Introduction and Historical Context
The history of extracorporeal life support (ECLS) and cardiopulmonary bypass (CPB) has been an exercise in making the impossible possible. Early acute extracorporeal membrane oxygenation (ECMO) prototypes involved machines that took up half the room, barely did what they were supposed to do, and had terrible outcomes (1). However, improved CBP technology and increased experience with circuits yielded pared down ECMO circuits with improved safety profiles and better reliability, eventually leading to better prospects (2).
In 2009 a virulent flu season caused many young people to succumb to ARDS, and it was then that a prospective study provided the first major evidence of ECMO providing benefit for severe ARDS (3-5). After this, physicians and scientists alike began to wonder if ECMO technology might have just needed time to mature. The CESAR trial demonstrated convincing data for regionalization for ECMO centers of excellence (5). While the intervention arm (i.e. getting transferred to an ECMO center if they had severe ARDS) had most patients just get more evidenced based ARDS care (and avoid going “on pump”), transfer to ECMO centers was generally associated with improved outcomes with a significant number of ECMO survivors. It was this cadre of studies that reinvigorated research and utilization of ECMO, and in 2018, EOLIA (a true randomized trial for severe ARDS and VV-ECMO) was performed. Though stopped for being unlikely to cross significance thresholds (demonstrating non-inferior outcomes for patients in severe ARDS), a thorough analysis of treatment groups showed high crossover rates into ECMO within the control group (6). The implication of EOLIA, along with evolving retrospective registry data, suggests that VV-ECMO is an important salvage modality that may lower risk of death substantially for several refractory disease states.
What is ECMO?
The premise of ECMO is basically a paired down CPB circuit: a pump sucks blood from the venous system, oxygenates it with a “membrane lung” or oxygenator, and then pumps the blood back into circulation (Figure 1). The membrane lung itself is a pretty cool piece of technology, and it is at the center of all gas exchange within the circuit. At a microscopic level, tubules of gas, temperature-controlled water, and blood flow via countercurrent exchange to maximize thermal and gas exchange (Figure 2). The result of this setup is flow dependent oxygenation and CO2 exchange that completely eliminates the need for the ventilator. Figure 2 also illustrates an important quirk in the physics of fluid, gas, and hemoglobin in the membrane lung: oxygenation is heavily dependent on blood flow through the lung (and oxygen content), whereas CO2 elimination is proportional to gas flow through the filaments (known as “sweep gas”) (1).
As Figure 1 already indicates, ECMO circuits sort out into a few different types based on their inflow and outflow sources. In veno-venous ECMO (VV), pump inflow comes from the venous circulation (either the caval system or the femoral vein) and then the pump outflow flows back into the venous system (the right atrium). Venous-arterial ECMO (VA) drains blood from the venous system, oxygenates blood, and then returns blood to the arterial system (via either central cannulation or retrograde perfusion up the descending aorta). Not shown here are other permutations, including VAV (venous inflow with both arterial and venous outflow) as well as AV (arterial inflow, oxygenation, and then venous outflow/ return).
But really that’s it: deoxygenated blood from patient🡪pump🡪 oxygenator🡪oxygenated blood back to patient (somewhere).
What is VV-ECMO?
VV-ECMO is a narrow application of ECLS that specifically addresses isolated pulmonary failure, either from hypoxemia (e.g. ARDS), hypercapnia (e.g. refractory status asthmaticus), or both (e.g. air leak syndrome or end-stage lung disease needing transplant). Since gas exchange takes place with venous inflow and outflow, NO direct augmentation of cardiac output occurs. This is a key difference from other types of ECLS, where pump flow either directly augments or even replaces flow from the heart. While VV-ECMO does improve oxygen delivery to the body (and therefore would improve myocardial ischemia), it is inappropriate for patients suffering from cardiomyopathies or native pump failure. VV-ECMO should likewise be approached with caution when right ventricular failure or severe pulmonary hypertension is present. While mild-moderate RV dysfunction from ARDS tends to tolerate VV-ECMO well, frank RV failure (e.g. from massive PE) will worsen from the mechanical stress/ flow from the circuit.
Patient Selection and Indications
The most important thing to remember about ECLS is that it is meant to buy time for a reversible disease. The price of that time, though, is paid not only in resource utilization but also the need for anticoagulation, bleeding complications, and intense physiologic stress. While VV-ECMO pump runs can persist for many weeks (at experienced centers, and usually for awaiting transplant), they typically last for a few days or 1-2 weeks. Whatever the indication, all patients need “somewhere to go” after therapy. There needs to be a multidisciplinary team, protocols in place, and common expectations across team members within a center. These patients require massive resource utilization and round-the-clock care daily. At most hospitals, these patients qualify as the most fragile patients on campus. In short, ECLS and VV-ECMO is a team sport that requires strategy up-front; it is not something one clinician can initiate in isolation.
The requirements of VV-ECMO are considerable. While modern circuits are heparin bonded, most centers require full anticoagulation initially to prevent thrombo-embolic complications (though this can change depending on patient needs). Invasive access is a must, with adult ECMO cannulas ranging from 15-25 French, with additional venous and arterial access required for medications and blood gas measurement (7). It’s common for patients on VV-ECMO to have “pump-runs” that range from 5-15 days, and then after that they can require long courses of mechanical ventilation, ICU stays, and prolonged rehabilitation (1, 8). All this means that VV-ECMO should be reserved for people who are sick from reversible disease, are refractory to evidenced based care, AND can withstand the degree of support. As an example, severe ARDS is a leading indication for VV-ECMO but should really only be attempted after maximizing the what we know saves lives in ARDS: good ARDSnet vent settings, trial of prone position, and diuretic/steroid administration as appropriate (9-15). See Table 1 for a breakdown of indications, contraindications, and cautions.
That caveat said, VV-ECMO remains a critical intervention for patients with devastating disease but high likelihood of recovery with support. Clinicians should be on the lookout for patients failing conservative therapy early in their course and initiate transfer to capable centers if needed.
Special Populations and Considerations
It’s incredibly important to maintain a euvolemic (if not slightly hypovolemic) state in VV-ECMO patients, especially given their high degrees of membrane-capillary leak. Sometimes early initiation of continuous renal replacement therapy (CRRT) can be used in cases of sub-optimal responses to diuretics or ongoing shock states. “Fluid Creep” very commonly occurs in ICU patients, usually from carrier fluid or unnecessary maintenance fluid (16). While protocols exist for connecting CRRT circuits with the VV-ECMO circuit, it tends to be seldom performed due to high pressures in the CRRT lines and a high need to maintain uninterrupted circuit flow. Assuming relative ease of access, many centers simply place a separate HD catheter and have the 2 circuits running in parallel, essentially independent of each other (17).
Another consideration would be the pharmacokinetics and pharmacodynamics associated with the ECMO circuit. Because the circuit drastically changes the volume of distribution for lipophilic drugs, it is important to consult with pharmacy routinely and especially when considering dosing of sedatives and antibiotics. For a deeper dive on this, refer to Lauren Igneri’s post.
- VV-ECMO is a branch of ECLS that provides supplementary gas exchange for reversible pulmonary disease.
- VV-ECMO is not for the chronically ill or for those with multi-organ failure. It’s best used early in otherwise healthy patients with devastating single-organ failure.
- With judicious patient selection and multidisciplinary support, it represents an important salvage modality for those suffering from pulmonary failure.
- Brogan, Thomas V., et al. Extracorporeal life support : the ELSO red book. Ann Arbor, Michigan: Extracorporeal Life Support Organization, 2017.
- Combes A, Brodie D, Bartlett R, et al. Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients. Am J Respir Crit Care Med 2014;190:488-496.
- Davies A, Jones D, Bailey M, et al. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA 2009;302:1888-1895.
- Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 2011;306:1659-1668.
- Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;374(9698):1351-1363.
- Combes A, Hajage D, Capellier G, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018;378(21):1965-1975.
- Jayaraman AL, Cormican D, Shah P, Ramakrishna H. Cannulation strategies in adult veno-arterial and veno-venous extracorporeal membrane oxygenation: Techniques, limitations, and special considerations. Ann Card Anaesth. 2017;20(Supplement):S11-S18.
- Yeo HJ, Kim YS, Kim D; ELSO Registry Committee, Cho WH. Risk factors for complete recovery of adults after weaning from veno-venous extracorporeal membrane oxygenation for severe acute respiratory failure: an analysis from adult patients in the Extracorporeal Life Support Organization registry. J Intensive Care. 2020;8:64.
- Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308.
- Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755.
- National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Moss M, Huang DT, et al. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019;380(21):1997-2008.
- Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107-1116.
- Roch A, Guervilly C, Papazian L. Fluid management in acute lung injury and ards. Ann Intensive Care. 2011;1(1):16. Published 2011 May 30. doi:10.1186/2110-5820-1-16
- Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(3):267-276.
- Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-2168.
- Van Regenmortel N, Verbrugghe W, Roelant E, Van den Wyngaert T, Jorens PG. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med. 2018 Apr;44(4):409-417.
- de Tymowski C, Augustin P, Houissa H, Allou N, Montravers P, Delzongle A, Pellenc Q, Desmard M. CRRT Connected to ECMO: Managing High Pressures. ASAIO J. 2017 Jan/Feb;63(1):48-52.