Blood Product Utilization in Pediatric Anesthesia

1. Blood Product Utilization in Pediatric Anesthesia Gamal Fouad S Zaki, MD Professor of Anesthesiology Ain Shams University

2. Outline • Why blood component therapy? • Why transfuse RBCs? • Hematologic and physiologic differences • Decision making for transfusion in pediatric surgical patients • Adverse reactions: metabolic, infectious, compatibility issues • Platelets, FFP and cryoprecipitate

3. Why component therapy? • RBCs • FFP • Platelets • Cryoprecipitate • Coagulation factors • Leukocytes

4. Why component therapy? • Storage of whole blood results in: • Shorter T1/2 of factors V and VIII (4-36 hrsin vivo, 7-14 days in vitro) • Refrigeration results in Platelets losing discoid shape, accelerated platelet storage defect, with reduced in vivo survival after transfusion • Separation of components aims at optimizing the number of transfusible components from a single donor to treat specific pathology Roseff et al. Transfusion 2002

5. Why transfuse RBCs? • The one and only reason should be to restore or maintain oxygen delivery to vital organs. Any other reason has no medical or physiological basis. Ward et al. in Perioperative Transfusion Medicine (2nd Ed.), 2006

6. Oxygen Delivery DO2 = CaO2 x COP Assessment Lactate Cyanosis HR SvO2 ABGs BP BE SpO2 CVP, Cap Rfl SaO2 HbConc Circ Volume HR, SV, ContrVasomotion

7. Physiologic differences • Higher oxygen consumption & COP to blood volume ratio • Transition from fetal to neonatal circulation leads to high PVR with impaired oxygenation Neonatal myocardium: • Operates at near maximum performance (baseline) may be unable to compensate for decreased oxygen carrying capacity by increasing COP • Decreased DO2:greater decompensation Optimal hemoglobin values in the newborn are generally higher than those of older patients

8. Hematologic differences • Normal term neonate Hb range 14–20 g/dl which gradually decrease over first months because of  erythropoietin,  RBC T1/2 , physiologic nadir at approx 2–3 months • Term infants with Hb<9 g/dl & preterm <7 g/dl should be investigated for hemoglobinopathyor other pathology (postpone elective surgery to evaluate, treat) • Raising Hb: transfusion, exogenous erythropoietin, or simply postpone until natural hematopoietic mechanisms take effect • HigherHb increases O2 carrying capacity & in prematures, may protect from postanestheticapnea of prematurity although transfusion for this purpose alone is not generally indicated • Avoid transfusion unless clinically important blood loss is likely Median, 95% confidence intervals

9. Hematologic differences • Fetal Hb(HbF) comprises 70% of full term & 97% of premis’ total Hb at birth • RBCs containing HbFhave shorter life span (90 days) than those containing HbA(120 days) • HbF interacts poorly with (2–3 DPG), P50(PaO2 at which Hbis 50% saturated)decreases from 26 with HbA to 19 mmHgwith HbF. This leftward shift of the oxygen–Hbdissociation curve results in decreasedoxygen delivery to tissue because of the high affinityof HbF for oxygen

10. Oxygen-Hb dissociation curve HbF 19 26 P50

11. Fetal Hb in infants • Younger infants have higher fraction of HbFand lower oxygen carrying capacity • Premishave higher % of HbF than full-term & decreased erythropoietin production: impaired response to anemia

12. Physiologic/Hematologic variables and decision to transfuse RBCs • Neonates may have decreased ability to oxygenate Hb: lung disease, CHD • Hb levels adequate for older patients may be suboptimal in younger infants or neonates • Threshold for RBCs Trx in neonate is at higher Hb trigger than older child or healthy adult

13. Decision to Transfuse RBCs

14. Ready to defend your decision? Decision should be based on evidence that anemia with reduced oxygen delivery is injurious and RBC transfusion will correct DO2 and improve outcome

15. Optimum Hb / Hct • Classical Teaching: >10g/dl do not transfuse, <7g/dl always transfuse “10/30 rule” (not useful) • Animal studies: Hct 30-40% for optimum DO2 (good O2carrying capacity, low viscosity), Hct 10-20% well tolerated in normal animals • Normal human volunteers:Hb 5g/dl tolerated with occasional signs of inadequate DO2: memory impairement, ST-segment change

16. Optimum Hb / Hct Surgical Patients: • Jehova’s Witnesses (n=125) no mortality if Hb>8 • Death more likely in pts with low Hb in the presence of coexisting cardiovascular disease Critically ill patients: • Comparing liberal (10-12g) & restrictive (7-9g) Trx strategy showed reduced mortality with restrictive strategy • In pediatric ptsrestrictive strategy seems not worse than liberal strategy “restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with AMI and unstable angina”

17. Decision to Transfuse RBCs • NoUniversal Indications or Triggers for RBC trx • Intraoperatively: decision is multifactorial: • rapidity of blood loss • Hb concentration • Hemodynamic instability • presence of impaired oxygenation (pulmonary or cardiac in origin) • Evidence of impaired O2 delivery • general medical condition of the patient

18. Dose • A transfusion of 10cc/kg will increase the hemoglobin 2.5-3.0 g/dl

19. Metabolic consequences Hypocalcemia: • Ca++ essential for initiation of coagulation • All blood products contain citrate • Degree of hypocalcemia depends on: • Type of blood product (FFP, whole blood) • Rate of administration • Hepatic blood flow and function • Risk with neonates, liver disease (decreased citrate metabolism)

20. Metabolic consequences Hypocalcemia: • Neonatal myocardium has reduced sarcoplasmic reticulum, is dependent on Ca++ to maintain function, and thus vulnerable to citrate-induced ionized hypocalcemia • Volatile anesthetics (given concomitantly) exert myocardial depression via blocking Ca++ channels • If hypotension with adequate volume: • Slow transfusion of citrate-containing product <1ml/kg/min • Decrease volatile inhaled agent concentration • Calcium chloride (2.5mg/kg) or gluconate (7.5mg/kg) in different IV line, or CaCl2 10-15mg/kg/hr for ongoing losses Equi-ionizable doses Cote et al. Anesthesiology, 1987

21. Metabolic consequences Hyperkalemia: • K+ leaks from older RBC as cell membrane deteriorate • Large volume Trx may result in fatal hyperkalemia in children with small bld volume • Highest K+ in whole blood, units near expiration date, irradiated units • Washed RBCs: reduced K+ • In neonates use “newer” units < 7 days old • If dangerous arrhythmia: CaCl2 15mg/kg q 2min, then definitive lowering of K+ by hyperventilation, glucose/insulin, B-adrenergic stimulants, ..

22. Metabolic consequences Hypomagnesemia: • Mg++: for RMP, cardiovascular & electrophysiologic stabilization • Ionized hypomagnesemia results from massive transfusion because of citrate chelation of Mg++ • Anhepatic phase of liver Tx • Arrhythmia refractory to CaCl2: give IV MgSO4 25-50mg/kg then infuse 25mg/kg/24hrs

23. Metabolic consequences Acid / Base disturbance • RBCs continue metabolism inside bag: PCO2 reaches 180-210mmHg, O2 consumed, lactate accumulates • Rapid whole blood trx causes transient metabolic & respiratory acidosis, CO2 excreted in lungs, lactate rapidly buffered (no need for ttt) • Metabolic acidosis during massive trx reflects inadequate perfusion, severe hypovolemia prior to Trx, sepsis, or hypoxemia • Citrate metabolism: causes delayed metabolic alkalosis (better limit empirical use of NaHCO3)

24. Metabolic consequences Hypothermia • Maintaining normothermia in children is challenging even without Trx:large BSA/Wt, GA-induced heat redistribution from core to periphery, respiratory & surgical evaporative losses, cold OR • Consequences: apnea, hypoglycemia, delayed drug metabolism and prolonged effects, left shift of oxyHb dissociation curve, increased oxygen consumption, coagulopathy, increased mortality • Type of warming device depends on rate of Trx

25. Infectious disease transmission risk • Risk less than metabolic & immunologic risks • Will further improve with wide adoption of nucleic acid amplification technique (PCR) • Viral risk includes Cytomegalovirus, hepatitis C, hepatitis B, HIV, and human T-lymphotropicvirus • Others: West Nile Virus, SARS, Malaria, Chagasdisease • In countries where testing is incomplete, anemia may be a better risk Evolution of viral risks of transfusion over time in the USA

26. Infectious disease transmission risk • Evidence exists that RBC transfusion is associated with impairment of immune mechanisms, possibly increasing risk of bacterial infection • Multiple observational studies link RBC transfusions with infection, immunosuppression, and mortality • Transfusion induce immunomodulation • Patients in a medical–surgical ICU had a 10% increased risk of nosocomial infection/unit of RBCs Taylor et al. Red blood cell transfusions and nosocomial infections in critically ill patients. Crit Care Med 2006; 34:2302–8.

27. Incompatibility & immunologic considerations • ABO incompatibility: acute hemolytic reaction, Clerical error is the most common cause: fever, tachycardia, hypotension, abn bleeding: stop Trx, maintain ABP, UOP • Transfusion-related graft vs host disease occurs in immuno-compromised ptswhen lymphocytes contained in a transfused blood component proliferate and cause host tissue destruction: TA-GVHDprevented by Gamma irradiation of bloodproducts (RBCs, platelets, granulocytes)

28. Transfusion-Related Acute Lung Injury TRALI: abrupt onset of respiratory failure within hours of the transfusion of a blood product. Usually caused by anti-leukocyte antibodies, resolves rapidly, low mortality. Most likely with plasma rich products: FFP, apheresis Platelets Clinically: a nonspecific constellation of dyspnea, hypotension, noncardiogenic pulmonary edema, fever,may overlap with ARDS: dyspnea, bilateral infiltrates, hypoxemia, &noncardiogenicedema Leading cause of transfusion-relatedmortality Prevention:Plateletpheresis from male donors and never pregnant females

29. Platelets • Either from platelet rich plasma or apheresis • Stored in a special permeable plastic at room temperature, high risk of bacterial contamination • Apheresis platelets: less donor exposure,decreased risk of disease transmission & allo-immunization, less exposure of platelets to centrifuge • Risks: TRALI, febrile reactions, circulatory overload. Observational data from CABG: association with increased risk of stroke, inotrope use, pulmonary dysfunction, death.Spiess. Transfusion.2004

30. Platelets • ABO compatible • Indications and dosage: not clear • Prophylactic: keep platelets above certain count, versus Therapeutic: transfuse only for active bleeding or before procedure • Dosage: • 1 Unit / 10kg Body Wt which is expected to raise the platelet count by 50,000 platelets/microliter • Higher doses can be considered in septic patients, or patients with DIC, or splenomegaly • Benefit / Risk consideration

31. FFP • Indications: prolonged PT, PTT, low fibrinogen • Dosage: 10cc’s/kg of ABO compatible product • Cryoprecipitateis made from FFP, contains higher concentrations of fibrinogen, von Willebrandfactor, and factor VIII • Risks: infection, allergic reactions, hemolysis, and volume overload. Risk of TRALI 1:60000/FFP unit. • Strong association of TRALI and female gender of donor. Hypothesis: pregnancy induces human leukocyte antibodies among female donors. Led to preferential use of male-derived plasma for FFP

32. Summary • Utilize blood products only when strongly indicated • In addition to hemoglobin concentration Consider comorbidity & rate of blood loss when giving RBCs • Blood Products are scarce resources • Remain conscious of complications: incompatibility, bacterial and viral transmission, TRALI • Each hospital should setup its own protocols