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Extracorporeal Membrane Oxygenation in Children

Editor: Shashikanth Ambati Updated: 7/10/2023 2:31:30 PM

Introduction

Extracorporeal membrane oxygenation (ECMO), synonymous with extracorporeal life support (ECLS), is used as a lifesaving mechanical form of bypassing a patient’s cardiopulmonary system when in failure. Historically, it was adapted during the 1970s from perioperative cardiopulmonary bypass performed during cardiac surgery and was initially pioneered for children. As a result, much of the knowledge about ECMO today has been extrapolated from the pediatric and neonatal populations. ECMO is a highly specialized technology with limited availability in children’s hospitals but is associated with improved survival.

ECMO use is increasing worldwide due to improved survival rates in children who have been placed on ECMO.[1] Optimal delivery of care remains challenging as substantial human and physical resource utilization is critical. To facilitate success, it is essential to have a comprehensive healthcare team that manages the pediatric patient using this artificial oxygenation machine, addresses any possible sequelae that may arise, and understands the implications of some technical challenges that may require a higher level of care.

Anatomy and Physiology

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Anatomy and Physiology

ECMO machinery consists of a mechanical pump, a membrane oxygenator (membrane lung), and a heat exchanger. The circuit generally involves blood drainage from a patient’s large blood vessel through an outflow cannula to a mechanical pump, pushing this blood towards a membrane lung. Gas exchange (oxygenation and decarboxylation) and rewarming of the blood both occur in this artificial lung. The membrane lung comprises thin, semipermeable, hollow fiber tubes that mimic alveoli within the human body and simulate diffusion across the interface.

A patient’s physiologic milieu is maintained by monitoring the pressure gradient between the patient’s blood flow and the sweep gas flow. The rate of sweep gas flow, which is the gas flow to the membrane lung in liters per minute, positively correlates with removing carbon dioxide from the blood. ECMO blood flow rate (blood volume passing through the circuit in liters per minute) positively correlates with the oxygenation of blood. Based on Poiseuille’s law, flow can be maximized by a cannula size with a larger diameter and shorter length. For neonates and infants weighing up to 15 kg, flow rates are typically 80 to 120 ml/kg/min and can range up to 1.7 L/min; for children above 15 kg, flow rates can reach 7.0 L/min. Blood that has been fully saturated with oxygen is then returned to the patient via an inflow cannula placed into a vessel. The patient’s cardiac output and hemoglobin concentration become ever more important as oxygenation relies on these factors.

There are two primary modes of ECMO, with each dependent on the physiologic state of the patient. Venoarterial (VA) ECMO is necessary if the patient is in cardiac failure. The presence or absence of respiratory compromise is arbitrary because the heart’s ejection fraction is diminished. Therefore, perfusion of the lungs through the pulmonary artery is insufficient, and the patient’s lungs become minimally involved in gas exchange. The drainage cannula is inserted into a large systemic vein (e.g., internal jugular vein) or the right atrium. Poorly oxygenated blood is taken from this site, which then travels to the membrane lung of the circuit, where it is oxygenated and warmed. Subsequently, it is infused back into the patient through an arterial line placed into a large systemic artery (e.g., internal carotid artery), bypassing the heart. By mixing this oxygen-rich blood with the patient’s oxygen-poor blood, the patient’s overall arterial oxygen concentration improves. The patient receives complete mechanical hemodynamic support, which is not possible in venovenous (VV) ECMO.

Venovenous (VV) ECMO provides oxygenation-ventilation support for isolated respiratory failure. It ultimately allows a patient’s impaired lungs to recover. Eligibility for this mode requires preserved cardiac pump function that can maintain pulmonary and systemic perfusion. VV ECMO also differs from VA ECMO in that the infusion catheter is placed in a venous line. Cannulation can be either be accomplished by separate cannulae that drain and infuse, or a single, dual-lumen cannula placed within the internal jugular vein, thus allowing both drainage and reinfusion through the same cannula. A single VV dual-lumen cannula has several pros, including the decreased risks with multiple access points (e.g., surgical site bleeding or infection), support for pediatric patients whose femoral vessels are otherwise not large enough, less sedation, and more freedom to ambulate out of bed.[2] 

Recirculation is a phenomenon exclusive to venovenous ECMO, in which reinfused oxygenated blood is withdrawn through the drainage cannula without passing through the systemic circulation. The problem of recirculation is usually diagnosed when there are low patient oxygen saturation and high pre-oxygenator saturations and can be identified by the proximity of the drainage and the reinfusion cannulae on the X-ray. Recirculation can be reduced by increasing the distance between drainage and reinfusion ports in a two-site venovenous ECMO configuration by withdrawing one or both cannulae. 

Factors determining oxygen saturation during VV ECMO include pump flow, degree of recirculation, hemoglobin concentration, residual lung function, and patients' systemic venous return and oxygen saturation. For persistent hypoxemia, strategies include increasing ECMO blood flow, increase hemoglobin concentration and cardiac output, reduce oxygen consumption by using sedation and neuromuscular blockade, and therapeutic hypothermia and reducing recirculation.

Indications

Cardiac

  • Pediatric/Neonatal
    • Structural congenital heart disease
      • Perioperative support
    • Nonstructural congenital or acquired heart disease
      • E.g., cardiomyopathy, myocarditis, myocardial infarction, intractable arrhythmias, acute right-sided heart failure secondary to pulmonary hypertension, hemodynamic deterioration secondary to intoxication, cardiac failure secondary to septic shock, bridge to heart transplantation, bridge to long-term mechanical ventilatory support (e.g., ventricular assist device), bridge to heart transplantation, post-heart transplantation support, high-risk cardiac catheterization, peri-procedural support (e.g., failure to wean from cardiopulmonary bypass)[2][3][4]

Respiratory

  • Pediatric
    • Impaired gas exchange as defined by oxygenation index (OI = mean airway pressure x FiO x 100/PaO) or respiratory acidosis
      • No threshold value for oxygenation; consider ECMO if OI not improving by day 2 of illness.
      • Recommended threshold pH < 7.0
    • E.g., acute respiratory distress syndrome, pneumonia, bridge to lung transplantation.
  • Neonatal
    • Impaired gas exchange as defined by OI
      • Recommended threshold OI > 40
      • Consider transfer to ECMO center when OI > 25
    • E.g., pulmonary hypertension, meconium aspiration syndrome, respiratory distress syndrome, congenital diaphragmatic hernia, air leak syndrome, pneumonia.[2][5][6]

Contraindications

As the number of absolute contraindications to ECMO decrease, more and more patients are being evaluated for candidacy on a case-by-case basis. Nevertheless, the most current contraindications are generally futile cases with high rates of morbidity and mortality.

  • Absolute contraindications[7][4][2]
    • Lethal chromosomal abnormalities (e.g., Trisomy 13 or 18)
    • Severe neurologic compromise (e.g., irreversible brain damage, grade III or higher intraventricular hemorrhage, severe hypoxic-ischemic encephalopathy)
    • Uncontrollable bleeding
    • Incurable malignancy
    • Prematurity < 30 weeks gestation
    • Low birth weight < 1 kg
  • Relative contraindications[7][4]
    • Duration > 2 weeks of mechanical ventilation before ECMO
    • Recent neurosurgical procedures or intracranial hemorrhage (< 7 days)
    • Preexisting chronic illness with poor long-term prognosis
    • Allogeneic bone marrow transplant recipients
    • Solid-organ tumors
    • Birth weight < 2 kg

Equipment

  • ECMO machine with vascular cannulae, blood pumps, monitoring devices, and membrane lung (with oxygenator and heat exchanger)
  • Pediatric or neonatal intensive care unit
  • Comprehensive clinical laboratory
  • Tertiary or quaternary hospital with access to a full range of pediatric specialists and subspecialists
  • Echocardiography

Personnel

  • Pediatric intensivists
  • Neonatologists
  • ICU nurses
  • Cardiothoracic, vascular, or trauma/acute care surgeons
  • Anesthesiology team
  • Critical care transfer team
  • ECMO coordinator and technicians
  • Perfusionist
  • Radiology department
  • Echocardiography technicians
  • Respiratory therapists
  • Rehabilitation specialists

Preparation

Preparing for utilization of ECMO in children requires experience, knowledgeability, proper stratification of who may be suitable candidates. ECMO needs to be executed in a center with a higher level of care since they are more adept at dealing with consequences. Specifically, if a patient needs ECMO management but is not at an ECMO center, there is a risk of managing them at their current hospital versus transferring to a specialized ECMO center. A cohesive critical care transfer team must be conveniently available.

Before administering ECMO, neonates or pediatric patients should undergo extensive evaluation, including thorough physical examination focusing on neurologic assessment, complete blood count, metabolic panel, lactate, arterial blood gas, chest x-ray, cranial ultrasound, or head CT scan, and echocardiography.[4] Furthermore, sedation is usually warranted to allow for patient comfort and safety while ensuring accurate serial examinations. Common analgesic choices include morphine, fentanyl, midazolam, propofol, and dexmedetomidine.[7]

ECMO surfaces elicit a systemic inflammatory response when blood is exposed to the circuit, causing a hypercoagulable state. Frequent monitoring of platelet and coagulation studies is important. Therefore, anticoagulation plays a key role in ECMO therapy. Unfractionated heparin remains the gold standard way to manage the body’s pro-thrombotic state, although there is a trend towards using direct thrombin inhibitors as alternative agents.[2]

From a nutrition standpoint, optimizing nutrition is especially paramount in pediatric ECMO. Not only is there a strong rationale to meet full growth potential and developmental needs, but underweight patients receiving ECMO have been found to have higher mortality than patients who were otherwise properly nourished. For ECMO in the neonatal setting, clinical guidelines proposed by the American Society for Parenteral Enteral Nutrition recommend starting nutritional support expeditiously and enteral nutrition as soon as the patient is clinically stable.[7]

Technique or Treatment

Among children and neonates, ECMO circuits and cannulas must cater to their variations in weight. Additionally, the sites where cannulae are placed differ between the adult and pediatric populations. In adults, the femoral vessels are generally utilized. In particularly young children, the femoral vessels have not developed enough to qualify for ECMO cannulation, so vascular access in pediatric ECMO cannulation is preferentially located in the larger neck vessels. The optimal age to transition from neck to femoral cannulation has been largely debated and requires further study.[2] The methods of cannula implantation are either via percutaneous placement by the Seldinger technique or by surgical cut-down to the vessels.[1]

Upon placement of the cannula, the circuit’s pump must be decided. Presently there are two main types of pumps to provide blood flow: roller pumps and centrifugal pumps. Roller pumps advance blood through tubing to a circular plate with a rotating lever arm that generates high pressure distally. This pump housing is dependent on gravity drainage to maintain preload. Suppose there is any interruption to flow, whether due to kinking or obstruction, detrimental circuit rupture may occur. There are built-in safety measures that terminate the pump if line pressures get too high. Roller pumps are currently predominantly used in the neonatal population (85%) because such patients with lower birth weights require a low perfusion rate, and roller pumps do not need a set flow rate to generate flow.[8] Roller pumps were primarily used during the early days of ECMO, but their use has since declined over the past 2 decades since the development of centrifugal pumps.[2]

Centrifugal pumps use a rapidly rotating vortex to create differences in pressure to propel blood. Blood flow is driven by these pressure gradients, so there is minimal risk for rupture. Compared to earlier models, newer generation models have shown a smaller risk of thromboembolic complications and hemolysis. In certain instances, ECMO can be performed without a pump if blood flow can be driven by a patient’s blood pressure or in patients with severe pulmonary hypertension.[7]

A bridge is a component that can be incorporated within the ECMO circuit as well. It is placed between the drainage and infusion limbs and allows patients to be taken off while keeping the circuit open. This may be indicated during weaning, needing to change part of the ECMO apparatus, or in emergencies like massive hemorrhage or circuit contamination from air or thrombus.[9]

Complications

Since ECMO was first successfully used, cumulative information regarding its use, including complications, has been collected by the Extracorporeal Life Support Organization (ELSO). The overall survival to hospital discharge for pediatric respiratory ECMO is 57%; for pediatric cardiac ECMO, it’s 50%.[7]

  • Technical complications
    • Inadvertent decannulation
    • Membrane lung failure
    • Tubing rupture
    • Pump malfunction
  • Medical complications
    • Neurologic (most common): intracranial hemorrhage, seizures, brain death, ischemic infarction
    • Hematologic: cannula site bleeding, surgical site bleeding, clots in the circuit, vessel injury from cannulation, pulmonary hemorrhage, gastrointestinal hemorrhage, hemolysis, disseminated intravascular coagulation, inadequate anticoagulation, limb ischemia
    • End-organ hypoperfusion: renal failure, liver failure
    • Cardiac tamponade
    • Infection
    • High-pressure system in neonates: increased hemolysis, hyperbilirubinemia, hypertension, end-organ damage with renal failure
    • Long term: poor growth, neurodevelopmental deficits, organ damage (e.g., sensorineural hearing loss, lung injury, renal dysfunction)[10][11][12][13]

Clinical Significance

ECMO, especially in the pediatric setting, is complex in that it requires meticulous comprehension of pediatric and neonatal physiology. Possessing a foundation in education of the most intricate details of oxygen delivery should be a mandatory aspect of care. ECMO entails many ethical dilemmas as it heavily involves children’s families in the decision-making process. When ECMO is being considered acutely, there is often limited time to assess the estimated course of the patient’s clinical condition, reversibility of the underlying disease process, actual candidacy for heart or lung transplant, and the balance between post-survival quality of life with the family’s goals of care.[5]

Challenges may include the moral distress of caregivers and providers during prolonged ECMO, the cessation of treatment, and considerable resource allotment. It is essential to be aware of the serious ramifications associated with each clinical choice.

Enhancing Healthcare Team Outcomes

Over the years, paying special attention to the technical approach of ECMO has led to its refinement. As it is necessary to have a vast composition of interprofessional teams, every member needs to be on board and have direct lines of communication when involved in the day-to-day clinical course. Effective teamwork must involve every healthcare team member, including clinicians (MDs, DOs, NPs, PAs) of all specialties, nurses, pharmacists, perfusionists, respiratory therapists, technicians—plays an invaluable role. Each patient has their own individualized management when initiating and weaning ECMO. This interprofessional approach will drive improved patient results. [Level 5]

Weaning trials should begin as soon as the patient has sufficiently recovered from their disease process and is hemodynamically stable. However, being prepared means that contingency plans are discussed beforehand and that all necessary personnel is accessible in case there is a need to go back onto full ECMO support. Being prepared also means acknowledging morbidity and mortality is inevitable. After all, ECMO is often utilized as a last resort to restore life in extremely sick children. Despite the delicacy and potential for adverse outcomes, there are decades of ongoing support for ECMO as a mainstream salvage therapy for neonatal and pediatric patients experiencing severe, medically refractory cardiorespiratory failure.[14][15][16] [Level I]

References


[1]

Erdil T, Lemme F, Konetzka A, Cavigelli-Brunner A, Niesse O, Dave H, Hasenclever P, Hübler M, Schweiger M. Extracorporeal membrane oxygenation support in pediatrics. Annals of cardiothoracic surgery. 2019 Jan:8(1):109-115. doi: 10.21037/acs.2018.09.08. Epub     [PubMed PMID: 30854319]


[2]

Valencia E, Nasr VG. Updates in Pediatric Extracorporeal Membrane Oxygenation. Journal of cardiothoracic and vascular anesthesia. 2020 May:34(5):1309-1323. doi: 10.1053/j.jvca.2019.09.006. Epub 2019 Sep 12     [PubMed PMID: 31607521]


[3]

Robb K, Badheka A, Wang T, Rampa S, Allareddy V, Allareddy V. Use of extracorporeal membrane oxygenation and associated outcomes in children hospitalized for sepsis in the United States: A large population-based study. PloS one. 2019:14(4):e0215730. doi: 10.1371/journal.pone.0215730. Epub 2019 Apr 26     [PubMed PMID: 31026292]


[4]

Etchill EW, Dante SA, Garcia AV. Extracorporeal membrane oxygenation in the pediatric population - who should go on, and who should not. Current opinion in pediatrics. 2020 Jun:32(3):416-423. doi: 10.1097/MOP.0000000000000904. Epub     [PubMed PMID: 32332330]

Level 3 (low-level) evidence

[5]

Lin JC. Extracorporeal Membrane Oxygenation for Severe Pediatric Respiratory Failure. Respiratory care. 2017 Jun:62(6):732-750. doi: 10.4187/respcare.05338. Epub     [PubMed PMID: 28546375]


[6]

Barbaro RP, Brodie D, MacLaren G. Bridging the Gap Between Intensivists and Primary Care Clinicians in Extracorporeal Membrane Oxygenation for Respiratory Failure in Children: A Review. JAMA pediatrics. 2021 May 1:175(5):510-517. doi: 10.1001/jamapediatrics.2020.5921. Epub     [PubMed PMID: 33646287]


[7]

Jenks CL, Raman L, Dalton HJ. Pediatric Extracorporeal Membrane Oxygenation. Critical care clinics. 2017 Oct:33(4):825-841. doi: 10.1016/j.ccc.2017.06.005. Epub 2017 Jul 29     [PubMed PMID: 28887930]


[8]

Nakanishi K, Kato T, Kawasaki S, Amano A. Usefulness of extracorporeal membrane oxygenation using double roller pumps in a low body weight newborn: A novel strategy for mechanical circulatory support in an infant. Annals of pediatric cardiology. 2016 Jan-Apr:9(1):85-6. doi: 10.4103/0974-2069.171403. Epub     [PubMed PMID: 27011702]


[9]

Meyer-Macaulay C, Rosen D. Paediatric extracorporeal membrane oxygenation and extracorporeal cardiopulmonary resuscitation. BJA education. 2018 May:18(5):153-157. doi: 10.1016/j.bjae.2017.12.003. Epub 2018 Mar 16     [PubMed PMID: 33456826]


[10]

van Heijst AF, de Mol AC, Ijsselstijn H. ECMO in neonates: neuroimaging findings and outcome. Seminars in perinatology. 2014 Mar:38(2):104-13. doi: 10.1053/j.semperi.2013.11.008. Epub     [PubMed PMID: 24580766]


[11]

Murray M, Nield T, Larson-Tuttle C, Seri I, Friedlich P. Sensorineural hearing loss at 9-13 years of age in children with a history of neonatal extracorporeal membrane oxygenation. Archives of disease in childhood. Fetal and neonatal edition. 2011 Mar:96(2):F128-32. doi: 10.1136/adc.2010.186395. Epub 2010 Oct 21     [PubMed PMID: 20971719]

Level 2 (mid-level) evidence

[12]

Ijsselstijn H, van Heijst AF. Long-term outcome of children treated with neonatal extracorporeal membrane oxygenation: increasing problems with increasing age. Seminars in perinatology. 2014 Mar:38(2):114-21. doi: 10.1053/j.semperi.2013.11.009. Epub     [PubMed PMID: 24580767]


[13]

Wightman A, Bradford MC, Symons J, Brogan TV. Impact of Kidney Disease on Survival in Neonatal Extracorporeal Life Support. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2015 Jul:16(6):576-82. doi: 10.1097/PCC.0000000000000414. Epub     [PubMed PMID: 25828782]


[14]

Bartlett RH, Roloff DW, Cornell RG, Andrews AF, Dillon PW, Zwischenberger JB. Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Pediatrics. 1985 Oct:76(4):479-87     [PubMed PMID: 3900904]

Level 1 (high-level) evidence

[15]

Yang L, Ye L, Fan Y, He W, Zong Q, Zhao W, Lin R. Outcomes following venoarterial extracorporeal membrane oxygenation in children with refractory cardiogenic disease. European journal of pediatrics. 2019 Jun:178(6):783-793. doi: 10.1007/s00431-019-03352-5. Epub 2019 Mar 4     [PubMed PMID: 30834480]


[16]

Xiong J, Zhang L, Bao L. Complications and mortality of venovenous extracorporeal membrane oxygenation in the treatment of neonatal respiratory failure: a systematic review and meta-analysis. BMC pulmonary medicine. 2020 May 7:20(1):124. doi: 10.1186/s12890-020-1144-8. Epub 2020 May 7     [PubMed PMID: 32380985]

Level 1 (high-level) evidence