Restricting and avoiding Blood Transfusions: What Options do we have?

1. Restricting and avoiding Blood Transfusions: What Options do we have? Rajeshwari Subramaniam Deptt. Of Anaesthesiology A.I.I.M.S. www.anaesthesia.co.inanaesthesia.co.in@gmail.com

2. Questions to be answered • What are the implications of anemia? • What are the benefits of a normal hematocrit? • How do we decide when to transfuse? • What are the risks of transfusion? • What are the alternatives to homologous transfusion?

3. What are the implications of Peri operative Anemia? • DO2 =CO x CaO2 [(%sat x 1.39 x Hb) + PaO2 x0.003] • Peri operative anemia usually co-exists with hypovolemia • Ability to tolerate reduction in DO2 depends on the ability to increase cardiac output • Myocardial contractility, HR, vascular tone with loss>15%

4. Problems of Peri operative Anemia • These responses are modified by: -age -co morbid illness (CAD,CNS) -pre existing Hb and plasma volume -β blockers, ACE inhibitors -rapidity of loss • THE PROBLEM IS TO IDENTIFY THE PATIENT ‘AT RISK’

5. Problems of coronary circulation and myocardium • Myocardium has high O2 extraction ratio • O2 delivery can be increased only by increasing flow • Tachycardia compromises diastolic flow • With normal coronary circulation Hb up to 7g% tolerated • ECG changes of ischemia at Hb≤ 5g% • Lactate production, death at Hb ≤ 3g%

6. What is the urgency of replacing volume & Hb? • Diversion of blood from skeletal, splanchnic beds to coronary and cerebral circulation • Mucosal ischemia-starting point of MODS, sepsis • Peri operative myocardial ischemia-high mortality • Un replaced blood loss  coagulation problems, DIC

7. Beneficial effects of normalisation of Hct • in RBC volume, restoration of plasma volume • Restoration of blood flow to GIT • Restoration of viscosity in shear stress, ADP production, platelet aggregation • Dispersal of platelets towards vessel wall

8. Anemia and NO • viscosity in anemia  flow, shear stress, NO production • Vasodilation at bleeding sites • in cyclic GMP in platelets, inhibition of platelet function, bleeding time • Hb best NO scavenger; oxidizes NO • Minimum shear stress seen at Hct 30-35%

9. Indications and Guidelines for intra-operative RBC Transfusion • Based on Acute blood loss: -15% loss in an adult(500-750 ml)-no need to transfuse -15-30%loss-crystalloids/synthetic colloids -30-40%(1500-2000ml)-rapid IV resuscitation± blood ->40%-rapid volume replacement+ blood

10. Guidelines for Transfusion-continued • Based on Hb concentration: • Actual and anticipated Hb>10g% • Indicated when Hb≤7g%,at the rate of ongoing blood loss • Patients ‘at risk’ trigger 8g%(consensus) • Consider if patient will bleed due to coagulation abnormalities • Give appropriate coagulation factor/s

11. Patients at Risk • Coronary artery disease • Valvular heart disease (AS) • CHF • H/O transient ischemic attacks • Previous thrombotic stroke • However, still no ‘consensus’ for transfusion trigger

12. Transfusion Strategy for Acute Blood Loss

13. Signs and symptoms Requiring Transfusion • Syncope • Dyspnea • Postural Hypotension • Tachycardia unresponsive to crystalloids • Angina/ECG changes • Transient ischemic attack

14. Patients under Anesthesia • If stable: -assess risk of myocardial/cerebral ischemia -in the absence of risks,transfusion NOT indicated,regardless of Hb -intravascular volume to be replaced • If unstable: -if at risk, transfuse -if not at risk,crystalloid+colloid initially -TRANSFUSE UNIT BY UNIT -autologous blood if available

15. Guidelines for Transfusion(cont’d) • Transfusion in the ICU: -Overtransfusion may increase mortality -Attention to volume, inotropic support -Maintenance of BP and CO -Crystalloids preferable

16. Guidelines for peri operative transfusion • Patient to be managed to avoid transfusion • Treat anemia before elective surgery • Discontinue anti platelet drugs • Reverse anticoagulation • Use pharmacologic agents to control bleeding • Strategies of autologous transfusion

17. Chronic Anemia • Do not transfuse if effective alternatives exist • Preferably transfuse at intervals to maintain Hb at lowest level not associated with symptoms • Consider recombinant erythropoietin -zidovudine-induced anemia,CRF -improves functional status

18. Risks associated with Transfusion VIRAL INFECTIONS • Hepatitis A- 1:1,000,000 • Hepatitis B- 1:50,000-1:150,000 • Hepatitis C- 1:1,900,000 • What’s new: Nucleic Acid Testing (NAT) • CMV-Up to 60% transmission from blood • Parvovirus B 19-Hydrops, Aplastic crisis

19. Risks of Transfusion…cont’d • Bacterial Contamination mortality Red cells 2/106 (yersinia sp) 60% Platelets 83/106 21% • Hemolytic Reaction Acute 1-4/106 0.67 Delayed 1000/106 0-4 • TRALI 200/106 60% • Transfusion-mediated immuno modulation -good for renal transplant, recurrent abortions -increased mortality in CV, colorectal Ca

20. Other Hazards • Mismatched transfusion-1:14,000-1:18,000 • Fatality-1:800,000 units • West Nile Virus-Meningitis,encephalitis • Creutzfeldt-Jakob disease

21. Alternatives to Allogeneic (Homologous) Blood • Techniques: -Deliberate Hypotension -’Bloodless’ Surgery -Tourniquet where appropriate • Drugs affecting coagulation -Aprotinin(1.4mg70mg/hr) -ε amino caproic acid(5-10g1g/hr) -Tranexamic acid(10mg/kg1mg/kg/hr) • Erythropoietin pre treatment • Re combinant factor VIIa

22. Autologous Blood Use • Pre operative Autologous Donation (PAD) • Acute Normovolemic Hemodilution (ANH) • Intra operative Cell Salvage and Re- infusion • Post operative collection and Re infusion

23. What are the Advantages of PAD? • Avoids complications of allogeneic blood • Prevents red cell alloimmunization • Useful for patients with rare blood phenotypes or allo antibodies • Supplements blood supply • Provides reassurance to patients concerned about blood risks

24. Patient Selection for PAD • Hb ≤ 11.0g/dl • No age or weight limits • Volume 10.5 ml/kg per donation • Usually once a week • Last donation > 72 hours before surgery • Patients with positive viral markers • Selected pediatric patients

25. Contra indications to PAD • Surgery unlikely to require transfusion • Evidence of infection/bacteremia • Scheduled surgery for AS • Unstable angina • MI /CVA < 6 months • Active seizure disorder • Unstable angina, left main coronary block • Cyanotic CHD • Uncontrolled HT/ Pulmonary/ other medical dis. • Pregnancy

26. Potential Problems with PAD • Risk of misidentification • Infection/contamination of stored units • Volume overload • Increased cost of collection & storage • Risk of patient becoming anemic • ‘Aggressive Phlebotomy’ and iron, Erythropoietin 3 weeks prior to surgery

27. Acute Normovolemic Hemodilution (ANH) • Blood removed shortly before surgery • Volume replacement with crystalloid/colloid* • Blood stored in OT at room temperature • Volume= EBV (Hi-Hf) ÷ Hav • Decrease in DO2, viscosity • Cardiac output, systemic vascular resistance, venous return • Oxygen extraction enhanced

28. Precautions • Hypovolemia, hypocapnia to be avoided • Oxygen supplementation • Reversible cognitive dysfunction in cerebral vascular disease • Coronary vasodilatation important to increase O2 delivery to myocardium • Store close to patient and label appropriately

29. Precautions…cont’d • Establish 2 IV lines • Routine monitoring • Contraindications • Transfused in reverse order of collection • Room temperature storage not > 8 hours • Increased HR : be warned • Advantages: all drawbacks of homologous blood eliminated; low cost; fresh whole blood

30. Red Cell Recovery and Re infusion • Blood from surgical field is collected into centrifuge bowl • Suction should be low, broad tipped • Large sponges rinsed in saline/RL • Heparin /ACD to be added (Ca reduces deformability) • Centrifuged to separate red cells from debris and WBCs • Washed with saline/glycine • Collected in reservoir with 40μm filter

31. The Cell Salvage System

32. Calculation of blood loss • ([Hs/Hp] x Vb xNb)/SE • E.g. THR ; 5 bowls(125 ml) used • HCT(bowls): 66,70,68,65,71%(av68%) • HCT(patient):32,30,34,30,28%(av30.8%) • Salvage efficiency 40% • Blood Loss=68% x 125 x5/ 30.8% x 40% = 3450 ml

33. What are the potential Complications of Cell Salvage? • Poor wash quality-’cell salvage syndrome’ (DIC, ARF) • Poor salvage rate due to non-dedicated personnel • Air embolism • Wrong wash solution

34. Current Status of Artificial O2 Carriers Necessary steps: • Stabilization to prevent dissociation into dimers (intravascular retention; nephrotoxicity) • Decrease O2 affinity • Polymerization to increase Hb concentration at physiologic colloid oncotic pressure • Emulsification of PFCs to make them water-miscible

35. Hemoglobin-based O2 Carriers • Exhibit a sigmoidal O2 dissociation curve • Provide O2 and CO2 transport • Sourced from outdated banked blood, bovine blood or genetically engineered • Undergo virus inactivation and removal • Protection against prion contamination • Stabilised,polymerised

36. Difficulties and Side effects of Hb solutions • Nephrotoxicity-eliminated • Vasoconstriction-systemic and pulmonary hypertension: causes-NO scavenging/increased O2 supply to arteriolar wall • Abdominal pain, esophageal dysmotility due to NO modulation of smooth muscle relaxation • Interference with mixed venous O2 saturation

37. Kinds of Artificial Hbs • Diaspirin-linked Hb (DCLHb): stopped due to jaundice,pancreatitis,mortality • Human recombinant Hb (rHb 1.1,rHb 2.0): genetically expressed in E.Coli in 1990.Stopped in 2003 • Polymerised bovine Hb based O2 carrier(HBOC-201): used in orthopedic & cardiac trials • Maleimide activated polyethylene glycol modified Hb(MP4):high mol. Wt.,oncotic pressure,Hb conc 28g/dl. Under trial.

38. Human Polymerised Hemoglobin (PolyHeme) • From outdated banked blood • Pyridoxylated and polymerized with glutaraldehyde • Has been tried in trauma and urgent surgery situations • 1u=50g in 500ml;171 patients with Hb<1g% survived after 20u(10l)

39. Per Fluoro Carbon (PFC) Emulsion (‘OxyGent’) • Carbon fluorine compounds with high gas dissolving capacity and low viscosity • Chemically and biologically inert • Dose 1.8g/kg • Taken up by RES;emulsion broken down,re absorbed into blood and circulates;excreted from lungs • Effective transport of dissolved O2 • Submicron size enhances microcirculatory O2 delivery

40. Nano-dimension artificial RBCs, Hb containing liposomes • Purified Hb +phospholipids +cholesterol + α tocopherol • Lead to rapid restoration of BP,microvascular blood flow and tissue oxygenation • ‘Augmented ANH’: A technique of ANH combined with administration of O2 carriers and crystalloids www.anaesthesia.co.inanaesthesia.co.in@gmail.com