Blood Product Utilization in Pediatric Anesthesia Gamal Fouad S Zaki, MDGamal Fouad S Zaki, MD Professor of AnesthesiologyProfessor of Anesthesiology Ain Shams UniversityAin Shams University

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

Why component therapy? RBCs FFP Platelets Cryoprecipitate Coagulation factors Leukocytes

Why component therapy? Storage of whole blood results in: – Shorter T 1/2 of factors V and VIII (4-36 hrs in 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

Why transfuse RBCs?Why transfuse RBCs? one and only 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 (2 nd Ed.), 2006

Oxygen Delivery S a O 2 Hb Conc S a O 2 Hb Conc Circ Volume HR, SV, Contr Vasomotion Circ Volume HR, SV, Contr Vasomotion

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 DO 2 : greater decompensation Optimal hemoglobin values in the newborn are generally higher than those of older patients

Hematologic differences Normal term neonate Hb range 14–20 g/dl which gradually decrease over first months because of  erythropoietin,  RBC T 1/2, physiologic nadir at approx 2–3 months Term infants with Hb <9 g/dl & preterm <7 g/dl should be investigated for hemoglobinopathy or other pathology (postpone elective surgery to evaluate, treat) Raising Hb: transfusion, exogenous erythropoietin, or simply postpone until natural hematopoietic mechanisms take effect Higher Hb increases O2 carrying capacity & in prematures, may protect from postanesthetic apnea 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

Hematologic differences Fetal Hb (HbF) comprises 70% of full term & 97% of premis’ total Hb at birth RBCs containing HbF have shorter life span (90 days) than those containing HbA (120 days) P 50 HbF interacts poorly with (2–3 DPG), P 50 (P a O 2 at which Hb is 50% saturated) decreases from 26 with HbA to 19 mmHg with HbF. This leftward shift of the oxygen–Hb dissociation curve results in decreased oxygen delivery to tissue because of the high affinity of HbF for oxygen

26 HbF 19 Oxygen-Hb dissociation curve P 50

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

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

Decision to Transfuse RBCs

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

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 DO 2 (good O 2 carrying capacity, low viscosity), Hct % well tolerated in normal animals Normal human volunteers: Hb 5g/dl tolerated with occasional signs of inadequate DO 2 : memory impairement, ST-segment change

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: liberalrestrictive Comparing liberal (10-12g) & restrictive (7-9g) Trx strategy showed reduced mortality with restrictive strategy restrictive strategy In pediatric pts restrictive 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”

Decision to Transfuse RBCs No Universal 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 O 2 delivery – general medical condition of the patient

Dose A transfusion of 10cc/kg will increase the hemoglobin g/dl

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)

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 CaCl mg/kg/hr for ongoing losses Equi-ionizable doses Cote et al. Anesthesiology, 1987

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,..

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 MgSO mg/kg then infuse 25mg/kg/24hrs

Metabolic consequences Acid / Base disturbance RBCs continue metabolism inside bag: PCO2 reaches mmHg, O 2 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 NaHCO 3 )

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

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-lymphotropic virus Others: West Nile Virus, SARS, Malaria, Chagas disease In countries where testing is incomplete, anemia may be a better risk Infectious disease transmission risk Evolution of viral risks of transfusion over time in the USA

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.

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 pts when lymphocytes contained in a transfused blood component proliferate and cause host tissue destruction: TA- GVHD prevented by Gamma irradiation of blood products (RBCs, platelets, granulocytes)

Transfusion-Related Acute Lung Injury plasma rich products 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, & noncardiogenic edema Leading cause of transfusion-related mortality Prevention: Plateletpheresis from male donors and never pregnant females

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: Risks: TRALI, febrile reactions, circulatory overload. Observational data from CABG: association with increased risk of stroke, inotrope use, pulmonary dysfunction, death. Spiess. Transfusion.2004

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

FFP Indications: prolonged PT, PTT, low fibrinogen Dosage: 10cc’s/kg of ABO compatible product Cryoprecipitate is made from FFP, contains higher concentrations of fibrinogen, von Willebrand factor, 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

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