Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines

Abstract

Why Consider ECPR for Cardiopulmonary Arrest in Children? Because Conventional CPR may not be Sufficient to Optimize Outcomes in all Pediatric Cardiopulmonary Arrests Situations Survival rates with good neurologic outcomes following conventional cardiopulmonary resuscitation (CPR) for cardiopulmonary arrest, either in the in-hospital (IH) or out-of-hospital settings, have improved but remain poor in children.1–3 In general, a longer duration of CPR before the return of circulation is associated with decreased probability of survival,4,5 worse neurologic6, and neuropsychologic outcomes among survivors.7,8 What is ECPR? It is the rapid deployment of venoarterial (VA) extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) to provide reperfusion with oxygenation and cardiovascular support in the context of cardiopulmonary arrest. In 2018, Extracorporeal Life Support Organization (ELSO) guidelines and Utstein guidelines harmonized their nomenclature and clarified the definition for ECPR.9 ECPR is defined when ECMO flow is instituted during conventional CPR, delivered with manual or mechanical compressions, or within 20 min of return of spontaneous circulation without ongoing compressions. As such patients cannulated after 20 min of sustained return of spontaneous circulation are classified as receiving VA ECMO, not as ECPR. The objective of ECMO in patients with cardiopulmonary arrest is to provide circulatory support and gas exchange – both delivery of oxygen and removal of CO2 and to decrease ischemic reperfusion injury. In this context, ECPR allows ECMO to serve as: a bridge to therapy, intervention, diagnostics, transport, and recovery, or a bridge to organ transplant or replacement with another device, or a bridge to palliative care. Emergency preservation and resuscitation (EPR) for cardiac arrest from trauma is different from ECPR; EPR involves rapid intra-aortic retrograde flushing of ice-cold preservation solution, venous drainage, and deep hypothermia (<10°C) within minutes; EPR trials are being conducted in trauma arrest.10 ECPR Outcomes and the ELSO Registry The ELSO Registry collects information on children undergoing ECMO cannulation during CPR since 1992. Published survival to hospital discharge in ECPR cases is summarized in Table 1 and spans from 38% in children overall to 42% in children with heart disease. In a study combining a contemporary era (2010–2014) of data in children, with ELSO and the American Heart Association Get With the Guidelines-Resuscitation Registry, the survival to hospital discharge was 31%.5 In general, survival to hospital discharge for children is higher compared to adults. Table 1. - Studies Reporting Survival to Hospital Discharge in Children with Supported With ECPR and Studies Reporting Longer-term Outcome Author Year Diagnosis Institution Total Survival del Nido11 1992 Cardiac Pittsburg 11 64% Dalton12 1993 Cardiac Pittsburg 29 45% Duncan13 1998 Cardiac Boston 11 54% Morris14 2004 All Philadelphia 64 33% Thiagarajan15 2007 All ELSO-R 682 38% Alsoufi16 2007 All Toronto 80 34% Chen17 2008 All Taiwan 27 41% Tajik18 2008 All Meta-analysis* 288 40% Chan19 2008 Cardiac ELSO-R 492 42% Kane20 2010 Cardiac Boston 172 51% Raymond21 2010 All GWTG-R 199 44% Wolf22 2012 Cardiac Atlanta 150 56% Lasa4 2016 All GWTG-R 591 40% Meert23 2019 All THAPCA 147 41% Bembea5 2019 All ELSO-R and GWTG-R 593 31% Longer-term outcomes studies with ECPR pediatric patients Lequier24 2008 Cardiac Edmonton 9 ECPR (of 39) At 2 years Garcia Guerra25 2015 All (2000–2010) Edmonton 55 ECPR 43% at 4.5 years Kuraim26 2018 Cardiac Edmonton Some ECPR variable Meert27 2019 All THAPCA 147 ECPR 41.5% at 1 year ELSO-R, Extracorporeal Life Support Organization Registry; GWTG-R, Get With The Guidelines Registry; THAPCA, Therapeutic Hypothermia in Pediatric Cardiac Arrest Trials. Better outcomes for children than in adults may be related to the fact that ECPR is largely offered to children who are in-patients and often are in intensive care unit environments, significantly shorter times between the start of cardiac arrest to return of extracorporeal circulation, and cannulation strategies that more often use neck or central vessels compared to femoral access. Early neurologic assessment at the time of hospital discharge among survivors suggests that they have good neurologic outcomes.4 Published longer-term outcomes of children exposed to ECPR are ill-defined and rare. How to Deploy High-quality ECPR? High-quality ECPR is a complex intervention and should not be applied in patients as an ad-hoc procedure. ECPR is best suited to select populations when delivered by organized systems with predefined guidelines and local protocols. Patient Selection, Context, and Setting Patient selection is important. In pediatrics, no randomized controlled trial has yet been conducted to compare conventional high-quality CPR to high-quality CPR with ECPR.28 The current guidelines are informed by consensus guidelines based on: physiology,29 literature of institutional clinical experiences,16 voluntary registry-based studies,4,5,15 secondary analyses of clinical trials,23 resuscitation guidelines,30 and clinical and preclinical CPB practices. For IH cardiopulmonary arrests, it is best to consider first children with and without cardiac disease. In children with cardiac disease, physiologic functional parameters that limit the effectiveness of conventional CPR may be important to consider when adapting resuscitation practices29: patients with limited stroke volume with chest compressions, limited effective pulmonary blood flow and oxygenation with compressions, and limited cerebral perfusion. In these three main groups, if resuscitation measures are provided, ECPR may need to be considered sooner rather than later – if patients are otherwise suitable – given that conventional CPR may have limited effectiveness. In addition, in special cardiac populations, optimal cerebral resuscitation may only be obtained with ECPR cannulation strategies tailored to their individual functional anatomy. Important differences in reperfusion approaches differ in the single ventricle and bi-ventricular physiology are illustrated in Figure 1A–H. Individualized cannulation strategies should be planned in advance.Figure 1.: A–H: Cannulation strategies for rapid venous and arterial accesses for ECPR: A, B, and C show strategies for structurally normal hearts or biventricular circulation. A, Central cannulation with venous access in the right atrium and arterial access in the aorta. B, Peripheral cervical cannulation with venous access in the internal jugular vein and arterial access in the common carotid artery. C, Peripheral femoral cannulation with venous access in the femoral vein and arterial access in the femoral artery. Left atrial decompression may need to be considered as an additional intervention in all these approaches. For patients with single-ventricle physiology stage 1 with a shunted or right-ventricle to pulmonary artery conduit physiology, strategies are shown in D and E. D, Stage 1 with central cannulation with venous access in the common atrium and arterial access in the aorta. E, Stage 1 with peripheral cannulation with venous access in the internal jugular vein and arterial access in the common carotid artery. Special care should be taken regarding cannula position in relation to the shunt as it may result in over circulation to the lungs or shunt. For patients with single ventricle physiology Stage 2 with a superior cavopulmonary anastomosis, strategies are shown in F and G. F – Stage 2 with central cannulation with venous access in superior vena cava or in common atrium and arterial access in aorta. G, Stage 2 with peripheral cannulation with venous access with internal jugular vein or femoral vein and arterial access with common carotid artery. If a femoral approach is only used for peripheral cannulation, one must remember that passive venous return must flow through the lungs and mechanical ventilation must be carefully optimized; added venous cannula may be required. For patients with single-ventricle physiology Stage 3 following a Fontan operation, a suggested strategy is shown in H and may be adapted to patient size. H, Peripheral cannulation with venous access in the internal jugular vein and or femoral vein with arterial access in the common carotid artery. Femoral venous cannula may be required depending on patient size and it is important to note that the femoral cannula should be long enough to reach the inferior vena cava drainage site into the Fontan baffle.In children without a primary cardiac disease, data are very limited, and the reported outcomes associated with ECPR are universally worse than in children with cardiac disease. These worse outcomes may be associated with: the primary cause of the event (e.g., cardiopulmonary arrest with prolonged preceding hypoxemia in asphyxia-related events), or the prolonged low flow and hypotension preceding ischemia (e.g., in severe septic shock). We suggest that institutions establish local protocols that guide their use of conventional CPR with or without ECPR. If institutions opt to deploy protocols that involve ECPR, one of the early steps of this protocol must include decision making by a senior clinician based on physiologic principles. Combining high-quality ECPR with high-quality conventional CPR may be considered if the cardiopulmonary arrest is witnessed and is associated with a reversible condition. Unwitnessed events in all settings have a poor prognosis and should be considered a relative contraindication for ECPR. Applying extracorporeal resuscitation measures must improve and not interfere with the quality of resuscitation measures. In some patients, early application of extracorporeal measures may be part of a predefined cardiopulmonary arrest care plan where conventional CPR is not expected to be effective.31 Such examples would include: 1) high-risk anesthesia induction with diseases associated with obstructed pulmonary blood flow from large pulmonary emboli and 2) cases of severe hyperkalemia with new-onset leukemia and tumor lysis syndrome. Out-of-hospital Pediatric Cardiopulmonary Arrest In children, there are insufficient data to support the recommendation for the use of ECPR for out-of-hospital cardiopulmonary arrest events, either applied in the field (e.g., trauma or remote retrievals of avalanche or drowning victims) or in the hospital after ongoing conventional CPR during transport. ECMO has been applied in victims of deep hypothermia associated with submersion in water or avalanches to rewarm and resume circulation. In these circumstances, ECPR is a technically attractive indication for ECMO and gradual rewarming; however, the neurologic consequences of indeterminate or prolonged hypoxic-ischemic injury may not be reversible with reperfusion with ECMO. Future evidence may be available from regions and countries with orchestrated emergency medical systems and their registries. Given the absence of clear evidence in favor of ECPR, systems that would opt to offer ECPR for out-of-hospital events should only do this with well-delineated protocols. Decision and Timing of ECPR The decision is made if the patient is suited to receive and benefit from extracorporeal resuscitation measures and when the clinician considers (or expects) the cardiopulmonary arrest to be refractory to conventional CPR measures. A lag time of 5–10 min that allows for high-quality CPR to be delivered and obtain spontaneous circulation is usually designed in institutional protocols. ECPR requires additional equipment, people, and resources which explain why a system’s launch time is based on the expected time needed to achieve all the steps to get to extracorporeal blood flow. Some organizational benchmarks are <30 min or <40 min for IH events. The decision to launch ECPR and the timing of launching ECPR should be built as separate steps in the institutional protocol. Resuscitation Measures, Duration, and Quality of CPR There is no consensus on how conventional CPR should be conducted before cannulating for ECMO. In general, there is a significant decrease in favorable outcomes when blood flow is achieved after 40 min of CPR, but some cases are found in registries where resuscitation measures longer than 60 min or longer have been reported with survival.4,5 More studies are needed to understand how to maintain high-quality conventional CPR when ECPR preparation, positioning, and cannulation are initiated.32 Age and Size In children, size, and maturity, more than chronological age are considered. Cardiothoracic surgeons are technically able to cannulate neonates and infants less than 2 kg or 3 kg; however, the underlying diseases associated with these cardiopulmonary arrest events may not be reversible and the reperfusion injury on the developing organs (brain, heart, bowel, and kidneys) may be significant. Differently, while obesity in adult series has not been associated with adverse outcomes,33 delivering high-quality resuscitation presents challenges for pediatric teams that may not have adapted resuscitation protocols for ‘adult size adolescents’. To provide high-quality ECPR across the weight ranges (2–130 kg) local protocols must include adapting approaches, medications, and equipment. In the context of cardiopulmonary cerebral resuscitation, ECPR and bridging with ECMO, must on balance, add value. Already Supported by ECLS In children already on an extracorporeal or paracorporeal devices, occasionally malfunction or disconnection can occur (e.g., while on ECMO, ventricular, or lung-assisted devices). Resuscitation protocols will include planning for cannulation and instructions on using or not using cardiac compressions.34 The Team ECPR requires a well-coordinated team of expert-trained professionals to ensure rapid and successful deployment (e.g., in Tables 2 and 3). Table 2. - Tasks and Team Members With Predefined Roles and Responsibilities Unit Type and Event Location ICU Cannulation-ready Location Non-ICU Cannulation-ready Location Non-ICUNot Cannulation Location Predefined cannulation locations Cannulation equipment and footprint approved room Cannulation equipment and footprint approved:•Image-Guided Laboratory•Cardiac Catheterization Cannulation equipment not available and footprint not Emergency and anesthesia locations (e.g., Tasks Members for Resuscitation clinician or clinician or Team ECMO Team ICU or or ICU or ICU or Event ICU 1 ICU ICU CPR team ICU 2 or ICU Conventional High-quality CPR ICU CPR Team CPR Team with ongoing CPR to ECMO cannulation 1 2 1 2 1 2 ECMO ECMO 1 ECMO 1 ECMO 1 1 or ECMO 2 1 or ECMO 2 1 or ECMO 2 CPR and and and 2 2 2 ICU and ECMO ICU and ECMO ICU and ECMO or support or support or support and time or or or may different of this based on the of event and the predefined locations for Team and Members are to to cannulation on their without time (e.g., ECMO and start Table - Roles and Responsibilities for ECPR Cannulation Location in ICU ICU 1 or Team on high-quality CPR ICU if not ICU 2 Event team weight and cannulation information patient and with ECMO to the of the event and informed team after patient on ECMO 1 support and resuscitation all equipment is available 2 to cannulating surgeons patient is in position with CPR patient and (e.g., Cardiothoracic 1 and 2 and neck or to cannulation approach all ECMO CPR with for cannulation ECMO blood and blood ECMO and time ECMO for surgeons with cannula and based on blood flow based on weight and cardiac and to only when are being patient with ICU when and if time to cannulation allows it 1 for and CO2 equipment for if patient not yet arterial blood gas 1 delivery access to patient and to patient to and when are given patient blood medical medications, 1 and 2 and and all and 1 or to resuscitation, and that and have been by using if of time of events of resuscitation and is in the room or in the involve some to this resuscitation measures should be by the first of who on high-quality CPR with before and during ECMO A team of is to ECPR who are with rapid cannulation and of the ECMO A team (e.g., team is used to the ECPR team and resources ECPR teams in across systems and ECPR teams may be available to deploy this may not be for all ECPR is a high-risk resources required for and team and using is to maintain the of the the to support this effective CPR and to ECPR, will be to both and clinical resuscitation events. for ECPR ECPR systems equipment that is for rapid or that can be on and with predefined gas and (or and may use either or are more and have improved compared to ECPR systems include a are used to for ECPR evidence one Some their with (e.g., or use or in ECMO deployment while the of blood for is not current protocols should be in based on blood and CO2 With ECPR There is no evidence to guide membrane gas during ECPR ECPR has been from CPB clinical For the IH some use on their ECMO and and will and to as it may reperfusion injury. There is no evidence to guide CO2 in ECPR. of CO2 is from the ECMO, and CPB Early of arterial blood on to and which cerebral blood flow and may neurologic For who provide ECPR in patients flow gas that low flow settings are needed to from rapid achieved with contemporary and Cannulation Cannulation for ECPR must be achieved or blood flow is by the cardiac with the patient size and by the physiologic need based on the underlying disease. cardiac compressions, peripheral cannulation is associated with less compared with central however, no evidence to support one approach over the Peripheral These are either with an or a or using a The selection of is by the size of the for drainage and for return of The right neck is the site to cannulate in children less than kg normal using the internal jugular vein as drainage and common carotid artery for the Femoral and are to be used in children and adult size cannulation may be associated with There is no data to which cannulation approach the best cardiopulmonary cerebral Central Cannulation used in patients who have a for In these the right atrium and are cannulated In these patients, the time to achieve cannulation and blood is usually on Children with heart may need their cannulation strategy to ECMO flow of cerebral and cardiac of cannulation strategies for special are illustrated for in Figure and these include patients with single ventricle physiology, before and after stage and for Stage and after stage Children who need a higher cardiac may or central (e.g., septic physiology or In children who have vessels may be or of strategy planning in the event of a cardiopulmonary arrest is best suited to these patients as it in to ECMO. approach is to for patients with to use equipment is for ECPR. that a of and that can be to the site of cannulation are or for cannulation should be available at the The for and the must be with the and equipment to the of should before cannulation based on local ECMO protocols. delivery is to local ECMO cannulation protocols may be different for peripheral or chest If access is not available during CPR cannulation may before or are should be delivered as as to the The may be used as an however, there is no reported evidence on this Location of Cannulation The equipment, and team in ECPR a large of for IH or out-of-hospital use a to team and equipment the that the of cannulation (e.g., of the cannulation and the ECMO and should locations suitable and predefined for cannulation (e.g., ICU or and have a protocol to the patient to these locations with ongoing a patient while undergoing CPR is complex and may the quality of however, cannulation and arrest care should be orchestrated in the that will patient the size, and of the to the of the team and the equipment (e.g., ICU is ECPR to ECPR have a local a of or a flow in to and are by different of Tables 2 and 3). include patient selection and launch of cannulation if not in the of the cardiac arrest, instructions for transport, and CPR measures. ECPR protocol should the for the of and the of A flow or may steps and to A duration of time between event start time and time to ECMO is important to an individual must be for and during the resuscitation and should the of and to cannulate at the of the arrest event or and CPR on the to to the cannulation these are internal measures the of ECPR These serve to in the (e.g., decision making cannulation and understand that times to blood flow are associated with worse For in-hospital cardiopulmonary arrests, some to have in to achieve within min or 40 min either by the return of extracorporeal circulation or spontaneous circulation. the lag times and the required to launch the ECPR team and have at the cannulation while high-quality CPR, and the the event during the to care launch decision and by the of These benchmarks are used for and for team and these are used as times to resuscitation measures. Arrest following ECPR in patients who receive ECPR after the return of circulation and gas exchange has been The is to reach ECMO to and oxygen ECMO flow by improved clinical and neurologic and of of ischemia (e.g., or and of support as as to and maintain patients with hypothermia for to neurologic outcomes no evidence of improved should not interfere with ECMO care should be defined by a based on patient or institutional protocols need to be central or would not be an cannulation, is or Therapeutic These include and cardiac These be planned and without Left atrial is a cardiopulmonary arrest, heart and lungs will from and children with of and pulmonary may ventricle can be achieved in children with central cannulation or the by a between the right and of neurologic injury is with ECPR patients compared to ECMO assessment may include with clinical or and with a assessment for is the of this but is an part of ECPR and Because of the rapid of ECPR deployment informed for ECPR may be to In and information is given and at the time of the anesthesia or which is often before a cardiopulmonary arrest In where ECPR is for informed is best with approaches used for conventional for ECMO or who may have to ECMO may not be suited for ECPR for ECPR. Patient and physiology related to cardiopulmonary arrest ECMO and ECPR These differences are to of children with complex (e.g., patients with severe pulmonary before a cardiac or for organ heart or In ECPR events, or (or should be informed after have been ECPR is best conducted on a which allows to be of the in and These the should include: for the cardiopulmonary arrest The for extracorporeal support based on institutional bridging The care plan that involves the of survival with and of The information is based on data that may be to Outcomes in ECPR Patient Team High-quality and patient and for and team Figure ECPR

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