Pediatric ECMO and CRRT NJ Maxvold MD Assoc Prof of Pediatrics, MSU DeVos Children’s Hospital Grand Rapids, MI

Pediatric ECMO and CRRT I would like to thank Dr Picca and Dr Bunchman for this conference I would like to thank Dr Askenazi for the incorporation of some of his slides into today’s presentation

Pediatric ECMO and CRRT Objectives: Review of ECMO in Pediatrics Indications/Limitations/Complications Survival Data Review of CRRT tandem to ECMO

ExtraCorporeal Membrane Oxygenation Respiratory Failure vs Cardiac Failure Reticent to Mechanical Ventilatory Equipment (HFOV,HFJV,BiLevel/APRV,NO/Surfactant, etc) Limit Vent-Induce Further Lung Injury Reticent Arrhythmias / CO unresponsive to meds or volume status/ noncandidates for VAD/Post Cardiac Surgery Limit End Organ Ischemia Time element to Mechanical Vent Equip support/levels that may increase ongoing pathology in lungs and render less successful ECMO support , 7 days/ 5 days for MAP > ?/40, OI> ?, FiO2> 70%, PaO2/FiO2<200/<150/? Post Pump Stun following Cardiac OR felt to be due to ? ?

ExtraCorporeal Membrane Oxygenation ECMO Limitations: Patient Size: Cannula/Catheters for Preterm/Small Infants Highly Catabolic-Hypermetabolic States Exceeding Flow Delivery Coagulopathy not correctable by therapeutic supports, or recent Intracranial Bleed Contraindications to system heparinization Irreversible Lung or Cardiac Failure not deemed a Transplant Candidate Severe Sepsis can produce Exaggerated Demand and tissue bed shunting unremitteant to Oxygen Delivery., ? Would cooling/ hypothermia help? Studies underway for cooling the resuscitated patient..

ExtraCorporeal Membrane Oxygenation ECMO Complications: Bleeding: Heparin Anticoagulation Embolic Events: Microemboli / Air emboli from the circuit Catheter Displacement Heparin induced thrombocytopenia ?? End Organ/Renal Effect of Continuous Flow The greatest complication/risk of ECMO is bleeding, full heparinization is required due to the large volume of extracorporial circuit, in neonate this risk is up to 50% of cases. ??? Check this with Doug and ELSO data.

ExtraCorporeal Membrane Oxygenation Russell et al Circulation 2009 End Organ Function Continuous Flow LVAD N= 309 pts, HeartMate II, 6 mo Follow Interval Two Group Analysis: Normal and Above Normal Laboratory Values BUN / Cr 37 / 1.8  23 / 1.4 mg/dL AST/ALT 121 / 171 gggg 36 / 31 IU T Bilirubin 2.1 gggg 0.9 mg/dL Conclusions: Continuous flow maintained or improved end organ function What do we know about continuous flow,? There has been Hypothetical belief that renal function may be impaired by a non-pulasatile flow. Is this true? this study by Dr Russell ------ looked at renal and hepatic organ function in patients on a continuous flow LVAD In the normal lab valued patients there was no change with continued normal lab values being maintained

ExtraCorporeal Membrane Oxygenation Ingyinn et al Perfusion 2004 Compared VV to VA Effect on Renal Flow in Lambs 3 Parameters: Systemic Blood Pressure, Renal Blood Flow, Plasma Renin Activity Levels VA and VV Partial Flow (120 mls/kg/min) VA Full Flow (200 mls/kg/min) No difference at partial flow between VV and VA parameters Full VA Flow Significant Increase of Blood Pressure Full VA Flow Flashing/Unclamp of ECMO Bridge BP i Renal Flow Conclusion: Potential cause of the Hypertension that is seen in some newborns after VA ECMO the group Looked at 3 measured parameters under three conditions of flow, ? What happened to the PRA in the Full supported VA group???

ExtraCorporeal Membrane Oxygenation Mussaro et al Pediatr Crit Care Med 2009 Evaluated Bloodless Bridge on VA ECMO (No Flashing/Unclamping) Retrospective comparison to the Earlier Bridge ECMO Setup Parameters: BUN, Cr, Fld Balance, Urine Ouput, Average and max SBP, mean BP No Difference in BUN, Cr, Fld Balance, Urine Output Lower % of HTN (Mean BP> 60), Lower SBP on Days 2, 3 Conclusion: Less HTN with the new bridge design that did not require flashing therefore improved maintenance of Renal flow Neonatal study where The group looked at the first three days on ECMO, Need the actual numbers the Mean BP and SBP, and BUN and stuff

ExtraCorporeal Membrane Oxygenation Basic ECMO Design / Setup: Venovenous Design: Outflow and Inflow catheters in Venous System VenoArterial Design / Setup: Outflow from Venous (R Atrium), Inflow Arterial (Aortic Arch) How does ECMO Work?? VV : Outflow Catheter is through the Internal Jugular vein into the Right Atrium, and Inflow catheter is returning to Femoral Vein in larger children., or in small infants/neonates back through a second lumen into the R Atrium. VA :Through the Internal Jugular into R Atrium usual Venous outflow site of cannulation and return via the Carotid Artery Cannulation to inflow into the Aortic Arch. , Careful postioning to minimaze jet backstream on the Proximal Aorta/ AV, ( this could increase afterload on the LV) Post op Cardiac Patients come often with direct cannulas through the chest/ Sternotomy into the R Atrium and Aorta.

VA vs. VVDL Cannulation

Typical VVDL catheter placement

ECMO Centrifugal Pump Setup

Centrifugal circuit design

ExtraCorporeal Membrane Oxygenation ECMO Neonatal/Pediatric Survival Data: ELSO Registry 1998-2008 Neonates ( </= 30 days old) N= 8958 Survival: 5776 (72.6%) NonSurvival: 2182 (27.4%) This neonate total survival is for respiratory / pu;lmonary ECMO those results are from the ELSO (Extracorporeal Life Support Organization) Registry, This currently has ~ 118 centers across the globe combineing their data for this registry. (1990 only 80 centers); Accumulativ ……

ExtraCorporeal Membrane Oxygenation ECMO and PCRRT Indications for CRRT tandem with ECMO Systems Set Up Design Publications reviewing PCRRT and ECMO Survival and Longterm Renal Outcomes What do we know about the kids who have renal failure and require Renal support as well as ECMO, we know Renal failure in Pediatric critically ill patients at large is an independent risk factor for Survival, as is the number of organ systems failing at the time of admission into a PICU.

PCRRT and ECMO CRRT/ECMO Indications ?? Fluid Overload > 10% ( Michael et al Pediatr Nephrol 2004) pRIFLECr maxF (Akcan-Arikan et al Kidney Int 2007) [Definition : i eCCl by 75% or <35m/min/1.73m2] Nutritional Limitation ( Due to Inadequate Solute/ Fluid Clearance) There are no clinical studies evaluating or defining hard preset criteria for beginning CRRT in Pediatric Critically ill Children let alone in Children on ECMO, therefore looking at studies where CRRT has been Utilized and at what level of renal Insufficiency it has begun may be helpful. Possibly pRIFLE Cr max I criteria ( eCCL  50%) should be used since 39% in this category progressed onto the pRIFLE Cr F category. pRIFLE maxUOP only did not identify those patients requiring RRT in this study , therefore thismay not be as helpful in determining timing of CRRT eCCl is calculated from the Schwartz formula, and the baseline eCCl was calculated from the lowest SCr found on the patient in the preceding 3 month period to the study/ PICU admission.

CRRT on ECMO “Homemade” system connected to the ECMO circuit IV infusion pumps used to control ultrafiltrate (if replacement desired) IV infusion pump to add replacement fluids Several sites to hook into circuit each with drawbacks ( shunting, bubble trap, flows) IV pumps are not engineered to maintain accuracy when flow/pressure above the pump is variable. Original CRRT circuits in line with ECMO where filters that were connected through IV infusion pumps to control inflow, outflow and ultrafiltration from a hemofilter, all w these pumps had large inaccuracys in measurements of flow/ volume set and actual delivered.

ECMO/CRRT Arrangement: Homemade System Set up looked something like this,

ECMO/CRRT Arrangement: RRT System Here is a representation of a roller pump ECMO circuit with the CRRT Machine introduced entirely before the bladder, very early in the circuit.

ECMO and CRRT Hemofilter (Homemade) CRRT Ultrafiltration control IV pump controlled CRRT machine controlled Metabolic Control NO YES ECMO Flow Blood Shunt decrease ECMO flow or decreased PaO2 to patient NO systemic changes Anti-coagulation Heparin This slide shows comparison of components found between the two setups

CRRT/ECMO in Tandem CRRT/ECMO Centrifugal Pump Santiago et al Kidney Int 2009 N= 6 children on VA ECMO Inlet line after the Centrifugal Pump Outlet/return line before the Oxygenator Mean Filter Life = 138 hours CRRT and ECMO system setup in tadem in children with a centrifugal pump was recent published from the Madrid group.

CRRT/ECMO in Tandem Advantages of Centrifugal pumps have increased the use of these as the flow generators on ECMO. No Occlusion pressure trauma to the red cell volume, therefore less //??? Free hemoglobin/igment generation.

CRRT/ECMO Outcomes Meyer RJ, et al Pediatr Crit Care Med 2001 15/ 35 ( 42.9 %) neonatal and pediatric survived 14/15 (93%) RENAL RECOVERY 1/15 (7%) – Wegener’s What is known or at least published in children supported by both ECMO and CRRT on their Outcomes?

CRRT/ECMO in Cardiac Newborns Shah SA et al. ASAIO J 2005 41/ 84 (48.9%) post-operative congenital heart disease patients with AKI CVVH NOT associated with : Ability to wean off ECMO Survival to discharge Kolovos et al. Ann Thorac Surg 2003 26 / 74 (35%) post-operative congenital heart disease patients Hemofiltration = 5.01 X increased risk of death Now we move on to what we know or at least has been published on outcome in children supported by both ECMO and CRRT.

CRRT/ECMO – Noncardiac Children Hoover et al. Intensive Care Med (2008) Case-control study Cases 26/86 - received CVVH for >24 hours Controls – no CVVH Significant differences in fluid balance Significant treatment differences No difference in survival or vent days during or after ECMO

ECMO/CRRT Asked the Question: ELSO Registry Data,1998-2008 Askenazi et al Abstract CRRT 2009 ELSO Registry Data,1998-2008 8958 patients age ≤ 30 days Asked the Question: Hypothesis: After controlling for demographic, complications, severity of illness, interventions, does AKI / RRT predict mortality in non-cardiac neonates who require ECLS? Dr Askenazii in a abstract presentation at CRRT in 2009 ask the question can AKI/RRT predict mortality in neonate on ECMO for non cardiac reasons?

Extracorporeal Life Support Organization (ELSO) Registry AKI Categorically defined Complication code of SCr ≥ 1.5 mg/dl or ICD-9 code of Acute renal failure Dialysis CPT codes used Survival Demographics, Complications, Co-Morbidities and Interventions Askenazi et al. Abstract CRRT 2009

ELSO Registry - Neonates 18 % of the Neonates received a Dialytic support therapy, ~8 % were demonstating AKI with 5 of the 8% supported by Dialytic therapy. Askenazi et al. Abstract CRRT 2009

ELSO Registry - Neonates Askenazi et al. Abstract CRRT 2009

ExtraCorporeal Membrane Oxygenation ELSO Pediatric Registry 1998-2008 N = 2514 Survival = 1410 (56%) ELSO Accumulative (1985-2008) N = 4065 Survival = 2247 (55.3%) Ped Pts Receiving Dialysis (1985-2008) N = 1616 (39%) Survival = 606 (37.5%) ELSO data of Pediatric Respiratory Runs, for above time intervals. Of the Dialysis rendered, N=1010 (62.5%) was a continuous form of support, mostly CVVH a few (227 )CAVH.

ELSO 1985-2008 Cardiac Runs Age Total Runs Survival Dialysis 0-30 days (37.4%) N=1595 (41.7%) N=354 (22.2%) 1-12 months N=2428 N=1058 (43.6%) N=926 (38%) N=244 (26.3%) 1-16 years N=2034 N=975 (47.9%) N=783 (38.5%) N=273 (34.9%) >16 years N=1113 N=388 ((34.9%) N=533 N=118 (22.1%) ELSO Accumulative data since it’s start pre”85-2008, for all (neonatal and Ped and adult) Cardiac Runs., and is broken apart by age sets. Dialysis is most frequently used in the neonate <1 month and the older Adolescent, this dataset also includes Adult Cardiac runs. The highest survival group of those requiring some form of Dialytic support was the pediatric 1-16 years old set,. Again, a continuous mode CVVH or CAVH represented the primary dialytic mode, , with 73.5%, 66.1%, 64.5%, 54.2% utilizing continuous forms, as age sets increased.

CRRT/ECMO Summary ECMO&CRRT Can be Safely done in a variety of setups No additional regional Anti-coagulation is needed since the patient and the entire circuit is already heparinized for ECMO Circuit prime for the CRRT can usually be saline Due to the relative size of the CRRT circuit in ratio to the larger ECMO circuit When starting Ultrafiltation careful monitoring of fluid goals over a time period will prevent  Hct and viscosity changes that are unwanted CRRT Support on ECMO Effect on Mortality is yet to be more clearly defined as to timing of Initiation of both supports and Subsequent Outcomes. UF error, too rapid a removal of plasma water can be hard to initially identify when on VA ECMO which provides a broad hemodynamic support base, Watch for decreasing measured circuit flow rates.

ECMO Circuit ECMO Circuit Priming the circuit begins with a CO2 flush, then a crystalloid solution. Albumin is added to decrease plate activation. Blood prime next. Calcium, heparin, albumin and THAM for buffering, bicarb to adjust pH since the volume is about twice the child's total blood volume. Platelets are infused immediately prior to connection of the patient to decrease dilutional thrombocytopenia. Blood drains by gravity from the child. A bladder serves as a regulator of flow. This is connected to a servo mechanism that controls the pump. A roller pump has proved reliable (little hemolysis). Membrane lung rated according to expected flow. It can serve as a bubble trap. Sweep gases regulate the blood gas of blood returning to the baby. The membrane lung can be thought of in the same way as a ventilator. Varying the gas and minute ventilation can achieve the blood gas desired. Because the volume of the blood outside of the baby is about twice the child’s total blood volume a heat exchanger is added too. A bridge allows flow in the circuit even when the child is clamped out of the circuit.