilation timereduced ventilation timereduced inotropic support at 24 hoursreduced hospital LOS reduced hospital LOS

It is unclear if this is a result of age of product or g pdonor exposures or both or something else entirely!

Independent effect on post-operative outcomesIndependent effect on post operative outcomesChest tube loss 24 hours

Lower platelet count), p<0.0001

Older age of blood p<0.0001

Higher number of exposures, p=0.06

Longer ventilation

Lower platelet count p<0.0001

Older age of blood p<0.0001

Higher number of exposures p<0.0001

RFWBControl

O t d St f RBCOutcomes and Storage of RBCs

R i i f 192 hild Retrospective review of 192 children

Centrifugal pump

Older blood >4 days

Results Risk of major morbidity only if blood prime Increased risk of postoperative complications

P l Pulmonary

Renal

Ranucci M, et al.

Hemostatic Consequences of Bl d P iBlood Prime

30 i 1 ld 30 patients <1yr old

Prime volumes 340/465mL

Target Hct .30

Leukoreduced product p Whole blood 2-7days (CPDA1) pRBC (CPDA1) plus FFP

Hornykewycz S, et al. Paediatr Anaesth. 2009 Sep;19(9):854-61. y y , p; ( )

R ltResults

N diff b h l bl d d No difference between whole blood and component therapy

Significant thrombocytopenia Significant thrombocytopenia

Significant reduction in: Fibrinogen Fibrinogen AT III Plasminogen

Fibrinogen

II, V, VII, VIII, X

M b F h Wh l Bl d?Maybe Fresh Whole Blood?

L i fl i d l bl di ? Less inflammation and less bleeding?

200 patients<1yr

Single OR team

Intention to treat and comparable groupsp g p

Whole blood CPD/pRBC Adsol or Optisol

Mou SS, et al.Fresh whole blood versus reconstituted bloodfor pump priming in heart surgery in infants. N Engl J Med. 2004 Oct 14;351(16):1635-44.

R ltResults

F h h l bl d h d Fresh whole blood has no advantage over component therapy

In fact In fact… Increased LOS in CCU Increased perioperative fluid overload

Fewer (by one!) donor exposures

M b N Bl d?Maybe No Blood?

Li i f h dil i ? Limits of hemodilution?

Hematocrit

Dilutional Coagulopathy

Thrombocytopeniay p

H t itHematocrit

Newburger JW, et al. Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery. J Thorac Cardiovasc Surg. 2008 infant heart surgery. J Thorac Cardiovasc Surg. 2008 Feb;135(2):347-54, 354.e1-4.

No difference between Hct 25% and 35%

Wypij D, et al.J Thorac Cardiovasc Surg. 2008 Feb;135(2):347-54, 354.e1-4. A hematocrit level at the onset of low-flow cardiopulmonary bypass of approximately 24% or higher is associated with higher Psychomotor Development Index scores and reduced lactate levels…..

This study cannot ascertain a universally "safe” hemodilution This study cannot ascertain a universally safe hemodilution.

A i P iAsanguinous Prime

I B fi i l? I A hi bl Is Beneficial? Less inflammation

Less blood transfusion

Is Achievable 120-200mL

Increased complexity

Similar outcomes? New oxygenators/filters

Remote pumpKoster A, et al A new miniaturized cardiopulmonary bypass system reduces transfusion requirements….J Thorac Cardiovasc Surg. 2009 Jun;137(6):1565-8. Epub 2008 Aug 16. Miyaji K, et al. The influences of red blood cell transfusion on perioperative inflammatory responses…Int Heart J. 2009 Sep;50(5):581-9. Golab HD, Bogers JJ. Small, smaller, smallest….Perfusion. 2009 Jul;24(4):239-42. Epub 2009 Oct 20. Durandy Y. The impact of vacuum-assisted venous drainage and miniaturized bypass circuits…ASAIO J. 2009 Jan-Feb;55(1):117-20.

N T f i ?No Transfusion?

N f i i h f ll!! Not often….it is heart surgery after all!! 13 neonates 1.7-4kg

11/13 transfused but only 2/13 given platelets

Koster et al JTCVS 2009 137(6):1565-8.

Delayed RBC transfusion reduces inflammatory markers CRP

Neutrophils

Body water gain Myaji et al, Int Heart J. 2009 0 8 9

y g2009 50(5):581-9.

N I t ti t f iNo Intra-operative transfusion:

P i l 110 L Prime volume 110mL

VAD

Acceptable Hgb 7g/dL during CPB

NIRSS

6/13 neonates had no perioperative transfusion All corrective procedures (TGA, HAA, IAA, TAPVD)p ( , , , )

K t t l JTCVS 2009 137(6) 1565 8 Koster et al JTCVS 2009 137(6):1565-8.

D l d T f iDelayed Transfusion

54 i 4 10k 54 patients 4-10kg

41% received RBC transfusion (leucocyte depleted)h Weight

CPB time

NIRS d SO2 d SVO2 l l t t NIRS and rSO2 and SVO2 plus lactate

No platelets or FFP administered

Elevated cRP and WCC in patients transfused on bypass

M ji l (I H J 2009 50 581 589)Myaji et al. (Int Heart J 2009; 50: 581-589)

A i P iAsanguinous Prime

C i i Composition Crystalloid Prime What solution?

Colloid Albumin

Starch Starch

Hypertonic Hyperoncotic Solutions I C di F tiImprove Cardiac Function

P CPB i l i f i f 6% HES 0 9%N Cl 4 l/k Post CPB single infusion of 6% HES vs 0.9%NaCl 4ml/kg

Increased CI

Decreased SVRI

Decreased extravascular lung waterg

Pediatrics. 2006 Jul;118(1):e76-84. Epub 2006 Jun 2.Schroth M, et al

High Colloid Pressure is helpful d i CPBduring CPB

25% lb i FFP 25% albumin vs FFP

Improved hemofiltration rates

Decreased weight gain

Comparable effects on renal functionC p

Loeffelbein F. et al.; Eur J Cardiothorac Surg 2008;34:648-652Loeffelbein F. et al.; Eur J Cardiothorac Surg 2008;34:648 652

I S In Summary

C di l i l i l d i b Cardiopulmonary prime solutions are partly driven by technological limitations.

The ideal CPB prime is probably an The ideal CPB prime is probably an asanguinous low volume high colloid osmotic pressure solution

The freshest blood possible should be acquired

L ki i t th f (?) di tLooking into the far(?) distance…

Therapeutic quandaries:Therapeutic quandaries:RIPCSuperhydrophobic surfacesBonded circuitsBonded circuits

Endothelium