Macau Society of Emergency and Critical Care Medicine Renal Support during ECMO

1. Macau Society of Emergency and Critical Care MedicineRenal Support during ECMO Dr Yan Wing Wa Department of Intensive Care Pamela Youde Nethersole Eastern Hospital Hong Kong SAR, China 1 February 2013

2. Scope of talk • Why CRRT commonly needed in ECMO? • Types of RRT available during ECMO • Types of connections • Pros and Cons • Regional citrate anticoagulation • Principles • Indications & contraindications • Complications & monitoring • Protocol

3. AKI during ECMO therapy • AKI common complication of shock/hypoxemia • Renal perfusion sacrifice first • Patients are usually in hypercatabolic state • Electrolytes disturbance and acidosis common • Fluid overload is common • May be iatrogenic • Further aggravate the oxygenation status – initial phase • Hinder weaning of ECMO – recovery state • Complication of ECMO • e.g. intravascular hemolysis with kidney impairment

4. Fluid overload • Respiratory failure  VV-ECMO preferred • First few days • SIRS with leaky capillaries, decrease effective circulating volume though lung congestion • IVC collapse with sudden dec. in ECMO flow  further decrease in SpO2 “Circuit shaking” • Treatment: dec. ECMO speed and slowly turn up again AND give fluid • The above process may be repeated many times • Aggravate the fluid overload • Difficult to detect because no desaturation or accept low SpO2 • Beware of daily I&O, CXR and echocardiography

5. Mixed blood O2 saturation Venous O2 saturation ECMO flow as % of total blood flow 5 5

6. Fluid overload • CXR remains diffuse air space shadows • Difficult to detect resolution of underlying pneumonia • Viral pneumonitis recovers within a few days only • Negative fluid balance by ultrafiltration or hemofiltration • Lasix bolus or infusion may not work • Aggressive fluid restriction after the first few days • Try to cut down the duration of ECMO as much as possible • ECMO complications increase with time (not linear but exponential) • Then monitor disease progression by assessing CXR, changes in lung mechanics, SpO2, ECMO flow needed, BP, pulse, temp, inotropes needed, WBC, platelet, INR, glucose tolerance, recovery of urine output, diuresis, RFT, feeding tolerance, …etc

7. Types of RRT possible with ECMO • Peritoneal dialysis (PD) • Inadequate because of high metabolic rate • Inherent complications of PD • Extracorporeal circuit • Hemofilter only • CRRT machines

8. Nomenclature • RRT • Arterial line lead to renal filter/dialyser • Venous line from renal filter/dialyser • ECMO • Venous line lead to oxygenator • Arterial line from oxygenator back to patient

9. CRRT • Separate CRRT circuit • Less complication related to ECMO • Access problem • No site • Risk of air embolism during insertion • Difficult venepuncture when ECMO is in-situ • May need to dec. pump flow transiently during insertion • CRRT circuit attached on to the EVMO circuit

10. Extracorporeal flow needed Separate cannulae needed or Avalon cannula 10000 Increasing size of cannulae 1000 ECMO Flow ml/min ECCO2R 100 IHD CRRT MARS Plasmaphoresis 10 Regional citrate anticoagulation possible 10

11. 1 3 2

12. Possible types of connection 12 13 23 21 31 32

13. Important points • Region 1: • Negative pressure • Once leak, air suck into circuit • Pump fails immediately and circuit stops if massive • Gas embolism if partial and prolonged • Some centres call this region “Virgin area” and cannot be touched • Cardiohelp no connection port in this region • Region 2: • Highest positive pressure • Once leak, blood out • Cardiohelp very much reduced because pump incorporated into oxygenator • Region 3: • Positive pressure, less than region 2 • Once leak, blood out • Oxygenator: • Also as a filter for gas and clot

14. Possible types of connection for Cadiohelp 23 32

15. Types of RRT • Haemofilter only • 23 or • 21 or • 31 possible • CRRT machine • CRRT machines • Prisma: +ve pressure not allowed in a-limb • Otherwise long alarm • Only 12 or13 possible • Prsimaflex: ok but needs adjustment • Haemodialysis machines • Ok but needs adjustment

16. Hemofilter alone - Across oxygenator 23 • Not suitable for PMP type of oxygenator • Maquet - Quadrox D, Medos – Hilite 7000 LT, Sorin – Lilliput 2, Eurosets – Eurosets ECMO, Terumo – Capiox EMS • Because of low pressure gradient across oxygenator  may be inadequate driving pressure for blood flowing through hemofilter • Coiled Silicone membrane, e.g. Medtronic Avecor 4500 • High resistance and therefore big pressure drop

17. Pressure drop across QuadroxD oxygenator

18. Hemofilter alone - 21 (across pump)or 31(across pump and oxygenator) • Feasible but • Connection over the pre-pump (negative pressure) • Increase risk of circuit gas embolism • Circuit stop • Patient gas embolism • Can be rapidly fatal • Simple but need very very close monitoring, e.g. in OT setting • Measure ultrafiltration volume • Even guarded with volumetric pump • Slow continuous ultrafiltration (SCUF) or • Continuous hemofiltration + replacement solution (somewhere)

19. Hemofilter alone • Not advisable “possible” in ICU setting • Volumes not accurate (need to measure Uf volume) • Measurement involve error which become significant over time • Circuit/air embolism • Need of very close monitoring • Consumable availability

20. CRRT machine across oxygenator12, 21, 1 3, 31 23 or 32 • CRRT flow maintained by internal motor of machine • Not influenced by access or return point pressures • Clearance rate much higher than SCUF • 20-25ml/kg/h for RRT • >50ml/kg/h for High Volume Hemofiltration (HVHF)

21. CRRT machine across oxygenator12, 21, 1 3, 31 Risk of circuit and gas embolism Not possible in Cardiohelp Not advisable

22. CRRT machine across oxygenator • Post-oxygenator  Pre-oxygenator (32) • Return part of oxygenated blood flow back to pre-oxygenator • More flow through oxygenator • Oxygenator act as an additional bubble trap in case air get into the CVVH circuit • Less systemic arterial embolism for VA-ECMO • Increase risk of oxygenator thrombosis • May increase need of change of oxygenator & • Associated risk related to oxygenator change and COST • Better CRRT circuit anticoagulation is preferred

23. Oxygenator Oxygenator itself as a filter for clot and gas

24. CRRT machine across oxygenator • Pre-oxygenator  Post-oxygenator (23) • Shunt part of the deoxygenated blood to patient blood • Decrease ECMO efficiency, may need increase pump flow • May not be possible if patient’s oxygenation status is very marginal & pump flow is pushed to maximum already • Inc. risk of patient embolism • Significant if VA-ECMO • Less significant if VV-ECMO (lung as filter) • Beware of PFO because of pulmonary hypertension • Circuit life may be higher

25. ECMO circuit priming with normal saline • Priming volume ~500ml as compared with normal blood volume ~5,000ml • Hemodilution • Lower hematocrit • Lower Ca++ • Lower drug levels • Inc. in volume of distribution • Except Na+ and Cl- • Consider priming with Lactated Ringer solution

26. CRRT Anticoagulation • No anticoagulation if patient is contraindicated for systemic anticoagulation • ECMO & the attached CVVH circuit still can last for days without anticoagulation • Bioline coating (Maquet-Quadrox D) of cannulae, tubing and oxygenator • Both Cardiohelp and Rotaflow • Try not to use protamine to reverse anticoagulation • decrease effect of Bioline coating

27. CRRT Anticoagulation • Regional citrate anticoagulation to CVVH circuit only, not the ECMO circuit • Beware of contraindication – hepatic impairment (hypoxic hepatitis, especially patients with high INR and hypoglycemia) • Good for other causes of bleeding tendency • Excellent anticoagulation property • Less effect on oxygenator and • patient

28. Regional citrate anticoagulation (RCA) Indicated in patients with high bleeding risk Thrombocytopenia Coagulopathy Pericarditis Recent surgery with bleeding complications Recent surgery after which bleeding would be very dangerous Brain or eye surgery Vascular or cardiac surgery 28

29. Citrate calcium interaction Citrate + iCa Calcium citrate Biologically inactive Measurable as total calcium

30. RCA Citrate binds with iCa to form Ca-citrate (partially removed in ultrafiltrate) Circuit [iCa] decreased to ~ 0.3mmol/l Systemic [iCa] normalized by Mainly by dilution of extracorporeal blood Calcium supplement is needed in long term because of extra loss in ultrafiltrate as Ca citrate Liberation of Ca from returned Ca-citrate Citrate3- 3HCO3- (buffer) 30

32. Longer Filter Life 32

33. Less Clotting 33

34. Less Inflammatory Activation 34

35. Less Transfusion 35

36. RCA Contraindications Significant liver impairment Massive blood transfusion Relative contraindication only 36

37. Citric acid cycle Gluconeogensis Lipid synthesis Pyruvate Endogenous citrate Phosphoenolpyruvate Oxidation Citrate Malate Malate NAD+ H2O NADH O2

38. Total to ionized calcium gap • If high rate of citrate infusion and/or hepatic dysfunction • Accumulation of calcium citrate (total) • Progressive decrease in systemic iCa level • Indicative of citrate accumulation/toxicity

39. Calcium Gap mmol/L

40. Calcium Gap

42. Complications of RCA Related to calcium chelation/replacement Hypocalcaemia Hypercalcaemia Skin necrosis due to extravasation Related to citrate metabolism Metabolic alkalosis Metabolic acidosis Related to sodium content Hypernatraemia Hyponatraemia Related to formulation Electrolytes imbalance Haemolysis

43. Monitoring of RCA [iCa] Total [Ca] to [iCa] ratio (<2.5) Metabolic acidosis & alkalosis ABG Sodium overloading (tri-sodium citrate/ACD-A)) Body fluid status [Na+] Phosphate & Magnesium level 43

48. Conclusion • Why CRRT commonly needed in ECMO? • Types of RRT available during ECMO • Types of connections • Pros and Cons • Regional citrate anticoagulation • Principles • Indications & contraindications • Complications & monitoring • Protocol

49. Thank you for your attention.