Laura DiChiacchio MD PhD,1 Gregory Boyajian MD,2 Iki Adachi MD,2,3 Neil Cambronero MD2,3
1Cedars-Sinai Medical Center
2Baylor College of Medicine
3Texas Children’s Hospital
July 21, 2024
Abbreviations & Definitions
ARDS – Acute respiratory distress syndrome
CO2 – Carbon dioxide
CPB – Cardiopulmonary bypass
CPR – Cardiopulmonary resuscitation
ECMO – Extracorporeal membrane oxygenation
ECPR – Extracorporeal cardiopulmonary resuscitation
MCS – Mechanical circulatory support
ROSC – Return of spontaneous circulation
TAH – Total artificial heart
VAD – Ventricular assist device
A. Extracorporeal Membrane Oxygenation
Indications & Guidelines for Management by Grade/Stage of Disease
ECMO should be considered when a reversible pathology is diagnosed (or suspected) and the benefit of providing ECMO support is estimated to outweigh the risks1,2
ECMO support should be considered for acute, severe respiratory failure or cardiogenic shock when refractory to maximal medical therapy and support1-3
Venovenous (VV) and venoarterial (VA) ECMO are the two primary modes of support
Indications for Support by Modality
| Support Mode | Indication | Criteria | Evidence |
|---|---|---|---|
| VV ECMO | Acute, severe, isolated respiratory failure (PaO2/FiO2 <80 mmHg, pH <7.25 with elevated PCO2, Pplat >30 mmHg) | Reversible etiology (e.g. ARDS, pneumonia, status asthmaticus, pulmonary hemorrhage, perioperative or pre-lung transplant) without prohibitive comorbidities | 1 |
| VA ECMO | Cardiogenic shock (end-organ malperfusion due to low cardiac output state) | Circulatory failure due to cardiogenic, obstructive or distributive etiologies, including cardiac failure secondary to severe respiratory compromise, without prohibitive comorbidities | 2 |
| ECPR | Cardiopulmonary arrest | Deployment of VA ECMO during conventional CPR or within 20 minutes of ROSC as a bridge to therapy, diagnostics, or recovery – including transplant, durable MCS, or palliative care | 3 |
Neuromonitoring6
| Monitoring Modality | Routine Use | High-Risk Groups (ECPR, CHD, Recent CPB) |
|---|---|---|
| Head ultrasound (HUS) | Before and after ECMO initiation; daily for 3-5 days in infants if abnormal | Before and after ECMO initiation; daily for 3-5 days in infants with open fontanel |
| Head CT | For clinical concern or abnormal HUS | Consider for new-onset seizures |
| Continuous cerebral oximetry | Consider in all patients | Should ideally be used in all high-risk patients |
| Continuous EEG | Consider within 12-24 hours of ECMO cannulation for 24-48 hours in all patients | Should ideally be used in all high-risk patients |
CHD: congenital heart disease; CT: computed tomography; EEG: electroencephalography
Anticoagulation7
Systemic anticoagulation is ideal to reduce the risk of circuit thrombosis; this must be weighed against the risk of bleeding complications7
The most used anticoagulant is unfractionated heparin (UFH);7 however, centers are increasingly utilizing bivalirudin8
The optimal method to measure anticoagulation efficacy on ECMO is not known, but should be tailored to each patient individually7
Partial Thromboplastin Time (aPTT) is generally considered the gold standard assay for UFH monitoring off ECMO7
| Anticoagulant | Half-Life | Mechanism | Monitoring | Advantages | Disadvantages |
|---|---|---|---|---|---|
| UFH | 35-75 minutes | Binds antithrombin, inhibiting thrombin and Factor Xa | ACT, aPTT, anti-Xa | Cost-effective, reversible with protamine | Risk of heparin-induced thrombocytopenia |
| Bivalirudin | 15-42 minutes | Binds thrombin | aPTT | Direct thrombin inhibitor | Renal clearance; variable dosing with renal impairment |
| Argatroban | 39-51 minutes | Binds thrombin | aPTT | Direct thrombin inhibitor | Hepatic clearance; variable dosing, worse with hepatic impairment |
ACT: activated clotting time; aPTT: activated partial thromboplastin time
Follow-Up10
| Considerations Prior to Discharge |
|---|
| Neurologic evaluation with relevant neuroimaging (low threshold to obtain brain MRI). |
| Plan in place for routine neonatal/pediatric care. |
| Plan in place for physical therapy, occupational therapy, speech, and language therapy as indicated. |
| Audiology assessment and plan. |
| Nutritional assessment and plan. |
| Family and community education. |
| Plan in place for social support for the patient/family. |
| Post-Discharge Follow Up |
| Follow up with a general neonatologist/pediatrician within 3 months of discharge. Follow up within 6 months of discharge at the ECMO center. Follow up one year following discharge, either at the ECMO center or locally, with a focus on neurodevelopmental assessment. |
| 2. Patients at risk for neurologic impairment should be referred to a neurologist or neuro-rehabilitation center. |
| 3. Disease-specific follow up, including congenital heart disease, lung impairment, chronic kidney disease. |
| 4. Ongoing community education, psychological, and social support for patient/family. |
Summary Table – Extracorporeal Membrane Oxygenation
| Recommendation | Evidence |
|---|---|
| ECMO should be considered in cases of acute, severe, reversible respiratory failure and/or cardiogenic shock (including cases of ECPR) | 1-3 |
| ECMO modality should be selected based on the organ system(s) requiring support | 1-3 |
| Cannulation strategy should be carefully selected based on the clinical situation and the advantages/disadvantages of each cannulation site | 4-5 |
| Multiple neuromonitoring modalities are available, and should be incorporated into the ECMO plan of care – especially for patients at high risk of adverse neurologic event | 6 |
| Systemic anticoagulation is recommended to reduce the risk of circuit thrombosis, although the optimal method to measure anticoagulant efficacy on ECMO is not known | 7-8 |
| Patients on ECMO should have prompt initiation of nutritional support | 9 |
| Discharge and follow-up planning should involve a multi-disciplinary process that involves multiple specialties as well as community and family resources | 10 |
Supporting Evidence for Current Indications & Guidelines
The above indications and guidelines for pediatric ECMO support all derive from Extracorporeal Life Support Organization (ELSO) guidelines; ELSO guidelines are considered expert consensus.
Ongoing Trials/Recent Publications
Trials related to neuromonitoring, anticoagulation, blood transfusion threshold, management of acute respiratory distress syndrome, and post-ECMO quality of life are ongoing
ASCEND – ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment will compare usual care ECMO to a rigorous ventilation protocol, reserving ECMO for protocol failure, focusing on long-term functional status and health-related quality of life at 1 year
TITRE – Trial of Indication-based Transfusion of Red Blood Cells in ECMO will compare restrictive red blood cell transfusion strategies to existing institutional hemoglobin thresholds, focusing on differences in neurodevelopment and organ dysfunction
Ongoing and recently completed trials can be found at clinicaltrials.gov
Expert Commentary
ECMO should be implemented as a bridge to recovery, durable device, operative repair, or transplantation
The past decade has seen a sharp rise in the use of ECMO across many disciplines; applications include ECPR, post-cardiotomy, difficult airways, and even due to airway malignancy
ECMO teams are becoming more facile, with better outcomes and lower ECMO-related morbidity
The only relative contraindication to ECMO support in the setting of a competent aortic valve is unsurvivable chronic disease or the presence of irreversible, extracardiac end-organ injury
In the future, increased utilization of mobile ECMO teams traveling to rural areas, and perhaps in the future with trauma medevac teams, is likely
B. Ventricular Assist Devices
Indications & Guidelines for Management by Grade/Stage of Disease
Ventricular assist devices (VADs) should be considered in pediatric patients with medically refractory heart failure11
Ideally, VADs should be implanted prior to evidence of severe end-organ dysfunction11
Of note, most centers implant fewer than 10 VADs annually11,12
The primary indication for pediatric VAD use is bridge to transplant, with bridge to recovery and destination therapy accounting for less than 10% of pediatric VAD use combined11
Patients in cardiogenic shock (INTERMACS 1) have increased mortality rates post-VAD, and should be medically stabilized prior to VAD insertion11
Assessment of RV function is an essential component of pre-operative VAD planning11
Types of Pediatric Ventricular Assist Devices
Temporary Paracorporeal11
| Device | Manufacturer | Size Criteria | Configuration Options | Maximum Flow |
|---|---|---|---|---|
| RotaFlow | Getinge | Any | LVAD, RVAD, or BiVAD | 10 L/min |
| CentriMag | Abbott | Any | LVAD, RVAD, or BiVAD | 10 L/min |
| PediMag | Abbott | <20 kg | LVAD, RVAD, or BiVAD | 1.5 L/min |
| TandemHeart | LivaNova | >1.3 m2 | LVAD, RVAD, or BiVAD | 5 L/min |
| Tandem Life Protek Duo | LivaNova | 29Fr sheath or larger | RVAD | 4.5 L/min |
LVAD: left ventricular assist device; RVAD: right ventricular assist device; BiVAD: biventricular assist device; kg: kilograms; m: meters; L/min: liters per minute
Temporary Intracorporeal11
| Device | Manufacturer | Size Criteria | Configuration Options | Maximum Flow |
|---|---|---|---|---|
| Impella 2.5, CP | Abiomed | >1 m2 | LVAD | 2.5 L/min, 4.3 L/min |
| Impella 5.0, 5.5 | Abiomed | >1.5 m2 | LVAD | 5 L/min, 5.5 L/min |
| Impella RP | Abiomed | >1.5 m2 | RVAD | 4 L/min |
Durable Paracorporeal11
| Device | Manufacturer | Size Criteria | Configuration Options | Maximum Flow |
|---|---|---|---|---|
| Berlin Heart EXCOR | Berlin Heart | >2.2 kg | LVAD, RVAD, or BiVAD | 8 L/min |
Durable Intracorporeal11
| Device | Manufacturer | Size Criteria | Configuration Options | Maximum Flow |
|---|---|---|---|---|
| HeartMate 3 | Abbott | >1.2 m2 | LVAD | 10 L/min |
| Jarvik 2015* | Jarvik | 8-30 kg | LVAD | 3 L/min |
| SynCardia TAH 50 cc, 70 cc | SynCardia | >1.2 m2, >1.7 m2 | BiVAD | 7.5 L/min, 9.5 L/min |
*Implanted as part of a clinical trial; results forthcoming
Summary Table – Ventricular Assist Devices
| Recommendation | Evidence |
|---|---|
| VADs are used for refractory heart failure, and should be implanted prior to severe end-organ dysfunction | 11 |
| Right ventricular function should be assessed prior to VAD initiation | 11 |
| VAD selection should consider intended duration of use, ventricles in need of support, patient size, and estimated flow requirement | 10, 12 |
Supporting Evidence for Current Indications & Guidelines
Current indications and guidelines are from expert consensus statements from the International Society for Heart and Lung Transplantation (ISHLT) as well as the analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) registry.10,11
Ongoing Trials/Recent Publications
PumpKIN* trial – feasibility study for implantation of the investigational, implantable Jarvik 2015 VAD will enroll 10 pediatric patients at up to 7 sites
EXCOR Active Driving System for the EXCOR Pediatric VAD IDE Study – will evaluate the performance, safety and effectiveness of the Berlin Heart EXCOR Active Driving System while in 40 pediatric patients at 15 sites
Current ongoing trials include studies on infection management, Berlin Heart EXCOR as bridge to transplant, and anticoagulation optimization
Ongoing and recently completed trials can be found at clinicaltrials.gov
Expert Commentary
As with ECMO, prior to implantation of any VAD, the goals of support should be considered: recovery, destination therapy, operative repair, or transplantation
Size matching between the patient and device, configuration, planned duration of support, and goals of support (e.g., bridge to recovery, bridge to transplant, destination therapy) should guide device selection and timing of implantation
TAH has primarily been used in the pediatric population to support complex congenital heart disease or transplant allograft failure
Advances in anticoagulation management and device development/optimization are continually improving outcomes in pediatric VAD and TAH support
Sources
- Maratta C, Potera RM, van Leeuwen G,et al. Extracorporeal Life Support Organization (ELSO): 2020 Pediatric Respiratory ELSO Guideline. ASAIO J. 2020 Sep/Oct;66(9):975-979.
- Brown G, Moynihan KM, Deatrick KB, et al. Extracorporeal Life Support Organization (ELSO): Guidelines for Pediatric Cardiac Failure. ASAIO J. 2021 May 1;67(5):463-475.
- Guerguerian AM, Sano M, Todd M, et al. Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines. ASAIO J. 2021 Mar 1;67(3):229-237.
- Harvey C. Cannulation for Neonatal and Pediatric Extracorporeal Membrane Oxygenation for Cardiac Support. Front Pediatr. 2018 Mar 19;6:17.
- Gajkowski EF, Herrera G, Hatton L, et al. ELSO Guidelines for Adult and Pediatric Extracorporeal Membrane Oxygenation Circuits. ASAIO J. 2022 Feb 1;68(2):133-152.
- Pandiyan P, Cvetkovic M, Antonini MV, et al. Clinical Guidelines for Routine Neuromonitoring in Neonatal and Pediatric Patients Supported on Extracorporeal Membrane Oxygenation. ASAIO J. 2023 Oct 1;69(10):895-900.
- McMichael ABV, Ryerson LM, Ratano D,et al. 2021 ELSO Adult and Pediatric Anticoagulation Guidelines. ASAIO J. 2022 Mar 1;68(3):303-310.
- Hamzah M, Seelhammer TG, Beshish AG, Bynes J, Yabrodi M, Szadkowski A, Lutfi R, Andrijasevic N, Hock K, Worley S, Macrae DJ. Bivalirudin or heparin for systemic anticoagulation during pediatric extracorporeal membrane oxygenation: Multicenter retrospective study. Thromb Res. 2023 Sep;229:178-186.
- Lee AE, Munoz E, Al Dabbous T, et al. Extracorporeal Life Support Organization Guidelines for the Provision and Assessment of Nutritional Support in the Neonatal and Pediatric ECMO Patient. ASAIO J. 2022 Jul 1;68(7):875-880.
- Ijsselstijn H, Schiller RM, Holder C, et al. Extracorporeal Life Support Organization (ELSO) Guidelines for Follow-up After Neonatal and Pediatric Extracorporeal Membrane Oxygenation. ASAIO J. 2021 Sep 1;67(9):955-963.
- Lorts A, Conway J, Schweiger M, et al. ISHLT consensus statement for the selection and management of pediatric and congenital heart disease patients on ventricular assist devices Endorsed by the American Heart Association. J Heart Lung Transplant. 2021 Aug;40(8):709-732.
- Blume ED, Rosenthal DN, Rossano JW, et al. Outcomes of children implanted with ventricular assist devices in the United States: First analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS). J Heart Lung Transplant. 2016 May;35(5):578-84.
