ELSO-EURO Rome June 2012 Oral abstract presentation ECMO Circuit Efficacy and Complications in patients on ECMO Without systemic Anticoagulation : a Case series in Asian population Department of Intensive Care Unit Queen Mary Hospital The University of Hong Kong Sin WC , Ngai CW , Chan WM

Background (1) The ELSO guideline suggested continuous infusion of heparin during ECLS despite the surface of some extracorporeal circuit and devices are heparin coated However, bleeding in ECLS resulted in significant morbidity and mortality

Background (2) Asian tends to bleed and Caucasian tends to clot Lower incidence of deep vein thrombosis in Chinese Absence of factor V gene mutation and prothrombin gene mutation in Chinese 1 Higher incidence of intracranial bleeding after warfarinzation for atrial fibrillation in Asian Differences in gene encoding vitamin K epoxide reductase complex haplotypes predictive of low maintenance dose of warfarin in 89% of Asian but 35% in Caucasian 2 Bleeding risk further increase in patients with underlying/ ongoing coagulopathy and platelet dysfunction Hong Kong Med Journal 2002 JACC 2007

Objectives to review circuit efficacy, safety and patient outcomes in ECLS without systemic anticoagulation in Asian population

ECLS for cardiopulmonary support since Nov 2010 14 cases recruited 6 without systemic anticoagulation heparin coated circuit and membrane oxygenation (Cardiohelp HLS set advanced 7.0 Bioline coating oxygenator; MAQUET, Germany) Percutaneous peripheral cannulation with seldinger technique

Protocol MAP 65-95 mmHg Conventional heparin for anticoagulation Blood flow 50-80ml/kg/min Gas flow 1:1 to blood flow SpO2 95% (VA) , 85-92% (VV) PaCO2 35-45mmHg Pre-oxygenator oxygenation> 65% Routine reperfusion catheter in superficial femoral artery Lung rest ventilator strategy MAP 65-95 mmHg Conventional heparin for anticoagulation ACT 170-200 sec APTT 1.5-2.0 times of normal Platelet > 100,000/mm3 Hb~10 g/dl pH 7.35-7.45

Six patients were considered to be at high risk of bleeding and systemic anticoagulation was not given They included 2 patients with ongoing bleeding Haemorrhagic gastritis Haemorrhagic cystitis 4 patients with underlying severe thrombocytopenia ± coagulopathy

Demographics Disease With anticoagulation Without anticoagulation VV ECMO Human swine flu x3 Viral pneumonitis Pneumocystis infection VA ECMO Viral myocarditis x2 Chemo- cardiomyopathy 1) Post BMT BOOP 2)Lymphoma CMV pneumonitis 3)Post BMT respiratory failure of unknown cause 4)Pneumonia, post renal transplant 1)VT storm 2) Decompensated DCMP

Demographics With anticoagulation (n=8) , IQR Without anticoagulation P value Age (year) 48(36-54) 54 (46-59) 0.21 Gender (M) 4 (50%) 3 (50%) 0.69 Weight (kg) 70.0 (60.7-80.0) 58.5 (44.1-76.2) 0.19 APACHE II 18 (16-27) 23 (19-28) 0.46 Mode of ECMO (VA/VV) 3/5 2/4 0.54

Clinical parameters during ECMO With anticoagulation Without anticoagulation p valve At presentation Hb (g/dL) Hct Platelet count (109/L) APTT (sec) PT (sec) INR (sec) 12 (10.8-15.5) 0.35 (0.32-0.45) 231(163-468) 27.7 (16-34.7) 12.6(11.8-18.0) 1.1 (1.0-1.1) 8.9 (7.8-10.7) 0.26 (0.22-0.30) 66 (16-138) 31(25-37) 20 (12-36) 1.4 (1.1-2.7) 0.02 0.34 0.18 0.08 Average during ECMO 9.5 (8.5-10.6) 0.26 (0.24-0.30) 180 (76-246) 49( 45-54) 13(12-14) 1.2 (1.0-1.3) 9.9 (8.2-10.5) 0.28 (0.25-0.30) 51 (32-54) 38 (31-42) 15 (12-45) 1.4 (1.1-3.6) 0.86 0.87 0.003 0.002 0.36 0.26

Transfusion requirement and complications With anticoagulation (n=8) Without anticoagulation (n=6) P value Transfusion Packed cell (units) Platelet (units) FFP (units) 3 (2-4.7) 1( 0-7) 0 (0-3) 4(0.75—6.5) 32 (8-45) 4(0-13.5) 0.68 0.008 0.351 CNS Ischaemia Bleeding 0 (0%) 1 (12.5%) 1 (16%) minor stroke 1.0 GI bleeding wound bleeding 4 (66%) without surgical intervention 0.55 Limb complications DVT 0(0%) 1(12.5%) 1(16%) mechanical complication RRT 2 (25%) 4 (66%) 0.30 Intracardiac clot Hemolysis

Circuit efficacy With anticoagulation (n=8) Without anticoagulation Circuit function With anticoagulation (n=8) Without anticoagulation (n=6) P valve Duration of ECMO support (hr) 155 (34-239) 184 (61-418) 0.63 ECMO flow (L/min) 3.07 (2.47-3.96) 3.08 (2.3-3.3) TMP (mmHg) 24hr 48hr 72 hr 144hr (6 days) 212hr (9 days) 288 hr (12 days) 360 hr (15 days) 12 (6-20) 13 (10-19) 14.5 (7.7-20.7) 12 (10.5-20) 12 (4.5-12) No data 13 (9-16) 16 (12.5-16.5) 16 (11.2-17.7) 13.5 (10.7- 16.2) 11 13 15 0.49 0.95 0.87 0.79 0.31 Thrombus in circuit (n%) 0 (0%) 1 (16%) 0.43 Plasma leakage (n%) Change of oxygenator (n%) 1(16%)

Empirical change of oxygenator No abnormality in TMPD and oxygenation function

Outcomes With anticoagulation (n=8) Without anticoagulation (n=6) P value Survival Overall VA ECMO VV ECMO 7(88%) 4(50%) 3(37.5%) 2(33%) 1(16%) 0.09 ICU LOS (days) 13 (8-20) 20 (12-24) 0.49 Hospital LOS (days) 33 (17-58) 50 (21-85) 0.41

Conclusion  Discussion Early experience Similar circuit efficacy No excessive clinical complications Trend toward higher mortality may be due to higher proportion of immunosuppressed patients Platelet transfusion Intrinsic defect in patients with hematological disease Excessive platelet transfusion cause oxygenator failure Packed cell transfusion Similar vs. anticoagulation free group Much lower vs. international reported data ? Peripheral , seldinger cannulation

Advance in technology PVC uncoated Bioline coating

Multifactorial Clot Red blood cell (Anaemia) Clotting factors Platelet (Ethnic difference) Coagulopathy Anti-thrombotic agent Platelet (Thrombocytopenia) Quantity and function Antiplatelet agent

Reasonable to lower the target of anticoagulation in patients with high bleeding risk

Thank You

Thromboelastogram

Comparison Kanji 2010 (peripheral VA ECMO with heparin) Lamarche 2010 (Central and peripheral VA ECMO – heparin free) Present cohort (VA + VV ECMO- heparin free) RC transfusion 7.9 18 unit 4(0.75—6.5) FFP 1.2 14±20 4(0-13.5) Platelet 4.4 5±9 32 (8-45) Limb ischaemia 18% 16% CVA 14% N/A Oxygenator change 9% Intra-cardiac clot 6% 0% survival 52% 44% 33%

Transfusion requirement

Ethnic difference DVT post op in HK , Taiwan and Singapore

Causade score anticoaguation 27 (20-47) No anticoagulation 60 (56-72) p value 0.028 ESC guideline 2011

ESC guideline 2011