BLOOD CONSERVATION STRATEGIES1

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BLOOD CONSERVATION STRATEGIES : 

BLOOD CONSERVATION STRATEGIES Dr. Gagan pal Singh SR, Cardiac Anaesthesia Max Devki Heart & Vascular institute, New Delhi

Importance of Blood Loss & Transfusion : 

Importance of Blood Loss & Transfusion Blood loss is an inevitable consequence of any form of any surgery 5% of patients bleed significantly after cardiac surgery 20% of cardiac surgery patients consume 80% of blood products

Blood Conservation : 

Blood Conservation Increasing interest in blood conservation over last 15 years Significant risks of allogenic blood transfusion Shortage of allogenic blood Patient choice Improvement in availability of transfusion alternatives

High risk predictors : 

High risk predictors Advanced age Low preoperative red blood cell volume (preoperative anemia or small body size) Preoperative antiplatelet or antithrombotic drugs Reoperative or complex procedures Emergency operations Noncardiac patient comorbidities.

Risks of Blood Transfusion : 

Risks of Blood Transfusion Type Occurrence in Red Blood Cell Units Transfused Infectious Human immunodeficiency virus 1 in 1.4–2.4×106 Hepatitis B 1 in 58,000–149,000 Hepatitis C 1 in 872,000–1.7× 106 Bacterial infection 1 in 2,000 Immunologic reactions Febrile nonhemolytic transfusion reactions 1 in 100 Anaphylactic transfusion reactions 1 in 20,000–50,000 ABO mismatch Hemolysis 1 in 60,000 Death 1 in 600,000 Leukocyte-related target organ injury 1 in 20 to 1 in 50 Transfusion-related acute lung injury 1 in 2000 Post-transfusion purpura Rare Transfusion services error 1 in 14,000

Benefits : 

Benefits Enhanced oxygen carrying capacity Improved hemostasis associated with blood component therapy Volume support of cardiac output

Interventions to Limit Blood Transfusion : 

Interventions to Limit Blood Transfusion Pharmacologic Agents Hemostatic Drugs With Antifibrinolytic Properties Erythropoietin DDAVP Recombinant Factor VII a Devices to Aid Blood Conservation Cell saver Ventilator-assisted Blood Conservation: PEEP Oxygenator Types Perfusion Blood Pumps Heparin-bonded Circuits Leukocyte Filtration

Interventions to Limit Blood Transfusion… : 

Interventions to Limit Blood Transfusion… Perfusion Techniques and OPCAB Heparin Management Protamine Dosing Acute Normovolemic Hemodilution Preoperative Autologous Blood Donation Minimized Extracorporeal Bypass Circuits Retrograde Autologous Priming Hemofiltration Off-pump Procedures for Blood Conservation Topical Agents/Tissue Glues Interventions Outside the Operating Room Catheterization Laboratory Interventions Preoperative Laboratory Testing Intensive Care Unit Processes and Practices

Pharmacological agents : 

Pharmacological agents

Antifibrinolytic Agents : 

Antifibrinolytic Agents Aprotinin A Serine Protease Inhibitor Binds with the human serine proteases: Trypsin Decreasing Plasmin affinity Plasma kallikrein Tissue kallikrein Elastase Urokinase Thrombin

Aprotinin : 

Aprotinin Pharmacokinetics Inactive via oral route Rapid distribution into total extravascular space Following redistribution, plasma half-life ~150 min Filtered by glomeruli and reabsorbed by proximal tubules Less than 10% excreted as unchanged drug Slowly degraded by lysosomal enzymes Terminal elimination phase half-life ~ 10 hr Does not cross the blood-brain barrier

Mechanism of Action : 

Mechanism of Action Inhibit serine proteases (e.g., kallikrein, plasmin) that attenuates: Inflammatory responses Fibrinolysis Thrombin generation Inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis Platelets - reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa) Granulocytes - prevents the expression of pro inflammatory adhesive glycoproteins (e.g., CD11b)

Aprotinin- Mechanism of Action : 

Aprotinin- Mechanism of Action Blood/Surface activation Intrinsic Pathway Plasmin Kallikrein Complement activation Clotting Fibrinolysis Kinins Cytokines/ Adhesion Molecules Systemic Inflammatory response Non Specific Serine Antiprotease:Aprotinin Heparin

Aprotinin……. : 

Aprotinin……. Dose: Low dose Regimen: Loading Dose: 1 million KIU Pump prime dose: 1mllion KIU Constant Infusion: 250,000 KIU/hr High dose Regimen: Loading Dose: 2 million KIU Pump prime dose: 2mllion KIU Constant Infusion: 500,000 KIU/hr

Adverse effects : 

Adverse effects Hypersensitivity Graft occlusion Heart failure Renal Dysfunction Stroke Mortality

Lysine Analogues : 

Lysine Analogues Epsilon Amino Caproic Acid Tranexemic acid MOA: They inhibit plasminogen by binding to the lysine binding sites on the plasminogen molecule. Spare platelet function by inhibiting the deleterious effects of plasmin. Tranexamic acid is similar in action to Epsilon-aminocaproic acid but it is approximately 10 times more potent.

Lysine Analogues : 

Lysine Analogues Dose: Intravenous loading dose of 10 mg/kg for tranexamic acid followed by 1 mg/kg/hr 100-150 mg/kg of ε-aminocaproic acid followed by infusions of 25 mg/kg/hr Readminister a bolus of EACA upon institution of CPB No need to readminister TA because of large volume of distribution

Comparison of Hemostatic Agents : 

Comparison of Hemostatic Agents Rates of Return to Operating Room for Postoperative Hemorrhage in Patients Treated With Aprotinin and Tranexamic Acid Treatment No Treatment Reexplore Reexplore Yes No Yes No RR CI Aprotinin 18 1,099 56 1,043 0.316 0.188–0.53 Tranexamic acid 14 354 17 362 0.848 0.429–1.674 * Results are pooled from 17 high-dose aprotinin studies and 11 tranexamic acid studies.

Safety Profile : 

Safety Profile *Dennis T. Mangano et al, N EJM 2006;354:353-65.

Low Dose Vs High Dose Aprotinin : 

Low Dose Vs High Dose Aprotinin *Dennis T. Mangano et al, N EJM 2006;354:353-65.

Erythropoeitin : 

Erythropoeitin Endogenous glycoprotein-stimulates red cell production in response to hypoxia and anemia. Recombinant EPO: Reduce preoperative anaemia in patients undergoing autologous blood donation Safe and effective Drawbacks Expensive Hypertension Lag period: 4-6 days-less effective post operatively Beta blockers and cardiopulmonary bypass inhibit effect Dose 50-150 U/kg s/c or I/v 3 times a week

Desmopressin (DDAVP) : 

Desmopressin (DDAVP) Releases Endogenous factor VIII precursors Von Willebrand factor Tissue type plasminogen activator. Not helpful prophylactically to reduce bleeding after cardiac procedures. Helpful in patients with demonstrable and specific platelet dysfunction known to respond to this agent (eg, uremic or CPB-induced platelet dysfunction, type I von Willebrand’s disease). Dose 0.3 μg/kg iv, sc or intranasal

Recombinant Factor VIIa : 

Recombinant Factor VIIa Vitamin K-dependent glycoprotein Currently FDA approved only for the treatment of severe bleeding episodes in hemophiliacs with factor inhibitors or patients with FVII deficiency Binds to tissue factor→ Activation of factor X (FXa) on the platelet surface (a phospholipid surface); FXa + Activated factor V→ prothrombinase complex → Thrombin formation.

Recombinant Factor VII a : 

Recombinant Factor VII a Plasma concentrations ~50 nM→ partial Thrombin Generation Plasma concentrations ~ 100 to 150 nM → Full activation of Thrombin (Thrombin burst) Recommended dose for bleeding in hemophiliac patients is 90 µg/kg i.v. Doses for the treatment of uncontrolled hemorrhage varied from 15 to 180 µg/kg i.v Recommended as rescue therapy for severe intractable bleeding without an identifiable surgical source that is unresponsive to routine approaches after cardiac procedures using CPB.

Devices : 

Devices

Cell Salvage systems : 

Cell Salvage systems 3 Applications Intraoperative recovery of blood Washing of blood collected in postoperative phase Sequestration

Dideco Compact Advanced Cell Seperator : 

Dideco Compact Advanced Cell Seperator IV pole Suspension Bar Hooks Alphanumeric Display Control Button Board Control Panel Roller pump Transport Handle Upper Panel Side panel Bubble sensor Centrifuge Cover Transport Handle & waste bag holder Electroclamps IV pole Locking Knob

Autotransfusion Procedure : 

Autotransfusion Procedure Collection Priming Washing Emptying

Autotransfusion Procedure : 

Autotransfusion Procedure

Sequestration Procedure : 

Sequestration Procedure Blood Taking Priming Spilling Emptying

Sequestration Procedure : 

Sequestration Procedure

Cell Salvage : 

Cell Salvage Advantages Disadvantages ↓ risk of infection ↓ risk of transfusion reaction Safer in patients with rare blood groups & multiple antibodies No immunosuppression ? Acceptable to Jehovah’s Witnesses ↓ demand for allogenic blood products ↑ cost- setup cost inc. staff training Unused blood wasted ↑ risk of bacterial contamination

Ventilator-assisted Blood Conservation : 

Ventilator-assisted Blood Conservation Positive End Expiratory Pressure Increased end-expiratory airway pressure (PEEP) exerts mechanical pressure on the myocardium and may limit microvascular bleeding after heart surgery. Use of prophylactic PEEP postoperatively is not effective.

Oxygenator Type : 

Oxygenator Type Membrane oxygenator systems during cardiopulmonary bypass are preferred for reduction in blood utilization and improved safety. Advantages Fewer cerebral emboli Better biocompatibility Reduced blood utilization

Perfusion Blood Pumps : 

Perfusion Blood Pumps Theoretical advantages in blood conservation seen with centrifugal pumps. Advantages Reduced complement activation Preserved platelet function No significant differences in bleeding or blood transfusion were found in patients perfused with roller or centrifugal pumps.

HEPARIN-BONDED CIRCUITS : 

HEPARIN-BONDED CIRCUITS Heparin coating of the oxygenator or of the entire bypass circuit Limits platelet activation Reduces complement activation Alters cellular adhesion to the bypass tubing Diminishes the inflammatory pulmonary injury seen after CPB Need of Low dose Heparin & consequently reduced protamine dose

LEUKOCYTE FILTRATION : 

LEUKOCYTE FILTRATION Benefits Improved neutrophil adhesion Better endothelial function and lung function Limitation of reperfusion injury Reduced rate of atrial fibrillation Improvement in brain function after circulatory arrest Concerns Leukocyte depletion during CPB may activate white cells Not recommended because of the lack of clinical benefit and the concerns about worsening leukocyte function

Perfusion Techniques : 

Perfusion Techniques

Heparin Management During CPB : 

Heparin Management During CPB Maintenance of higher or patient-specific heparin concentrations during CPB to reduce hemostatic system activation, reduce consumption of platelets and coagulation proteins, and reduce blood transfusion.

Protamine Dosing : 

Protamine Dosing Use either protamine titration or empiric low-dose regimens (eg, 50% of total heparin dose) to lower the total protamine dose and lower the protamine-to-heparin ratio at the end of CPB.

ACUTE NORMOVOLEMIC HEMODILUTION (INTRAOPERATIVE AUTOLOGOUS DONATION) : 

ACUTE NORMOVOLEMIC HEMODILUTION (INTRAOPERATIVE AUTOLOGOUS DONATION) Removal of one to two units of blood immediately before surgery To maintain circulating blood volume, the volume is replaced with crystalloid / colloid. Contraindications: Evolving acute myocardial infarction Unstable angina Cardiogenic shock Preoperative anemia Sepsis known bacteremia. Relative contraindications Low EF (< 30%)

ACUTE NORMOVOLEMIC HEMODILUTION : 

ACUTE NORMOVOLEMIC HEMODILUTION Principle Lowering the red blood cell concentration (hematocrit) during surgery decreases the reduction in red cell mass lost for any given volume of blood lost. In cardiac surgery The blood removed before the institution of CPB is “protected” from the potential deleterious effects of platelet activation and consumption, hemolysis, complement activation, and the production of a variety of inflammatory cytokines associated with extracorporeal circulation

PREOPERATIVE AUTOLOGOUS BLOOD DONATION : 

PREOPERATIVE AUTOLOGOUS BLOOD DONATION Autologous blood donation of as much as 2 units a few days to a few weeks preoperatively. Not routinely employed in cardiac surgery, because of possible increase in the incidence of myocardial infarction or hemodynamic instability. Useful in carefully selected (mostly elective) patients particularly when coupled with appropriately dosed erythropoietin therapy and/or iron therapy.

Minimized Extracorporeal Bypass Circuits : 

Minimized Extracorporeal Bypass Circuits Use low prime and minimized extracorporeal bypass circuits to reduce the fall in hematocrit during CPB.

RETROGRADE AUTOLOGOUS PRIMING : 

RETROGRADE AUTOLOGOUS PRIMING Replaces the crystalloid prime volume of the CPB circuit with the patient’s own blood immediately before beginning cardiopulmonary bypass The arterial limb of the circuit is cleared retrograde through back bleeding from the aortic cannula, and the venous limb is cleared antegrade using the blood pump. The displaced crystalloid is collected and excluded from the circuit.

PUMP SALVAGE AND INTRAOPERATIVE AUTOTRANSFUSION : 

PUMP SALVAGE AND INTRAOPERATIVE AUTOTRANSFUSION Shortly after the completion of CPB, salvage of pump blood, either administered without washing or after washing with a cell-saving device, is a mean of blood conservation.

Hemofiltration : 

Hemofiltration Conventional ultrafiltration (CUF) Remove the excess fluid associated with the priming volume Reduction in the systemic concentration of inflammatory mediators ↑ plasma oncotic pressure & reduces edema Modified ultrafiltration (MUF) Performed for a period of time after CPB is completed. Particularly in paediatric patients Causes reductions in removal of plasma water, inflammatory mediators and improvement in hemodynamic indices

OFF-PUMP PROCEDURES : 

OFF-PUMP PROCEDURES Off-pump coronary artery bypass (OPCAB) is a reasonable means of blood conservation, provided that emergent conversion to on-pump bypass is unlikely either based on surgeon experience or patient characteristics.

Topical Agents/Tissue Glues : 

Topical Agents/Tissue Glues Fibrin glue preparations Bovine thrombin Aprotinin Containing Preparations Topical sealants are used to assist in the repair of complex, high-risk cardiac and aortic procedures (e.g, left ventricular free wall rupture and aortic dissection)

Interventions outside Operating Room : 

Interventions outside Operating Room

Catheterization Laboratory Interventions : 

Catheterization Laboratory Interventions Access site complications occur 1% to 9% of the time paticularly if potent antiplatelet agents are used. 5% of patients will require a transfusion after catheterization. Closure devices or collagen plug devices that directly control bleeding at the access site are preferred in patients who require operation within 24 hours of catheterization.

Preoperative Laboratory Testing: : 

Preoperative Laboratory Testing: Recommendations Preoperative screening of the intrinsic coagulation system is not recommended unless there is a clinical history of bleeding diathesis. Screening preoperative bleeding time is not unreasonable for high-risk patients, especially those who receive preoperative antiplatelet drugs. Preoperative hematocrit and platelet count are indicated for risk prediction, and abnormalities in these variables are amenable to intervention. Alternatives to laboratory blood sampling (eg, oximetry instead of arterial blood gases) are reasonable means of blood conservation before operation. *STS and SCA Clinical Practice Guideline Ann Thorac Surg 2007;83:27-86

Intensive Care Unit Processes and Practices : 

Intensive Care Unit Processes and Practices Use of small-volume tubes Elimination of arterial line blood discard Drawing as few blood specimens as possible Use of oximetry instead of intra arterial blood gas monitoring systems

Multimodal algorithm : 

Multimodal algorithm

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