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
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