Update on ECMO in paediatric patients New Perspectives in ECMO 2012 III International meeting, 5 October, 2012 Milan Update on ECMO in paediatric patients Gianluca Brancaccio MD, PhD Ospedale Pediatrico Bambino Gesù, Rome, Italy

Background ECLS is constantly improving since it was first used in critically ill patients with respiratory failure over 40 years ago. To date over 50.000 patients were treated with ECMO, been neonates and infants the majority. Aim of this overview is to illustrate the changing in environment, equipment and management in ECLS over time.

Runs by Year ELSO Registry July 2012 Neonatal ECLS has shown a progressive decline in the number of patients treated per year ELSO Registry July 2012

Neonatal Respiratory Cases Peaking at about 1500 cases in the early 1990s, recent years have seen an average of 800 patients treated per year. These changes may reflect better prenatal care and perinatal preventive medecine as well as the availability of alternative therapies for support of neonatal respiratory failure, such as high frequency ventilation, inhaled NO and surfactant. In particular, randomized studies of inhaled NO in neonatal respiratory failure and pulmonary hypertension showed that NO reduces the need of ECMO in about one-third of patients Clark RH et al. N Engl J Med 342: 469-474, 2000 ELSO Registry July 2012

Cumulative Survival in Neonatal Respiratory Support There has been concern that the availability of alternative therapies leads to a delay in ECMO institution and may be responsible in part for the poorer outcome noted in recent years of neonatal ECMO. Survival between 1995 and 2011 has fallen from 76% in 1995 to 62% in 2003. There is little “hard evidence” to show that the decline in neonatal ECMO survival is due to “sicker” patients receiving ECMO. ELSO Registry July 2012

Neonatal Cases by Year and Diagnosis It is true that the simple neonatal patient with meconium aspiration, an entity with high rate of survival with ECMO, is found less frequently in the ELSO registry than in earlier years. Patients with congenital diaphragmatic hernia also form a larger proportion of neonatal ECMO patients compared with earlier years. These patients also have decreased survival as compared with other groups. ELSO Registry July 2012

Neonatal Diagnoses and Survival ELSO Registry July 2012

Initial Mode of Neonatal Respiratory Support Veno-arterial access remains the most common mode of support in neonatal respiratory failure, but the number managed with VV access using a double lumen catheter has grown to over 20% of cases. Traditionally, VV ECMO has been avoided in pts requiring inotropic support because of concerns of inadequate cardiac support with this method of ECMO. Many reports suggestes that an inotropic score more than 100 is a controindication for VV ECMO. Thus, the application of VV ECMO to patients who have cardiac compromise may be a viable option, especially once a ventilation support and oxygen delivery are established. Additionally, VV ECMO provides well-oxygenated blood directly to the pulmonary bed , which may reduce pulmonary hypertension and improve right ventricular output. Data from microsphere studies have shown that, even during VA ECMO with a cannula in the ascending aorrtic arch , the majority of coronary blood flow is provided by native left heart ejection and not from arterial ECMO return. Thus, coronary perfusion and improved myocardial oxygen delivery may be better during VV ECMO than VA . Another aspect of VV ECMO is the avoidance of the need to cannulate right carotid artery, reducing neurologic complication and the risk for stroke later in life. While the debact is stille exists, there is a movement to use a VV ECMO whenever possible. ELSO Registry July 2012

Pediatric Respiratory Cases Pediatric ECMO patients include those who are over the age of 30 days and less than 18 years. The number of pediatric pts supported for respiratory failure is showed in the slide. Survival remains relatively stable at 56%. As shown in this slide we observes the incresing number of ECMO over time, particularly in last years in which a new “respiratory diseases” developed such as H1N1 or different forms of SARS. ELSO Registry July 2012

Pediatric Cases by Year and Diagnosis Perhaps the biggest change that has occurred over time in pediatric ECMO is the expansion to patient groups who would have been excluded from ECMO support in years past. Recent reports of succesfull treatment with ECMO has been described in pts with trauma, immunosoppression, burns, underlying bleeding disorders (hemophilia), established MOF amd malignancies. One example of these changes is in the approach to the patient with sepsis and MOF. While these characteristics would likely have excluded pts from ECMO consideration a few years ago, the use of ECMO in sepsis is now an accepted therapy. In fact ECMO is part of algorithm in different guidelines for hemodinamic support in pts with severe septic shock cathecolamine-resistant. ELSO Registry July 2012

Initial Mode of Pediatric Respiratory Support The most common mode of support in pediatric pts remains VA. Lack of double-lumen single cannulas large enough to support older children and insufficient size of femoral vessels for venous cannulation are cited as reasons for the predominance of veno-arterial cannulation. Experience is showing, however, that children can tolerate femoral venous access at ages as low as 5 or 6 years, and this may shift the support modality in the future. VV ECMO has accounted for one-third of pediatric respiratory cases in the past years. ELSO Registry July 2012

Cardiac ECLS by Diagnosis 0 – 30 days old The largest area of growth in application of ECMO has undoubtedly occurred in cardiac population.While the majority of pts are those with CHD in the postoperative period, pts with myocarditis, cardiomyopathy, and other forms of cardiovascular collapse have also received ECLS support. ELSO Registry July 2012

To decrease the time for ECMO start, many centers now maintain systems which can be rapidly deployed for ECLS support. Some centers utilize a regular roller-head, silicone membrane lung system that is saline-primed and kept sterile for up to 30 days. Others use a centrifugal pump and hollow fiber oxygenator circuit which can be ready for use within minutes.

Cardiac Cases By Year 0 – 30 days old The breakdown of cardiac pts from the Registry is shown in the slide. One of the reasons for the increase in cardiac ECMO has been the increasing complexity of cardiac repairs now undertaken in small infants and for the paucity of VAD devices for this category of pts. ELSO Registry July 2012

Cumulative Survival in Cardiac Support 0 – 30 days old Overall survival for neonatal cardiac cases has been declined slightly, likely as a result of ECMO being applied to more and more complex cardiac diseases such as HLHS. One alteration in traditional ECMO with cardiac pts such as HLHS is that, since respiratory function may be normal, there is no specific need for a membrane oxygenator. This form of extracorporeal support has become colloquially known as “NOMO”, simplifing the circuit and reducing the amount of anticoagulation. ELSO Registry July 2012

Cardiac Cases By Year Under 16 years As mentioned before, we assist an increasing number of cases that needing ECMO support for cardiovascular collapse. In this area of age the major part is reprented by pts with CHD in postoperative period, but patients with myocarditis and cardiomyopathy and other forms of cardiovascular collpase are supported by ECMO ELSO Registry July 2012

Cumulative Survival in Cardiac Support Under 16 years of age Based on the success ECMO in supporting cardiac patients, there has been a paradigm shift over the past few years. While once applied only in the most desperate cases, ECMO is now applied earlier in cardiac dysfunction and to a greater variety of pts. ELSO Registry July 2012

Cardiac Survival by Diagnosis and Year Under 16 years One group which reprents a novel but increasingly important segment of ECLS is the category of ECPR. Althuogh the succesfull use of the ECMO during cardiac arrest was described over 10 years ago, it has found renewed enthusiasm as more reports of succesfull outcomes have appeared in the literature. ELSO Registry July 2012

HOW HAS ECLS EQUIPMENT CHANGED Tubings heparin-bounded Pumps Roller pump Centrifugal pump Cannulae (Avalon) Plastic oxygenators Silicone membrane oxygenators Hollow-fiber membrane oxygenator (HFMO) ECMO equipment has undergone substantial changes in the last 5 yrs with newer and different cannulae, plastics, oxygenators, and pumps. The newer tubing materials and coatings which are designed to be more “biocompatible” seem to have decreased the inflammatory profile and systemic response to the ECMO circuit. Similarly, heparin bounded circuits may help to reduce thrombotic complications but have not removed the need for anticoagulation.

Over the past several years, the semi-occlusive roller head pump, which has been the mainstay of ECMO support for so many years, has been supplanted by newer models of centrifugal pumps. Earlier versions of centrifugal pumps had limited use during ECMO for small patients due to observed hemolysis at low flow rate (< 1L) and short lifespan of pump heads that required frequent replacement. The newest magnetically levitated centrifugal pumps are now the most popular pump in ECMO circuits for adult pts but now also in pediatric and neonatal pts. Concomitant to new pump head devices, hollow fiber oxygenators with polymethyl pentene have also become available. These have largely supplanted the silicone membrane lung that has been the “workhorse” in ECMO for many years. Polymethil pentene oxygenators have low resistance to flow, provide excellent gas exchange, and can be primed for use in a matter of minutes. The combination of centrifugal pumps and low-resistance oxygenators has opened a new era in ECMO support, which is easily implemented across a wide range of patient ages and sizes.

Avalon Elite™ Bi-Caval Dual Lumen - Triple lumen cannula ↓ recirculation Good flow dynamics Sizes from 13 Fr to 31 Fr. The recent single triple lumen cannula (Avalon) which uses venous drainage ports at the SVC/RA and IVC/RA junction with inflow return directed to the tricuspid, may have less recirculation difficulties than other forms of VV support and has rapidly become a preferred cannula in larger patients, especially for the wide range of sizes. In pediatric population we use the size of 13 and 16 Fr.

Conclusions The field of ECMO is currently in a state of flux. Many patients denied ECMO support in the past are now being considered for ECMO support and obtaining long-term survival. The experience and knowledge gained over the past 20 years or more of ECMO has resulted in making this therapy more accessible, safer, and efficient. The revised interest in use of ECMO in cardiac arrest, sepsis and other populations may herald an increase in the use of ECLS in future days.

Experience OPBG A total of 93 veno-arterial ECMOs were delivered to 90 patients: in 3 cases two separate ECMO sessions were necessary; 3 patients were bridged from ECMO to ventricular assist device

ECMO indications low cardiac output syndrome (LCOS) in 10 cases post-operative LCOS in 61 patients respiratory support in 20 children sepsis in 2 patients

Results Children who survived on ECMO had a significantly shorter treatment duration: 4 (2.7-7) vs. 9 (5.7-16) days p<0.0001

Results-2 Age, weight, RACHS score, indication to treatment, pump type, cannulation site, need for renal replacement therapy and the presence of univentricular anatomy were not significantly associated with an increased ICU mortality (p>0.05).

Overall Patient Outcomes Finally, more patients in recent years fall into the category of “others”, which often means they have unusual disorders outside the traditional diseases which ECMO has been assosciated in the past. The majority of patients are neonatal, with an overall survival of 75%. ELSO Registry July 2012

Cannulation Central vs. peripheral cannulation Jugular-carotid Femoro-femoral VA ECMO Femoro-femoral VV ECMO Veno-venous vs. veno-arterial ECMO Percutaneous cannulation Many improvements on outcomes and results are secondary to technical advances. These can be considered as peripheral cannulation vs. central and variations of VV and VA. The main access sites in neonates is jugular and right carotid artery for a VA ECMO. Femoro-femoral VA ECMO is useful in circumstances where access to the chest or neck is not readily available (ECPR). Patients >15 Kg or > 2 yrs are expected to have femoral vessels of sufficient size for cannulation and adequate support. One concern with femoral venoarterial bypass is that with severe respiratory failure, blood from the left ventricle will be about the same saturation is that in the right atrium, and this relatively desaturated blood will be what is perfusing the upper body, especially the head and the heart. This can result in a “blue upper body and red lower body” phenomenon. If the patient is exhibiting signs of inadequate cerebral or myocardial oxygenation, there is indication to direct oxygenated blood upside with a second cannulation of axillary artery Y connected with femoral artery.

Results-3 However, a trend to increased mortality was evident in RRT patients. Furthermore, in our patients, respiratory ECMOs showed a better chance to be weaned off than cardiac ECMOs (75% vs 43%, OR 3.8, 95% C.I. 1.7-11, p:0.01). However, ICU survival was not significantly different (55% vs 40%, OR 1.9, 95% C.I. 0.7-5.3, p:0.2).