ICU Management of the bleeding surgical patient Cardiac Aaron M Cheng

Post-operative bleeding 5-7% patients 2000+ ml chest tube drainage/1st 24hrs post-op 5% require re-exploration for bleeding Increased morbidity & mortality Increased resource utilization

Patients known to be at increased risk for mediastinal bleeding Patient variables Preop Meds Procedure variables Older Female/small BSA Preop anemia Adv cardiac disease Comorbidities Known coagulopathies Hi dose ASA Plavix/Prasugrel LWMH ~18h Fondaparinux ~ 48h Warfarin Emergency surgery after thrombolytic or IIb/IIIa inhibitors Complex operations, esp. DHCA Emergent/ Urgent operations Re-operations Use of bilateral mammary grafts

Adverse effects of re-exploration for bleeding 4.7 fold increase in mortality Increased renal failure ± RRT (14% vs. 5.5%; 6.7% vs. 1.9%) Prolonged Mechanical ventilation (42% vs. 12%) Increased length of stay > 14d (26% vs. 12%) Ann Thor Surg 2011; 91:1780-90

Return to the Operating Room After Cardiac Surgery Washington State

Medical Coagulopathy Versus Surgical Bleeding

Factors for increased bleeding unique to cardiac surgery Dilutional coagulopathy Hypothermia Activation of coagulation, fibrinolytic, and inflammatory pathways

Surgery with cardiopulmonary bypass Unique features Blood is circulated for a prolonged period of time using plastic tubing Massive anticoagulation by large bolus dosing Divert blood away from surgical field (contrary to other surgeries) hemostasis (temporarily) is not essential for the surgical success

Elements of the CPB procedure Priming fluid Hypothermia Oxygenator Pumps Reservoir Cardiotomy Cardioplegia Anticoagulation

Dilutional coagulopathy: priming fluid Typical adult circuits require 1.5-2 liters of crystalloid or colloid Prevents pumping air to patient; removes microparticulate of circuit Significant hemodilution ~ 20-30% CPB Hct = Blood vol. X Pre-CPB Hct Blood vol. + Prime vol.

Effect on platelets activation aggregation injury Cardiopulmonary bypass: effects of contact with circuit tubing & oxygenator Effect on platelets activation aggregation injury

CPB Thrombocytopenia & Platelet dysfunction

Fibrinolysis

Fibrinolysis during cardiopulmonary bypass

Bleeding assessment in the ICU Obtain immediate CXR as baseline—mediastinal & pleural spaces Quantify bleeding amounts frequently—make sure tubes are patent Optimize hemodynamics, temperature, acid-base status Avoid Hypertension Consider adding PEEP Obtain coagulation studies—repeat after blood products administered Repeat CXR if concerned about tamponade or undrained blood Obtain ECHO if concerned about tamponade

General guidelines for re-exploration > 400 mL/h for 1 hour (> 200 mL/m2) > 300 mL/h for 2-3 hours ( > 150 ml/m2/h X 2-3h) > 200 mL/h for 4 hours ( > 100 mL/m2/h X 4h) Imminent cardiac tamponade better to avoid cardiac arrest & emergent ICU re-sternotomy

Laboratory Tests for severe post-op bleeding Keep it simple Fewer tests means more rapid results Is there enough to make a clot? Platelets: number and function Coagulation Factors: PT or PTT Is the clot stable? Fibrinolysis/DIC: Fibrinogen Are there enough red cells? Anemia: Serial HCT

The Emergency Hemostasis Panel: Does the patient need. . . . Prothrombin Time/ INR/ aPTT FFP? INR ≤ 1.5 Protamine? 5-15mg * Platelet count Platelets? Plt > 100 Fibrinogen Cryoprecipitate? Fibrinogen ~ 200 Hematocrit pRBCs? Hct ~ 30

Relationship of hematocrit & platelet function Effect of 2-unit RBC apheresis or plateletpheresis on bleeding time Valeri et al. Transfusion 2001;41:977-83.

Other prohemostatic agents Protamine Desmopressin (DDAVP) Antifibrinolytic agents: Lysine analogs Prothrombin Complex Concentrates (PCC) Recombinant Factor VIIA (rFVIIa) Calcium

Protamine Reverses unfractionated heparin (does not reverse LMWH) Can cause multiple adverse reactions (Anaphylaxis, acute pulmonary vasoconstriction, RV failure, hypotension) Use small doses (5-15mg) for heparin rebound effects Short ½ life of Protamine—virtually eliminated in 30min Larger doses can elevate ACT and cause bleeding (Increase plt dysfunction, fibrinolysis, decrease clot strength)

Desmopressin (DDAVP) V2 analog of arginine vasopressin Induces release of normal VWF & Factor VIII Can be used post-operatively in patient’s with von Willebrand’s disease (quantitative defects) May be useful in Uremia?? Dose 0.3 ug/kg IV over 20 min to avoid hypotension Probably limited usefulness in patients with significant post-op bleeding & in patients already on vasopressin pressor therapy

Antifibrinolytics Epsilon-Aminocaproic Acid (EACA) & Tranexamic acid—synthetic antifibrinolytics inhibits activation of plasminogen to plasmin Demonstrated to reduce bleeding & transfusion requirement in cardiac surgery TXA associated with increased convulsive seizures Blocks GABA receptor in frontal cortex AMICAR given intraoperatively at UWMC

Prothrombin Complex Concentrate PCC (Mixture of Vit K dependent products) 3 factor (II, IX, X) or 4 factor (II, VII, IX, X) Clotting factors 25 X higher than normal plasma PCC vs. FFP (for reversal of coumadin anticoagulation) Faster correction of INR Less volume Less risk of infections transmission/TRALI Quicker to prepare—no cross matching required Used in peri-op setting to reverse INR in patients with life-threatening intracerebral bleeding

NOVOSEVEN (rVIIa) rVIIa used off label for life-threatening hemorrhage Binds to tissue factor at site of vascular injury to produce thrombin In cardiac surgery (40-80 ug/kg): Decreased reoperation for bleeding Decreased blood product usage Decreased chest tube drainage Increase risk of arterial thromboembolic events 5.5% vs. 3.2% (placebo) Coronary thromboembolic events (2.9% vs. 1.1%) Subset at highest risk Age 65+ (9.0% vs. 3.8%) NJEM 2010; 363(19): 1791-1800

COSTS BLOOD PRODUCT UWMC COST ($) pRBC 209.00 Platelets-apheresis 637.00 Platelets-pooled (5-unit pool) 707.00 FFP 72.00 Cryoprecipitate 328.00 Leukoreduction 41.00 Irradiation 11.00 Volume-reduction 59.00 Bebulin (3-factor PCC) 2479.00 (2530 units) NOVOSEVEN (rVIIa) 5400.00 (4ml vial: 1mg/ml)