Lesta Whalen, MD Medical Director, Sanford ECMO Pediatric Critical Care

Lesta Whalen, MD Medical Director, Sanford ECMO Pediatric Critical Care

Disclosures I have no financial disclosures. The use of certain devises for providing long-term cardiopulmonary support is investigational. I will discuss the use of one of these products.

Objectives History of ECMO What is ECMO? Risks and Benefits of ECMO Complications of ECMO Patient Selection Outcomes Future applications Research

History of ECMO First ECMO Patient 1971 First Pediatric Patient (Esperanza Spanish) in 1975 Meconium Aspiration On for 72 hours with decannulation, recovery and normal life. Extracorporeal Life Support Organization (ELSO) Formed in 1989 Purpose: pool common data, compare outcomes and exchange ideas for optimal use of ECMO support

Number of Centers Number of Runs Active ECLS Centers 350 8000 300 7000 250 200 150 100 6000 5000 4000 3000 2000 50 1000 0 0 2014 2012 2010 2008 2006 2004 2002 2000 1998 1996 1994 1992 1990 Centers Cases ELSO Registry January 2016

Is ECMO proven benefit for Respiratory Failure? Neonatal Respiratory Failure Bartlett et al, Pediatrics, 1985 Survival with ECMO vs standard therapy was superior (P = 0.0000001) O Rourke Et al, Pediatrics, 1989 19/20 (97%) survival in ECMO arm vs 60% in standard therapy. UK Collaborative, Lancet, 1996 60% survival in ECMO vs 40% in Standard therapy (NNT 3-4)

Annual Runs Cumulative Runs Neonatal Respiratory Cases 1600 1400 1200 1000 800 600 400 200 0 35000 30000 25000 20000 15000 10000 5000 0 ELSO Registry January 2016

Is ECMO proven benefit for Respiratory Failure? Pediatric Respiratory Failure Green Et al, Crit Care Med 1996 Decreased Mortality from 47.2 to 26.4% Patients in the 50 th to 75 th percentile mortality risk group had significantly lower mortality than matched control patients with standard therapy.

Is ECMO proven benefit for Respiratory Failure? Pediatric Predictors of Survival Moler et al, Crit Care Med, 1993/1994 Younger age (23 vs 49 months) Ventilator days pre-ecmo (5.1 vs 7.3) Lower PIP, lower A-a gradient Green Et al, Crit Care Med 1996 No difference in survival if >2 weeks ECMO

Annual Runs Cumulative Runs Pediatric Respiratory Cases 600 500 400 300 200 100 0 8000 7000 6000 5000 4000 3000 2000 1000 0 ELSO Registry January 2016

Is ECMO proven benefit for Respiratory Failure? Adult Respiratory failure Slow acceptance due to: Adult NIH study, 1971 90% mortality with no benefit with VA ECMO in moribund patients Gattinoni, early 1990 s Non randomized experience shows 49% survival Morris, AJRCCM, 1992 No statistical significant survival benefit of ECMO vs computerized vent management protocol This was changed by the CESAR trial Peek et al, Lancet 2009 Utilized referral and ECMO center with randomization similar to UK peds study Significantly improved intact survival when compared with standard therapy Publication coincided with H1N1 pandemic.

Annual Runs Cumulative Runs Adult Respiratory Cases 2000 1800 1600 1400 1200 1000 800 600 400 200 0 10000 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 ELSO Registry January 2016

Types of ECMO: Veno-Venous Blood from large central vein. Returned to venous system near right atrium Support for respiratory failure WITHOUT major cardiac dysfunction Improves oxygenation by oxygenating blood before going through lungs Removed CO 2 from blood Allows weaning of injurious ventilator settings.

Veno-Venous ECMO

Types of ECMO: Veno-arterial Blood from large central vein. Returned to major artery Support cardiac failure with/without lung disease Improves oxygenation by bypassing lungs if diseased, and increasing cardiac output Allows weaning of injurious ventilator settings

Veno-Arterial ECMO

CARDIOHELP: ECMO in a box

Components of Circuit Centrifugal Pump Oxygenator

Benefits Patient lives Provide cardiac support for failing/failed heart while awaiting definitive treatment. Minimize lung injury from mechanical ventilation while oxygenating and ventilating. Help prevent multi-organ injury by maintaining cardiac output and matching demand.

When ECMO Rescue Therapy Likely death without Bridge to survival/transplant/device Lessen complications of therapy Ventilator induced lung injury Air leak Excessive Inotropic Support No other means of Support Airway Compromise Cardiac Cath Lab

ECMO Indications Supportive, NOT Curative Must have a reversible disease Success rates and issues differ by disease and ECMO therapy used Risk/Benefit 2 Physician Decision Basically: Don t go on if you can t get off

Risks Bleeding Hemolysis Thrombosis Infection Renal Failure Mechanical Complications

Neonatal Complications Neurologic Insult Most impactful on morbidity and mortality Poor developmental outcome in 20-40% Most issues minor ICH is most common reported Related to reperfusion injury, hemodynamic and cerebrovascular instability, systemic heparin, increased CVP Hypoxia and acidosis increases risk argument for instituting ECMO early

Neonatal Complications Respiratory ECMO Complication % Reported % Survived Oxygenator Failure Surgical Site bleeding 5.6 53% 6.2 42 DIC 2.6 35 Seizure Clinical 9.3 60 Seizure EEG 1 44 CNS Infarct 7.2 55 CNS hemorrhage 7.3 44 Complication % Reported % Survived Dialysis 3.2 39 Hemofiltration 15.7 53 CPR 2.3 39 Myocardial Stun 4.7 58 Pneumothorax 5.8 56 Pulmonary Hemorrhage Cx proven infection 4.4 44 5.5 51

Pediatric Complications Bleeding and thrombosis most common complications (26% and 34%) Neurologic complications and infectious also high More common in peds than neonates Complication rates correlate with decreased survival

Pediatric Complications Respiratory ECMO Complication % Reported Oxygenator Failure Surgical Site bleeding 10.8 41 13.7 45 DIC 6.3 27 Seizure Clinical Seizure EEG 5 32 1.5 28 CNS Infarct 3.8 33 CNS hemorrhage 6.3 24 % Survived Complication % Reported % Survived Dialysis 13.1 33 Hemofiltration 24.5 47 CPR 6 63 Myocardial Stun 1.5 21 Pneumothorax 12.2 40 Pulmonary Hemorrhage Cx proven infection 8.5 30 16.1 46

Adult Complications Similar to pediatric data: Bleeding and thrombosis most common Neurologic complications and infectious also high Complication rates correlate with decreased survival Increased overall morbidity in adults when compared with pediatric

Adult Complications Respiratory ECMO Complication % Reported Oxygenator Failure Surgical Site bleeding 8.5 40 14.8 41 DIC 3.3 23 Seizure Clinical Seizure EEG 1 31 0.4 44 CNS Infarct 1.6 23 CNS hemorrhage 2.7 14 % Survived Complication % Reported % Survived Dialysis 12 39 Hemofiltration 14.8 43 CPR 6.9 16 Myocardial Stun 0.8 34 Pneumothorax 9.3 35 Pulmonary Hemorrhage Cx proven infection 7 35 15.5 43

Patient Selection Estimated Mortality 75% No Evidence base for parameters Sick, but not too sick Green 1996: Patients with a 50-75% mortality risk were the most likely to benefit from ECMO Perhaps most useful: Inadequate response to maximal medical therapy Clinical judgment of imminent death

Pre-ECMO Evaluation ECMO Consult Will discuss patient status and asses if qualifications/contraindications met Should be initiated when patient has severe respiratory and/or cardiac failure with approximately 50% or greater chance of dying.

Pre-ECMO Evaluation Consider ECMO: Risk of mortality is 50% or greater PaO 2 /FiO 2 < 150 on FiO 2 > 90% Murray score 2-3 OI 20 ECMO Indicated: Risk of 80% or greater PaO 2 /FiO 2 < 100 on FiO 2 > 90% Murray score 3-4 OI 40

Pre-ECMO Evaluation CUS/Head CT ECHO P/F = PaO 2 /FiO 2 Peds/Adults OI = (MAP x FiO 2 x 100)/ PaO 2 Neo/Peds

Patient Qualifying Criteria - VV P/F <150 mmhg on >90% PaO 2 < 60 for > 2 hours or <40 and unresponsive to interventions Oxygenation Index > 35 or > 25 for 4-6 hours ph < 7.1 for > 2 hours

Patient Qualifying Criteria - VV Uncompensated CO 2 retention PaCO 2 > 80, with inability to ventilate using conventional methods. PIP > 40 or severe air leak <35 in neonates On HFOV: MAP > 30-35 or severe air leak >25-30 in Neonates Shock and hypotension unresponsive to fluid resuscitation and maximum inotropes Indicated by degree of acidosis and decreased urine output for > 6 hours.

Patient Qualifying Criteria - VV Weight > 2Kg Gestational age 34 weeks Murray score 2-3 http://cesar.lshtm.ac.uk/murrayscorecalculat or.htm

Patient Qualifying Criteria - VA Inadequate tissue perfusion Hypotension and low cardiac output despite adequate intravascular volume. Shock despite volume administration, inotropes and vasoconstrictors as appropriate

Who Shouldn t Go On Age: 34 wks gestation, >65 years Weight: 2000 gm, 140 Kg Lethal Malformations Prolonged Mechanical Ventilation > 14 days if not lung transplant candidate

Who Shouldn t Go On Irreversible lung disease in non-transplant candidate Irreversible pulmonary hypertension (chronic, severe) Uncorrectable cardiac lesions in nontransplant candidate Un-witnessed cardiac arrest or CPR prior to commencement of ECMO >60 min. with ACLS, >15 min. without ACLS

Who Shouldn t Go On Aortic dissection Severe aortic valve regurgitation Non-recoverable neurologic disease Pts with hypoxia or hypoperfusion assessed prior to initiating ECMO Recent Neurosurgical procedure or intracranial bleeding (<10 days)

Who Shouldn t Go On Contraindication to systemic anticoagulation Intracranial Bleeding (>Grade1) Uncontrolled Bleeding or coagulopathy

Who Shouldn t Go On Significant Immunodeficiency ANC <400 Active malignancy 30% Survival Graft vs. Host Disease S/P BMT 5% Survival

Think Twice About Mechanical ventilation for respiratory disease > 10 days if not lung transplant candidate Multiple organ system failure Major immunodeficiency Severe coagulopathy or bleeding Trauma with multiple bleeding sites Pregnancy Severe right or left heart failure (EF< 25%)

Special Circumstances Obesity May need central cannulation Myocarditis/Cardiomyopathy Ensure adequate LV emptying Pulmonary Hemorrhage Doable with careful anticoagulation and lung protective strategy Sepsis Vasodilation high flows, vasoconstrictive agents

Special Circumstances Congenital Diaphragmatic Hernia Special patient selection considerations Ensure adequate lung tissue for survival & absence of other critical defects Sat >85% / PaO 2 >70 Collaborative Discussion with Neonatology and pediatric surgery Pertussis 70% mortality Higher in infants Higher in fulminant pertussis Inflammatory State

Overall Patient Outcomes Total Surv ECLS Surv to DC Neonatal Respiratory 28,723 24,155 84% 21,274 74% Cardiac 6,269 3,885 62% 2,599 41% ECPR 1,254 806 64% 514 41% Pediatric Respiratory 7,210 4,787 66% 4,155 58% Cardiac 8,021 5,341 67% 4,067 51% ECPR 2,788 1,532 55% 1,144 41% Adult Respiratory 9,102 5,989 66% 5,254 58% Cardiac 7,850 4,394 56% 3,233 41% ECPR 2,379 948 40% 707 30% Total 73,596 51,837 70% 42,947 58% ELSO Registry January 2016

Neonatal Outcomes ECLS Survival - 84% Survival to DC/Transfer: Respiratory 74% Cardiac 41% ECPR 41% Outcomes are affected by the critical illness that prompted ECMO as well

Total Runs ELSO Registry January 2016 Neonatal Diagnoses and Survival 10000 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 51% 94% 77% 84% 73% 61% CDH MAS PPHN/PFC RDS Sepsis Other Died 3719 570 1149 249 783 1243 Surv 3865 8345 3862 1307 2101 1946

Neonatal Cases by Diagnosis No. Runs % Survived MAS 8,915 94 CDH 7,584 51 Sepsis 2,884 73 PFC/PPHN 5,011 77 RDS 1,556 84 Other 3,189 61 ELSO Registry January 2016

Neonatal Outcomes Neurodevelopmental outcome 60-70% of ECMO survivors normal at 1-2 years of age Significant handicap ranging from 10-15% at 1-2 years of age 5-year data indicates to a higher risk of learning disabilities (~55% in these infants) 30-50% incidence of progressive sensorineural hearing loss (>CDH group of patients)

Pediatric Outcomes ECLS Survival - Respiratory 66% Cardiac 67% ECPR 55% Survival to DC/Transfer: Respiratory 58% Cardiac 51% ECPR 41% Outcomes are affected by the critical illness that prompted ECMO as well

Total Runs Pediatric Diagnoses and Survival 3000 2500 52% 2000 1500 65% 55% 1000 500 59% 68% 56% 0 Viral Bacterial Aspiration ARDS Acute resp Other pneumonia pneumonia pneumonia failure Died 543 301 102 333 593 1265 Surv 1021 435 220 429 738 1375 ELSO Registry January 2016

Pediatric Cases by Diagnosis Runs % Surv Viral Pneumonia 1,564 65 Bacterial Pneumonia 736 59 Aspiration 322 68 ARDS 762 56 Acute Resp Failure, Non-ARDS 1,331 55 Other 2,640 52 ELSO Registry January 2016

Pediatric Long-term outcomes Little data available in respiratory patients for long-term outcomes Ct or MRI prior to discharge PCP Education and yearly follow-up 50% of cardiac patients have abnormal neurodevelopmental outcomes Unclear how much pre-ecmo pathology plays into this

Adult Outcomes ECLS Survival - Respiratory 66% Cardiac 56% ECPR 40% Survival to DC/Transfer: Respiratory 58% Cardiac 44% ECPR 30% Outcomes are affected by the critical illness that prompted ECMO as well

Total Runs Adult Diagnoses and Survival 4500 4000 3500 3000 2500 2000 1500 1000 500 0 66% 61% 64% 55% 56% 56% Viral Bacterial Aspiration ARDS ARF, non- Other pneumonia pneumonia pneumonia ARDS Died 256 479 68 552 700 1924 Surv 495 760 122 671 897 2407 ELSO Registry January 2016

Adult Cases by Diagnosis Runs % Surv Viral Pneumonia 751 66 Bacterial Pneumonia 1,239 61 Aspiration 190 64 ARDS 1,223 55 Acute Resp Failure, Non-ARDS 1,597 56 Other 4,331 56 ELSO Registry January 2016

Adult Long-term outcomes No good data

Future Application of ECMO Many of these are actually being done! Mobile ECPR Bridge to transplant Ex vivo organ support Artificial Placenta

Future Direction at Sanford Neonatal & Adult Programs Develop an ECMO transport team Ventricular assist program in adults ECPR

ECMO Research Many questions remain Patient selection Sedation Monitoring Coagulation Outcome Answering questions highlights need for a research consortium Single center data hard to extrapolate to field at large Too much variability in practice, definitions, equipment Not enough patients at any one site to achieve adequate power to determine answers to questions ELSO data helpful but not well validated and missing important variables (new database fields will be helpful)

Questions?