Invasive Hemodynamic and Physiologic Considerations in Patients Undergoing Extracorporeal Membrane Oxygenation

Abstract

EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) is a therapeutic modality used in patients with pulmonary, cardiac, or combined cardiopulmonary failure when other methods of organ support have failed.1Baran DA. Extracorporeal membrane oxygenation (ECMO) and the critical cardiac patient.Current Transplantation Reports. 2017; 4: 218-225Crossref PubMed Scopus (26) Google Scholar, 2Napp LC Kühn C Bauersachs J. ECMO in cardiac arrest and cardiogenic shock.Herz. 2017; 42: 27-44Crossref PubMed Scopus (71) Google Scholar, 3Makdisi G Wang I-W. Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology.J Thorac Dis. 2015; 7: E166-E176PubMed Google Scholar Venovenous (VV) ECMO is used in patients suffering from refractory hypoxemia or hypercapnia due to a range of pathology including but not limited to acute respiratory distress syndrome, pneumonitis, or status asthmaticus. Venoarterial (VA) ECMO can be used in patients suffering from cardiogenic shock due to etiologies such as myocardial infarction, viral myocarditis, or postcardiotomy shock.3Makdisi G Wang I-W. Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology.J Thorac Dis. 2015; 7: E166-E176PubMed Google Scholar,4Combes A Hajage D Capellier G et al.Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.N Engl J Med. 2018; 378: 1965-1975Crossref PubMed Scopus (839) Google Scholar Less-invasive monitors, such as the Vigeleo, Flotrac, and esophageal cardiac output monitors, are not validated for ECMO patients and are unreliable in this population due to the presence of arrhythmia, right ventricular dysfunction, false elevations or reductions in central venous pressure, minimized ventilator settings, and the assumption that blood flow is out of the heart instead of concomitantly toward it.5Marik PE. Noninvasive cardiac output monitors: A state-of the-art review.J Cardiothorac Vasc Anesth. 2013; 27: 121-134Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar The physiology of ECMO is complex and makes routine measurements of right atrial (or central venous) pressures, pulmonary artery pressures, pulmonary capillary wedge pressures, and cardiac output context-dependent and complex. A thoughtful approach is important to avoid misinterpretation of important physiologic parameters, which can result in incorrect management decisions. What follows is a brief description of considerations for invasive cardiovascular monitoring in patients on VV and VA ECMO, with special considerations for various cannula configurations. For VV ECMO patients, the three most common cannulation strategies are (1) femoral vein drainage to internal jugular vein return, (2) dual femoral vein cannulation with a return cannula in the right atrium and a drainage cannula in the inferior vena cava, and (3) a single “dual-lumen” cannula strategy through the right internal jugular vein (eg, Avalon-Elite or Crescent cannulas).6Banfi C Pozzi M Siegenthaler N et al.Veno-venous extracorporeal membrane oxygenation: Cannulation techniques.J Thorac Dis. 2016; 8: 3762-3773Crossref PubMed Scopus (36) Google Scholar,7Squiers JJ Lima B DiMaio JM. Contemporary extracorporeal membrane oxygenation therapy in adults: Fundamental principles and systematic review of the evidence.J Thorac Cardiovasc Surg. 2016; 152: 20-32Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar In all of these strategies, right atrial pressure may not be reflective of volume status depending on where it is measured. The proximity of the port of a central line or Swan-Ganz catheter to the distal end of a cannula can result in either a falsely low pressure reading (in the case of a drainage cannula), or a falsely high pressure reading (in the case of a return cannula). In these circumstances, a reliable method of approximating the right atrial pressure can be obtained from measuring the right ventricular end-diastolic pressure (RVEDP) from a pulmonary artery catheter with a right ventricular port. Another method of obtaining the right atrial pressure is by subtracting the pressure gradient across the pulmonary valve (obtained by measuring the velocity time integral from a properly aligned continuous-wave spectral Doppler profile across the pulmonic valve) from the pulmonary artery diastolic pressure. When the RVEDP is calculated, it may be substituted for the true right atrial pressure unless the patient has tricuspid valve stenosis, which would necessitate adding the trans-tricuspid valve gradient to the RVEDP to approximate the true right atrial pressure. Failure to recognize the possibility of a falsely elevated central venous pressure in these circumstances can lead to inappropriate diuresis with suction events on the ECMO circuit and subsequent hemolysis or an incorrect suspicion of right ventricular dysfunction with inappropriate use of inotropic support. Patients requiring VV ECMO support will have inaccurate Fick cardiac output measurements due to oxygenated blood being returned to the venous system. Measuring the mixed venous gas from the PA catheter will yield an arterial-like oxygen saturation. The Fick method of cardiac output calculation is calculated using the following equation: CO = VO2 / (CaO2–CvO2). CO is cardiac output, VO2 is oxygen consumption, CaO2 is pulmonary vein oxygen content (approximated by arterial oxygen content), and CvO2 is pulmonary arterial oxygen content.8Narang N Thibodeau JT Levine BD et al.Inaccuracy of estimated resting oxygen uptake in the clinical setting.Circulation. 2014; 129: 203-210Crossref PubMed Scopus (46) Google Scholar Thermodilution cardiac outputs also are inaccurate due to the drainage cannulae aspirating part of the injectate, which traverses the circuit to the return cannula.9Haller M Zöllner C Manert W et al.Thermodilution cardiac output may be incorrect in patients on venovenous extracorporeal lung assist.Am J Respir Crit Care Med. 1995; 152: 1812-1817Crossref PubMed Scopus (38) Google Scholar Hence, the most appropriate way to calculate cardiac output in VV ECMO is with echocardiographic interrogation of the left ventricular outflow tract (LVOT) pulse-wave Doppler and the LVOT diameter using the formula: CO = HR*stroke volume = HR*3.14*(LVOT diameter/2)2*(LVOT VTI). CO is cardiac output, HR is heart rate, and VTI is velocity time integral.10Porter TR Shillcutt SK Adams MS et al.Guidelines for the use of echocardiography as a monitor for therapeutic intervention in adults: A report from the American society of echocardiography.J Am Soc Echochardiogr. 2015; 28: 40-56Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar This equation assumes equal stroke volumes with every beat, and that the left ventricular outflow tract is close to a perfect circle. Of note, the assumption of the LVOT being a circle is often incorrect, and can underestimate the LVOT area, and, subsequently, the cardiac output.10Porter TR Shillcutt SK Adams MS et al.Guidelines for the use of echocardiography as a monitor for therapeutic intervention in adults: A report from the American society of echocardiography.J Am Soc Echochardiogr. 2015; 28: 40-56Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar11Jainandunsing JS Mahmood F Matyal R et al.Impact of Three-dimensional echocardiography on classification of the severity of aortic stenosis.Ann Thorac Surg. 2013; 96: 1343-1348Abstract Full Text Full Text PDF PubMed Scopus (29) Google ScholarIn patients with arrhythmias, it is important to average multiple beats in order to obtain a more accurate cardiac output. In patients undergoing VA ECMO support, cannulation strategies include femoral venous drainage with femoral arterial return, right atrial drainage with aortic return (central ECMO), femoral venous drainage with axillary or subclavian arterial return, and right internal jugular venous drainage with axillary or subclavian artery return (“sport model”).7Squiers JJ Lima B DiMaio JM. Contemporary extracorporeal membrane oxygenation therapy in adults: Fundamental principles and systematic review of the evidence.J Thorac Cardiovasc Surg. 2016; 152: 20-32Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar,12Rao P Khalpey Z Smith R et al.Venoarterial extracorporeal membrane oxygenation for cardiogenic shock and cardiac arrest: Cardinal considerations for initiation and management.Circ Heart Fail. 2018; 11e004905Crossref PubMed Scopus (126) Google Scholar VA ECMO drains venous blood and returns oxygenated and ventilated blood to the arterial system. In VA ECMO patients, blood flow in the native pulmonary vascular system is not reflective of total blood flow. Pressure is the product of flow and resistance and, as such, the reduced flow in the pulmonary circuit requires a thoughtful interpretation of measurements of CVP, PA pressures, and wedge pressures. Unfortunately, there is no formula to provide a direct correlation between ECMO flow rate and a set of filling pressures due to the variability in intravascular volume status and pulmonary vascular resistance, in addition to the evolution of biventricular failure on ECMO. Any set of filling pressures must be accompanied by circuit flows to allow for proper interpretation. For example, at high flow rates in a patient supported by VA ECMO, a larger amount of the venous return to the heart is drained into the ECMO circuit. More drainage results in a lower central venous pressure, lower pulmonary artery pressures and, potentially, a lower pulmonary capillary wedge pressure if there is sufficient left ventricular ejection without significant aortic insufficiency (either by native function, with the assistance of inotropes, or with a mechanical method of decompressing the left ventricle). If increasing ECMO flows result in a higher pulmonary capillary wedge pressure, echocardiography can be used to assess the contribution of aortic insufficiency to elevated left ventricular end-diastolic pressures. Cardiac output in patients undergoing VA ECMO support is difficult to measure. As with VV ECMO, in patients undergoing VA ECMO support, oxygen and carbon dioxide gas exchanges occur at both the oxygenator and the lungs; thus, traditional assumptions regarding estimates of oxygen consumption are no longer valid, making the Fick method of cardiac output calculation inaccurate.13Miodownik S Carlon VA Ferri E et al.System of automated gas-exchange analysis for the investigation of metabolic processes.J Appl Physiol (1985). 2000; 89: 373-378Crossref PubMed Scopus (10) Google Scholar,14Fowler KT Hugh-Jones P Mass spectrometry applied to clinical practice and research.Br Med J. 1957; 1: 1205-1211Crossref PubMed Scopus (27) Google Scholar Thermodilution cardiac output also is inaccurate in part because the injectate is partly aspirated into the venous limb of the ECMO circuit.15Hoyler MM Flynn B Iannacone EM et al.Clinical management of venoarterial extracorporeal membrane oxygenation.J Cardiothorac Vasc Anesth. 2020; 34: 2776-2792Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar,16Cavarocchi NC Pitcher HT Yang Q et al.Weaning of extracorporeal membrane oxygenation using continuous hemodynamic transesophageal echocardiography.J Thorac Cardiovasc Surg. 2013; 146: 1474-1479Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar As a caveat, when VA ECMO flows are decreased in a “turn-down”, or weaning trial to minimal flows (for example, 0.5 L/min after appropriate systemic anticoagulation), cardiac output estimations by pulmonary artery catheter are fairly accurate due to the minimal presence of mechanical support. At any given ECMO flow rate, assuming equal beat-to-beat stroke volumes, native cardiac output may be calculated by the LVOT VTI method as above, though circuit flow rate will have a major impact on native cardiac output. The degree of pulsatility on the arterial waveform also can play a major role in evaluating native cardiac output and recovery. If the blood pressure displays pulsatility, measuring the LVOT VTI can be useful to determine native CO; however, if the patient is not pulsatile, then an LVOT-derived CO cannot be calculated. It is unknown what degree of left ventricular pulsatility is necessary to facilitate a CO measurement via echocardiography,although the more pulsatility that is present, the higher the LVOT VTI will be, making measurement more straightforward. In conclusion, we wish to stress the importance of a thoughtful interpretation of hemodynamic parameters in patients undergoing ECMO support in order to make appropriate management decisions. A previous work in this Journal by Hoyler et al provided a thorough review of other important considerations in venoarterial ECMO patients, such as evaluation for complications, weaning, and venting.15Hoyler MM Flynn B Iannacone EM et al.Clinical management of venoarterial extracorporeal membrane oxygenation.J Cardiothorac Vasc Anesth. 2020; 34: 2776-2792Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar The difficulty of measuring cardiac output in patients on ECMO likely makes it an inappropriate endpoint for clinical research purposes. Pulmonary artery catheter pressure analysis, more so than cardiac output measurements, are extremely important in the management of ECMO, and may be supplemented by echocardiographic estimations of pulmonary artery and right ventricular pressures.17Parasuraman S Walker S Loudon BL et al.Assessment of pulmonary artery pressure by echocardiography—A comprehensive review.IJC Heart & Vasculature. 2016; 12: 45-51Crossref Scopus (88) Google Scholar Proper use and interpretation of pulmonary artery catheters allow for the diagnosis and prompt response to early signs of RV dysfunction in acute respiratory distress syndrome patients on VV ECMO and for assessment of myocardial performance in VA-ECMO. Appropriate use of pulmonary artery catheters also can assist in volume management, the application of pulmonary vasodilators, left ventricular venting to reduce the negative pulmonary effects of elevated pulmonary capillary wedge pressure, and weaning of ECMO therapy. None.